The Biology of Resilience
Condition: Oxytocin; Placebo
Study type: Interventional

Summary: 
      Positive social relationships have consistently been associated with better health, although
      the neurobiological underpinnings of these observed effects remain largely unknown. The
      overall goal of the proposed work is to explore novel biological pathways that may explain
      how social relationships influence health. Recent theorizing suggests that the oxytocin
      system may underlie some of the observed beneficial effects. Four hypotheses will be
      examined:

        1. Oxytocin ameliorates the deleterious neuroendocrine, cardiovascular, and subjective
           effects of stress.

        2. Oxytocin and social support have similar and additive stress-buffering effects.

        3. Effects of oxytocin are evident among younger and older adults.

        4. Effects of oxytocin are stronger in women vs men.
    

Detailed description: 
      Positive social relationships have consistently been associated with better health, although
      the neurobiological underpinnings of these observed effects are not well understood. Valuable
      insight may be gained by a life course perspective as it is becoming increasingly apparent
      that early life social experiences are crucially related to later life functioning and
      well-being. The overall goal of the proposed work is to explore novel biological pathways
      that help to explain how social relationships influence health. Recent theorizing on the
      biology relating positive social and emotional factors to health and patterns of resilience
      suggest that the oxytocin system may underlie some of the observed beneficial effects.
      Historically, most work on the oxytocin system in humans has been tied to reproductive
      outcomes (e.g., lactation), with more limited work on children and young adults. A growing
      body of experimental research with animals suggests that early in life, oxytocin not only
      creates powerful social bonds between a mother and child but may also stimulate growth and
      restorative processes as well as buffer deleterious stress-related neuroendocrine activation
      throughout the life course. Moreover, the animal literature has suggested that oxytocin is
      more potent in the presence of higher estrogen levels, leading investigators to hypothesize
      that effects of oxytocin are stronger in women than men, but few studies have tested this
      hypothesis in humans. A better understanding of the inter-relationships between oxytocin,
      social relationships, stress, and health will be gained by examining these factors in a
      controlled laboratory setting. The immediate goal of this research is to determine whether
      oxytocin plays a critical role in determining neuroendocrine, cardiovascular, and subjective
      responses to stress across age and gender, and to examine the effects of oxytocin in relation
      to those of social support. To achieve these goals, experimental research is proposed to
      examine the effects of exogenously administered (intranasal) oxytocin on psychological and
      physiological outcomes, under conditions of stress. The specific aims of this exploratory
      project are to test the following hypotheses:

        1. Oxytocin ameliorates the deleterious neuroendocrine, cardiovascular, and subjective
           effects of stress.

        2. Oxytocin and social support have similar and additive stress-buffering effects.

        3. Effects of oxytocin are stronger in women versus men.

        4. Effects of oxytocin are similar across a range of younger and older adult ages.

      Hypotheses will be tested via a placebo-controlled double blind study using a sample of
      healthy men and women recruited from the community (overall n = 320). The proposed
      experimental study will consider oxytocin effects on a range of outcomes. These include
      autonomic reactivity as measured by blood pressure responses and high frequency heart rate
      variability (measure of vagal tone). Stress-related cardiovascular phenotypes as
      characterized by the patterning of ventricle contractility, vascular resistance, and cardiac
      output will also be assessed. Other outcomes include measures of neuroendocrine effects as
      measured by levels of cortisol and dehydroepiandrosterone (DHEA) hormone, subjective distress
      and positive affect. Participants will be randomly assigned to receive either exogenous
      oxytocin or placebo. They will undergo a social stress manipulation with or without social
      support (randomly assigned), and outcome measures will be obtained at multiple times during
      the experimental procedure. The experiment will test whether effects of oxytocin and social
      support are similar and additive, and will also compare effects of oxytocin and social
      support across men and women of varying ages. This multidisciplinary study uses a
      biobehavioral framework to examine interactions between psychological, social, and biological
      levels of functioning, and is informed by theories of how key early life exposures may impact
      health over the life course. The provision of an R21 award for this work will facilitate
      novel research that could have a major impact on our understanding of whether and how
      oxytocin influences responses to stress in humans. The proposed exploratory research will lay
      the groundwork for the submission of an R01 grant proposal that will have greater resources
      for addressing both the questions that cannot be addressed with this more limited mechanism
      as well as new questions that will undoubtedly arise. Ultimately we expect this project will
      provide a solid platform from which to launch a larger program of research aimed at
      identifying how positive social and emotional experiences influence adult health and
      longevity. A neurobiological understanding of resilience can inform efforts for both
      prevention and intervention of diseases or problems common in later life.
    

Intervention name(s): intranasal oxytocin; Placebo; Social support; No Social Support
Intervention type(s): Drug; Drug; Behavioral; Behavioral
Intervention description(s): The aqueous form of oxytocin (oxytocin injection, synthetic) in 10 ml vials is inserted into a spray bottle. The spray bottle is calibrated so that emptying the spray bottle results in delivering 24 IU of oxytocin. No dilution of the original aqueous form of the oxytocin is necessary. 24 IU of oxytocin will be administered at one time only during the procedure. Approximately half the dose will be sprayed into each nostril. Administration will stop after 24 IUs of oxytocin have been administered. Duration of administration is anticipated to be 2-5 minutes; Participants in the placebo condition receive an equivalent amount of saline for intranasal spray administration. The placebo will be administered at one time only during the procedure. Approximately half the dose will be sprayed into each nostril. Administration will stop after the full amount in the spray bottle has been used. Duration of administration is anticipated to be 2-5 minutes; Prior to coming to the laboratory, participants are randomly assigned to one of two conditions, requiring them to appear alone or accompanied by a partner. If instructed to bring a same-sex close friend (excluding spouses, participants are joined by their support partners join participants at the start of the stress exposure. The social support condition includes a number of strategies designed to standardize the type of support available to participants across individuals.; Prior to coming to the laboratory, participants are randomly assigned to one of two conditions, requiring them to appear alone or accompanied by a partner. They are then instructed to bring a same-sex close friend (excluding spouses) with them, or to come alone. If they come to the laboratory without a friend, they engage in all the laboratory procedures without a friend present.
Other intervention name(s): Pitocin
Intervention MeSH terms: Oxytocin
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Stress; Oxytocin; Social Support; Resilience