**National Institute on Aging**

**Behavioral and Social Research Program**

**Workshop on Social Neuroscience of Aging**

**Doubletree Hotel Washington**

**Washington, D.C.**

**February 7--8, 2007**

***Executive Summary***

This report summarizes the proceedings of a Workshop on Social
Neuroscience of Aging held on February 7--8, 2007 in Washington, DC.
This workshop brought together invited speakers from several
disciplines, including behavior genetics, biodemography, social and
personality psychology, psychiatry, social cognitive and affective
neuroscience, sociology, health psychology and psychoneuroimmunology, as
well as representatives of NIA, the National Institutes of Health (NIH)
Office of Behavioral and Social Sciences Research, and the NIH Center
for Scientific Review. Workshop goals were to develop a common language
for discussing aging relevant issues in social neuroscience, facilitate
collaborations across disciplines, identify research gaps and
opportunities, and identify methodological challenges and potential
solutions. Drs. Lisbeth Nielsen and Jennifer Harris co-chaired the
workshop. Dr. Richard Suzman, Director of the Behavioral and Social
Research Program at NIA, also attended.

Through targeted presentations and extended dialogue, participants
addressed successful approaches, pitfalls, gaps in knowledge, next
steps, and opportunities and needs for aging research in social
neuroscience, as well as ways in which NIA and the scientific community
could support development of this research area. Discussions focused
both on research that takes a life-course perspective (i.e., the
influence of social behaviors and events in early life on late-life
health) and on research addressing the individual problems of older
people (i.e., morbidities, mortality, social environmental factors).

Dr. Suzman pointed out that BSR is interested in supporting basic
research that does not have immediate relevance to aging, as long as it
will eventually be relevant to issues related to aging. He added that
the field as a whole must determine where it can provide answers of
social, economic, individual, and translational importance. In this way,
investigators can increase their chances of receiving additional funding
from NIA and NIH. Drs. Suzman, Nielsen, and Harris encouraged workshop
participants and members of the scientific community to contact NIA with
ideas for research.

**Emerging Themes**

-   **The importance of context and lifecourse approaches in social
    neuroscience studies.** Workshop participants discussed the
    biological and social conditions and contexts underlying the effects
    of social behavior on health, and emphasized the need to focus on
    the entire lifespan, including midlife (age 20--60 years), as
    opposed to focusing only on each end of the lifespan (i.e., children
    and the elderly). Although lifecourse studies are invaluable, it is
    also important to remember the "people already out of the starting
    gate," individuals who are reaching old age and will be living
    longer because of medical advances. NIA-supported research should
    thus consider ways to improve and enhance the later years of life.

-   **Understanding how social factors affect the individual.** Several
    studies have associated social contact, social connectedness, and
    lack of loneliness with good health outcomes. Understanding how
    these social factors "get under the skin" and promote healthy aging
    needs to be addressed in future research on social neuroscience of
    aging. Key questions concern how social factors affect the
    pathophysiology of disease, how they affect the way individuals
    process information, whether effects are reversible, and how effects
    differ with age. Existing data and connections between behavioral
    and physiological measures can be used to identify sustainable
    predictors of social effects on physiology.

-   **Defining the study question.** Several themes have emerged in
    social neuroscience, including neurobiological mechanisms underlying
    social behaviors, differences associated with various life stages,
    and the neurobiological pathways mediating the effects of social
    connectedness and social relationships on health. One goal for the
    workshop was to identify the research questions ripe for approach
    from the perspective of aging research.

-   **Longitudinal studies and the use of existing populations.**
    Participants were interested in designing studies that are
    complementary to existing longitudinal studies supported by NIA that
    include extensive social, psychological and health-related data from
    large nationally representative samples (such as MIDUS and the HRS).
    Data from some of these studies is publicly available for secondary
    analysis and hypothesis testing. Principal investigators of existing
    studies must also make connections with outside researchers to
    exploit the potential of these datasets. Future studies should
    consider cohort changes, and the social, cultural and environmental
    factors that drive them. For example, consider children who are on
    chronic medications to modify social behaviors and will be
    pharmacologically dependent as they reach adulthood and old age.

-   **Methods.** A full understanding of social neuroscience phenomena
    will require multiple methods, including traditional methods such as
    self-reports, interviews, and observational studies, in combination
    with new tools available from neuroscience and genetics. In
    addition, microcosm approaches, in which interviewers also observe
    behavior at a certain point of time, can reveal seemingly short-term
    processes that, upon further study, turn out to be snapshots of
    long-term processes.\
    \
    New methods also are needed, but these will require innovative,
    high-risk studies that NIH study sections have not traditionally
    supported.

-   **The use of animal models.** Researchers interested in social
    neuroscience of aging should identify basic questions on which
    animal models could be brought to bear. These questions should
    address demographic, behavioral, physiological, and molecular
    levels. They also should focus not on 1:1 concordances, but on
    general principles that can be found across species. These
    principles or themes include temperament, predisposition, early
    intervention, and functional gene polymorphisms.

-   **Mapping neuroimaging studies to the real world.** Most fMRI
    studies are done at the individual level, but many studies of
    sociological interest take place within social groups. Mapping
    imaging studies onto phenomena that take place in the real world has
    proven difficult. Large studies can be used to identify mechanisms
    underlying meaningful real-world experiences, and imaging studies
    can be used to observe the brain activity underlying those
    mechanisms and to develop tasks that study participants can
    undertake while in a scanner. On the basis of these studies, analogs
    corresponding to real-world experiences can be created and
    translated to tasks undertaken in a scanner.

-   **Understanding social behaviors from an aging perspective.**
    Research in social neuroscience of aging should combine approaches,
    paradigms, and models from multiple disciplines. It should not,
    however, attempt to repeat in older adults paradigms established in
    younger adults. Collaboration can be facilitated through additional
    workshops and symposia that bring together investigators of
    different disciplines. A common language also is needed to
    facilitate collaboration.

-   **Bringing attention to the field of social neuroscience of aging,
    and garnering interest among researchers.** Small RFAs, workshops,
    symposia, special journal issues, and books published by the New
    York Academy of Sciences were suggested as ways to promote this
    field of research.

**Existing Longitudinal Cohorts of Interest to Researchers in Social
Neuroscience of Aging**

-   Midlife in the United States: A National Study of Health and
    Wellbeing (MIDUS)
    \<[http://www.midus.wisc.edu](http://www.midus.wisc.edu/)/\>

-   Coronary Artery Risk Development in Young Adults (CARDIA) Study
    \<<http://www.cardia.dopm.uab.edu/>\>

-   Health and Retirement Study (HRS)
    \<[http://hrsonline.isr.umich.edu](http://hrsonline.isr.umich.edu/)/\>

-   National Social Life Health and Aging Project (NSHAP)
    \<[http://www.norc.org/NSHAP](http://www.norc.org/NSHAP/)/\>

-   Chicago Health, Aging, and Social Relations Study (CHASRS)
    \<<http://psychology.uchicago.edu/people/faculty/cacioppo/CHASRS.shtml>\>

**Specific Suggestions for Research Needs and Questions**

-   Creation of a toolbox of measures of social factors, such as
    attachment styles, inhibitions, exploration, impulsivity,
    self-control and sensation seeking that can be tracked across the
    lifespan. These data can be culled from existing longitudinal
    studies, and new studies can build these measures into their data
    collection. Recorded social behaviors, such as videos, can be
    included in this bank.

-   Studies of nervous system evolution, including the autonomic nervous
    system, as well as what happens as a person's nervous system ages
    and how this development is impacted by and impacts social behaviors
    and the social environment.

-   Methods to relate biological markers to social behaviors,
    relationships and environments.

-   Studies of the potential differences between social and non-social
    stressors, as well as between acute and chronic social stressors;
    their differential impact on lifecorse trajectories of physical and
    mental health, and older vs. younger individuals.

-   Studies of the role of psychosocial factors in promoting well-being
    in older age, and the neurobiological and genetic pathways that
    support positive aging.

-   More careful assessments of the social environment as it relates to
    aging.

-   Studies of adaptive social behaviors associated with healthy aging.

-   Interfaces between dyadic interaction studies (that permit direct
    and continuous observation of social behaviors) and existing
    longitudinal cohorts.

-   Interfaces between stigma research, including the study of self and
    other stereotypes of aging and their neurobiological correlates and
    consequences, and research on aging.

-   Studies teasing apart components of ageism. The use of animal models
    in exploring the evolutionary aspects of prejudice and ageism.

-   Studies of the role of oxytocin and other neuropeptides and hormones
    in age-related changes in sociality and loneliness.

-   Studies on sources of pleasure and pain, particularly those of a
    social nature, and how these sources change with age.

**Challenges and Solutions**

-   With notable exceptions, most existing longitudinal studies of aging
    do not include extensive social and behavioral factors in their data
    collection. This challenge could be addressed partly by adding
    measures of perceived stress, social support, self-esteem,
    self-regard, and theory of mind. Many of these measures are
    relatively short and therefore easy to add to an existing study.

-   New and junior investigators might shy away from engaging in social
    neuroscience of aging research, because of the extra challenges
    involved or lack of familiarity with aging issues. Grant agencies
    can establish mechanisms to facilitate collaborations and find ways
    for investigators to enter the field without being penalized for it.
    NIH should work with institutions to ensure that the value of
    participating in such collaborations is recognized.

**National Institute on Aging**

**Behavioral and Social Research Program**

**Workshop on Social Neuroscience of Aging**

***Table of Contents***

[List of Abbreviations viii](#list-of-abbreviations)

[Introduction 1](#introduction)

[Session I: Parsing Socioemotional Behaviors: Directions for Aging
Research
3](#session-i-parsing-socioemotional-behaviors-directions-for-aging-research)

[Dimensions of Emotional Function 3](#dimensions-of-emotional-function)

[Social Judgment 4](#social-judgment)

[Social Cognition 6](#social-cognition)

[Self-concept, Motivation, Context 7](#self-concept-motivation-context)

[Session I Discussion---Using Longitudinal Studies to Assess Social
Neuroscience across the Lifespan
8](#session-i-discussionusing-longitudinal-studies-to-assess-social-neuroscience-across-the-lifespan)

[Session II: Multilevel Approaches to Studying Neurobiological
Mechanisms and Pathways Involved in Socioemotional Function
9](#session-ii-multilevel-approaches-to-studying-neurobiological-mechanisms-and-pathways-involved-in-socioemotional-function)

[Neuropeptides (Human and Animal Studies)
9](#neuropeptides-human-and-animal-studies)

[Psychoneuroimmunology and Genetics
10](#psychoneuroimmunology-and-genetics)

[Neuroimaging and Social Psychology
11](#neuroimaging-and-social-psychology)

[Neuroimaging and Genetics 12](#neuroimaging-and-genetics)

[Lesion Studies, Eye Tracking 14](#lesion-studies-eye-tracking)

[Session II Discussion---Research Opportunities, Gene-Environment
Interactions, Practical Considerations for Social Neuroscience in Aging
15](#session-ii-discussionresearch-opportunities-gene-environment-interactions-practical-considerations-for-social-neuroscience-in-aging)

[Session III: Psychosocial Stress, Health, and Aging: Emerging
Perspectives on Pathways and Mechanisms
16](#session-iii-psychosocial-stress-health-and-aging-emerging-perspectives-on-pathways-and-mechanisms)

[Cellular Mechanisms and Allostatic Load
16](#cellular-mechanisms-and-allostatic-load)

[Gender-specific Motives and Mechanisms
18](#gender-specific-motives-and-mechanisms)

[Session III Discussion---Telomere Length, Differences in Stress
Response, Changes across the Lifespan
19](#session-iii-discussiontelomere-length-differences-in-stress-response-changes-across-the-lifespan)

[Session IV: Loneliness, Social Connectedness, and Healthy Aging:
Emerging Perspectives on Pathways and Mechanisms
20](#session-iv-loneliness-social-connectedness-and-healthy-aging-emerging-perspectives-on-pathways-and-mechanisms)

[Social Bonds and Attachments 20](#social-bonds-and-attachments)

[Marriage and Caregiving 20](#marriage-and-caregiving)

[Session IV Discussion---Associating Biological Markers with Social
Relationships and Environment, New Methods Development
21](#session-iv-discussionassociating-biological-markers-with-social-relationships-and-environment-new-methods-development)

[Session V: Evolution and Development of Social Behaviors: Opportunities
Presented by Animal Models
23](#session-v-evolution-and-development-of-social-behaviors-opportunities-presented-by-animal-models)

[Biodemography of Sociality and Lifespan
23](#biodemography-of-sociality-and-lifespan)

[Session V Discussion---Applying Biodemographic Principles to Social
Neuroscience of Aging
25](#session-v-discussionapplying-biodemographic-principles-to-social-neuroscience-of-aging)

[Primate Social Behaviors 25](#primate-social-behaviors)

[Session V Discussion---Rearing Conditions in Rhesus Macaques and
Possibilities for Translation to Human Studies
27](#session-v-discussionrearing-conditions-in-rhesus-macaques-and-possibilities-for-translation-to-human-studies)

[Session VI: Social Behaviors, Social Environments, Genetics, and Aging:
Opportunities in the Study of Human Populations
28](#session-vi-social-behaviors-social-environments-genetics-and-aging-opportunities-in-the-study-of-human-populations)

[Gene-environment Interplay: Age Moderation of Genetic Effects
28](#gene-environment-interplay-age-moderation-of-genetic-effects)

[Session VI Discussion---Genetics and Environment, Adaptive Behaviors in
Late Life
29](#session-vi-discussiongenetics-and-environment-adaptive-behaviors-in-late-life)

[Session VII: Measurement of Social Environments and Social Behaviors of
Relevance to Aging: Ecologically Valid Methods
30](#session-vii-measurement-of-social-environments-and-social-behaviors-of-relevance-to-aging-ecologically-valid-methods)

[Dyadic Interaction 30](#dyadic-interaction)

[Session VII Discussion---Recording Dyadic Interactions
32](#session-vii-discussionrecording-dyadic-interactions)

[Implicit Measures 32](#implicit-measures)

[Session VII Discussion---Subtle Prejudice
33](#session-vii-discussionsubtle-prejudice)

[Oxytocin and Bonding 34](#oxytocin-and-bonding)

[Session VII Discussion---Oxytocin as Biomarker in Aging
34](#session-vii-discussionoxytocin-as-biomarker-in-aging)

[Session IX: Lab-Survey Partnerships and Other Integrative
Approaches:Challenges and Benefits of Trans-disciplinary Collaborations
36](#session-ix-lab-survey-partnerships-and-other-integrative-approacheschallenges-and-benefits-of-trans-disciplinary-collaborations)

[Sexual Behavior; National Social Life, Health, and Aging Project;
Chicago Health, Aging, and Social Relations Study
36](#sexual-behavior-national-social-life-health-and-aging-project-chicago-health-aging-and-social-relations-study)

[Session IX Discussion---NSHAP, CHASRS
37](#session-ix-discussionnshap-chasrs)

[The University of California, Los Angeles (UCLA) Study
38](#the-university-of-california-los-angeles-ucla-study)

[Session IX Discussion---The UCLA Study
39](#session-ix-discussionthe-ucla-study)

[Session X: General Discussion 40](#session-x-general-discussion)

[Workshop Participants 47](#workshop-participants)

[Literature Cited 48](#literature-cited)

# List of Abbreviations

5-HIAA 5-hydroxyindoleacetic acid

5-HT serotonin

5-HTT serotonin transporter

5-HT~1A~ serotonin receptor

ACTH adrenocorticotropic hormone

AD Alzheimer's disease

ApoE apolipoprotein E

BOLD blood oxygenation level-dependent

BSR Behavioral and Social Research Program

CARDIA Coronary Artery Risk Development in Young Adults

CRF corticotrophin-releasing factor

CRP C-reactive protein

CSF cerebrospinal fluid

fMRI functional magnetic resonance imaging

HPA hypothalamic-pituitary-adrenal

HPV human papillomavirus

HRS Health and Retirement Study

IL-6 interleukin 6

LSADT Longitudinal Study of Aging Danish Twins

MAOA monoamine oxidase A

MIDUS Midlife in the United States: A National Study of Health and
Wellbeing

MMSE Mini-Mental State Examination

NIA National Institute on Aging

NIAAA National Institute on Alcohol Abuse and Alcoholism

NIA C Clinical Aging Review Committee

NIDA National Institute on Drug Abuse

NIMH National Institute of Mental Health

NYAS New York Academies of Science

PFC prefrontal cortex

RFA request for applications

SBIR Small Business Innovation Research

SES socioeconomic status

SON supraoptic nucleus

TNF-α tumor necrosis factor alpha

vACC ventral anterior cingulate cortex

**National Institute on Aging**

**Behavioral and Social Research Program**

**Workshop on Social Neuroscience of Aging**

**National Institute on Aging**

**Behavioral and Social Research Program**

**Workshop on Social Neuroscience of Aging**

# Introduction

### Lisbeth Nielsen, Ph.D., National Institute on Aging

Social neuroscience encompasses several themes, including the
neurobiological and genetic underpinnings of social behaviors and the
impact of social relationships and social environments on
neurobiological processes relating to psychological and health outcomes.
Social behaviors are seen as embedded in a causal nexus, both as
mediating factors for other outcomes and as outcomes in themselves. The
field of social neuroscience has experienced rapid growth over the past
decade, as evident in the publication of special journal issues, the
number of new U.S. laboratories dedicated to social neuroscience, and
major initiatives by the National Institute on Drug Abuse and the
National Institute of Mental Health. Despite increasing interest in
social neuroscience, and despite work showing age-associated changes in
basic cognitive functions, emotional regulation, and management of
social relationships, few studies have focused on aging.

Themes inherent in social neuroscience can advance behavioral and social
research on aging, as discussed in *When I'm 64*[^1], a report by the
Committee on Aging Frontiers in Social Psychology, Personality, and
Adult Developmental Psychology. This report, commissioned by the
National Institute on Aging (NIA) Behavioral and Social Research Program
(BSR), discusses the benefits of social neuroscience approaches for
advancing work on four major themes in the psychology of aging,
including socioemotional influences in decision making, motivation and
behavioral change, social engagement and cognition, and stereotypes of
self and others. Social neuroscience research can address relationships
among social behaviors, emotional dispositions, social environments, and
neurobiological pathways, processes, and mechanisms. Such research can
elucidate how age-related social phenomena, such as stereotypes of
aging, bereavement, and loneliness, "get under the skin" and compromise
late-life health. Innovative methods will be needed to answer these
questions, and translational approaches will be needed to link these
studies to potential interventions.

BSR has identified the field of social neuroscience as a priority area
for program development. To promote social neuroscience with an emphasis
on aging, BSR has conducted several scientific activities. In 2006, a
joint request for applications (RFA) in the field of social neuroscience
was released by the National Institute of Drug Abuse, The National
Institute of Alcohol Abuse and Alcoholism, and the National Institute on
Aging, resulting in three new R01 grants. BSR has identified social
neuroscience as a priority area for research training, and has sponsored
scientific symposia on social neuroscience themes including one with the
Society for Psychophysiological Research and one at the Fourth Annual
Chicago Biomarkers Workshop. In March 2006, BSR conducted conference
calls focused on methods for exploring the neurobiological bases of
social behaviors using approaches from a broad range of disciplines,
including sociogenomics, behavioral and neuroeconomics, and personality
and social psychology. These calls began a planning process for this
workshop.

What advances in behavioral and social research on aging are likely to
come from taking a social neuroscience approach? With regard to the
social and personality psychology of aging, social neuroscience research
can address whether social behaviors and emotional dispositions change
with age because of underlying changes in neurobiological function or
whether changes in social motives alter neurobiological processes.
Research focused on social factors promoting health and resilience can
begin to determine which neurobiological pathways mediate the effects of
protective social environments or individual differences on healthy
late-life development[^2]^,3^. Likewise, research focused on
psychosocial stress and health can address the neurobiological pathways
and mechanisms through which social stressors, such as caregiving,
stereotypes of aging, bereavement, and loneliness "get under the skin"
and compromise late-life health. Thus, aging research would benefit from
a social neuroscience approach.

Recent work in social bonding, emotional regulation, loneliness, and
sterotypes of aging point to several research opportunities in the
social neuroscience of aging. For example, studies have shown that
social bonding and soothing behaviors can mitigate the destructive
effects of stress on health and well-being^5^ and that lack of general
contact is associated with increased mortality. House and colleagues
found that the relative risk for all-cause mortality is greater for
social isolation than that reported for cigarette smoking. ^6^ Work by
Cacioppo and colleagues demonstrated that loneliness is associated with
elevated systolic blood pressure^7^ and that loneliness is a heritable,
stable trait affecting how people perceive and interact with others.^8^
In addition, numerous studies have demonstrated beneficial effects of
marriage on health. Marriage is thought to be a reliable proxy measure
of relationships defined by strong emotional bonds, interdependence, and
security, and represents an optimal context for exploring how social
relationships buffer against stress (Coan, Shaeffer & Davidson, 2006).
Coan and colleagues have proposed that positive social relationships
confer health benefits by offering a form of emotional regulation. In a
recent study^10^ these investigators used functional magnetic resonance
imaging (fMRI) to assess social regulation of the neural response to
threat in married couples selected for their high relationship
satisfaction. Women entered the fMRI scanner and viewed images that were
either neutral or represented the threat of a mild electric shock. Their
husbands, outside the scanner, held their hands on some of the trials.
In this study, participants felt more negative emotion when they viewed
threatening stimuli without physical contact, but they were subjectively
less negatively aroused when holding hands with their spouses. As shown
by fMRI, hand-holding attenuated the neural stress response. This
attenuation was more pronounced when participants held hands with their
spouses, than when they held hands with strangers or were alone. In
addition, higher marital quality predicted less threat-related neural
activity in the right insula, right superior frontal gyrus, and the
hypothalamus. Extension of this research to aging, in couples who have
been in long term marriages, or in couples who are coping with chronic
illness and the potential of loss, could shed light on the
neurobiological basis of long-term social bonds, and what happens when
these relationships are threatened or challenged. It also suggests a
variety of translational opportunities for studying the role of social
contact in illness recovery and management of anxiety in health care
settings.

Other research opportunities are been suggested by studies focused on
stereotypes of aging. The stereotypes people hold about old age have
been shown to predict a variety of behavioral and health outcomes. Data
from a study conducted in a British sample suggest that the perceived
age of entering middle age predicts health outcomes and mortality.^11^
Other research shows that elders' stereotypes predict hearing
outcomes.^12^ The *When I'm 64* report asks whether negative
expectations affect perceptions of older persons' abilities and whether
positive expectations have the opposite effect.^1^ Translational
research in this area might point to positive stereotypes of aging as a
way to reduce disability.

Opportunities abound for social neuroscience research focused on
methodological innovations, including:

-   Methods to measure social behaviors relevant to older adults in the
    laboratory, field, and neuroimaging environments.

-   Incorporation of neurobiological and behavioral measures of social
    behaviors in older adults in ongoing longitudinal studies of aging.

-   Assessments of the reliability of neurobiological measures of social
    behaviors in older adults.

-   Approaches to understanding the mechanisms linking social behaviors
    to genetic expression across the lifespan.

-   Data on generalizability of lab findings to real-world social
    behavior.

Other promising approaches toward social neuroscience in aging include a
lifespan approach in assessing the neurobiological underpinnings of
social behavior, a refined ability to measure and identify phenotypes
and endophenotypes with respect to aging, advanced methods to measure
social environments relevant to aging outcomes, and an exploration of
social and cultural context effects on social behaviors and their
neurobiological correlates. Social neuroscience research should seek to
bridge these approaches to interventions and translational research.

# Session I: Parsing Socioemotional Behaviors: Directions for Aging Research

***Goals of Session I:** To describe some of the fundamental building
blocks of social and emotional behaviors with discussion of current
knowledge related to age-related differences or change, and suggestions
how to direct aging research on these themes.*

## Dimensions of Emotional Function

### Robert Levenson, Ph.D., University of California, Berkeley

*Dr. Levenson's presentation briefly identified the multiple components
of emotional function that are integral to social behavior, then
highlighted what is known about how they change with age, and ended by
indicating where he sees important knowledge gaps or emerging
opportunities for study of their function in aging.*

Emotions are critically related to the major determinants of successful
aging, including social relationships, cognitive processes, late-life
"wisdom," dementing disorders, psychopathologies, and general
well-being. Contrary to classic views proposed by Banham , Jung, and
Looft, in which old age is seen as a time of dampened, rigid, and flat
emotionality, recent evidence suggests that older persons exhibit
greater emotional control,^13^ same or greater well-being,^14^ greater
emotional understanding,^15^ and greater emotional refinement.^16^
Illnesses, particularly disorders associated with late life, appear to
have a devastating effect on emotional functions. Thus, the
relationships of physical health and brain diseases to emotions must be
considered in research focused on late life.

Some view emotional functioning as a monolithic system, all of which
stops working when any part is injured. However, evidence from lesion
and patient studies has revealed discernible and separate circuits for
different aspects of emotional functioning. *Reactivity* includes the
behavioral, physiological, subjective, and language responses that
accompany positive, negative, and self-conscious emotions. *Emotion
regulation* includes spontaneous or intentional down-regulation and
up-regulation of emotional responses. *Emotional knowledge* includes
cognitive empathy (knowing what others feel) and emotional
expertise/wisdom. *Socioemotional* includes social interest, emotional
empathy (feeling what others feel), attachment and bonding, and social
concern and sympathy. Thus, a complete assessment of emotional
functioning in later life will require a consideration of each of these
aspects of emotional functioning.

Emotion in aging is studied using questionnaire and survey methods,
which generate self- and informant-reports and have been used in large
epidemiological studies, and laboratory methods (e.g. behavioral,
psychophysiological and fMRI studies), which are still relatively new in
the field of aging research. Several laboratory studies suggest that
most aspects of emotional reactivity, regulation, knowledge, and
socioemotional functioning are maintained in healthy elders, although
the magnitude of cardiovascular responses might decline.

In the context of frontotemporal lobar degeneration (FTLD), however,
large areas of emotional functioning are devastated. Thus FTLD offers a
window onto the specific neural circuitry necessary for maintaining
socioemotional functioning in older age. NIA has supported a great deal
of research in Alzheimer's disease (AD), which can address the immense
social cost associated with this disease, as well as inform what is
understood about the neural circuitry necessary for normal cognitive
function, especially in domains such as memory and spatial processing.
However, areas of the brain critical for emotional functioning may be
relatively spared in the early stages of AD. Determining how the various
aspects of emotional functioning and their underlying neurobiological
systems are maintained or change with age can potentially advance an
understanding both of psychological functioning in late life and of
emotion.

## Social Judgment

### Susan Fiske, Ph.D., Princeton University

*Dr. Fiske's presentation identified the core components of social
judgment, from a social psychological perspective, then highlighted what
is known about how they (or their importance) change(s) with age, and
ended by indicating important knowledge gaps or emerging opportunities
for study of their function in aging.*

A variety of social judgment processes can be placed along a continuum
ranging from automatic, unintentional, and unconscious processes to more
controlled, goal-directed, and conscious processes (Fiske and Taylor,
*Social Cognition: From Brains to Culture*, in press). The field of
social psychology has seen an explosion in the number of dual-process
models, including peripheral versus central persuasion, dispositional
versus situational attribution, category versus individuating
impressions, heuristic versus rational choice inference, and dominant
versus appropriate self-regulation.

Older age is associated with declines in cognitive control functions,
and the impact of these changes on social judgment is virtually
unexplored. Age-related declines in control may involve several
components, such as reductions in domain-general resources, executive
selection processes, information seeking, working memory capacity,
related to functional and structural changes in the prefrontal cortex
(PFC). This might lead to a stronger reliance on automatic processes and
heuristics rather than processes that require someone to work through
details. Persuasion might be based on superficial cues, or communicator
credibility, and past decisions. Attribution might rely more on
person-based inference. Impressions might be more stereotypic,
inferences more heuristic, and self-regulation based more on dominant
responses.

Fiske and colleagues combined a classic paradigm of dispositional
attributions, the Kelley-McArthur Attributions with neuroimaging.^17^ In
the Kelley-McArthur Attributions paradigm, people are presented with a
statement, "Mark believes the operation will be a success," and asked
why they think this is. In a 2x2x2 matrix based on consensus (no one
else does it), distinctiveness (he does it only to all targets), and
consistency (he does it every time), one condition involves
dispositional inference: that where consensus and distinctiveness are
low and consistency is high. In their imaging studies, Harris and
colleagues found activation in the superior temporal sulcus and the
medial PFC associated with dispositional inferences. However, this study
was done in college students. If it is true that with age, people rely
more on heuristics that have served them well, it is likely that the
specialization seen in college-age students will not be apparent in
older persons. One would predict less use of information, more
dispositional inferences, and thus less behavioral and neural
differentiation.

Fiske and colleagues also have explored how age is associated with being
a target of social judgment.^18^ Social perception involves two
dimensions: *intent*, which involves judging someone as good or bad and
is based on perceived warmth and trustworthiness; and *capability*,
which is an assessment of a person's competence and skill. In other
words, when someone encounters someone else, the first thing they want
to know is what that person's intent is and whether that person can
enact his or her intent. In a stereotype content model, distinct
societal groups are rated as high or low on each of these dimensions,
and each combination of traits leads to a specific kind of
discrimination. For example, older, disabled, or mentally retarded
people are perceived as high on warmth but low on competence and
engender pity. On the other hand, Jews, Asians, rich people, and
professionals are perceived as highly competent but cold, which promotes
feelings of envy. Dr. Fiske's group has shown this to be universal in
various samples, including one representative of the United States
population (Cuddy, Fiske, and Glick, *J Pers Soc Pscyhol*, in press). In
another study, this group showed individual photos of societal groups
and imaged brain activation. When participants saw groups and felt
pride, envy, or pity, the medial PFC was activated.^19^ When
participants saw groups that made them feel disgust, however, no medial
PFC activation was observed, suggesting that no social cognition was
occurring. Thus, people do not see these groups as "us versus them";
more likely, they do not see members of these groups as people at all.

These findings are important, because they identify the specific types
of behavioral discrimination that may arise as a function of unique
combinations of stereotyping and emotional prejudices. For example,
while older people might receive active help from others in society, at
the same time they might suffer from passive neglect. Future studies in
aging should examine neural correlates of both empathic and stereotyped
attitudes toward aging.

## Social Cognition

### Ralph Adolphs, Ph.D., California Institute of Technology

*Dr. Adolphs focused on what is known about how social cognition is
instantiated in the brain, emphasizing the role of feedback-feed forward
networks, and suggested directions for future study.*

Most cognitive and behavioral neuroscience studies begin with a stimulus
input that goes through a series of processes whereby more complex
properties of the stimulus are abstracted to generate a rich thought of
the world. This type of study design assumes a unidirectional flow of
information, when most likely there are multiple tracks of information
processing in the brain, some emotional/automatic and some reflective.
These different tracks have been associated with various neural
structures. For example, the amygdala, insula, and somatosensory cortex
are involved in emotional responses, whereas other regions of prefrontal
cortex are known to be involved in more reflective and regulatory
processing.

Higher-order perceptual processes, such as those used in the perception
of faces, might rely on feedback loops to construct a final percept. In
one loop, for example, the amygdala could associate the face with its
emotional meaning, resulting in an empathic or simulation-like emotional
response to the stimulus that could in turn then be represented in
cortex. The unfolding perceptual processing of a stimulus would thus be
influenced by the emotional value attached to that stimulus and would
generate complex social judgments that could differ depending at what
point in time the judgment was sampled. The unfolding perceptual
processing of a stimulus would thus be influenced by the emotional value
attached to that stimulus and would generate complex social judgments
that could differ depending at what point in time the judgment was
sampled. It may be also that extraneural loops that involve the body
trigger responses in the body that would affect how one feels about a
stimulus.

Aging research in social cognition should elucidate which of these
processes change the most with age and how this affects function in the
feedback-feed forward networks for (1) perception, or how one processes
information; (2) evaluation, or how one evaluates what he or she sees;
and (3) regulation, or how one controls his or her response.

It may be that changes in social cognition and pathology with aging
result primarily from changes in connectivity among brain regions. The
bulk of what is known about white-matter connections comes from
tracer-injection studies done in monkeys with the assumption that these
connections can be extrapolated to the human brain. Tools like diffusion
tensor imaging are now available to examine white-matter connections,
which differ among various brain regions. Future studies should explore
the development and change in these structures (and their
interconnections) and functions across the entire lifespan, as opposed
to focusing only on declines associated with old age.

## Self-concept, Motivation, Context

### Todd Heatherton, Ph.D., Dartmouth College

*Dr. Heatherton highlighted the ways in which self-concept, motivation,
and social context are integral to a psychological understanding of
social behavior, highlighting what is known about how they change with
age, and indicating where there are emerging opportunities for aging
research on these themes.*

Functions of the social brain include (1) self-awareness, or insight
into one's own behavior; (2) theory of mind, or insight into other
people's thoughts; (3) threat detection with respect to ingroups versus
outgroups; and (4) self-regulation, which controls health behaviors and
inhibits inappropriate social actions. It is well established that the
aging brain shows diminished frontal lobe volume, diminished task
activity and increased nonspecific (and possibly compensatory) activity,
and diminished functional connectivity. It remains to be shown how these
age-related brain changes influence social cognition and social
behavior. Future research in social neuroscience should consider how
these systems interact and how those interactions change with age. In
addition, early aging should be distinguished from later aging.

*Self concept and motivation.* Carstensen's Socioemotional Selectivity
Theory suggests that older people are surprisingly happy, that they
avoid negative social cues, and that they avoid new social contacts.^4^
What do we know about the neural basis of positive self concept and
their relation to aging? Changes in the medial PFC have been associated
with increased happiness over the life course,^20^ and AD has been
associated with reduced activity in this region.^21^

Socioemotional Selectivity Theory also suggests that with age motivation
changes from knowledge acquisition and competition to emotional
satisfaction. Studies of self-regulation, motivation and behavioral
change indicate that younger people make frequent efforts to change but
fail; whereas older adults are resistant to change but are more
successful at maintenance. What do we know about the neural basis of
motivation and their relation to aging? Studies of dementia and apathy
show changes in the medial PFC and the ventral anterior cingulate cortex
(vACC).^22^

*Context*. Studies of stereotype threat expose individuals to negative
stereotypes and assess the impact of this exposure on behavior. Studies
that expose adults to negative stereotypes of cognitive function in
aging have shown that the impact of stereotype threat on cognition rises
with age but levels off in the very old.^23^ Recent studies have shown
that belief systems affect cognitive performance under stereotype threat
in younger adults, but not in very old adults; that is, very old adults
do not appear to suffer stereotype threat effects.^23^ Other research
has shown that older adults are more likely to blurt out stereotypical
beliefs.^24^

How does social context relate to successful aging? It is possible to
generate hypotheses based on available behavioral and neural evidence.
One could hypothesize that older persons lack both understanding of
social context as well as the inhibitory mechanisms that prevent
dominant reactions. Whereas some studies have suggested reductions in
theory of mind abilities with age and failures to monitor social cues,
this may be a malleable feature of aging. Successful aging may depend on
increased reliance on social context. This might suggest ways to slow or
prevent age-related declines.

Social neuroscience offers many exciting opportunities to explore
research questions of relevance to aging in the areas of self-concept,
motivation, and context effects. Future studies should form hypotheses
of what should and should not change with age, how the neural basis of
social cognition changes, and how processes interact with age.

## Session I Discussion---Using Longitudinal Studies to Assess Social Neuroscience across the Lifespan

Drs. Shelley Taylor and Elissa Epel raised the point that the processes
examined in aging research are the end products of development across
the lifespan. For example, studies by the McArthur Research Network on
Socioeconomic Status (SES) and Health suggest that events in childhood
can serve as predictors for later life outcomes. Yet how to translate
these ideas methodologically is unclear. Longitudinal studies might
provide the best information, but funding remains a barrier. In
addition, many experimental neuroimaging studies yield valuable
information, but they are isolated from the context of markers
identified in cohort studies.

Investigators interested in changes across the lifespan could interface
with ongoing developmental studies and tap into existing longitudinal
cohorts. In addition, participants for some neuroimaging studies should
be drawn from known epidemiological and social science cohorts. For
example, Dr. Taylor described a partnership with the Coronary Artery
Risk Development in Young Adults (CARDIA) study that has assessed early
family processes and is relating them to health outcomes across the
lifespan. Dr. Nielsen added that a component of the Midlife in the
United States (MIDUS) study, which is supported by BSR, channels
participants into a biomarker clinical laboratory and, ultimately, into
a psychophysiology laboratory for neuroimaging. BSR also supports the
Health and Retirement Study (HRS), which has experimental modules
attached to it. Dr. Levenson also suggested revisiting cohorts studied
previously. For example, his group worked with a cohort of 60-year-olds
20 years ago; the group is now returning for neurological testing and
assessments of cognitive functioning.

In addition to forming data-sharing or participant-sharing ties with
existing longitudinal studies, investigators also should pay careful
attention to the design of new studies, particularly the kinds of
information will be useful in the future. The quality of early data on
social and behavioral factors is often an obstacle to using existing
cohorts (with notable exceptions, such as the Dunedin Study). The group
discussed what sorts of data would be most likely to be useful in the
long term, and should be routinely banked, based on what is known now.
Suggestions included assessments of trait-like social qualities
established early in life, such as attachment styles, inhibitions,
exploration, delay of gratification, and sensation-seeking. Recorded
social behaviors were thought to be particularly valuable resources for
later analysis. For example, Elaine Walker collected home movies of
young children and was able to identify motor behaviors that predicted
schizophrenia later on. Coding methods can be developed later, but the
real need is for these data to be banked.

The majority of existing longitudinal studies do not include social and
behavioral factors in their data collections. Measures of individual
differences that predict how successfully people manage stress, as well
as measures of social support, self-esteem, and self-regard, could
easily be inserted into existing studies. Well-validated instruments for
assessing a variety of individual difference factors such as optimism,
mastery and control, social support, and risky family environments,
already exist. Scales developed by Baron-Cohen and colleagues to assess
empathizing versus systematizing might also prove useful. Behavioral
videos that record people trying to delay gratification, entering a
social group, regulating an emotional response, or immersed in an
environment with no obvious stimuli might also be beneficial.

# Session II: Multilevel Approaches to Studying Neurobiological Mechanisms and Pathways Involved in Socioemotional Function

***Goals of Session II:** To provide perspectives from a variety of labs
with different core areas of expertise on how to advance multi-method
studies of social behaviors. Each presenter was asked to discuss
interesting ways his or her laboratory has combined multiple methods to
gain deeper understanding of the neurobiological basis of social
behaviors, and to indicate promising directions for the future and for
aging research, in particular.*

## Neuropeptides (Human and Animal Studies)

### C. Sue Carter, Ph.D., University of Illinois at Chicago

*Dr. Carter's laboratory uses both human and animal studies to explore
the role of oxytocin and other neuropeptides in the regulation of social
behaviors. In her presentation she described the current understanding
of the role of these chemical mediators of social behaviors based on
convergent findings from these two tracks of research. Her presentation
emphasized the need to consider social behaviors in the context of
evolution.*

Oxytocin is a short neuropeptide produced in the brain, primarily in the
supraoptic nucleus (SON) and paraventricular nucleus (PVN) areas of the
hypothalamus. Cell bodies and fibers stained for oxytocin
immunoreactivity extend from the PVN through the posterior pituitary
gland, from which oxytocin is released into the blood supply. On the
basis of mouse studies, oxytocin is known to be essential for normal
lactation, which is a chronic and well-understood condition and
therefore can serve as a model for studying the neurochemistry of human
social behavior. Although it is not essential, oxytocin also plays a
role in birth. The role of oxytocin is complex, and the process is
poorly understood.

Vasopressin is a sibling hormone produced from a gene adjacent to the
one coding for oxytocin. Like oxytocin, vasopressin is produced in the
hypothalamus. However, these hormones differ by two amino acids and
serve as antagonists to each other. Moreover, vasopressin is sexually
dimorphic: it is dependent on androgens during early life, and
vasopressin-positive projections extending from the bed nucleus of the
stria terminalis and medial amygdala are denser in males than in
females. Oxytocin is somewhat dimorphic; blood oxytocin levels are
higher in prairie voles than rats and sometimes higher in females than
males.^25^ Although much has been learned about these hormones, their
receptors are poorly understood. What is known is that oxytocin and
vasopressin receptor distributions differ from each other and are
species specific. For example, differences in receptor distribution have
been found between prairie voles, which are socially monogamous, and
montane voles, which are not. Moreover, receptor distribution is
individual and can be affected by early exposures to other hormones.

In addition to playing a role in physiology, oxytocin also influences
behavior, and though it has sometimes been called a "female hormone,"
its effects are not limited to females. Oxytocin down-regulates stress,
which acts through the hypothalamic-pituitary-adrenal (HPA) axis. When
exposed to a social stressor, men who are given intranasal oxytocin and
have social support produce less cortisol and report less anxiety.^26^
Oxytocin also appears to play a role in trust. In studies by Kosfeld and
colleagues,^27^ Swiss men given intranasal oxytocin were more willing
than control participants to give away money, on the assumption that the
money would be returned. In other studies, intranasal oxytocin improved
men's ability to read the emotions of others, simply by looking at
pictures of their eyes.^28^

It is possible, then, that the health consequences of social bonds and
perceived social support are mediated in part by oxytocin activity.
However, the factors regulating oxytocin production or function are
poorly understood. Both oxytocin and vasopressin have several targets
and complex effects, and they can be affected by stressors differently
in different contexts. Although males and females share this system,
they differ in the way they solve problems. In animal studies, females
appear to be less sensitive to the activating effects of vasopressin.
Sex differences in humans should be explored further, as well as
possible age and developmental trajectories for oxytocin should be
explored.

It should be noted that some groups have experienced difficulty
obtaining permission from the U.S. Food and Drug Administration to use
intranasal oxytocin. Syntocin, the medical product based on oxytocin,
has been taken off the market in the United States. However, several
laboratories in the country have investigational new drug approvals
(INDs), which might facilitate the use of intranasal oxytocin for
research purposes.

## Psychoneuroimmunology and Genetics

### Janice Kiecolt-Glaser, Ph.D., Ohio State University College of Medicine

*Dr. Kiecolt-Glaser's program of research in psychoneuroimmunology and
behavioral medicine explores the physiological consequences of severe
and chronic stressors such as caregiving for a spouse with dementia.
Recently, she has extended this work to look at the genetic basis for
vulnerability to adverse outcomes associated with caregiving. Her
presentation focused on the potential in combining these methods to
address questions about psychosocial influences on health.*

Several studies have identified behavioral and psychological influences
on immune function. Interest is growing in genetic influences on these
relationships, related to how behavioral and/or immunological
polymorphisms may enhance risk. For example, many studies have focused
on serotonin (5-HT), which has been implicated in the pathogenesis of
depression and anxiety disorders. Genes encoding the 5-HT transporter
(5-HTT) and the 5-HT receptor 1A (5-HT~1A~) have been suggested as
candidate genes involved in susceptibility to depression and anxiety. In
a study conducted in a large cohort of 21- to 26-year-olds facing
stressful life events, polymorphisms in 5-HTT appeared to moderate the
negative health effects of stress.^29^ Epigenetic modifications, which
reflect gene changes without altering the DNA sequence and indirectly
affect expression of that gene, appear to play a role in the effects of
stress on health. These modifications present another variable to be
considered.

Immunological polymorphisms, such as those that enhance production of
the proinflammatory cytokine interleukin 6 (IL-6), have been associated
with diseases related to aging, such as cardiovascular disease,
osteoporosis, arthritis, and type 2 diabetes. IL-6 also has been
implicated in the stress response. In a longitudinal study of 119
caregivers and 106 non-caregivers, Kiecolt-Glaser and colleagues
measured IL-6 levels, health behaviors associated with IL-6, and
depressive symptoms. The age-related rate of increased IL-6 production
among caregivers was four times that of non-caregivers.^30^ Once
caregiving ended, the rate of annual change in IL-6 production did not
change. The rate among former caregivers mirrored that of current
caregivers, even 3 years post-bereavement. In normal bereavement, a
higher incidence of anxiety and depression is observed among widows and
widowers within the first few months after the spouse's death, compared
with non-bereaved controls. Typically, the two groups appear to be no
different in follow-up data collected 1 to 2 years later in terms of
anxiety and depression.^31-34^ However, on the basis of the rate of
change in IL-6 production, caregivers do not appear to be recovering.

Several biological mechanisms may explain the persistent changes in
caregivers. Johnson and colleagues found that prior stressor exposure
appeared to prime proinflammatory cytokine responses such that
subsequent immunological challenge resulted in a larger or more rapid
induction of these cytokines in stressed rats, compared with
non-stressed controls.^35^ Pace and colleagues found that patients with
major depression showed a larger nuclear factor kappa B (NF-κB) and
serum IL-6 response to a lab stressor than did non-depressed men.^36^
Glaser and colleagues suggested that higher levels of depressive
symptoms effectively prime the inflammatory response, resulting in
larger and more persistent inflammatory responses to later
challenges.^37^ Thus caregivers' history of stress and depressive
symptoms could place them at greater risk for exaggerated and prolonged
inflammatory responses to stressors or antigen challenges. An NIA-funded
study is under way to assess the relative contributions of 5-HT
polymorphisms, IL-6 polymorphism G174C, and a polymorphism in tumor
necrosis factor alpha (TNF-α) in caregivers and non-caregivers.

## Neuroimaging and Social Psychology

### Todd Heatherton, Ph.D., Dartmouth College

*Dr. Heatherton's presentation focused on the potential of neuroimaging
studies to test social psychological theories about social cognition and
social behaviors, giving examples from his own work on the neural
correlates of self processes.*

A well-established social psychological phenomenon is the fact that
information encoded with references to self is better remembered than
that encoded with reference to someone else. It is not clear whether
this phenomenon results from the self being a special mnemonic device or
a specialized level of processing effect. Behavioral studies cannot
distinguish between these competing ideas, but imaging has proven
helpful. Initial ideas about the neural correlates of self processes
come from patients with frontal lobe injuries who exhibit lack of
insight and self-awareness. Imaging studies have revealed a region of
the medial PFC that is activated to a greater degree when someone
engages material with references to self than it is with material
encoded in references to someone else.^38^ In addition, the medial PFC
is deactivated when other tasks are performed, but not when a person
enters a self-reflective state. Further study shows that activity in the
medial PFC can predict whether someone is likely to remember items based
on self-reference.

The activity of the medial PFC increases linearly the more self-relevant
something is, while in contrast, the negative or positive valence of an
item is encoded in the vACC. In studies by Mayberg and colleagues,
electric stimulation of the vACC alleviates depression in many patients
with chronic depression.^39^ Heatherton and colleagues explored what
this brain area was doing in social tasks. In a study in which
participants learned of other's judgments of themselves as likeable or
non-likable, Heatherton and colleagues found differential activation in
reward centers as a function of whether the individuals expected to be
liked by the people they thought were judging them. However, vACC
distinguished the experience of social acceptance from social rejection,
particularly in individuals with low self-esteem.^40^ In another study,
women who were faced with a stereotype threat showed less activity in
the parietal regions and increased activity in the vACC, compared with
women in the control group (Krendl AC, Richeson JA, Kelley WM, and
Heatherton TF. The negative consequences of threat: an fMRI in
investigation of the neural mechanisms underlying women's
underperformance in math. Manuscript submitted for publication).

Combining neurobiology and social psychology offers several
translational opportunities for social neuroscience of aging. Studies
focused on aging and the processing of emotional cues can explore areas
connected to well-established behavioral differences between older and
younger adults. Age-related structural and functional changes have been
documented in the medial PFC and vACC ; thus, reasonable predictions can
be made for how older adults will perform in social cognitive tasks, and
extensions to neuroimaging will allow us to relate behavioral findings
to what is already know about neurobiological change in aging. Other
brain regions that might be affected by aging could be identified by
mapping brain activity from neuroimaging studies and linking findings
from these studies to what has been observed in the patient literature.

## Neuroimaging and Genetics

### Andreas Meyer-Lindenberg, M.D., Ph.D., M.S., National Institute of Mental Health

*Dr. Meyer-Lindenberg and colleagues at NIMH have combined neuroimaging
with genetic approaches to understand the neural circuitry underlying
disorders of social behavior and social cognition.*

Translational approaches can be used to bridge the complex path between
genes and behavior by assessing the effects of genes on molecular
alterations in the cell and how those effects influence neural
systems.^41^ Intervening variables, such as cognition, should be
considered in these studies, and investigators should look for
convergence between neural systems identified by biological approaches
and those described in the cognitive neuroscience literature so that
translational approaches are bidirectional. Because one gene affects
several neural systems and participates in many processes, one cannot
say that one gene encodes one particular behavior. Translational
approaches therefore should also focus on interactions.

This approach is exemplified in work done by Meyer-Lindenberg and
colleagues in the study of neurodeveolpmental disorders affecting social
behaviors. Their particular focus has been on the circuitry involved in
social behavior, with an emphasis on the amygdala and the brain regions
that talk to it. Their work represents a bottom-up approach (mechanisms
to behaviors) that links to the top down (theory to mechanism) approach
discussed by Todd Heatherton.

Studies by Meyer-Lindenberg and colleagues of individuals with Williams
Syndrome illustrate the use of this approach. Williams syndrome arises
from a hemizygous deletion of approximately 28 genes on chromosome
7q11.23 and encompasses several somatic abnormalities, visuoconstructive
deficit, and hypersociability. Patients with Williams syndrome are
likable and trusting and show a high degree of empathy as a result of
social fearlessness. However, non-social fear is increased in these
patients; they exhibit general anxiety symptoms, and 97 percent of them
have specific phobias.

In a study exploring neural mechanisms of hypersociability, patients
with Williams syndrome were presented with socially relevant
fear-inducing stimuli in the form of fearful and angry faces, and
socially less-relevant fear-inducing stimuli in the form of scenes
devoid of faces or social interactions.^41,42^ Activation of the
amygdala tracked with fear profiles: It was hypoactivated in response to
fearful or angry faces but hyperactivated in response to irrelevant
fear. Activation differences likely arise in part from regulation of the
amygdala by the vACC, the orbitofrontal cortex, and the dorsolateral
PFC. This dissociation in responses to social and non-social fear
stimuli suggests specialized neural circuitry for processing social
threat.

This approach can be extended to studies of social behavior in the
general population. Genes involved in psychosocial behaviors interact
with the environment, as illustrated by the Caspi study of 5-HT and
interactions between childhood maltreatment and genotype.^29^ Results
from this study suggest that events in the remote past can precipitate
depression in the present through the action of the 5-HTT polymorphism
5′-HTTLPR. fMRI studies can be used to assess the neural systems
mediating this effect, and random effects analysis can be combined with
known genetic information to produce a group map suggesting areas where
genetic variation affects brain activation. For example, the amygdala is
hyperreactive in persons with the short form of 5′-HTTLPR,^43^ who carry
the risk for depression.^29^ This polymorphism also affects the
structure of the amygdala and cingulate.^44^ In persons with the long
variant of the 5′-HTTLPR polymorphism, areas in the brain are wired such
that the input between the amygdala and ACC are bidirectional. In
carriers of the short form, however, the input back into the amygdala,
which is involved in fear extinction, is not functional. These findings
suggest a functional circuit whereby the dorsal ACC inhibits the
amygdala, such that fear extinction only works if this circuit is
operating correctly. This fits with the story regarding early exposure
to stress (i.e. the more bad things that happen to you, the more you
have to extinguish the amydgala response). This cingulate-amygdala
uncoupling thus explains the harm avoidance trait.

Other genetic mechanisms of social cognition and emotion
regulation^42,45-47^ include the role of oxytocin in shutting down the
amygdala and uncoupling it from its effector functions. Genes for
violence have been associated with a reduction in cingulate volume and
differences in functional activation. Recent studies imaging oxytocin
and vasopressin receptors have shown that amygdala regulation is
augmented by superordinate cortical control and cortical effector nodes.

Thus a social imaging and genetic approach is feasible, can identify
neural mechanisms that clarify mediating mechanisms, and identify
potential treatment targets. Future studies should examine genes
cross-sectionally and across the lifespan.

## Lesion Studies, Eye Tracking

### Ralph Adolphs, Ph.D., California Institute of Technology

*Dr. Adolphs' laboratory combines studies of patients with neurological
lesions and disorders and psychophysiological methods ranging from
eye-tracking to fMRI to study the neural basis of social cognition.*

It is well known that different techniques to study the relationship
between brain and behavior differ in invasiveness and in resolution of
space and time, thus each offering advantages and limitations. Placing
single electrodes into cells offers superb resolution, but it is
invasive and provides too narrow a picture to assess more systems-level
functioning. Lesion studies and fMRI are coarser and more macroscopic,
but they are well suited to understanding cognitive function in humans
because the field of view is larger. A standard approach in these kinds
of studies is hypothesis driven, focusing on a certain process or
structures of interest. However, data-driven approaches with no initial
hypotheses allow room for serendipity. In addition to meta-analytic
approaches, which will be very important as more data accrue, there are
several data-driven methods available to particular studies.

As one example, how the distribution of performance changes among
patients with brain lesions can be assessed by partitioning these
patients based on performance, then finding what distinguishes low
performers from high performers. We have recently undertaken such
analyses, which depend on the availability of registries with large
numbers of patients whose lesions have all been mapped. Another example
comes from our recent study to assess the role of the amygdala in
recognizing fear from faces, which explored what parts of the face drive
that recognition. Participants went through thousands of trials where
they were shown parts of faces.^43^ Recognition of happiness was based
on the mouth, whereas recognition of fear was based on the eyes. We
found that a patient with amygdala damage was unable to use information
from the eye region of faces, likely explaining her impaired recognition
of fear in facial expressions. This study has been now repeated in
patients with autism and has revealed, for example, that patients with
autism make more use of the mouth to recognize fear.[^3]^9^

Another useful data-mining approach involves eye-tracking to assess
where study participants look when they are shown faces. Use of this
technique has shown, for example, that individuals with autism fixate on
photographs differently from those who do not have autism. Eye-tracking
approaches can be extended to studies that simulate real world social
stimuli and social interactions. In ongoing studies in healthy
individuals, patients with autism, and patients with brain lesions,
highly trained actors are used as interviewers posing questions in a
face to face context while data on eye movements is recorded. These more
naturalistic studies of eyetracking have revealed that amygdala lesions
also impair eye contact with real people[^4]^00^. Studies of eyetracking
are now being combined with other methods such as fMRI as well.

Other ongoing studies that exemplify the power of combining techniques
have involved engaging patients with focal amygdala lesions in a task
that normally activates the PFC, then assessing how activation in the
distal areas differs between the lesion patients and controls. This
approach thus combines lesion studies with functional imaging. Other
studies have assessed brain areas that are activated in response to
faces, then used diffusion weighted imaging to determine whether and how
those areas are connected to other regions of the brain. All of these
aim to inform one large domain of missing data with respect to the human
brain: its connectivity (both structural and functional).

Through the combination of methods and the development of ecologically
valid social tasks, data-mining approaches are feasible, but
investigators must consider whether their studies can afford such an
approach. Data mining becomes even more powerful when methods are
combined, but establishing such combinations will require collaboration
among laboratories with expertise in different areas.

## Session II Discussion---Research Opportunities, Gene-Environment Interactions, Practical Considerations for Social Neuroscience in Aging

Neuroimaging has yielded a lot of information and interpretations about
changes in the brain, and myriad opportunities exist for future studies.
However, these opportunities must be organized based on what is
important. Understanding the evolution of the nervous system, including
the autonomic nervous system, is one step in determining what is
important for future research. Understanding the maturation of the
nervous system also will be important.

An increased understanding of interactions between genes and environment
is also important, and environments must be characterized appropriately.
Dr. Taylor pointed out that the Caspi study looked at the relation of
5-HTT to major depression and showed a nice effect, but the measure of
environment did not include assessment of supportive environments. The
nature of the environment might be important; studies have shown that
children predisposed to hyperreactivity fare worse in an unstable
environment. A full range of environments should be assessed in
conjunction with a full range of the gene, and may lead to different
interpretations of the cross-over interaction seen in the Caspi study.
Another interpretation, consistent with data in both humans and primates
suggests that carriers of the SS allele are especially sensitive to the
environment generally, not that they are uniquely sensitive to harsh
environments or particularly depression prone. Appropriate
characterization of the environment is highly relevant to aging
research, as changes in the environment can be engineered and assessed
in relation to genetic polymorphisms of interest.

Dr. Carter noted that oxytocin and serotonin both play a role in these
interactions and highlighted the importance of looking at the
interactions of these systems.

In addition to interactions between genetic sensitivity and environment,
potential interactions between environment and emotion- or
self-regulation should be assessed. A dimension of self-regulation that
might have been ignored is the extent to which regulation is from the
self outward, as opposed to the environment inward. Dr. Heatherton noted
that initial self-regulation, attitude, and persuasion studies suggest
that the world attempts to regulate the individual and convinces that
individual to regulate him- or herself. Dr. Fiske added that
understanding how individuals adapt to other people is important and
that a lot of work is focused on this. Whether this adaptation or
self-regulation in response to social cues is an important function of
aging is not known. Evolutionary models should be consulted in
determining why an individual should be sensitive to social norms and
where that breaks down.

Practical matters must be considered in research on social neuroscience
of aging. Though procedures developed for college student samples may
require some adaptation for use with older age groups, there are no
particular logistical obstacles to neuroimaging older participants, and
several workshop participants attested to the ease of recruiting and
working with these samples. Access to subject populations may initially
pose a challenge for those who have relied primarily on undergraduates.
Problems unique to the elderly include vascular considerations and
medications that might inhibit skin conductance. As well, BOLD fMRI
signals change with aging. Other practical matters and challenges
include selecting a representative study sample, addressing biological
measures affecting self-reports, and possible differences in people's
motivation for participating in studies.

The usual paradigm for aging research attempts to apply studies done in
younger adults to older adults, but many qualitative and quantitative
differences appear between younger and older adults, and new behaviors
emerge with age. Thus, repeating brain mapping studies in the elderly as
they were done in younger adults might not be useful. Instead,
investigators should start with what is known about social cognition in
older adults, assess how the brain changes with age, and determine how
these changes explain changes in behavior. Validating methods and
exploring contrasts between younger and older adults will be important
to aid in the interpretation of data

One challenge in expanding social neuroscience research is that of
training and encouraging new investigators. Grant agencies can
facilitate interactions and collaboration across areas, but junior
faculty engaged in interdisciplinary research in social neuroscience may
find extension of their research to aging as an additional challenge at
the start of their careers. NIA has employed some mechanisms to
encourage principal investigators to consider research on social
neuroscience in aging, but institutions must also recognize the value of
participating in these collaborations.

# Session III: Psychosocial Stress, Health, and Aging: Emerging Perspectives on Pathways and Mechanisms

***Goals of Session III:** To highlight new multilevel approaches to
studying the biological mechanisms by which psychosocial stress is
mediated, with a discussion of both laboratory and natural social
stressors, gender differences, and lifecourse perspectives on
mechanisms.*

## Cellular Mechanisms and Allostatic Load

### Elissa Epel, Ph.D., University of California, San Francisco

*Dr. Epel discussed how her research program on telomeres and telomerase
developed, how it has benefited from trans-disciplinary collaborations,
and how this kind of approach can advance what is understood of the
pathways linking psychosocial stress to health outcomes and to the
refinement the concept of allostatic load. She concluded with a
discussion of crucial next steps in this research program.*

Although human beings are equipped to handle stressors and maintain
homeostasis or allostasis, the system responsible for maintaining
homeostasis becomes damaged over time.^49^ The most familiar example of
allostatic load can be found with blood pressure and its connections
with heart disease, metabolic syndrome, and other disease. Yet once a
person is diagnosed with hypertension, there are underlying disease
processes that must be considered. Thus, research in aging should look
for biological markers that are not confounded by disease.

Mitotic cells undergo a finite number of cellular divisions. This
process is regulated by an internal clock that depends on the telomeres,
or the caps at the ends of chromosomes.^50,51^ Telomeres protect cells
and chromosomes from fusions that cause genomic instability and from
loss of cell replenishment. However, as cells age, telomeres shorten in
length, similar to aglets at the ends of shoelaces. Recent work has
shown that telomere length in mid-life predicts mortality.^52^ Telomere
length also has been associated with several diseases, including heart
disease,^53-55^ diabetes,^56^ vascular dementia,^57^ and obesity and
insulin resistance.^58,59^ In addition, telomere length has been shown
to predict mortality in AD patients with the apolipoprotein E\*4
(ApoE\*4) allele^60^ and to mediate response to statin treatment.^54^

Recent findings suggest that telomere length is affected by psychosocial
factors. Chronic stress produces a linear effect on telomere length,
both in young women and in older women caring for dementia patients.^61^
Other studies have revealed a relationship between socioeconomic factors
and leukocyte telomere length. Ongoing work by Epel and colleagues
focuses on the psychosocial processes and biochemical determinants of
changes in the function of telomerase, the enzyme responsible for
maintaining telomeres. This group is able to measure basal, stable
telomerase activity and telomerase activity in response to stress.

Several transdisciplinary collaborations are under way. One such
collaboration is conducting *in vitro* studies that parallel stress
hormone exposure, metabolic hormone exposure, and cellular mechanisms
*in vivo*. Other collaborations are conducting animal studies, including
studies of early experience in rats and social hierarchies and rearing
in monkeys. Clinical samples under study include caregivers, patients
with depression, and patients with posttraumatic stress disorder, and
other population studies such as CARDIA are under way. Intervention
studies are focused on stress reduction and meditation, pharmacological
treatments, and lifestyle interventions. All these studies can yield
information about changes across the lifespan. It should be noted that
rodents provide a limited model for disease and mortality because their
telomeres are so long to start with.

Future research should address the biochemical factors that shorten
telomeres; the perinatal, demographic, psychosocial, and behavioral
factors related to telomere shortening over the lifespan; and whether
telomere shortening can be reversed. There are also larger questions
with regard to telomere length. For example, it is not known whether
telomere length is a causal mechanism in aging, disease pathways, or
maintenance of good health. Nor is it known whether telomere length
serves as a cumulative marker for oxidative stress or inflammation. The
effects observed on leukocyte telomeres could result from immune aging,
or they could serve as a proxy for whole-body or brain aging.

To answer these questions, investigators will have to find ways to more
easily measure natural (unstimulated) telomerase activity in cells. At
present, only average telomere length can be observed. The *in vivo*
relationship between telomerase and telomere length also should be
determined in humans. In addition, it is not known whether leukocyte
telomere length is related to telomere length in cells that are easy to
sample. Descriptive studies will be needed.

What is known about telomeres can be used to refine the definition of
"allostatic load." It also offers an alternative to the developmental
model of disease, where potential origins are confounded by the disease
itself. Telomere length offers a new view from the cell's perspective.
It changes before disease onset, thus providing a forecast. It also
might serve as an early building block in tissue aging. Bidirectional
relationships between allostatic load and telomere length will have to
be measured through traditional approaches.

## Gender-specific Motives and Mechanisms

### Shelley Taylor, University of California, Los Angeles

*Dr. Taylor discussed what is known about gender-specific motives and
mechanisms linking psychosocial stress to health outcomes, and
age-related changes in their function, and where there are major
knowledge gaps. She offered her views on best approaches to studying
individual differences in psychosocial stress-health relationships from
a life course perspective.*

Fight or flight, which is part of the human stress response, involves a
biological component including the sympathetic nervous system, as
illustrated by elevated heart rate and blood pressure, and the HPA axis,
characterized by the secretion of glucocorticoids such as cortisol. The
response also includes a behavioral component involving aggression and
confrontation (fight) or withdrawal and substance abuse (flight).

Most of the early studies of the stress response were done in male
animals, and this approach was extended to studies in humans. As a
result, males were overrepresented in the stress-response literature
until the mid-1990s. Men are more likely than women to engage in
assaultive, homicidal, and suicidal behaviors; social withdrawal; and
substance abuse in response to stress. This may help to explain the
earlier mortality observed among men in all countries where men and
women have equal access to health care.

From an evolutionary perspective, fight or flight might not be the best
or only characteristic of the human stress response. Fighting might
leave offspring unprotected and result in death or injury to their
caregivers. Fleeing, on the other hand, might lead to abandonment of
offspring. As suggested by meta-analyses,^62^ women's response to stress
might be better characterized by "tend and befriend" than by "fight or
flight." Tending would involve caring for offspring, protecting or
soothing them in times of stress, which reduces biological stress
responses in both the caregiver and the offspring. Befriending would
involve turning to the social group for help, protection, and support.

Oxytocin production, which underpins a broad array of affiliative
behaviors, often increases in response to stress and is regulated by
estrogen. In a model used by Taylor and colleagues, which focuses on
affiliative responses to stress, oxytocin levels are higher in women
experiencing gaps in relationships, suggesting that the stress response
depends on the type of affiliative contact. In a study of postmenopausal
women, oxytocin appears to increase in women taking estrogen-replacement
therapy, and again, there is a negative correlation between oxytocin
levels and gaps in contact. A strong negative relationship between the
quality of a marital relationship and oxytocin levels also has been
observed. These findings suggest that oxytocin may act in women as a
signal to seek out social support. Elevated oxytocin has also been
associated with stronger stress responses as measured through cortisol
levels.

At present, changes in oxytocin levels best describe the stress response
in women. Men tend to use social support less than women do in response
to stress. Yet paternal caregiving and male collective activity in
response to stress has been observed in primates and humans. A good
candidate for driving the biological model of men's stress response is
vasopressin, which has been associated with guarding territory and mate.
Studies of vasopressin so far have been inconclusive.

Thus, existing research supports the view that men rely more on fight or
flight than women do in response to stress, whereas women affiliate more
and seek a broader array of contacts for social support. These
differences persist across the lifespan into old age. An oxytocin-based
mechanism might account for some of these sex differences.

## Session III Discussion---Telomere Length, Differences in Stress Response, Changes across the Lifespan

Telomere length is a marker that changes slowly over time. How well it
captures the social context is still under study. Investigators focused
on the effects of social interaction on telomere length are attempting
to define whether this is a malleable marker and how interventions, such
as stress reduction and pharmacological interventions, alter potential
relationships. It will be important to note the differences between a
stressful life event and chronic stress, and stored blood samples will
be useful in determining whether lifelong stressors also have an impact
on telomere length. When asked whether telomere length could be used to
distinguish new neurons in the hippocampus from old ones, Dr. Epel
responded that telomere length could crudely indicate how long the
neurons have to proliferate. Relationships between leukocyte telomeres
and neuronal telomeres, as well as the relationship between telomere
length and hippocampal volume, would have to be clarified.

Dr. Carter suggested that sex differences in stress response might arise
from differences in vigilance and non-reactivity. Vasopressin is
involved in increased vigilance and internal defensiveness and that it
raises blood pressure. Thus, fight or flight is easy, but holding still
proves difficult. Males might therefore be more vulnerable in situations
where they are called upon to be vigilant.

Dr. Taylor pointed out that the way women manage stress is similar
across the lifespan. Studies in monkeys, however, suggest that males
become less aggressive and more affiliative with age. This might result
from the trajectory of androgen production across the lifespan.
Vasopressin also might play a role. Although vasopressin and oxytocin
have opposite effects on blood pressure, both hormones promote
friendliness. In studies by Thompson and colleagues, male college
students given intranasal vasopressin saw neutral faces as hostile,
whereas females given vasopressin became more affiliative. Whether this
changes with age is not known.

One challenge in studying oxytocin and vasopressin is the reliance on
blood samples and the fact that no functional receptor changes have been
observed. In addition, human studies cannot use invasive techniques that
could answer questions unanswered by blood samples. More cooperation
between investigators conducting animal and human studies is therefore
needed. Studies of oxytocin and vasopressin also should account for the
fact that oxytocin reactivity differs with the time of day.

# Session IV: Loneliness, Social Connectedness, and Healthy Aging: Emerging Perspectives on Pathways and Mechanisms

***Goals of Session IV:** To highlight new multilevel approaches to
studying the biological mechanisms by which loneliness, social
connectedness and relationship quality influence health, with a
discussion of the relationship between these constructs, individual
differences, social context effects, and lifecourse perspectives on
mechanisms.*

## Social Bonds and Attachments

### C. Sue Carter, Ph.D., University of Illinois at Chicago

*Dr, Carter's presentation focused on the neurobiological underpinnings
of social bonds and attachments and mechanisms whereby social
experiences influence later life social behaviors and health outcomes.
She discussed ways to advance understanding of the causal pathways
involved.*

Prairie voles are socially monogamous and, like humans, might be
especially sensitive to living in a social group or pair, versus social
isolation. Indeed, Grippo and colleagues have shown that prairie voles
have comparatively low heart rates and human-like vagal tone (Grippo,
Carter, et al. *Physiol Behav*, in press).^63-65^ Thus prairie voles
provide a useful model for analyzing the physiological effects of social
interactions or isolation.

Recent work suggests that social isolation is indeed a powerful
stressor, especially in female prairie voles (Grippo et al., *Psychosom
Med*, in press; unpublished data).^66^ Blood corticosterone and
vasopressin immunoreactivity in the central nervous system increase, as
does corticotrophin-releasing factor (CRF) immunoreactivity in the
PVN.^67^

Regulation of the autonomic nervous system, HPA axis, and emotional
reactivity are important functions of both social behaviors and
neuropeptides such as oxytocin, vasopressin, and CRF. Vasopressin and
CRF are usually considered to be components of the sympathetic nervous
system and HPA axis and are thus associated with increased mobilization,
vigilance, and emotional arousal. In addition, vasopressin is more
abundant in males in the extended amygdala and lateral septum. Oxytocin,
on the other hand, can down-regulate the sympathetic nervous system and
HPA axis, and its receptors are abundant in the amygdala, hippocampus,
lateral septum, dorsal motor nucleus of the vagal nerve, and the HPA
axis. Oxytocin thus might be critical to coping with stressors,
particularly in females.

The fact that oxytocin both down-regulates the stress response but is
high in cases of gaps in social relationships is somewhat intriguing.
Future work should explore the interaction between oxytocin elevation
and affiliation preferences.

## Marriage and Caregiving

### Janice Kiecolt-Glaser, Ph.D., Ohio State University College of Medicine

*Dr. Kiecolt-Glaser's presentation focused on the neurobiological
mechanisms whereby relationship quality and relationship strain
influence health, highlighting particular issues related to the study of
marriage and caregiving. She shared her ideas on how to advance social
neuroscience research on marital relationships and marital role
transitions to further understanding of the causal pathways linking
relationship quality and health in later life.*

In studies assessing how the quality of the marital relationship affects
physiology,^68^ partners were asked to describe areas of disagreement
and rate the chronicity of the disagreement, independently of each
other. Interviewers then brought the partners back together, identified
the hottest and most timely topics, and asked the couple to resolve them
within the next half hour. The interviewers left the immediate area,
observed the behaviors between the partners, and coded these behaviors.
Blood was drawn from each partner throughout the test. Behaviors were
coded by using the Marital Interaction Coding System. In this system,
"criticize" defines a hostile statement of unambiguous dislike or
disapproval of a spouse's specific behavior. This behavior uses a
non-neutral voice tone. "Interrupt" describes the listener breaking in
and disrupting the flow of the other's speech. "Put down" describes a
comment intended to demean or embarrass the spouse. Sarcasm is often
apparent in this behavior. "Turn off" describes nonverbal gestures that
communicate disgust, displeasure, disapproval, or disagreement.

Among newlyweds, higher levels of negative behaviors were associated
with higher levels of epinephrine, norephinephrine, and
adrenocorticotropic hormone (ACTH). Results were similar in a study of
90 newlywed couples and a study in couples in which the partners were
between the ages of 45 and 95 years.

Wound-healing, an important health outcome mediated by the immune
system, is an excellent, stress-responsive model. This model was used in
a recent study to assess the effects of marital behavior on immune
function.^69^ In this study, 40 couples were admitted to the Ohio State
Clinical Research Center twice, to separate the effects of acute stress
associated with a marital conflict from the chronic stress associated
with marital dissatisfaction. One visit was supportive, whereas another
focused on conflict. When the analysis ignored hostile behavior, time to
healing took 1 day longer following the conflict visit than that
following the supportive visit. When hostile behavior was included, the
median time to healing across the two visits was 2 days longer for the
same-size wound. The increase in IL-6 production in low-hostile
participants was roughly the same over 24 hours following a supportive
or conflict interaction. In high-hostile participants, however, IL-6
production increased from 45 percent following a social support task to
113 percent following conflict. Thus, a couple's behavior influences how
fast wounds will heal.

## Session IV Discussion---Associating Biological Markers with Social Relationships and Environment, New Methods Development

Studies by Kiecolt-Glaser's group are consistent with others showing
that IL-6 production responds to stress. IL-6 responses have been
observed 1 to 2 hours following exposure to a stressor, although how
long IL-6 stays elevated is not known. In response to questions from Dr.
Suzman about IL-6 and wound healing in real-life situations such as
combat, Dr. Kiecolt-Glaser noted differences between local and systemic
inflammatory responses, and she pointed out that local responses are
needed in combat situations. In response to questions about IL-6
manipulations in general, Dr. Kiecolt-Glaser cautioned that IL-6
undergoes diurnal variation and that it is responsive to sleep
deprivation.

Discussion focused on methods for associating biological markers with
social relationships and environment. Physiological measures can be
combined with surveys and interviews, as was the case in a study of air
traffic controllers and another study using survey interviews to assess
wellness. Changes in these markers could be viewed as outcome measures
associated with chronic diseases that have manifested, and they may be
useful in identifying causal relationships.

The value and feasibility of salivary measures for various biological
markers is still evolving. One group of investigators is developing a
salivary assay for C-reactive protein (CRP), and other investigators
have looked at IL-6 and TNF-α. Thus far, no relationships between
salivary cytokine levels and stress have been found, and it is not clear
whether saliva and cheek-scraping assays are reliable for measuring
these markers. Another marker, fibrinogen, has been difficult to obtain
by salivary assays and by venipuncture. Salivary levels of oxytocin,
however, do appear to vary based on lactation.

Other methods, particularly more sensitive ones, should be developed to
better relate these markers to social environments and behaviors.
However, the tight funding environment and the experience of study
sections hamper research that could lead to methods development. Some
RFAs and Small Business Innovation Research (SBIR) grants are in place
at NIH to address these needs. Dr. Waite also pointed out that a
blood-spot assay for several inflammatory markers is under development.
Dr. Carter cautioned, however, that this method must be standardized and
might only work for large differences. Methods development at present is
more likely to go through a commercial route.

Another issue in associating biological markers with social
relationships and environment is the potential differences between
social and non-social stressors. The distinction between the two is not
clear. Dr. Taylor described a review by Dickerson^70^ suggesting that
social stressors are strong elicitors of the HPA axis. She added that
IL-6 and TNF-α are affected more by social stressors, such as
humiliation and embarrassment. Thus, it might be that social stressors
are not different from other stressors, but more potent. What is
recruited to a particular situation, and how multiple systems in the
brain are involved, should be studied further, particularly in light of
arguments that emotional bonding and regulation develop in a social
context. For example, humans who differ in the degree at which they hold
on to a mental stressor might differ in the recruitment of an
arousal/activation module that could be dangerous in certain situations.

Differences in responses to immediate versus long-term stressors also
should be explored. For example, Dr. Kiecolt-Glaser noted a paper^71^
that describes different patterns in immune function based on the
duration of the stressor. This area of study could be applied to
real-world situations such as job burnout or the development of blunted
emotions in people serving in the military.

In terms of emotion specificity, care should be taken in selecting which
biological markers to follow. As noted by Dr. Epel, it is unlikely that
cortisol, which has so many known functions during stress and rest,
could be mapped to certain emotions except to say it is linked to
positive or negative affect. Research on emotion specificity should not
be pursued naively, but rather recognizing the challenges of linking a
cortisol blip to an affect. Other pathways may be more specific, such as
the autonomic nervous system or hormones w/ more specific functions.
Oxytocin regulates the HPA axis, but the role of other pathways in this
function and what happens centrally are not clear.

Studies by Mendes and colleagues^72,73^ have found that a sense of
social threat results in less cardiac output and more total peripheral
resistance. However, these studies also showed that positive stress led
to more DHEA activation, suggesting a role for social and environmental
factors in well-being. Yet most NIH Institutes focus on specific
disorders or organ sites; there is less of a focus on well-being. A
language for positive emotions, resilience, or positive stress does not
exist. Because differences promoting well-being become more important as
people age, research on aging would be a good field to pursue studies on
how these factors promote well-being.

# Session V: Evolution and Development of Social Behaviors: Opportunities Presented by Animal Models

***Goals of Session V:** To describe potential contributions of
biodemography and naturalistic studies of primates to our understanding
of the evolution and development of social behaviors of relevance to
aging.*

## Biodemography of Sociality and Lifespan

### James Carey, Ph.D., University of California, Davis

*Dr. Carey's presentation described research approaches in biodemography
and explored how biodemographic principles and methodologies can be used
to advance social neuroscience research on aging.*

Biodemography is rooted in demography and thus in social sciences and
mathematics, and biodemographical approaches can answer questions not
answerable by either biology or demography. Biodemography is one of an
increasing number of social science subdisciplines that embraces
biology, and it links lower mechanistic levels of biological
organization with higher functional levels. Thus, biodemography is well
situated to engage with and contribute to research in social
neuroscience in aging.

Carey and colleagues have conducted research on comparative lifespans
across mammalian, avian, and insect species. This research has
established a range of lifespans within each class, and it has revealed
several universal themes. Large, social, armored, and subterranean
species live longer, and birds live longer than mammals of similar size.
The relationship between size and longevity does not hold within orders
or between some orders such as bats and rodents. Extremely long-lived
species exist in all groups. Among mammals, primates are especially long
lived, and humans are long-lived primates. Among insects, there is a
5000-fold difference in lifespans, and beetles, social insect queens,
primitive spiders, and ticks tend to live longer. Two orders among
insects, *Isoptera* (termites) and *Hymenoptera* (bees and wasps), are
especially long lived. These comprise social species in which the
workers live 4 to 6 weeks but the queens can live anywhere from 20 to 30
years.

Lifespan evolution provides an operational framework. One component of
lifespan evolution involves phylogeny, which provides a floor plan for
species built to live longer. The other component, however, is life
history, which selects for long or short life and is an adaptation much
like white fur on polar bears or long necks among giraffes. Lifespan is
naturally or environmentally selected based on uncertainty and resource
scarcity, and socially selected based on monogamy, kin groups and
parental care, sociality, and eusociality. Natural, sexual, and kin
selection all work within the realm of social selection.

Humans have evolved a long lifespan in the context of sociality and as
part of a primate phylogenetic heritage. What is known about sociality
and lifespan among social insects can be used as an example; that is,
general principles arising here might be applicable to humans. As
reviewed by Carey and Judge,^74^ the evolution of longer lifespan among
wasps began with the emergence of a nest, a mechanism of mass
provisioning where a group of parasitic individuals brought food back
and colonized an area. Within the nest emerged parenting, or progressive
provisioning in which adults fed the young. As a key intermediate step,
the lifespan of females was prolonged to overlap with that of offspring,
which in turn promoted kin groups and incipient sociality. This was
followed by the emergence of a queen. In this model, longevity and
sociality go hand in hand; extended longevity is a precondition for
sociality, which in turn creates conditions that further extend
longevity. The extension to monogamy requires extended longevity and a
minimal gender gap.

Both longevity and sociality are self-reinforcing, and this
reinforcement contains both a demographic and economic component. From a
demographic perspective, increased survival of offspring reduces the
number of offspring desired by parents. Parents remain healthier because
of the reduced drain of childbearing and rearing. They thus raise
healthier children, which leads to higher survival and further
reductions in fertility. Healthy parents thus become healthy
grandparents, who can further assist parents in childrearing. From an
economic perspective, increased longevity increases the parent- and
grandparent-years used to subsidize offspring. This leads to better
educated, more skilled, and more innovative children who generate
technological innovations that improve health. Higher adult survival and
health from these innovations then allows adults to reinvest in children
and grandchildren

Work by Judge and Carey^75^ suggests that post-reproductive life among
humans can be predicted from primate patterns, which may provide clues
into the evolved lifespan of humans if they are considered simply as a
another primate species. On the basis of primate patterns, the evolved
lifespan among humans would be 72 to 91 years. Moreover, a lifespan
exceeding that of the female reproductive system is part of the
phylogenetic legacy, rather than a recent development. This prediction
is supported by the Cave of La Marche, in France, which contains
drawings that are 12,000 years old.^76^ In this cave are pictures of a
young girl in her teens, a woman in her mid-40s, a man in his mid-50s, a
man in his mid- to late-60s, and even a man in his mid- to late 70s and
possibly his early 80s. Thus, the idea that people did not live long
thousands of years ago is not necessarily true.

The paradigm inherent in the literature on animal behavior traditionally
has not included an examination of behavioral changes across the
lifespan. Papadopoulos and colleagues have monitored male medflies
throughout their lives to capture individual-level events and cohort
survivorship.^77^ Younger flies engage in calling, walking, and resting
behaviors. As they approach death, however, they undergo a shutting-down
process, as illustrated by increased frequency of a supine behavior
where flies fall and cannot get back up. The transition from healthy
pre-supine fly to supine fly to dead fly is universal, progressive,
predictive, and irreversible. Thus subcategories of age- or
time-dependent behaviors can be correlated with lifespan, time to death,
and chronological age. This principle could be applied to other species.
Ongoing work by Carey and colleagues is focused on a life course
"microanalysis," including the development of tools to measure or record
behaviors from the first day to the last day of life. This tool will aid
in mapping behaviors across the lifespan and making predictions about
mortality.

Research in social neuroscience of aging can use similar approaches of
identifying general principles in insects and applying them toward
humans. The field of social neuroscience in aging also should work
toward a biological coherence between development and aging to further
tease out relationships between early and late life. Embryology and
general developmental studies can be combined with gerontology and
general degenerative studies, and, along with ecology, evolution, and
behavior, can be folded into a new life synthesis of life course
biology. Such an approach will address emerging evidence indicating that
degeneration does not begin with old age.

## Session V Discussion---Applying Biodemographic Principles to Social Neuroscience of Aging

As noted by Dr. Suzman, many researchers are interested in detailed
participant observation to determine what changes as people age and
record what happens over the lifespan. This should be done not only for
activity or impact of disease but also for cognitive and social
functions. Tools under development by Carey and colleagues might be
connected to the work of others in this area by conducting microlevel
sampling and determining what can be obtained with these tools that
cannot be obtained with other methods. Similar approaches are used in
sleep research.

One could argue that whether someone reaches 70 or 80 years of age does
not matter so much as the floor plan set for the species and cultural
differences in that floor plan. Dr. Levenson expressed concern that
future research might focus too narrowly on random perturbations or
noise. Dr. Carey agreed and clarified that every species has an evolved,
Darwinian segment to its lifespan and that sociality and lifespan must
work together. There is also a post-Darwinian segment to the lifespan,
which could be affected by events in early life.

Whether epigenetic phenomena occur throughout the lifespan and whether
these phenomena might provide a mechanism for extending longevity are
interesting questions. Dr. Harris cited honeybee studies in which social
behaviors and context appear to influence genomic structure and
connected these to Dr. Carey's discussion of sociality and lifespan.
Genes reside at the mechanistic level of evolutionary changes. Once a
parasitoid begins to make a nest, and once parenting behaviors begin,
mortality factors change, and genes underlie all these changes. How
social structures influence genomic structure is not clear.

Whether non-degenerative behaviors emerge with age is not known.
Combining approaches from developmental biology and aging biology may
provide clues. The time frame over which changes in social behavior
drive differences in longevity also is not clear, although this might
operate at an individual level.

## Primate Social Behaviors

### Steve Suomi, Ph.D., National Institute of Child Health and Human Development

*Dr. Suomi discussed potential contributions from naturalistic studies
of primate social behaviors to an understanding of the evolution and
development of social behaviors of relevance to aging.*

Rhesus macaques live in large social groups that range from 30 to 100
members and center on female-headed, multigenerational families.
Multiple dominance hierarchies exist within every troop: one between
families; one within families, where the younger females dominate; one
among males, which depends on their tenure and therefore their
sociality; and one among infants, depending on the positions of their
mothers. Survival in the troop thus requires a complicated behavioral
repertoire and the ability to process a large amount of information.
Individuals must know kinships, dominance hierarchies, enemies, allies,
and who the strangers are.

Once an infant is born, it maintains a 24-hour attachment to its mother
and forms an attachment bond. Once this bond is established, the infant
spends more time away from the mother and, setting the mother as a
secure base, begins to explore its surroundings. As the infant matures,
its interactions begin to focus on peers. Macaques are seasonal
breeders; thus, an infant has several peers with which to interact. The
macaque spends several hours a day with its social peers until the
fourth year of life. This stage of interacting with peers perfects
social behaviors, such as mating and aggression, which are needed for
the rest of the macaque's life.

Morphological changes associated with puberty occur in the third year
for females and in the fourth year for males. At puberty, males leave
the troop and join all-male gangs. The mortality rate at this stage is
approximately 40 percent. Males eventually work their way into another
troop, where they might stay the rest of their lives or transfer, based
on their success in moving up in the dominance hierarchies. Females stay
with the troops in which they were born, and although the birth of an
infant is a major social event, females continue to be active in social
life even after they have stopped producing infants of their own.
High-ranking families fall in the hierarchy when the matriarch dies.

In the wild, rhesus macaques live up to 20 years. Under captive
circumstances, however, the macaques can live to their late 20s or early
30s. They die of extremely old age and have evidence of age-related
diseases similar to those in humans, including cancer and dementias. The
data regarding age-related changes in behavior are limited, although
there are indications that macaques become less aggressive and more
affiliative as they age.

Suomi and colleagues study the effects of altering rearing and social
conditions in early life. If infants are separated from their mothers
and allowed 24-access to their peer groups, they become more attached to
each other and explore their environments less than infants reared by
their mothers. Hyper-attachments appear to persist much longer
throughout development. Play is limited and unsophisticated among
peer-reared macaques, even when they move to a group of mother-reared
infants. During the first year of life, peer-reared infants exhibit
higher levels of HPA activity, compared with mother-reared infants. As
they mature, they are more fearful and reactive and show high levels of
aggressive, spontaneous, inappropriate, impulsive, and explosive
behavior. In alcohol studies done by the National Institute on Alcohol
Abuse and Alcoholism, both male and female peer-reared monkeys tend to
drink more than their mother-reared counterparts. Thus, early rearing
conditions affect behavioral development and emotional activity.

Peer-reared macaques show defects in 5-HT metabolism, as illustrated by
consistently lower levels of 5-hydroxyindoleacetic acid (5-HIAA) in the
cerebrospinal fluid (CSF).^78^ Recent imaging studies have shown more
5-HT--binding potential in infants raised by their mothers than in those
reared by their peers, suggesting that rearing conditions in early
childhood also affect brain structure. Findings from recent studies of
5-HTT polymorphisms in macaques suggest that macaques are more likely to
be highly aggressive and drink more when they carry the long form of
5-HTT and are raised by their peers. If macaques carrying this allele
are raised by their mothers, however, the allele becomes less of a risk
factor.^79^ Similar patterns have been observed with polymorphisms in
the monoamine oxidase A (MAOA) gene. The allele encoding a
less-efficient form of MAOA is associated with a higher level of
aggression, but only among peer-raised macaques. These differences
persist into early adulthood. New evidence also suggests that maternal
characteristics and styles that result in protection are passed from
generation to generation through non-genetic pathways.

The longevity and stability of these gene-environment interactions have
not been studied. Future research should explore whether they continue
to operate throughout the lifespan. In addition, it is likely that these
interactions result from epigenetic phenomena working at the molecular
level. Future research should address whether these events continue
throughout the lifespan, particularly during major social changes, such
as joining a group or losing dominance.

## Session V Discussion---Rearing Conditions in Rhesus Macaques and Possibilities for Translation to Human Studies

How parenting behaviors in macaques are transmitted from generation to
generation can be further studied by separating mothers and daughters
when the daughter has a baby. Such an example could tease apart the
extent to which a mother shows her daughter what to do and the modeling
the daughter observes during her early development. Dr. Suomi cited
evidence that all maternal characteristics are passed from generation to
generation but in different ways. For example, a daughter models the
attachment she received as an infant, but her punishment patterns mimic
what she sees her mother or grandmother doing at the same time she is
raising her infant. The ability to handle stress in the context of
childrearing appears to be a genetic factor. Each macaque mother has an
individual combination of maternal characteristics. For example, she
might be strong in forming attachments but weak in punishment patterns.
Studies in humans show similar patterns of explicit teaching versus
modeling.

Dr. Erica Spotts noted work by Sanchez and colleagues showing that
offspring rejected by their mothers look like peer-reared infants. She
added that peer-rearing can serve as a proxy of extreme parenting
styles. None of the studies discussed has assessed the effects of early
social and rearing conditions on morbidity and mortality. The
peer-reared macaques studied by Dr. Suomi's group are not yet old enough
for investigators to assess any differences.

Dr. Suzman cited a longitudinal mid-life study of interventions for bad
childhood experiences \[reference?\] and asked how the findings
described by Dr. Suomi could be translated to new longitudinal studies
in humans. He also asked whether it was feasible to obtain retrospective
cohort data, for example, assessments of childhood and social
environment. The ability to collect retrospective data will depend on
who is conducting the study. A group at Harvard University is following
a Rhode Island cohort who experienced perinatal difficulties; this might
be one source of data. Home movies might be useful in showing early
interactions and parenting styles. Good medical records, for example,
for children who often come to pediatric wards, might also be useful.
Genetic data can be collected at any time. However, collecting
retrospective data from scratch might prove difficult.

Participants at a recent biomarker workshop debated the usefulness of
protected versus natural environments in primate aging research. The
work described by Dr. Suomi has been done in a macaque colony in
Poolesville, Md. Dr. Nielsen asked about the usefulness of this colony
for investigating social behaviors in later life. Dr. Suomi noted that
the Poolesville population is not vastly different from that found in
the wild and that his group is taking great care to determine which
findings can be generalized. He also pointed out that workers in the
Cayo Santiago colony keep detailed records and know when each individual
macaque is born and dies; thus, records from this colony would be a good
resource. Efforts are under way to obtain DNA samples and to reconstruct
maternal patterns to assess long-term life expectancy in macaques from
high-ranking families. Collecting DNA from bone is also feasible.

Epigenetic studies are ongoing, and Dr. Suomi's group is now assessing
peripheral markers and considering human studies.

# Session VI: Social Behaviors, Social Environments, Genetics, and Aging: Opportunities in the Study of Human Populations

***Goals of Session VI:** To describe methods for studying gene
environment interplay over the lifecourse, including opportunities
presented by twin studies, with a focus on social behaviors and social
environments.*

## Gene-environment Interplay: Age Moderation of Genetic Effects

### Matt McGue, Ph.D., University of Minnesota

*Dr. McGue discussed approaches to studying gene environment interplay
over the life course and age moderation of genetic effects, drawing on
examples from the Minnesota Twin Study of Adult Development and the
Longitudinal Study of Aging in Danish Twins. He focused on findings
regarding social relationships and social engagement, with some
discussion of methodology and opportunities presented by twin studies
for advancing research on these topics.*

Denmark has a population of about 5 million, and the average lifespans
for men and women are identical to those in the United States. The
Longitudinal Study of Aging Danish Twins (LSADT) sampled older twins
every other year, from 1997 through 2005. The participation rate for
LSADT was about 80 percent, and almost 5,000 people completed the intake
assessment. Outcome measures included lifespan, disability, depression,
Mini-Mental State Examination (MMSE) scores, and cognition. The age
range for this study population ranged from 70 to 100 years.

Mean profiles from the LSADT indicate a vast amount of change over time,
particularly in terms of physical and cognitive functions. These changes
are apparent at both the individual and population levels. Depression
symptom scores decline in middle age, but they begin to increase between
the ages of 70 and 100 years. Although the typical nonagenarian reports
being happy, these scores suggested that he or she is not as happy as
the typical octogenarian. A lot of reassortment occurs over 10 years,
but entry-level functions account for only 16 percent to 25 percent of
variance 25 years later. Thus, initial scores are not indicative of
later scores. Early life experiences appear to affect later life, but
data from the LSADT suggest that events in late life are just as
important, making it difficult to predict for a person age 70 years what
will happen when he or she reaches 80 years.

One could hypothesize that the domains of late-life functions are
strongly heritable at earlier life stages. Thus, one would expect
genetic factors to be important in late-life functioning. Heritability
estimates across these domains are moderate and somewhat lower than what
would be expected for other data (McGue and Christensen, *Twin Res Hum
Genet*, in press). A study based in Sweden has yielded similar findings;
genetic contributions to how people change with age are not that strong.
Lifespan correlations for Danish twin pairs, however, indicate little
heritability in early death and strong heritability in late death.^80^
This result is consistent with other sibling studies showing that
extraordinary lifespan might be exceptionally heritable.^81^ Follow-up
studies have shown no associations between extraordinary longevity and
candidate genes such as the angiotensin-converting enzyme gene,^82^ the
gene associated with Werner syndrome,^83^ and a gene encoding
catalase.^84^ ApoE, on the other hand, shows a consistent relationship
with extreme longevity.^85,86^ These studies suggest that genetics is an
important factor, but not the most important factor, in late life.

Gene-environment interactions might be one reason for the diminished
importance of genetic factors. Shanahan and Hofer have proposed a
taxonomy of gene-environment interaction.^87^ Within this taxonomy,
context serves as a trigger; environmental provocation triggers an
inherited vulnerability. This is illustrated by the Caspi study showing
a relationship between life stress and 5-HT polymorphisms in influencing
the risk for depression.^29^ The taxonomy also proposes context as a
control; environment suppresses genetic effects by constraining
individual choice. McGue and Christensen have studied how physical
disability can limit individuals' ability to control environment and how
that affects genetic factors (McGue and Christensen, submitted
manuscript). As expected, the measure of disability correlates with the
level of depression. Surprisingly, however, data from the LSADT suggests
that genetic factors are moderated by environmental exposure. This
finding is consistent with those from studies in Japan. Further study by
McGue and Christensen suggests that more socially active individuals are
less likely to be depressed, disabled, or cognitively impaired. There
was a selection effect: Monozygotic twins are more likely to have
similar levels of social activity than dizygotic twins. Data mining
efforts have shown that the percentage of individuals reporting social
isolation increases with age and that 25 percent of people in their
nineties report being alone all the time.

These findings suggest that although genetics and environment are both
important in late life, future studies of this life stage will require
careful assessments of environment. Moreover, the form of interactions
between genetics and environment might differ between late life and
earlier life stages. Although context in early life has important
implications for later life, the substantial individual differences
observed at later life suggest that context in late life is just as
important. Better incorporation of laboratory findings into large-scale
longitudinal studies is needed.

## Session VI Discussion---Genetics and Environment, Adaptive Behaviors in Late Life

McGue and Christensen's study did not include nursing home residents in
the sample, nor did it control for dementia. Even so, the studies
described by Dr. McGue suggest that many people are isolated in late
life, which might be an important factor in understanding various
functions in older people. How loneliness is assessed is important. As
Dr. Levenson reported, someone describing their loneliness on a
questionnaire might be different from someone going 5 to 7 days without
interacting with anyone. Dr. Suzman added a caveat about study
populations; for example, there is evidence that Danes tend to overstate
their happiness. Study participants appear willing to report on their
depression. Dr. McGue noted that his earlier suggestions of measuring
depression were rebuffed, but when these questions were added later on,
participants appeared grateful that someone asked about it. How people
handle their loneliness, for example, by reminiscing or establishing
relationships with imaginary friends, might be an interesting question
to study.

Associations between disability and depression might have more to do
with acquired disability, which breaks down individuals' ability to
engage in activities that bring them pleasure. In addition, when people
age and acquire disabilities or engage in caregiving, for example, they
might no longer be able to make choices they made earlier in life.
Separating gene-environment correlations from gene-environment
interactions is somewhat difficult, as there is no one genotype to
relate to environment.

Dr. Heatherton pointed to the insect data discussed by Dr. Carey,
particularly the supine behavior observed in medflies, and suggested
that research should explore the adaptive behaviors of aging and genes
that might be involved in them. The elderly play a role in social
environment, as evidenced, for example, by weakened cohesiveness in
extended families after the oldest patriarch dies. Adaptive behaviors
may be needed as people age and transition from providing social
benefits to becoming a social cost. Age-related declines of this sort,
which appear to be irreversible and cascading, have not been plotted
over time.

# Session VII: Measurement of Social Environments and Social Behaviors of Relevance to Aging: Ecologically Valid Methods

***Goals of Session VII:** To advance discussion on improved measurement
of social behaviors and social environments in laboratory and
population-based research on aging.*

## Dyadic Interaction

### Robert Levenson, Ph.D., University of California, Berkeley

*Dr. Levenson discussed the advantages of dyadic interaction paradigms
in the study of social behaviors of older adults, with examples from his
own research on marital interactions.*

Most human emotions are dynamic and occur within an interpersonal
context. When a person experiences an emotion, he or she acts on the
world in some way, someone else responds, and the person responds to
that feedback. Emotions are not punctate, isolated events; they flow
dynamically in the course of interaction. Research on emotion thus
benefits from studies in a naturalistic dyadic setting, as well as from
studies of the full range of emotions.

Early studies of emotion represented a simple migration from stress
research. As extensions of fight-versus-flight studies, this work relied
on anger or fear manipulations, eliciting quite intense emotions by
staging elaborate events that frustrated and threatened participants.
With increasing sensitivity to protecting human subjects, these kinds of
studies gave way to work that used visual and imagined stimuli to elicit
emotion. These new techniques were limited in the range and intensity of
emotions they elicited. Thus photographs and films are good for
eliciting disgust and amusement, but not anger. In many ways, the change
of stimuli caused emotion research to transition from "fight and flight"
to "chuckles and yucks." This is unfortunate, because emotions such as
anger, sadness, and fear have great relevance for mental health and
illness and for understanding individuals' social worlds.

To address the need for methods that produce a full range of emotions,
capture the dynamics of emotion, and allow for continuous measurement of
behavior, physiology, and subjective experience, investigators turned to
the study of dyadic interaction. Early methods involved the talk table,
in which the interaction was halted after each participant spoke so that
rating scales of emotions and intentions could be completed. This
resulted in a very disjointed kind of exchange with artificial delays
introduced between action and reaction.

To capture interaction and the attendant emotions more realistically,
Levenson and Gottman developed a new method for observing interpersonal
interactions without interruption. In this method, a couple comes to the
laboratory following 8 hours of separation. The couple sits alone in a
room, with each spouse attached to devices that record cardiovascular,
electrodermal, thermal, and somatic responses. They engage in several
15-minute unrehearsed conversations while their interaction is
videotaped. Typically couples discuss the events of the day, then a
problem area, then a pleasant topic. The average couple produces a
codable emotion two to three times a minute, and most couples display
the full range of emotions during the course of a conversation.

This approach provides continuous observation or measure of behavior and
physiology, but it does not provide a continuous, record of subjective
emotional experience. Levenson and Gottman thus have added a recall
session, in which partners watched a videotape of their session and used
a "rating dial" to indicate how they were feeling. Analysis of
physiological measures obtained during this recall session indicated
that, when watching the videotapes, most partners physiologically
"relived" the responses they had had during the original interaction.
Other comparisons (e.g., coders ratings versus self-ratings) all
suggested that the self-ratings obtained using this method were valid.

Emotional behavior during these interactions is typically coded by
trained observers using Gottman's Specific Affect Coding System. This
coding system focuses on specific emotions and emotion-related behaviors
(e.g., validation), using facial emotion, voice tone, language, and
other cues. In addition to physiological, subjective, and behavioral
responses, verbatim transcripts of the conversations are analyzed using
text analysis. All data are continuous and thus are amenable to power
time series and sequential analysis techniques. This method has been
used with dating and married couples, same sex and cross-sex couples,
couples of all ages, and couples from difficult cultures. In an ongoing
study in Levenson's laboratory, these methods have been used to assess a
group of middle-aged and elderly couples longitudinally over a 20-year
period.

## Session VII Discussion---Recording Dyadic Interactions

The method described by Dr. Levenson generates a rich set of data.
Processing this data typically takes 2 to 3 years and involves a
constant process of coding and transcribing tapes and entering these
codes into a database. Data management, reduction, and analysis are all
very challenging.. The method has the advantage of ecological validity,
but it lacks experimental control (e.g., each couple has its own unique
conversation).

As suggested by Dr. Adolphs, this approach provides a rich opportunity
for data mining, and automated processes for doing so would be useful.
Such a process would be useful not only for research in social
neuroscience of aging, but also in matters of interest to the Department
of Defense and the Department of Homeland Security. At present, however,
the use of computers for pattern recognition is problematic when
conditions are less than optimal. Human judgment remains the best tool
for assessing this type of data. Coding is tedious, but it includes
everything from watching an interaction and completing a scale to
judging every facial muscle movement during an interaction.

Interfaces between dyadic interaction studies and longitudinal cohorts,
such as the HRS, have not been well developed. As pointed out by Dr.
Suzman, many longitudinal studies funded by NIA offer a large array of
cognitive measures, blood samples, and DNA samples. The approach
described by Dr. Levenson has been used in his own longitudinal studies
with Carstensen and Gottman, which stitch together 40 years of late
adult life from two 20-year panels. These studies offer the advantage of
having emotional behavior captured when it occurs rather than relying on
retrospective report. Nonetheless, tapping into existing longitudinal
cohorts can be useful in studying the long-term effects of social
interactions, and NIA is interested in supporting this kind of work..

## Implicit Measures

### Susan Fiske, Ph.D., Princeton University

*Dr. Fiske discussed the advantages of using implicit measures to study
social behaviors, with a focus on how these methods can be leveraged to
advance social neuroscience research on aging.*

Prejudice exists in a continuum from blatant prejudice, which is hot and
direct and results from a perceived threat, to egalitarian prejudice,
which is open, liberal, and humanitarian and results from security and
values. In between these extremes is subtle prejudice, which is cool and
indirect and results from societal norms. Most people engage in some
type of subtle prejudice, although whether this is because people
internalize cultural biases is under debate.

Subtle prejudice is automatic, as demonstrated by work using the
Implicit Association Test.^88^ These studies have demonstrated reliable
effects for a wide range of ingroups/outgroups or society valued/society
unvalued. People instantly categorize others by race, sex, and age and
distinguish their ingroups as positive and their outgroups as negative.
Results are consistent across various measures, including subliminal
cues,^89^ millisecond reactions,^90,91^ and neuroimaging data.^19,92-94^

In priming studies done by cognitive and social psychologists, white
participants were primed by photos of a black face or a white face, then
assessed for how fast they could recognize a word. Participants could
quickly recognize a relevant word when primed with photos of a black
face, but not with those of a white face. This priming effect was
accompanied by rapid activation of the amygdala. In subsequent studies,
participants viewed photos under social categorization by age; social
individuation, which focused participants on vegetable preference; and
simple visual search, which involved detection of a dot. Under the goal
of categorization, photos of black faces produced an effect, and
signaling was observed in the left amygdala. Under the goal of
individuation, however, photos of white faces produced an effect
associated with activation in the right amygdala. Under the goal of
visual search, black and white were viewed as equal, and no activation
in the amygdala was observed. Measurements also depended on context.
What participants thought they were doing as they emitted these
responses could shift amygdala activation. Thus subtle prejudice is
automatic, but it can be changed.

Subtle prejudice is also ambiguous, resulting more from an attitude of
"I love us" than one of "I hate them." It results in ingroup favoritism
in which the ingroup is viewed as good and outgroups are viewed as less
than good. This favoritism is characterized by the withholding of
admiration, sympathy, and rewards from members of the outgroups. In
addition, subtle prejudice is ambiguous. For example, older adults are
viewed as warm but stupid, and younger adults neglect them but want to
help them. Subtle prejudice therefore predicts awkward personal
interactions, in which discomfort, anxiety, and avoidance lead to
self-fulfilling behaviors. Subtle prejudice also predicts policy
preferences against outgroups if unprejudiced excuses can be found.
Thus, decisions about employment, housing, and education tend to favor
the ingroup.

Subtle prejudice originates from internal conflict. Individuals want to
comply with anti-prejudice ideals established either by personal values
or societal norms. However, they also deal with unconscious cultural
influences such as media associations or inexperience with outgroups.
Thus, subtle prejudice can change. People can be educated about
unintentional prejudices and motivated by egalitarian goals and values.
Subtle prejudice also can be addressed by constructive contact, which is
sanctioned by authority and is characterized by equal status in a
setting, significant interactions, and shared goals. Addressing subtle
prejudice through constructive contact provides opportunities for
intergroup friendship.

## Session VII Discussion---Subtle Prejudice

As Dr. Suzman pointed out, studies on how prejudices and status
hierarchies get under the skin are also important, because they might
identify ways to protect those stigmatized by stereotypes from potential
effects. He cited as an example a study on hierarchies within the
British Social Service and the effects of structural perceptions and
behaviors associated with status hierarchies. Dr. Fiske added that a
large amount of work has been done on stigma and its effects, but this
work has not interfaced with aging research. In addition, the effects of
acute, discreet events versus chronic experiences of prejudice should be
explored further.

Self-concept, for example the age at which a person believes he or she
is old, might influence the effects of prejudice and stereotypes on
older people. Dr. Fiske noted that people internalize stereotypes of
older adults. Dr. Suzman reminded workshop participants of the study
relating attitudes toward aging with a 7- to 8-year difference in life
expectancy. For the most part, the boundary at which people classify
themselves as older adults is a moving one.

As noted by Drs. Fiske and Levenson, terror management theory, which
proposes that people reminded of their own mortality cling to things
that outlast them, might be relevant to prejudices against the elderly.
The need for most humans to separate themselves from death and decay
might explain the conflicting views of older people as wise, admirable
and respected, on the one hand, and pitied and decayed on the other.
More work is needed to tease out the various aspects of this ambiguity
and determine what cues veneration and sympathy versus disgust.

Dr. Fiske noted work suggesting that people are predisposed to value
their ingroup and want to fit into their niches. The evolutionary
aspects of prejudice should be explored further. Animal models such as
those using the rhesus macaque could be useful in studying possible
evolutionary roots.

***Session VIII:* Biomarkers of Social Behaviors: Emotion Regulation,
Intimacy, and Bonding**

***Goals of Session VIII:** To explore the potential for novel uses of
biomarkers of social behaviors in laboratory and survey research on
aging.*

## Oxytocin and Bonding

### C. Sue Carter, Ph.D., University of Illinois at Chicago

*Dr. Carter discussed the use of oxytocin as a biomarker of trust,
bonding, affiliation motive, or other social phenomena -- whether and
how it can be measured in laboratory or survey contexts with humans and
potential applications to social neuroscience research.*

Oxytocin is a small peptide that exhibits many broad and integrated
functions. Made in the PVN of the hypothalamus, oxytocin is released
from the PVN and the SON into the general circulation at the posterior
pituitary gland. Thus, oxytocin sits in the center of the nervous system
and regulates both peripheral and autonomous processes, which have been
understudied. Oxytocin concentration can be measured in the blood or in
the saliva, but its concentrations tend to be low. It is not known
whether the oxytocin released in the brain and that released in the
periphery are tightly correlated. And although the action of the
oxytocin receptor is important, little is known about it. Even with
these caveats, however, oxytocin holds promise as a biomarker, and
several studies are under way to correlate it with physiological and
psychological processes. fMRI studies and methods for distinguishing
plasma oxytocin from brain oxytocin will be useful in addressing these
questions.

## Session VII Discussion---Oxytocin as Biomarker in Aging

Because of its myriad roles, oxytocin is not a biomarker of any one
function. It can, however, be used to measure individual differences in
sociality, emotion, and personality. Oxytocin has been studied in women
on hormone replacement therapy and in studies where participants rate
faces. Correlations between oxytocin and schizophrenia are under study
because of its presence in the interior hippocampus, which has been
associated with regulated emotion and schizophrenia. It is possible that
oxytocin serves as a connector between the cortical and limbic systems.
How oxytocin affects neurotrophic factors in the brain is not clear.
Animal models or *in vitro* studies might be useful, but the
neurotrophic effect of oxytocin might be hard to measure.

Dr. Carter cited evidence that oxytocin promotes the proliferation of
stem cells that eventually become cardiomyocytes. Oxytocin and its
receptor can be found in the heart and thus might represent an internal
peripheral system for natural repair following a heart attack. A similar
hypothesis for oxytocin might explain how healthy relationships promote
physical health. Work in prairie voles and with human couples might shed
further light.

Although oxytocin appears to be critical during lactation and possible
in cementing the bond between mother and infant, how this role can be
applied to aging is not clear. Dr. Taylor speculated that in one
respect, oxytocin might not be a useful marker for aging because older
people's interpersonal habits likely become independent of hormonal
regulation. On the other hand, humans might become used to a certain
level of oxytocin in the system, and declines in estrogen levels in
later life are accompanied by changes in oxytocin levels. In this
scenario, identifying conditions that elevate oxytocin levels might be
rewarding, particularly among older women, in ways that are not easily
understood. Oxytocin might be connected with age-related changes in
sources of pleasure, the importance of the social world, and the
changing sociality of men, but these connections are not clear. Studies
in knockout mice and fMRI studies in autistic children suggest that
oxytocin is needed for social perception.

The role of oxytocin in trust is another area with potential relevance
to aging, particularly in light of suggestions in the literature that
older people are more trusting. How oxytocin changes in response to
loneliness is another area. It should be noted that oxytocin is not "the
trust hormone," as has been suggested by the media. Rather, oxytocin has
been associated with positive or upbeat behavior, of which trust is a
manifestation. Dr. Taylor argued against attempts to draw a tight
relationship between a psychological state and a possible biological
underpinning. Dr. Levenson also noted the importance of developing a
common language when assessing behavioral manifestations. For example,
the kind of "trust" one might associate with oxytocin is not the same
type of "trust" involved in susceptibility to frauds.

In most human studies exploring the effects of oxytocin on behavior,
there have been no discernible differences between oxytocin and placebo,
and effects that have been observed only appear in social situations.
Although studies suggest that oxytocin increases one's ability to
interpret sadness, increases in oxytocin also have been observed in a
broad array of situations that are not valence balanced. Oxytocin might
be associated more with motivation than with emotion; thus attempts to
study it as an emotional factor might prove problematic.

The gene for oxytocin evolved from the split between invertebrates and
vertebrates, about 4 million years ago. Insects have a variant of the
gene which produces oxytocin and another hormone. On the basis of gene
expression, oxytocin is the most abundant chemical in the hypothalamus.
It is part of the basic chemical system involved in homeostasis, and
although it has only one known receptor, it also acts through
vasopressin receptors. How the functions of oxytocin are specified is an
important area of research.

# Session IX: Lab-Survey Partnerships and Other Integrative Approaches:Challenges and Benefits of Trans-disciplinary Collaborations 

***Goals of Session IX:** To provide examples of creative lab-survey
integration for advancing social neuroscience research on aging,
including a discussion of challenges and obstacles to progress.*

## Sexual Behavior; National Social Life, Health, and Aging Project; Chicago Health, Aging, and Social Relations Study

### Linda Waite, Ph.D., University of Chicago

*Dr. Waite described the NSHAP study, with particular focus on the
lab-survey interface, and the unique opportunities it presents. She
described the biomarkers related to sexual behavior and intimacy used in
NSHAP, including vaginal swabs and measures of sensory function. She
highlighted what is currently known about how these biomarkers relate to
social behaviors, social relationships, and social environments,
particularly in adulthood and older age. She also described John
Cacioppo's CHASRS study and how biomarkers have been incorporated to
study the effects of loneliness on health in the CHASRS sample.*

National Social Life, Health, and Aging Project (NSHAP) is a
population-based sample of more than 3,000 community-dwelling adults
aged 57 to 85 years, with a minority oversample. Participants engage in
a 120-minute in-home interview, complete a questionnaire, and undergo
biomeasure collection. Interviews and questionnaires ask about social
domains, including social networks and support, activities and exposure,
caregiving, romantic partners and sexuality, mental health, employment
and finances, religion, and physical contact. Other health domains
include HIV status and physical health, and participants are asked to
show the interviewer all their medication bottles, including
over-the-counter and natural or homeopathic medicines. Despite the large
time-commitment, the response rate for this sample has been high.

For many biological or biologically derived indicators of disease, there
are no previous data from population-based samples. Thus, the NSHAP is
breaking new ground in the collection of biomeasures, using survey
interviewers with no formal medical training. These biomeasures include
anthropometrics such as height, weight, body mass index, and waist
circumference. Functional status is measured using the Get-Up-and-Go
test and cognitive function also is measured. Blood spots are also
collected, dried, and sent to laboratories that measure CRP,
Epstein-Barr virus, antibody titers, and hemoglobin A1c. Genetic mapping
and testing based on blood spots are under consideration. Salivary
samples are also obtained and tested for cotinine, dehydroandrosterone,
estradiol, HIV, progesterone, and testosterone. Vaginal swabs are tested
for bacterial vaginosis, cell cytology, human papilloma virus (HPV), and
yeast vaginosis. HPV testing uses an assay that can assess subtypes,
particularly those shown to be oncogenic. NSHAP participants also are
tested for sensory function; specifically vision, taste, touch, and
smell are measured. Hearing function was based on self-report for the
first wave, but a hearing test will be included in the next wave. The
biomeasure response rate is about 68 percent for vaginal swabs and
almost 100 percent for all other measures. Women who do not provide
vaginal swabs are usually older and worried that they can not physically
manage the procedure.

One aspect of the NSHAP is its focus on intimacy and sexuality at older
ages. There is a bidirectional relationship between health and
sexuality. Health alters attitude, opportunity, and physical capacity
for intimate activities, but sexual expression is a key component of
healthy aging. NSHAP participants were asked whether they had had a
current partner---almost always their spouse---and whether they had had
partnered sexual activity within the past year. Only 32 percent of much
older women in excellent health reported having partners. Possible
reasons for this low percentage include the longer life spans of women
than men, the high rates of widowhood among older women, and higher
remarriage rates for widowed men than for widowed women. The probability
of having had sex during the past year was lower for women than for men
at all ages and in all levels of health. By age 85, half the men and a
third of the women in the sample reported being sexually active with a
partner in the past year. When asked whether they were having as much
sex as they wanted, less than they wanted, or more than they wanted,
most women who reported not having sex appeared to be satisfied with the
amount of sex. Participants were also asked about masturbation, sexual
dysfunction, and duration of dysfunction symptoms. Erectile dysfunction
was the primary symptom among men, whereas pain, failure to lubricate,
and lack of interest were reported most frequently by women.

The Chicago Health, Aging, and Social Relations Study (CHASRS) is a
population-based sample of 229 older adults from Cook County, Illinois
and born between 1935 and 1952. The sample is representative: 36 percent
of participants are white, 35 percent are black, 29 percent are
Hispanic, 48 percent are male, and 52 percent are female. In this study,
Cacioppo and colleagues found that loneliness and depressive symptoms
reported during the first year predicted changes in depression over the
next two years.^8^ Loneliness also affected self-rated health; an
increase in loneliness by one standard deviation increased the
likelihood of lower self-rated health.^95^ Cortisol response to
awakening also was higher among lonely participants, compared with
participants who were socially content.^96^ In a time-lagged analysis,
loneliness reported one day predicted for a higher cortisol response to
awakening on the next day, and higher cortisol response in the morning
was associated with less fatigue on the same day.

Prior research by Cacioppo and colleagues had shown that lonely young
adults were characterized by higher total peripheral resistance
(vascular resistance), compared with nonlonely young adults. As would be
expected based on the Framingham Study, CHASRS revealed that systolic
blood pressure was also higher in lonely participants than in
participants who were socially content.^7^ This difference, although
substantial, only appeared in older adults. A longitudinal analysis
revealed that with each additional year, lonely participants experienced
fairly substantial increases in systolic pressure. Recent work based on
the CHASRS has shown that work stress is an independent predictor of
systolic blood pressure.

## Session IX Discussion---NSHAP, CHASRS

In response to questions, Dr. Waite noted that the study team does
consider the fact that a large percentage of older people are on
antihypertensives, and she speculated that participants whose blood
pressure was controlled would not show the reported increases. She also
noted that participants provide background information, including number
of children, number of sexual and romantic partners, age at menopause,
number of surgeries, and hormone replacement therapy. This information
does not include the age at which participants had their children. Data
from the NSHAP will be available to the public in March 2007, and papers
on various topics have been completed and are under way.

NSHAP participants were not asked about the age at which sexual
difficulty occurred. They only reported on what had happened during the
past year. Problems reported by participants aged 50 to 55 years were
similar to those reported by participants aged 80 to 85 years. For types
of dysfunction associated with women, physical activity appeared to
alleviate symptoms. Work with retrospective cohorts might provide a
better idea of the ages at which sexual dysfunction occurs.

As suggested by the findings that women who were not having sex were
still satisfied, the role of sexuality in well-being might decline in
later life. The NSHAP uses good measures of marital quality, physical
and emotional satisfaction with sex, depression, loneliness, resources,
demands from partners, and social networks. However, potential declines
in the role of sexuality in well-being have not been shown. In response
to questions, Dr. Waite reported that many respondents said that sex was
very important to them.

Other age-related changes do seem apparent. Dr. Waite described data
showing that the social and kin networks decline for older adults but
that participation in non-kin social activities, such as religious
groups and volunteer activities, increases. Dr. Levenson also described
work in his group showing that hedonics and sources of pleasure change
as participants age from 40 to 60 years. Dr. Waite reminded workshop
participants that the NSHAP asks about intimate partners and physical
touch, and she added that project investigators are interested in
non-sexual touch and people who were not sexual partners for
participants but might be emotionally close to them.

A second wave of the NSHAP has been proposed. Workshop participants
suggested that data be collected on the effects of online/Internet
activity on sexual activity, the amount of time spent watching
television, and the amount of intimacy derived from watching television
or reading. Dr. Suzman noted that time use might provide a better
measure of physical, cognitive, and social function. Dr. Waite added
that the NSHAP collects MMSE data, but investigators hope also to use
measures designed for the HRS. Dr. Taylor suggested creating a measure
of participants' most pleasurable activities. Such a measure could be
based on self-report and could provide a sense of how sources of
pleasure change over time. Dr. Suzman added that misery, or the absence
of any pleasurable activity, could be included in this measure.

## The University of California, Los Angeles (UCLA) Study

### Shelley Taylor, Ph.D., University of California, Los Angeles

*Dr. Taylor described her social neuroscience collaborative study at
UCLA, with particular focus on the unique opportunities offered by this
kind of multi-method, multi-lab study for advancing social neuroscience
research on aging.*

Taylor and colleagues have characterized a theoretical model of stress
processes throughout the lifespan. One component of the study focuses on
the impact of early environmental factors, such as SES, family
environment, and genetic factors in the 5-HT and dopamine systems, on an
individual's lifespan and ability to develop psychosocial resources. The
work uses questionnaires and blood draws, as well as fMRI, to assess
amygdala, ACC, hypothalamus, and PFC responses to stress. Study
participants undergo the Trier Social Stress Test, and immune responses
are assessed based on IL-6 and TNF-α levels. Mental and physical health
is also examined.

The UCLA Study has helped to unravel puzzles such as the association
between the MAOA polymorphism and aggressive behavior. The long form of
MAOA (MAOA-L) might be associated with low sensitivity to the social
environment, in which case aggression results from a person not caring
about the social costs of harming others. On the other hand, this form
might be linked to hypersensitivity to the social environment, in which
case a person might overreact to offenses by others and, as a
consequence, be defensively aggressive. Study participants completed
questionnaire assessments of aggression and social hypersensitivity.
They also underwent a virtual episode of social exclusion in which they
engaged in a ball-tossing task and were progressively left out by the
other two people playing with them. fMRI images were taken as
participants performed this task. Individuals homozygous for MAOA-L
reported more aggression over a broader range of circumstances.^97^ They
were also hypersensitive, as illustrated by the ease at which they were
offended and by a greater response in dorsal ACC during the virtual
task. Thus, an integration of approaches facilitated a psychobiological
explanation for associations between MAOA-L and aggression.

Another example in which this approach has been useful is the study of
early experiences and stress. Harsh early environments have been related
to strong autonomic and HPA-axis responses to threat across the
lifespan, but the mechanisms underlying this observation have been
unclear. Participants in the UCLA Study completed a questionnaire
assessing early family environment, then engaged in tasks while they
were in the scanner.^98^ In the first task, they observed threatening
faces, which evokes the amygdala. In the second task, they labeled the
faces, which evokes the PFC. Relationships between activity in the
amygdala and that in the PFC were assessed. Participants from nurturing
environments responded to faces as expected, with activity in the
amygdala when they observed faces and activity in the PFC when they
labeled them. Also as expected, this activity was negatively correlated
during the labeling task. Participants who had grown up in harsh
families showed little amygdala activation when they observed faces,
consistent with other findings that individuals from a harsh early
environment tend to tune things out. When these participants were asked
to label faces, however, responses in both the amygdala and PFC were
stronger and tightly positively correlated. These findings suggest a
type of dysregulation in which people from harsh early environments try
to cope but are unsuccessful. All participants are equally accurate in
ascertaining what the expressions are.

The UCLA Study team also is testing its theoretical model of stress
response with the CARDIA sample, which includes white and African
American participants followed over a 15-year period. Data were
collected on early family environment and childhood resources, and CRP
and metabolic syndrome were assessed as health outcomes. Metabolic
syndrome was measured by the CARDIA study based on blood pressure, lipid
profiles, and adiposity. Findings from this work suggest that the model
explains the significant variations for both health outcomes.
Longitudinally, and with respect to aging, this model might also explain
observed variability in adverse health outcomes. A laboratory study
including white, African American, Hispanic, and Asian older adults is
planned.

## Session IX Discussion---The UCLA Study

In response to questions, Dr. Taylor pointed out that the UCLA Study
group has information on participants' coping skills, along with
findings from previous studies showing that growing up in a harsh family
environment interferes with the development of coping strategies. A
harsh environment does not mean an abusive one. "Harsh" is based on
family conflict, cold or unaffectionate parenting, or situations in
which children are left to fend for themselves. The study team used
interviews to assess early environments and found correlations between
this data and the Risky Families measure. In response to questions from
Dr. Epel about appraisal versus active coping efforts, Dr. Taylor noted
the strength of the positive interaction and speculated that although a
deliberate process is being imposed, participants are not given much
time during the task. Thus, the response may be more automatic.

It is not completely clear how people who experience early life stress
move to a "bad trajectory" and how late in life the negative effects
will be observed. However, Taylor and colleagues' work suggests that
changes in biological stress regulatory systems and in immune
functioning provide potential mechanisms. To a degree, attempts to
answer this question are limited by the types of assessments that can be
done in children. However, Matthews and colleagues have found
cardiovascular effects in boys as young as 7 or 8 years old, but not in
girls. More thought should be given to what should be tracked early on.
Possible moderation effects are not known, although Dr. Waite noted
studies showing that effects are smaller for people who achieve and that
childhood health and childhood SES have an effect on health later on.

Genetic data have not been collected, for example, for the work with the
CARDIA sample. Possible genetic components to SES are not known,
although this is an interesting question. Genetic components of juvenile
delinquency, relationships between conduct disorders and marital
discord, and the relationship between MAOA-L and aggression are all
examples of interesting questions regarding genetics and behavior. NIA
is funding a project focused on the genetic determinants of economic
behavior.

# Session X: General Discussion

***Goal of Session X:** To build on issues raised in discussion
throughout the workshop and to consider ways NIA and the scientific
community can support research in social neuroscience of aging.*

In discussions throughout the workshop, participants considered
potential collaborative opportunities, potential roadblocks, immediate
needs, and current translational opportunities in advancing the field of
social neuroscience of aging. The last sessions of the workshop were
focused on further discussion of these questions, and participants also
considered ways NIA and the scientific community could support research
in this field. The following themes emerged from all discussions.

-   **The importance of context in social neuroscience studies.** Most
    workshop participants agreed that studying the biological and social
    pathways underlying the effects of social behavior on health was
    important. Some noted that this understanding was necessary to
    identify potential interventions, whereas others suggested that
    intervention studies could be used to further understanding of these
    pathways. Dr. Carter noted that some themes appeared to be conserved
    from the cellular level up to the social level. Some participants
    suggested, however, that understanding how group-level interventions
    get under the skin was not necessary to identify ways to address
    those issues.\
    \
    Many of the studies presented during this workshop focused on the
    elderly or on children and adolescents, leaving out persons age 20
    to 60 years. Cognitive aging research has traditionally examined
    what happens in the very old and the very young, but it is now
    beginning to focus on what happens at mid-life. Several NIA-funded
    studies, including the MIDUS II Study, are focused on midlife, and
    are incorporating neuroimaging assessments of social and emotional
    function and studies of relationships between social stressors and
    cortisol. Workshop participants emphasized the importance of social
    neuroscience research focused on changes across the entire lifespan.

-   **Understanding how social factors affect the individual.** Dr.
    Levenson noted the number of studies associating social contact,
    social connectedness, and lack of loneliness with good health
    outcomes. Understanding how these social factors "get under the
    skin" and promote these outcomes will form a large component in
    future research on social neuroscience in aging. Future research
    should assess how social factors affect the pathophysiology of
    disease, how they affect the way individuals process information,
    whether effects are reversible, and how effects differ with age.
    Moreover, investigators should use existing data, including
    interview transcripts and observations of affect, to identify
    sustainable predictors of social effects on physiology.\
    \
    Several biology-level tools and analytical methods were discussed at
    this workshop, and as noted by Dr. Nielsen, how these measures can
    be related to social behavior and social environment will depend on
    how fine-grained the measures of social behaviors are. Dr.
    Kiecolt-Glaser described work in her laboratory connecting
    behavioral data with physiological measures. She acknowledged that
    connecting these measures could be expensive and time-consuming but
    feasible. Dr. Epel also pointed out factors that could be easily
    measured, such as early events, early childhood, parental SES, big
    life events, adiposity, early puberty, and social demographic
    factors.

-   **Defining the study question.** Several themes have emerged in
    social neuroscience and in this workshop, including neurobiological
    mechanisms underlying social behaviors, differences associated with
    various life stages, and the effects of social connectedness and
    social relationships on health. However, specific research questions
    are not clear. Dr. Taylor suggested that these questions will depend
    on what NIA sees as the constituencies for the emerging body of
    knowledge. If the constituency is NIH itself, specific questions
    will have a strong emphasis on health. For policymakers considering
    the elderly, on the other hand, research questions will focus on
    disability and specific interventions. She noted that some themes,
    such as comorbidities between physical and mental health and
    longitudinal models showing effects across the lifespan, point to
    research questions focused on mechanisms, health, and mental
    health.\
    \
    Dr. Nielsen responded that NIA is interested in basic social
    neuroscience research that can advance our understanding of how
    social behaviors are related to health outcomes, as well as
    translational and interventional research. She added that social
    neuroscience can be defined in many ways, that NIA has adopted a
    fairly inclusive definition at the outset, as it explores research
    needs, gathers information and assesses where to invest its
    resources. There is also a strong emphasis on "people already out of
    the starting gate," individuals who are reaching old age and will be
    living longer because of medical advances. NIA-supported research
    should thus consider ways to improve and enhance the later years of
    life.

-   **Longitudinal studies and the use of existing populations.** Dr.
    Nielsen asked what it would take to interest investigators in
    longitudinal studies using existing populations. Workshop
    participants described unsuccessful attempts to tap into
    longitudinal studies conducted by the NIA Intramural Program and
    asked whether these studies were open to complementary studies from
    the outside. Dr. Nielsen responded that several of these studies
    have outside collaborators but that the principal investigators of
    the NIA studies must make these connections. Dr. Harris added that
    restrictions vary from study to study and that investigators can
    visit study Web pages and apply for data.\
    \
    Dr. Carter pointed out that large numbers of children are now being
    given prescription drugs early in life and that these children might
    ultimately wind up taking multiple drugs. She speculated that an
    entire generation will be pharmacologically dependent as they reach
    adulthood and older ages. She noted that discussions at this
    workshop assume an initial biological substrate but that this
    substrate might change in this cohort of children. Dr. Suomi
    described collaborative efforts among NIMH, the National Institute
    of Child Health and Human Development, NIDA, and the NIAAA to assess
    the long-term consequences of chronic Prozac use.

-   **Methods.** Interviews and observational approaches were discussed.
    Dr. Carey noted that observational studies can be done in both
    humans and animals, and Dr. Levenson mentioned anthropological
    approaches that simply observe "what people do." Some workshops
    participants suggested that observation could be advantageous to
    self-report, because individuals tend to report their emotions
    inaccurately. Dr. Waite noted that in some cases, the interviewer is
    also an observer. The interviewer might observe the interaction
    between two partners in a home, the overall environment of the home,
    and the environment within the neighborhood. Workshop participants
    pointed out that this method captures only a moment in time and that
    random error is inherent in behavior. Yet thin slices of behavior
    can be powerful. Workshop participants also noted the value of
    self-reports, although these must be viewed as separate from
    behavior.\
    \
    Dr. Levenson noted that traditional methods might not account for
    important sources of variance. He described a recent dissertation in
    his laboratory in which a student first removed all of the variance
    in marital satisfaction that could be accounted for by behavioral,
    subjective, and physiological responses during marital interaction.
    She found that, beyond this, spousal beliefs about the kind of
    marriage they had (e.g., "how egalitarian," "how warm") accounted
    for significant additional variance in marital satisfaction. Dr.
    Levenson suggested that a full understanding of such phenomena as
    marital and life satisfaction would benefit from using multiple
    methods. New measures are also needed to tease out the independent
    effects of beliefs and expectations. In addition, microcosm
    approaches, in which interviewers also observe behavior at a certain
    point of time, can reveal seemingly short-term processes that, upon
    further study, turn out to be snapshots of long-term processes.\
    \
    Workshop participants agreed that research on social neuroscience of
    aging would benefit from the development of new methods. However,
    they also noted that methods development often involved high-risk
    studies that do not generally receive support from study sections at
    NIH. Dr. Suzman acknowledged that some review groups were too narrow
    in scope, particularly for training grants, and that NIA is
    considering ways to bring in reviewers with broader backgrounds. He
    also suggested complementary training grants; the addition of an
    aging component to existing training grants; K-mechanism awards,
    such as the K07, which are awarded to investigators organizing a
    field; and F-mechanism awards, which are for predoctoral students
    and post-doctoral researchers. K-mechanism awards in this area are
    reviewed by the Behavior and Social Science of Aging Review
    Committee or the Clinical Aging Review Committee (NIA-S and NIA-C).
    The NIA C tends to require a gerontology focus, but social
    neuroscience projects have fared well in this committee.\
    \
    Dr. Suzman also pointed out that the program project provides the
    best chance for unusual or high-risk projects and that of all NIH
    Institutes and Centers, NIA had funded the highest proportion of
    program projects. These projects offer the advantage that applicants
    receive an onsite review and can request a review team that reflects
    the blend of disciplines included on the application. Dr. Suzman
    cautioned, however, that the total expenditure for these awards is
    capped at \$1.5 million in direct costs per year.\
    \
    Workshop participants suggested supplements to existing grants, both
    competitive and non-competitive, as another way to support methods
    development. Dr. Suzman agreed with this idea, although he cautioned
    that supplements should be requested through existing NIA grants and
    not through NIA-funded centers. Competing supplements are reviewed
    by CSR study sections, while administrative supplements to active
    grants can be requested directly from the NIA Programs, but are
    typically reserved for time sensitive, unforeseen opportunities.\
    \
    Dr. Carey pointed out the difficulty of finding funding for emerging
    disciplines, such as biodemography. Dr. Nielsen responded that
    applications that included demography and social aspects would tend
    to come to BSR and that the Biology of Aging Program also has some
    interest in these phenomena.\
    \
    Dr. Suzman also suggested that investigators could include basic
    research in their applications when the Roybal Centers come up for
    recompetition. Identifying ways to use existing efforts, such as
    those supported by SBIR grants, was also suggested.

-   **The use of animal models.** Dr. Carey suggested that researchers
    interested in social neuroscience of aging should identify basic
    questions on which animal models could be brought to bear. These
    questions should address demographic, behavioral, physiological, and
    molecular levels. Dr. Carey also pointed out the importance of
    bidirectional cross-talk between human studies and animal studies.
    Dr. Suomi agreed that general principles should be found across
    species, and he cautioned against attempts to identify 1:1
    concordances. He cited the example of cross-fostering studies done
    in rhesus macaques. These studies raised the principles of
    temperament, predisposition, and early intervention, which can be
    addressed in human studies. Dr. Suomi cited functional MAOA
    polymorphisms as another example. Although the molecular
    characteristics of different alleles might differ among species, the
    functional characteristics (i.e., one being associated with more
    aggressive behavior) could be similar. Other potential models
    included models for sexual interest and motivation and a rat model
    assessing interactions among age, salt consumption, and blood
    pressure.\
    \
    Again, context must be considered in studies using animal models.
    Dr. Levenson cited studies showing different impacts on development
    resulting from exactly when rats were socially isolated. Workshop
    participants agreed that studies should assess what happens in a
    naturalistic context.\
    \
    Workshop participants pointed out that the BSR has historically
    shunned animal models. Drs. Suzman and Nielsen acknowledged this
    tradition, but they also acknowledged the importance of these
    models. They pointed out that BSR was making efforts to include more
    of these applications and that BSR would fund applications that
    received a good score during review. Dr. Harris added that an
    animal-model component could be added to existing P01 grants.

-   **Mapping neuroimaging studies to the real world.** Dr. Waite noted
    that most fMRI studies are done at the individual level, but many
    studies of sociological interest take place within social groups.
    For example, studies have demonstrated that religious participation
    is predictive of long-term mortality, suggesting physiological
    changes associated with religious participation. Workshop
    participants acknowledged the difficulty in mapping imaging studies
    onto phenomena that take place in the real world. Some suggested
    brain studies on a subgroup of participants from larger study
    populations. However, this approach does not address changes that
    take place when a social group is gathered. Dr. Heatherton pointed
    out that cognitive neuroscientists have realized the value of
    studying social behavior but are still considering how to think
    about it.\
    \
    Dr. Fiske suggested that imaging studies are best suited to
    answering focused questions when an investigator already has a good
    idea of what is happening. Big studies should be used to identify
    profoundly meaningful experiences and possible mechanisms for them,
    and imaging studies should be used to assess how these mechanisms
    translate to brain activity and how that can translate to a task to
    be undertaken in a scanner. Dr. Kiecolt-Glaser added that the
    creation of such an analog can be used to demonstrate which
    mechanisms work and that less expensive approaches can be used to
    assess how often that mechanism works.

-   **Combining disciplines and approaches.** Workshop participants
    agreed that research in social neuroscience of aging would benefit
    from studies that combine approaches. Dr. Adolphs suggested that
    potential studies in this field should first consider significance:
    What the important questions are, based on existing data, and how
    those questions can be answered using current paradigms and models.
    All workshop participants agreed that research in this field should
    not merely try to repeat paradigms established in younger adults.
    Dr. Adolphs suggested a collaborative approach in which
    investigators conduct questionnaire- and population-based studies
    are used to determine what matters in aging, then determine whether
    these issues can be studied further by using available
    neuroscientific tools. Workshop participants suggested additional
    workshops and scientific symposia that bring different disciplines
    together as a way to facilitate more collaboration.\
    \
    Development of a common language is crucial. Interactions between
    social psychologists and geneticists were discussed as an example.
    Although geneticists understand interactions between genetics and
    environment, they are still unsure of how to measure the full range
    of the environment or which environments to include in their
    studies. They could consult social psychologists, but social
    psychologists might not understand the questions geneticists are
    asking. As Dr. Epel pointed out, the definition of "environment"
    might differ between disciplines.

-   **Bringing attention to the field of social neuroscience of aging,
    and garnering interest among researchers.** Dr. Heatherton pointed
    out that small RFAs often bring attention to a new area of research
    and suggested that NIA consider issuing one. Dr. Suzman agreed but
    cautioned that fewer RFAs are approved because of the decreased
    funding line. Dr. Carter also noted that many new investigators find
    themselves shut out because more established investigators, who have
    done most of the work and thus have a track record, are more
    successful in competing for these awards.\
    \
    Dr. Nielsen discussed the recent RFA focused on the neuroeconomics
    of aging. NIA received a large number of applications in response to
    this RFA, more than NIA can fund. However, Dr. Nielsen expressed the
    hope that by issuing this RFA, NIA has signaled to the scientific
    community that this is an area of interest and that investigators
    would be encouraged to refashion their ideas and resubmit
    applications to regular reviews. Dr. Sidney Stahl also pointed out
    the good working relationship between NIA and the Center for
    Scientific Review, which sometimes alerts a committee's Scientific
    Review Administrator to a particularly interesting application. Dr.
    Suzman added that investigators can write letters to a program about
    special review considerations.\
    \
    NIA also could bring attention to this research area by holding
    workshops and symposia. BSR already has held symposia with
    scientific societies. Dr. Nielsen encouraged workshop participants
    who belonged to scientific societies to identify ties between their
    societies' focus and social neuroscience of aging and to talk
    further with BSR about holding additional symposia. Drs. Carey and
    Carter discussed their experiences in organizing workshops,
    particularly challenges in continuing with the field once the
    workshop was over. Dr. Carey discussed two workshops that had
    brought prominent researchers together to discuss biology and
    demography but had gone nowhere. He then discussed a workshop that
    brought together experts in the two disciplines, as well as the
    promise of funding. This workshop resulted in the publication of a
    special journal issue and the organization of a P01 grant. Dr.
    Carter discussed efforts to organize a meeting with the New York
    Academy of Sciences (NYAS). She noted that NYAS is self-supporting
    and can quickly bring together an interdisciplinary effort, and she
    pointed to the NYAS book as another venue NIA can use to bring
    attention to the social neuroscience of aging.\
    \
    Publishing special journal issues is another way NIA can bring
    attention to this area. Workshop participants suggested *SCAN* as
    one journal. Dr. Adolphs also noted that a special issue of *Nature
    Neuroscience*, which would focus on emotion across the lifespan, has
    been suggested. Dr. Nielsen pointed out that BSR has funds available
    to commission papers, though it was not yet clear whether the field
    was ready for a volume on the social neuroscience of aging. Dr.
    Carter expressed concern about narrowing a topic through the
    publication of a special journal issue, and she emphasized the
    importance of putting together the right keywords to point potential
    investigators to this field.\
    \
    Dr. Suzman emphasized that BSR is interested in supporting basic
    research that does not have immediate relevance to aging, as long as
    it will eventually be relevant to issues related to aging. He added
    that the field as a whole must determine where it can provide
    answers of social, economic, individual, and translational
    importance. In this way, investigators can increase their chances of
    receiving additional funding from NIA and NIH. Drs. Suzman, Nielsen,
    and Harris encouraged workshop participants to contact NIA with
    ideas for research.

# Workshop Participants

Ralph Adolphs, Ph.D., Department of Psychology and Neuroscience,
California Institute of Technology

James Carey, Ph.D., Department of Entomology, University of California,
Davis

C. Sue Carter, Ph.D., Department of Psychiatry, University of Illinois
at Chicago

Elissa Epel, Ph.D., Department of Psychiatry, University of California,
San Francisco

Susan Fiske, Ph.D., Department of Psychology, Princeton University

Todd Heatherton, Ph.D., Department of Psychological and Brain Sciences,
Dartmouth College

Janice Kiecolt-Glaser, Ph.D., Ohio State University College of Medicine

Robert Levenson, Ph.D., Department of Psychology, University of
California, Berkeley

Matt McGue, Ph.D., Psychology Department, University of Minnesota

Shelley Taylor, Ph.D., Department of Psychology, University of
California, Los Angeles

Linda Waite, Ph.D., Department of Sociology, University of Chicago

Andreas Meyer-Lindenberg, M.D., Ph.D., M.S., Genes, Cognition, and
Psychosis Program, NIMH, NIH

Stephen Suomi, Ph.D., Laboratory of Comparative Ethology, National
Institute of Child Health and Human Development, NIH

***NIH Staff***

Ronald Abeles, Ph.D., Office of the Director, Office of Behavioral and
Social Sciences Research (OBSSR), NIH

Neil Buckholtz, Ph.D., NNA, NIA, NIH

Jeffrey Elias, Ph.D., BSR, NIA, NIH

Anneliese Hahn, M.S., BSR, NIA, NIH

Jennifer Harris, Ph.D., BSR, NIA, NIH

Venkata Mattay, M.D., Genes, Cognition, and Psychosis Program, National
Institute of Mental Health (NIMH), NIH

Michael Micklin, Ph.D., CSR, NIH

Lisbeth Nielsen, Ph.D., BSR, NIA, NIH

Anna Riley, Ph.D., CSR, NIH

Erica Spotts, Ph.D., BSR, NIA, NIH

Sidney Stahl, Ph.D., BSR, NIA, NIH

Richard Suzman, Ph.D., BSR, NIA, NIH

Molly Wagster, Ph.D., NNA, NIA, NIH

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