UNIFORMEDSERVICES
UNIVERSITY
11th Annual Amygdala,Stress and
PTSD Conference:
The Effects of Stress and Loss
CENTER FOR THE STUDY OF TRAUMATIC STRESS

11th Annual Amygdala, Stress and PTSD
Conference: The Effects of Stress and LossAPRIL 19, 2016
Sanford Auditorium & Lobby, Building B
Uniformed Services University
Bethesda, MD

www.AmygdalaPTSDconference.org
SPONSORED BY:
The Center for the Study of Traumatic Stress (USU), Department of Psychiatry (USU),
Neuroscience Program (USU), Department of Family Medicine (USU), andDepartment of Psychiatry (WRNMMC)

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11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss2

11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

UNIFORMED SERVICES UNIVERSITYCENTER FOR THE STUDY OF TRAUMATIC STRESS

11th Annual Amygdala, Stress and PTSD
Conference: The Effects of Stress and LossAPRIL 19, 2016
Sanford Auditorium & Lobby, Building B
Uniformed Services University
Bethesda, MD

www.AmygdalaPTSDconference.org
SPONSORED BY:
The Center for the Study of Traumatic Stress (USU), Department of Psychiatry (USU),
Neuroscience Program (USU), Department of Family Medicine (USU), andDepartment of Psychiatry (WRNMMC)

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11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Background
The Amygdala Conference series is sponsored by the Center for the Study of TraumaticStress under the direction of Robert J. Ursano, MD, the USU Graduate Neuroscience
Program under the direction of Sharon L. Juliano, PhD, and also by the Department of
Family Medicine under the direction of Mark Stephens, MD.

411th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Table of Contents
Small Table Discussion Groups.................................................................................... 2
Agenda............................................................................................................................. 3
Conference Speakers...................................................................................................... 4Moderators...................................................................................................................... 7
Conference Leadership.................................................................................................. 8
Conference Committee............................................................................................... 10
Conference Posters....................................................................................................... 11
Continuing Education Credit..................................................................................... 261

11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Small Table Discussion Groups
USU Cafeteria 0800–0850
Please join our small group discussions from 0800–0850 in the USU cafeteria,
Building B. Each of the conference speakers will be available for more
personalized and direct interaction with conference attendees. Separate
registration for the discussion sessions is not necessary. Everyone registered forthe conference is welcome and encouraged to attend.

Speakers
Table 1: Mar Sanchez, PhD
Developmental Impact of Early Life Stress on
Primate Emotional and Stress Regulation:
Prefrontal-Amygdala Circuits

Table 4: Michael S. Fanselow, PhD
Neural Mechanisms of Post Traumatic Stress Disorderas Seen Through Stress-Enhanced Fear Learning
Table 5: David S. Krantz, PhD
Stress, Anger, and Coronary Heart Disease:
Downstream Effects of PTSD

Table 2: Patrizia Casaccia, MD, PhD
The Stress of Aging and Isolation on Epigenetic
Regulation of Myelination
Table 3: Naomi M. Simon, MD
Understanding the Diagnosis and Treatment ofComplicated Grief: A Post-Loss Stress Disorder2

11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

AGENDA
0800-0900

Registration, Small Group Discussions and Poster Review

0900-0905

Conference Announcements — Gary H. Wynn, MD

0905-0915

Welcome and Introduction — Robert J. Ursano, MD

0915-1000
		Mar Sanchez, PhD — Developmental Impact of Early Life Stress on Primate Emotional 			and Stress Regulation: Prefrontal-Amygdala Circuits		

1000-1045
		Patrizia Casaccia, MD, PhD — The Stress of Aging and Isolation on Epigenetic 				Regulation of Myelination		

1045-1115

Coffee Break and Poster Review in Lobby

1115-1145

Discussion Panel 1 — Moderator, William P. Nash, MD

1145-1245

Lunch

1245-1330
		

Naomi M. Simon, MD — Understanding the Diagnosis and Treatment of Complicated Grief: 		
A Post-Loss Stress Disorder1330-1415
		

Michael S. Fanselow, PhD — Neural Mechanisms of Post-Traumatic Stress Disorder 			as seen through Stress-Enhanced Fear Learning

1415-1445

Coffee Break and Poster Review in Lobby

1445-1530
		David S. Krantz, PhD — Stress, Anger, and Coronary Heart Disease: Downstream 			Effects of PTSD

1530-1600

Discussion Panel 2 — Moderator, Patcho N. Santiago, MD, MPH

1600-1615

Robert J. Ursano, MD — Closing Remarks

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11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Conference Speakers
Patrizia Casaccia, MD, PhD

Michael S. Fanselow, PhD

Patrizia Casaccia, MD, PhD is
an internationally recognizedexpert in the field of myelination and axonal damage indemyelinating disorders. She
is a Professor of Neuroscience,
Genomics and Multiscale
Biology, and Neurology at the
Icahn School of Medicine atMount Sinai in New York. She
received her medical degreein Rome, where she was also a resident in Neurology.
Dr. Casaccia then moved to the United States where she
obtained a PhD in Neurobiology. After her post-doctoral work at Weil Cornell Medical Center in New York, she
moved to the Skirball Institute for Biomolecular Medicine at NYU and then to Robert Wood Johnson Medical
School (Rutgers Medical School). In 2008 she moved to
Mount Sinai, where she directs the Center of Excellence
on Myelin Disorders at the Friedman Brain Institute.
Her Research has a translational focus by investigating
molecular and cellular mechanisms underlying myelin
formation and neuroprotection.
Dr. Casaccia’s research is funded by grants fromthe National Institute for Neurological Disorders andStroke, by the Department of Defense and by the National Multiple Sclerosis Society. She has more than 110
publications in top peer-reviewed journals, including
Nature, Genes and Development, Nature Neuroscience,and Neuron. She has also received many honors andawards including the New Jersey Cancer Commission
Award for Scientific Excellence (2001) and Recognition Award Rutgers Women in Neuroscience. (2005). Dr.
Casaccia is on the editorial board of multiple peer-reviewed journals and serves on grant advisory panels for
the National Institutes of Health, the Department of the
Army and for the National Multiple Sclerosis Society.

Dr. Michael Fanselow isDistinguished Professor,
Psychology and Psychiatry
Departments at the Universityof Los Angeles, CA. He also
holds the Staglin Family Chairin Psychology and is Directorof the Staglin Music Festival
Center for Brain and Behavioral Health.
Dr. Fanselow received his MS degree from Brooklyn
College in 1976, and his PhD from the University ofWashington in 1980. Following his graduate work heheld Assistant/Associate Professorships at Rennselaer
Polytechnic Institute and Dartmouth College.
Dr. Fanselow’s laboratory has a long-standing
interest in the nature and function of fear. “We want tounderstand the adaptive function of normal fear andhow those systems go awry to produce anxiety disorders
such as PTSD.” A series of questions of particular interest is how fear is learned and how fear memories are
stored in the brain. That research concentrates its efforts
on forebrain regions such as the amygdala, hippocampus, and neocortex. “In terms of neurotransmitter/modulator systems, we have been concentrating our effort on
glutamate, GABA, acetycholine, and opioids. More thansimply tracing the circuits, we are trying to determine
the specific contributions that different componentsof the circuit contribute to the complete experience ofan emotional memory.” Another important question is
how fear memories are translated into specific behavior
patterns. That work primarily focuses on the midbrain
periaqueductal gray. The laboratory uses rat and mousemodels featuring site-specific pharmacological, optogenetic and chemogenetic manipulations. Much of thecurrent work examines behavior in genetically modified
mice. “Our mission is to use every technique available toderive a complete understanding of fear-motivated behavior and how to return the pathologically frightened
brain to a state where fear and anxiety again serve theadaptive healthy defensive function they evolved for.”4

11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

David S. Krantz, PhD

Mar Sanchez, PhD

David S. Krantz, PhD is
Professor and former Chairin the Department of Medical
and Clinical Psychology at
Uniformed Services University (USU), and a member of
the Scientific Advisory Boardof the Center for the Studyof Traumatic Stress (CSTS).
He received his BS from the
CCNY and PhD in Psychology from the University ofTexas at Austin. Dr. Krantz has authored more than 180
scientific and professional publications on the effects ofpsychosocial stress on physical health, with a particularemphasis on psychosocial and biobehavioral factors in
cardiovascular disorders. Dr. Krantz was the recipient of
the American Psychological Association’s (APA) Early
Career Scientific Award in 1982, and Annual Awards
from the APA Division of Health Psychology in 1981
and 2000. He is a former Editor-in-Chief of the journal
Health Psychology, Past-President of the APA Divisionof Health Psychology, and a Past President of the Academy of Behavioral Medicine Research.
For more than 20 years, the primary focus of Dr.
Krantz’s work has been on the effects of acute stress as a
trigger of clinical coronary heart disease events such as
myocardial ischemia and malignant arrhythmias. In thisresearch, he has collaborated with a multi-disciplinary
team of cardiologists and psychologists to examine theprevalence, mechanisms, and prognostic significanceof mental stress-induced ischemia. This work was later
extended to investigating the effects of mental stress onmarkers of vulnerability to malignant arrhythmias. Currently, he is Principal Investigator of the BETRHEART
Study, which investigates the role of biobehavioral
factors in the progression of heart failure, and is also apart of a team examining psychosocial influences oncoronary heart disease in women (the NHLBI WISE
study). Most recently, he has begun collaboration with
Dr. Vincent Ho and other colleagues at USU on a“brain-heart initiative” to study the study the complex
relationships between PTSD, mTBI, and coronary arterydisease among combat veterans.

Dr. Sanchez is an Associate Professor in the Department of Psychiatry & Behavioral Sciences,
Emory University School of
Medicine and Affiliate Scientist
in the Division of Developmental and Cognitive Neuroscience,
Yerkes National Primate Research Center, Emory University.
Dr. Sanchez received her
PhD in Neurobiology and Cell Biology from the Complutense University of Madrid, Spain and has expertisein stress neurobiology and behavioral neuroscience.
Her lab studies the neurobiology of stress and emotional regulation during development, using nonhumanprimate models. The main focus of her research program is to understand how early life stress (in particular,
alterations in maternal care) affects the development ofbrain circuits that control emotional and stress reactivity from infancy through adolescence, leading to psychopathology and pathophysiology characteristic of anxiety
and mood disorders. These brain systems include prefrontal-amygdala circuits. She uses a multidisciplinary
approach, including analysis of neuroendocrine stresssystems, social and emotional behavior and brain development using in vivo neuroimaging techniques (MRI,
DTI, PET and resting state fMRI) and in vitro assays ofbrain neuropeptide and corticosteroid systems. She has
established a successful research program, supported
by NIH and NSF funding and by awards from private
foundations (e.g. NARSAD, ASF and KTGF). Current
awards include R01 grants from NIH/NICHD and
NIH/NIDA and is co-PI in a project part of the Emory
Autism Center of Excellence. Dr. Sanchez’s multidisciplinary and translational research bridges different
disciplines and strong collaborations with clinical andbasic researchers that study human developmental
psychobiology, psychopathology, behavioral genetics/
epigenetics and psychoneuroimmunology at Emoryand other universities (Minnesota, Madison-Wisconsin,
Maryland, OHSU, Pittsburgh, NYU, UNC) and the NIH.
She is a member of the NIH CSR Biobehavioral Regulation, Learning and Ethology (BRLE) Study Section andserves in the editorial board of several journals, including Psychoneuroendoendocrinology and Development
and Psychopathology.

511th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Naomi M. Simon, MD
Dr. Naomi M. Simon is Professor of Psychiatry, Harvard
Medical School, Director of
the Center for Anxiety andTraumatic Stress Disorders,
Director of the Complicated Grief Program at MGH,
and Chief Medical Officer ofthe Red Sox Foundation and
Massachusetts General Hospital Home Base Program.
Dr. Simon’s major clinical and research interests include
optimizing initial and next step psychotherapy andmedication treatments for anxiety and stress relateddisorders, and understanding the presentation and thebiological impact of trauma, loss, and anxiety disorders.
She has served as a principal investigator or co-investigator on numerous studies aimed at improving ourunderstanding and treatment of post-traumatic stressdisorder, panic disorder, generalized anxiety disorder,social anxiety disorder, and the syndrome of complicated grief. As Chief Medical Officer at Home Base,she guided development of a novel clinical care modeland the Home Base Training Institute through a public
private partnership with MGH and the Red Sox Foundation to address the unmet needs of returning veterans and their families impacted by deployment related
stress, PTSD, and traumatic brain injury.
Dr. Simon is Vice Chair of the Scientific Council of
the Anxiety Disorders Association of America, a Distinguished Fellow of the American Psychiatric Association,
and a Member of the American College of Neuropsychopharmacology. She received an MD from Harvard
Medical School, and completed a medical internshipand residency in psychiatry at Columbia Presbyterian
Hospital/New York State Psychiatric Institute. In addition, she completed fellowship training in consultation
psychiatry at MGH and has a Masters in Epidemiology
from the Harvard School of Public Health.

611th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Moderators
William P. Nash, MD

Patcho Santiago, MD, MPH
CDR, MC, USN

Before becoming the Directorof Psychological Health for
the U.S. Marine Corps in May
2015, Bill Nash was a psychiatric researcher, educator,and consultant in posttraumatic stress and moral injury
prevention and treatment for
DoD and the VA. While onactive duty in the Navy, CAPT
Nash provided far-forward psychological health services
to the 1st Marine Division during the Second Battle of
Fallujah, for which he was awarded a Bronze Star, andhe led the development of the current Navy and Marine Corps doctrine for Combat and Operational StressControl, including its acknowledgment of moral injury
and loss as important mechanisms of psychologicalinjury. Dr. Nash has led or collaborated on research on
risk and protective factors for combat-related PTSD,
new measures for early recognition of traumatic stressinjuries, and new cognitive-behavioral treatments forcombat-related PTSD. He holds academic appointments
at the University of California, San Diego, and Virginia
Commonwealth University. Dr. Nash served as a member of the Institute of Medicine’s Committee for Assessment of the Effectiveness of PTSD Treatment in DoD
and the VA, and he co-chaired the recently completed
Chairman of the Joint Chiefs’ High-Risk Behavior
Working Group.

Dr. Santiago is the Program
Director of the National Capital Consortium Psychiatry
Residency at the Walter Reed
National Military Medical
Center in Bethesda, Maryland.
He is a board certified psychiatrist and Associate Professor,
Department of Psychiatry at
the Uniformed Services University (USU), Bethesda, MD. As billeted faculty at USU,
Dr. Santiago served as the USU Program Manager for
the Army Study to Assess Risk and Resilience in Service
members (Army STARRS) as well as the Associate Program Director for the Disaster and Preventive Psychiatry Fellowship.
Dr. Santiago graduated from Yale University with a
Bachelor of Arts in economics and earned his medical
degree from Jefferson Medical College under the Navy’s
Health Professions Scholarship Program. After completing his psychiatry residency at the Naval Medical Center
San Diego, his first duty assignment was at the Naval
Hospital Camp Pendleton, California. From there, hedeployed to the Expeditionary Medical Facility at Camp
Arifjan, Kuwait in support of Operation Iraqi Freedom.
Dr. Santiago subsequently completed a Disaster andPreventive Psychiatry Fellowship at USU, earning his
Masters in Public Health, and ultimately joining thefaculty at USU, having research interests in psychiatricepidemiology and mental health promotion. From USU,
Dr. Santiago deployed to Operation Enduring Freedom
as the Officer-in-Charge of the Navy Mobile Care Team,based out of Bagram Air Field, Afghanistan.

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11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Conference Leadership
Gary H. Wynn, MD
LTC, MC, USA

Robert J. Ursano, MD
Dr. Ursano is Professor of
Psychiatry and Neuroscience
and Chairman of the Department of Psychiatry at the
Uniformed Services Universityof the Health Sciences, Bethesda, Maryland. He is founding
Director of the Center for the
Study of Traumatic Stress. In
addition, Dr. Ursano is Editorof Psychiatry, the distinguished journal of interpersonal and biological processes, founded by Harry Stack
Sullivan. Dr Ursano completed twenty years service in
USAF medical corps and retired as Colonel in 1991. He
was educated at the University of Notre Dame and Yale
University School of Medicine and did his psychiatrictraining at Wilford Hall USAF Medical Center and Yale
University.
Dr. Ursano served as the Department of Defense
representative to the National Advisory Mental HealthCouncil of the National Institutes of Mental Health andis a past member of the Veterans Affairs Mental HealthStudy Section and the National Institute of Mental
Health Rapid Trauma and Disaster Grant Review Section. He is a Distinguished Life Fellow in the American
Psychiatric Association and a Fellow of the American
College of Psychiatrists. Dr. Ursano was the first Chairman of the American Psychiatric Association’s Committee on Psychiatric Dimensions of Disaster. This work
greatly aided the integration of psychiatry and publichealth in times of disaster and terrorism. Dr. Ursano
was an invited participant to the White House Mental
Health Conference in 1999. He has received the Department of Defense Humanitarian Service Award andthe highest award of the International Traumatic StressSociety, The Lifetime Achievement Award, for “outstanding and fundamental contributions to understanding
traumatic stress.” He is the recipient of the William C.
Porter Award from the Association of Military SurgeonsContinued

Dr. Wynn is Assistant Chair andAssociate Professor, Departmentof Psychiatry, Uniformed Services University and Scientist,
Center for the Study of Traumatic Stress. After graduating from
West Point in 1996, Dr. Wynn
received his medical degreefrom the Uniformed Services
University (USU) in Bethesda,
MD. Dr. Wynn completed a residency in Psychiatry andInternal Medicine at Walter Reed Army Medical Center.
After completing his residency, he spent a year as theDivision Psychiatrist for the 2nd Infantry Division atCamp Casey, Korea. Dr. Wynn spent the next three
years as the Assistant Chief of Inpatient Psychiatry at
Walter Reed Army Medical Center where he worked
with service members returning from the conflicts in
Iraq and Afghanistan. From 2009 through 2013, Dr.
Wynn worked as a research psychiatrist in the Military
Psychiatry Branch of the Center for Military Psychiatry
and Neuroscience at the Walter Reed Army Institute of
Research in Silver Spring, MD. In July, 2013, Dr. Wynn
joined the USU Department of Psychiatry. He has
published textbooks on the topics of drug interaction
principles for medical practice and the clinical management of post traumatic stress disorder (PTSD) as well as
fourteen book chapters and seventeen journal articles.
His presentations at national and local conferences havecovered topics ranging from drug interactions to PTSD
and mild traumatic brain injury.

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11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Robert J. Ursano, MD, Continuedof the United States, the William Menninger Awardof the American College of Physicians and the James
Leonard Award of the Uniformed Services University.
He is a frequent advisor on issues surrounding psychological response to trauma to the highest levels of the
US Government and specifically to the Department of
Defense leadership.
Dr. Ursano has served as a frequent member of
the National Academies of Science, Institute of Medicine Committees and working groups including theCommittee on Psychological Responses to Terrorism,
Committee on PTSD, the Committee on Compensation
for PTSD in Veterans and the Committee on Nuclear
Preparedness; and the National Institute of Mental
Health Task Force on Mental Health Surveillance After
Terrorist Attack. In addition, he has served as a memberof scientific advisory boards to the Secretary of Healthand Human Services for disaster mental health andthe Centers for Disease Control for preparedness andterrorism. Dr. Ursano is co-principal investigator of thelargest NIMH grant ever given for the study of Suicidein the U.S. Army. In collaboration with his co-principal
investigators at Harvard University, the University ofMichigan and Columbia University the Army- STARRS
grant will be the Framingham Study of suicidal behavior, and address a national as well as DoD mental healthneed. In 2014, Dr. Ursano and Dr. Matthew Friedmanof the VA National Center for PTSD co-founded theFriedman-Leahy Brain Bank supported through Senator
Patrick Leahy (D-VT). It is the first human brain bankdedicated to PTSD. This joint effort of many people wasa 12 year project developing concepts, pilot data andsupport. Dr. Ursano has over 300 publications. He is
co-author or editor of eight books.

911th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Conference Committee
Kwang Choi, PhD
Department of Psychiatry and Program in
Neuroscience
Center for the Study of Traumatic Stress
Uniformed Services University

Robert J. Ursano, MD
Professor and Chair
Department of Psychiatry
Director
Center for the Study of Traumatic Stress
Uniformed Services University

F. Julian Lantry, BA
Research Assistant
Department of Psychiatry
Center for the Study of Traumatic Stress
Uniformed Services University

Gary H. Wynn, MD, 2016 Chairman
Assistant Chair and Associate Professor
Department of Psychiatry
Scientist
Center for the Study of Traumatic Stress
Uniformed Services University

Jorge M. Hastings,TSgt, USAF, CADCNCOIC, Department of Psychiatry
Center for the Study of Traumatic Stress
Uniformed Services University

David Mears, PhD, 2016 Co-Chairman
Associate Professor
Department of Anatomy, Physiology and Genetics
Uniformed Services University

Syrus Henderson, MSgt, USAF
Senior Enlisted Advisor, AF Element
Flight Chief, Department of Psychiatry
Additional Duty First Sergeant
Unit Reserve Coordinator
Uniformed Services University

Mary Lee Dichtel, RN
Senior Medical Editor
Program Coordinator
Educational Support Management Services, LLC
Ronald J. Whalen, PhD
LTC, MSC, USA
Assistant Professor, Counseling Services
Department of Family Medicine
Uniformed Services University

Gwendolyn Morris
Program Support Specialist
Department of Psychiatry
Uniformed Services University
We extend special thanks to:
Robyn Hulvey, CMP, CGMP
Assistant Director of Meetings
Office of Education and Meetings
Henry M. Jackson Foundation for the 		
Advancement of Military Medicine

K. Nikki Benevides, MA
Assistant to the Director and Scientific Program
Coordinator
Center for the Study of Traumatic Stress
Department of Psychiatry
Uniformed Services University

Sebastien Dery
Cover Photograph
McGill University (Creative Commons)1011th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Conference Posters
Presented in the Lobby
Use of Ecological Momentary Assessment Methodology in the Study of PosttraumaticStress Symptoms in U.S. Military Service Members................................................... 12
Longitudinal Assessment of White Matter Microstructure Integrity Following Combat
Deployment Relates to Posttraumatic Stress Disorder Symptom Severity in Service
Members with a History of Traumatic Brain Injury: A Pilot Study ......................... 13
A Comparison of Two Sub-Anesthetic Intravenous Ketamine Doses in Rat: A Pilot
Study................................................................................................................................. 14
Examination of the Gateway Hypothesis in Rats .............................................................. 15
Riluzole for PTSD: Efficacy of a Glutamatergic Modulator as Augmentation Treatment
for Posttraumatic Stress Disorder................................................................................. 16
Cerebrovascular Reactivity and Neuropsychological Function in Chronic TBI ........... 17
The Amygdala as a Brain Network Hub in Health and Disease: Findings from Graph
Theoretical Studies.......................................................................................................... 18
In Vivo Brain Regional Glucose Uptake Following Intravenous Morphine Selfadministration in Rats: 18FDG-PET Study .................................................................. 19
The Behavioral and Physiological Effects of Maternal Separation on Spraque-Dawley
Dams and Pups................................................................................................................ 20
Organization of Cortico-amygdala Afferents Provide a Scaffold for Age Dependent
Retrieval of Contextual Fear.......................................................................................... 21
Effects of Non-Combative Military Humanitarian Aid and Disaster Relief on Mental
Health of U.S. Service Members.................................................................................... 22
Calbrain is Reduced in PTSD Orbitofrontal Cortex in Parallel with Reductions in
Dendritic Spine Density................................................................................................. 23
Genetic Risk Mechanisms of Post-Traumatic Stress Disorder in Human Brain............ 24
Transcriptional Effects of Radiation and GT3 Radioprotection on the Rhesus MacaqueBrain, and Anatomical Subregions Associated with the Fronto-Limbic System..... 25

1111th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Use of Ecological Momentary Assessment Methodology in the
Study of Posttraumatic Stress Symptoms in U.S.
Military Service Members
Authors

Method: Sixty-nine current or former U.S. military
service members completed paper and pencil orelectronic questionnaire assessments of PTSS using
EMA methods. Assessments were administered fourtimes daily (fixed interval, four hours apart) for 15
days. Data collection is ongoing.

Affiliations

Results: Preliminary analyses indicate that participants in both paper and electronic questionnairegroups report that daily assessments increase awareness of their mental and physical states. Participants
who completed electronic questionnaires weresignificantly more likely than those who completed
paper questionnaires to report that they would use
daily assessments on their own if the questionnaires
were made available. We will present data on questionnaire completion rates and helpfulness of daily
assessments.

Quinn M. Biggs, PhD1, Carol S. Fullerton, PhD1,
Deborah Probe, MA1, Russell B. Carr, MD1,2, Nicole
Dacuyan, BS1, Mackenzie Franz, BA1, Maegan 		
Paxton, BS1, Leming Wang, MS1, Robert J. Ursano,
MD1
1. Center for the Study of Traumatic Stress,
Department of Psychiatry, Uniformed Services
University of the Health Sciences, Bethesda, MD,
USA
2. Walter Reed National Military Medical Center,
Bethesda, MD, USA

ABSTRACT

Background: Rates of trauma-related distress arehigh in U.S. military service members. Assessmentsof post traumatic stress symptoms (PTSS) and associated disorders (e.g., PTSD and depression) havetraditionally been done retrospectively with paper
and pencil assessments. Retrospective assessment
methods are susceptible to biases in memory, errors
in reporting, and do not account for daily symptomchanges. Ecological momentary assessment (EMA)
methods involve repeated sampling of current symptoms and experiences while respondents are engaged
in normal daily routines; as such, EMA methods
may provide more detailed, reliable, and up-to-dateassessments compared to retrospective assessments.

Conclusion: Repeated symptom assessment by
paper or electronic questionnaire may have intrinsic
benefits for those who complete the assessments and,
when shared with a behavioral health care provider,
may be a rich resource to inform decisions about
treatment.

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11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Longitudinal Assessment of White Matter Microstructure Integrity
Following Combat Deployment Relates to Posttraumatic Stress
Disorder Symptom Severity in Service Members with aHistory of Traumatic Brain Injury: A Pilot Study
Authorsa clinical diagnosis of PTSD, within 2 months of
return from deployment followed by follow-up evaluations 3-6 months later.

Michelle E. Costanzo, PhD , Suzanne Leaman,
PhD1, Dzung Pham, PhD3, Krista B. Highland,
PhD1,2,3, David Keyser, PhD4, Dominic E. Nathan,
PhD2,4, Paul Rapp, PhD4, Michael J. Roy, MD1,3
1,2,3

Method: Using the Clinician-Administered PTSD
Scale (CAPS) to assess PTSD symptoms and DTI
fractional anisotropy to assess the white matter
microstructure, we examined 14 service members (7with a history of combat TBI and 7 deployed controls) to explore if psychological distress influences
brain structure and behavioral symptoms overtime.

Affiliations

1. Uniformed Services University of the Health
Sciences, Department of Medicine, Bethesda,
MD, USA
2. The Henry M. Jackson Foundation, Bethesda,
MD, USA
3. Center for Neuroscience and Regenerative
Medicine, Bethesda, MD, USA
4. Uniformed Services University of the Health
Sciences, Traumatic Injury Research Program,
Department of Military and Emergency
Medicine, Bethesda, MD, USA

Results: Our results revealed that white matter
microstructure of the uncinate fasciculus (UF)and cingulum was not significantly correlated withCAPS scores at baseline or follow-up in the control
group. For those with a history of TBI, re-experiencing symptoms at baseline was positively correlatedwith left (r=.87, p<.05) and with right (r=.77, p<.05)
cingulum at follow up and hyperarousal symptoms
at baseline positively correlated right (r=.79, p<.05)
cingulum at follow up. Avoidance symptoms (r=.80, p<.05) and total CAPS score (r=-.86, p<.05) atbaseline were negatively correlated with left UF atbaseline. No significant correlations were observed
between follow up CAPS scores and white matter
microstructure.

ABSTRACT

Background: Diffusion tensor imaging (DTI) holds
promise for distinguishing posttraumatic stress disorder (PTSD) from the underlying physical damage
associated with mild traumatic brain injury (mTBI).
This is important given the significant symptom
overlap between PTSD and mTBI. Moreover, examining service members (SMs) immediately following
combat deployment may be important for understanding the interaction between psychologicalhealth and brain injury recovery.

Conclusions: This suggests recent proximity to combat stress may influence the relationship between
symptom severity and white matter microstructure
both immediately following deployment and overtime in those in those with a history of head injury.

Objective: The goal of this study was to examine acohort of combat veterans with a history of mTBI
who do not have the severity of symptoms to have13

11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

A Comparison of Two Sub-Anesthetic Intravenous
Ketamine Doses in Rat: A Pilot Study
Authors

Method: Jugular vein cannulated maleSprague-Dawley rats (300±50g) were given IV ketamine doses (0, 2, & 5 mg/kg) in a counter-balanced
design. Locomotor activity (over 15 min), ASR/PPI(at 20 min), and hotplate latency (20 to 50 min) were
measured. Serum ketamine/norketamine (NKT)
levels were measured using liquid chromatography/
mass spectrometry in a separate group of animals.
Locomotor and hotplate latency were analyzed with
two-way ANOVA. ASR/PPI and ketamine/NKT
serum levels were analyzed with one-way ANOVA.

Kennett Radford, MS, CRNA1, Thomas Park, BS2,
Sean Moran, PhD4, Lisa Osborne, PhD, CRNA1,
Kwang Choi, PhD1,2,3

Affiliations

1. Daniel K. Inouye Graduate School of Nursing,
Uniformed Services University of the Health
Sciences, Bethesda, MD, USA.
2. Department of Psychiatry, Uniformed Services
University of the Health Sciences, Bethesda, MD,USA.
3. Center for Study of Traumatic Stress, Uniformed
Services University of the Health Sciences,
Bethesda, MD, USA.
4. Department of Biochemistry and Molecular
Biology, Uniformed Services University of the
Health Sciences, Bethesda, MD, USA.

Results: Ketamine 2mg/kg increased locomotor
activity (0–3 min), had no change in ASR or PPI,and produced antinociception (vs saline) through40 minutes. Ketamine 5mg/kg induced rapid dissociative symptoms (through 4 min), increased
locomotion (4–9 min) after dosing, no effect on ASR
but impaired PPI at 100dB (20 min), and produced
significant antinociception (vs saline and 2mg/kg)
through 50 minutes. Serum ketamine rapidly peaked and decreased while NKT gradually increased
during 50 minutes after injection.

ABSTRACT

Background: Ketamine is a short-acting dissociative
anesthetic that is used to treat chronic pain, depression, and treatment refractory post-traumatic stressdisorder. Intravenous (IV) ketamine infusions areused in clinical practice, however, researchers primarily use intraperitoneal (IP) injections in rodent
studies. Pharmacokinetic differences between thetwo routes lead to difficulty in translating rodent
models to human clinical practice. Our primary aim
was to compare the effects of two sub-anesthetic
IV ketamine doses on locomotion, acoustic startle
reflex (ASR)/pre-pulse inhibition (PPI), and hotplate
latency in rats.

Conclusion: IV ketamine dose-dependently increased locomotor activity, disrupted PPI, andproduced significant antinociception. Disrupted
PPI with 5mg/kg IV is similar to previous ASR/
PPI studies using larger IP ketamine doses. Therefore, sub-anesthetic IV ketamine is a valid route forrodent behavior models. This pilot-study is the firststep in a program of research exploring the impactof anesthetic agents following traumatic injury on
development of stress related disorders.

1411th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Examination of the Gateway Hypothesis in Rats

Authorsthat models effects of ½-1 pack human daily cigarette use. The nicotine paradigm was followed by IVmorphine self-administration. Male and female rats
(N=32) were exposed to nicotine or saline, followedby the opportunity to self-administer morphine for10 days.

Kathryn E. Eklund, BS1, Kevin Nishida, BS2, Erin B.
Barry, MS3, Kwang H. Choi, PhD2, Neil E. Grunberg,
PhD1,3Affiliations

1. Department of Medical & Clinical Psychology,
Uniformed Services University, Bethesda, MD,
USA
2. Department of Psychiatry, Uniformed Services
University, Bethesda, MD, USA
3. Department of Military & Emergency Medicine,
Uniformed Services University, Bethesda, MD,
USA

Results: Rats pre-exposed to nicotine self-administered significantly less morphine compared to rats
pre-exposed to saline. This finding was significant
for male and female rats.
Conclusion: The results contradict a causal mechanistic interpretation of the Gateway Hypothesis,
at least with regard to adult rats. It may be that thisanimal model does not parallel the human condition, but this interpretation is unlikely because thenicotine and opiate paradigms that were combinedin the present experiment have produced findings
consistent with human studies of cigarette andopiate use. Alternatively, the age of the animals may
matter because the Gateway Hypothesis has been
based on initial soft drug exposure during childhood
and adolescence. Another possibility is that reverse-drug tolerance may be occurring which would
be reflected by the present findings, yet could still beconsistent with the Gateway Hypothesis in humans
if people increase the likelihood of using a second
drug but without actually using more of it.

ABSTRACT

Background: Kandel (1977) proposed the “Gateway
Hypothesis” that use of a “lower or softer” drug (e.g.,cigarettes) increases the likelihood of subsequent useof a “higher or harder” drug (e.g., opiate). Whether
this sequence involves causality, accessibility, cultural
norms, or other factors is not clear because the hypothesis is based on epidemiological data. Yet, public
policies, drug prevention programs, and treatments
have inferred a causal relationship from use of softerto harder drugs.
Method: The experiment evaluated the Gateway Hypothesis in a rat model. Nicotine was administered
to rats via a paradigm (SC osmotic minipumps)

15

11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Riluzole for PTSD: Efficacy of a Glutamatergic Modulator as
Augmentation Treatment for Posttraumatic Stress Disorder
Authors

Method: Up to 100 OEF and OIF veterans at Walter
Reed National Military Medical Center (WRNMMC) and the Syracuse VA Medical Center with
suboptimal response to SSRI/SNRI treatment for
PTSD are currently being enrolled in this 8-week
RCT. Participants continue on their current medication and are randomized to augmentation witheither riluzole or placebo. A subgroup of eligible participants from WRNMMC are undergoing 1H MRSscans before and after treatment to evaluate changes
in N-acetyl asparate (NAA) levels in the amygdalaand ACC.

Patricia T. Spangler, PhD , James C. West, MD ,Brian Andrews-Shigaki, PhD2, Kyle Possemato, PhD3,
Shannon McKenzie, BA3, Maegan Paxton, BS1, Tung
Tu, BS1, Krista Engle, BA1, David M. Benedek, MD1,4
1,2

1,2

Affiliations

1. Center for the Study of Traumatic Stress
2. Uniformed Services University of the Health
Sciences
3. Syracuse Veterans Administration Medical
Center
4. Center for Forensic Behavioral Science at Walter
Reed National Military Medical Center

Results: Preliminary results from WRNMMC sample (n=10) indicate that participants randomized toriluzole had increases in NAA in both amygdala and
ACC, whereas participants randomized to placebo
had NAA concentration decreases in both regions.
On psychometric measures (n=15), there was atrend toward significant difference in depression
change scores, such that participants randomized toriluzole had greater decreases in depression than did
those randomized to placebo.

Abstract

Background: Because current pharmacologicaltreatments for PTSD, and particularly combat-related PTSD, are suboptimal, there is an urgent need todevelop novel treatments that rapidly and robustly
improve symptoms. Drugs that reduce glutamate
activity may help reverse loss of neuronal integrity
and focal atrophy in brain regions implicated in
PTSD pathophysiology. Riluzole is a glutamatergic modulator that inhibits glutamate release andenhances AMPA trafficking and clearance of excessive synaptic glutamate resulting in neuroprotective
properties. The objective of this study is to evaluate
the efficacy of acute riluzole augmentation treatment
in active duty and combat veterans with PTSD, withor without mild TBI.

Conclusions: Given the very small sample size forthese analyses, results should be viewed with caution
and should not as yet be taken as evidence of riluzole’s efficacy. The results do show, however, that wehave been able to successfully collect psychometricand neuroimaging data for this medication trial.

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11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Cerebrovascular Reactivity and Neuropsychological
Function in Chronic TBI
Authors

Methods: 55 gender and age matched adults wereenrolled: healthy controls (HC) (n=20), moderate/
severe TBI (n=35). The subjects were 79% male,mean age 39±9 years, mean 16±3 years of education, and mean 32 months after injury. HC (n=16)
and TBI (n=32) subjects underwent baseline fMRI,
clinical and neuropsychological evaluation (TMT-A,
TMT-B, WAIS-Processing Speed Index (PSI), CVLT,WRAT) and completed symptom questionnaires(RPQ-13, BSI) for post-concussive symptoms (PCS).

Aaron Wolfgang, BA , Kimbra Kenney, MD , Franck
Amyot, PhD2, L. Turtzo, MD, PhD3,4, Carol Moore,
MA3, Erika Silverman, BA2, Christian Shenouda,
MD3, Emily Spessert, BA2, Leah Harburg, BA2, Eric
Wassermann, MD3,4, Ramon Diaz-Arrastia, MD,
PhD1,2
1

1,2

Affiliations

1. Uniformed Services University of the Health
Sciences, Bethesda, MD
2. Center for Neuroscience and Regenerative
Medicine, Rockville, MD
3. National Institute of Neurological Disorders andStroke, Bethesda, MD
4. National Institutes of Health, Bethesda, MD

Results: Mean CVR measures are lower in TBI
patients than HC. HC: WB CVR 0.226±0.022, GM
CVR 0.269±0.034, WM CVR 0.152±0.020; and TBI:WB CVR 0.182±0.059, GM CVR 0.214±0.0699, WM
CVR 0.127±0.046. All CVR measures distinguished
TBI from healthy controls (Cohen’s d = 0.988, 1.001
and 0.705 for WB, GM and WM CVR; p = 0.006,
0.006, and 0.048, respectively). Receiver Operator
Characteristic analysis yielded Area Under Curve
discriminating TBI from HC of 0.744 (p = 0.007) for
WB, 0.748 for GM (p = 0.007), and 0.682 for WM(p = 0.043) CVR. Among TBI subjects, the WAISPSI correlated with GM CVR (r = 0.369, p = 0.045).
There was a trend towards significance for correlation between GM CVR and CVLT (r = 0.332, p =0.07). There was no relationship between PCS andCVR measures.

ABSTRACT

Background: MRI blood oxygen level dependent(BOLD) with hypercapnia challenge reliably measures cerebrovascular reactivity (CVR) and canassess traumatic vascular injury. Understanding
relationships among CVR and neuropsychological function may be informative for the design oftherapies directed at post-traumatic cerebrovascular
dysfunction.
Objective: To investigate relationships between CVR
in the whole brain (WB), gray matter (GM), andwhite matter (WM), and neuropsychological function after traumatic brain injury (TBI).

Conclusion: All CVR measures distinguish TBI
from HC, with GM CVR showing the largest effectsize. GM CVR correlates weakly with neuropsychological function, but not with PCS.

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11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

The Amygdala as a Brain Network Hub in Health and Disease:
Findings from Graph Theoretical Studies
Authors

Method: We reviewed published studies in whichgraph theory was applied to structural or functional
brain networks, to identify works that specificallyreported on the nodal properties of the amygdala.
We then summarized what has been found to date
about the role of the amygdala as a hub in different
brain networks.

David Mears, PhD1 and Harvey B. Pollard, MD,
PhD1,2Affiliations:

1. Department of Anatomy, Physiology & Genetics,
Uniformed Services University of the Health
Sciences, Bethesda, MD, USA
2. Collaborative Health Initiative Research Program(CHIRP), Uniformed Services University of the
Health Sciences, Bethesda, MD, USA

Results: We found that a small subset of the hundreds of graph theory studies of the brain havereported specific metrics for the amygdala. The
nodal properties of the amygdala were variable inthese works. Nevertheless, a consistent finding wasobserved regarding measures of the centrality of theamygdala, where centrality refers to the importanceof a node within a network. Specifically, the centrality of the amygdala was found to be increased in
networks for normal emotional processing. A similarfinding was reported in several studies of resting
brain networks in depressed patients.

ABSTRACT

Background/Objectives: In recent years, the concepts of graph theory have been applied with increasing regularity to study the features of complex
brain networks. In these studies, graph theory is
typically used to calculate simplified metrics forcomparing the global features of brain connectivity networks. However, graph theory also provides unique connectivity measures for individual
elements (“nodes”) within large networks, whichyield novel insights into the importance of specificstructures for information processing within specific networks. Our objective was to use these recent
studies to examine the role of the amygdala as a hub
in normal and pathological brain networks.

Conclusions: We believe that the continued application of graph theory to brain networks will yield
important new insights into the role of the amygdala in normal brain function and the pathogenesisof psychiatric disorders. Graph theory also offers
promise as a potential diagnosis aid and as a tool for
predicting and evaluating therapeutic outcomes.

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11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

In Vivo Brain Regional Glucose Uptake Following Intravenous
Morphine Self-administration in Rats: 18FDG-PET Study
Authors

Method: Jugular vein cannulated male SpragueDawley rats were allowed to self-administer intravenous saline or morphine (0.5 mg/kg/infusion,
4hrs/day) for 12 days. The animals were scanned
at a baseline (pre-MSA), and after 2 and 7 days of
withdrawal from the self-administration. PET/CT
images were acquired using an Inveon multimodality preclinical scanner (Siemens Medical Solutions,
Erlangen, Germany) in the small-animal Translational Imaging Facility at USUHS. PET/CT data
were analyzed using Vivoquant software (inviCRO,LLC Boston, MA) for volume of interest (VOI) andSPM12 for voxel-based analysis (VBA).

Thomas Park, BA1,2, Kevin Nishida, MS1,2, Colin M.
Wilson, MA4, Shalini Jaiswal, MS3,4, Andrew R. Hoy,
PhD3,4, Robert J. Ursano, MD1,2, Bernard J. Dardzinski, PhD3,4, Kwang H. Choi, PhD1,2

Affiliations

1. Department of Psychiatry, Uniformed Services
University of the Health Sciences, Bethesda, MD,USA.
2. Center for Study of Traumatic Stress, Uniformed
Services University of the Health Sciences,
Bethesda, MD, USA.
3. Department of Radiology and Radiological
Sciences, Uniformed Services University of the
Health Sciences, Bethesda, MD, USA.
4. Center for Neuroscience and Regenerative
Medicine, Uniformed Services University of the
Health Sciences, Bethesda, MD, USA.

Results: The animals readily acquired MSA andexhibited locomotor hyperactivity, constipation andless weight gain as compared with the saline controls. Iso-flurane anesthesia reduced glucose uptake
in cortex, olfactory, basal ganglia, and thalamus
while increasing glucose uptake in hypothalamus,
hippocampus, midbrain and cerebellum as compared to the awake 18F-FDG uptake. Chronic MSA
increased glucose uptake in the striatum in anesthetized, but not in the awake, 18F-FDG uptake condition.

ABSTRACT

Background: Opioid abuse and the developmentof psychiatric disorders are major public healthproblems in the U.S. Abnormal brain energy metabolism following chronic opioid use may contributeto this problem. However, detailed mechanisms bywhich opioid drugs impair brain energy metabolism
remain unclear. Using in vivo 18fluorodeoxyglucose
positron emission tomography/computed tomography (18F-FDG PET/CT), and intravenous morphineself-administration (MSA), we investigated theeffects of two different 18F-FDG uptake conditions(awake vs. anesthetized) and voluntary opioid intake
on regional glucose metabolism in laboratory rats.

Conclusion: Baseline regional glucose uptake pattern is different depending on whether the animals
were anesthetized or awake during the 18FDG uptake
period. Increased glucose uptake in the striatum
following MSA may be a biomarker for opiate
addiction. This study is the first step in a programof research exploring the impact of opioid drug use
on addiction and stress-related disorders following
trauma.

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11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

The Behavioral and Physiological Effects of Maternal
Separation on Spraque-Dawley Dams and Pups
Authors

were tested in the Morris water maze (MWM). Anxiety-like behaviors were assessed on the elevated zeromaze (EZM). An ELISA assay was used to measurecorticosterone levels from tail blood in response toa single episode of restraint stress, which was compared across treatment groups.

Susan Weiner1, Ryan Healy,1, Christina McKittrick,
PhD1

Affiliations

1. Drew University, Madison, NJ, USA

ABSTRACT

Results: Separated pups showed significantly moredepression like behaviors on the forced swim test,
spending more time immobile and having shorter
latencies to immobility that the control rats. Separated pups also showed significant deficits during thelearning trials of the Morris water maze, having longer latencies to platform. Body weights of stressedpups also stayed significantly lower than those ofcontrol pups over time. There were no significant
results of the corticosterone ELISA or the memory
trial of the Morris water maze. Dams of the separated litters showed significant deficits on both theforced swim test and the elevated zero maze.

Background: Stress serves an adaptive function bycausing the body to react to perceived threats tohomeostasis. While acute stress is largely beneficial,chronic stress can have deleterious effects throughover-activation of the hypothalamic-pituitary-adrenal (HPA) axis. Previous research has demonstrated
that chronic stress associated with early life traumas
can have effects lasting into adulthood. This study
investigated the behavioral and physiological effects
of chronic maternal separation on Spraque-Dawley
pups and dams.
Method: Four litters of Sprague-Dawley pups wereused in this experiment, each with eight pups andcounterbalanced for sex. From postnatal day 7 to14, stress pups were separated from dams once dailyfor 3 hours, along with the rest of their littermates.
The effect of this chronic stressor on depression-likebehaviors was assessed in the forced swim test (FST),
whiles its effects on spatial learning and memory

Conclusion: Maternal separation increased depression like behaviors in the force swim test, but did
not have a significant effect on learning and memoryin the Morris water maze or on anxiety behaviors
in the elevated zero maze. There was a trend forthe dams of the separated pups to show behavioral
changes as well.

20

11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Organization of Cortico-amygdala Afferents Provide a
Scaffold for Age Dependent Retrieval of Contextual Fear
Authors

fluorogold into the BLA to label cortical afferents.
Following infusion, rats were exposed to a single trial contextual fear conditioning procedure consistingof either an immediate or delayed shock, and tested
for retrieval 24 hours later. Brains were then harvested and sliced for immunohistochemical analysis.
Prelimbic (PL), infralimbic (IL), anterior cingulate(ACC), and entorhinal (EC) cortices were assessed
for co-labeling of fluorogold and the immediate
early gene c-fos.

Anthony J. Santarelli, BS1, Rogger F. Gutierrez1,
Andrew M. Poulos, PhD1

Affiliations

1. State University of New York, University at
Albany, Albany, NY, USA

ABSTRACT

Background: Mammalian species evolved a precise
defensive system capable of associating environmental stimuli with aversive events. The basolateral
amygdala complex (BLA) is the primary region
involved in both the learning and retrieval of fear
memories. During retrieval, cortical afferents of the
BLA signal the presence or absence of associations
that lead to defensive freezing. The cortico-BLA
system is subject to structural and functional change
across development, which produces age dependent
responding to aversive associated environments.
Here we aim to describe the connectional structureof the cortico-BLA system and its activity during
retrieval of fear memories across juvenile, pre-adolescent, adolescent, and adult rodents.

Results: We observed an emergence of freezing behavior at P24 with increasing duration progressing
into adulthood. We also observed reduced corticalafferents in P19 and P24 rats throughout the PL,
IL, and EC that did not reach full expression until
P90. During retrieval, c-fos labeled BLA afferents
emerged in the PL and EC at P24, albeit at reduced
expression from P90 rats. Double labeling of EC
neurons was only observed in rats capable of retrieving the contextual fear association.
Conclusions: Our results suggest the emergence ofan age dependent contextual retrieval circuit that
centers on the EC and BLA. Future studies will dissect this circuit in vivo to elucidate its function.

Method: Long Evans rats at post-natal day 19, 24, 35,
or 90 were infused with the retrograde tract tracer

21

11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Effects of Non-Combative Military Humanitarian Aid andDisaster Relief on Mental Health of U.S. Service Members
Authors

Method: We analyzed the 2011 Health Related Behavior survey to examine: 1) factors associated withparticipation in HA/DR; 2) the relationship between
HA/DR and mental illness; and 3) the relationshipbetween HA/DR and mental health treatments. The
analytic sample consisted of (n=573) adults who
participated in recent HA/DR compared to (n=399)
those who participated in older HA/DR prior to
2010.

Yeong Kim, MHAP1 and Patrick Richard, PhD2

Affiliations

1. Center for Global Health Engagement, Rockville,MD
2. Uniformed Services University of the Health
Sciences, Bethesda, MD

ABSTRACT

Results: Marginal effects from logistic regression
models showed that junior enlisted members weremore likely to report symptoms of PTSD (0.21,
p<0.01) and anxiety (0.24, p<0.01) than senior
officers. Conversely, subjects with at least an associate’s degree were less likely to be affected by military
related stress (-0.13, p<0.05) than those with only
high school diplomas. Marines were more likely toreport anxiety (0.27, p<0.01) and seek treatment(0.19, p<0.05) than Coastguard members.

Background/Objectives: There is a scarcity of
research establishing a relationship between mental illness and U.S. military service members who
participate in the field of military humanitarianassistance/disaster relief (HA/DR). One of the few
studies on this subject showed that mental illness
such as depression were not associated with military
HA/DR; however, this study was limited by sample
size. We examined the association between predisposing, enabling, behavioral, and military-related
factors and mental health outcomes by modifying
the frameworks of Aday/Andersen’s Behavioral
Model and Grossman’s Demand for Health Model.
This study hypothesized that enabling factors are theprimary channels through which HA/DR relates tomental health outcomes.

Conclusion: There is a need to further investigate
the impact of enabling factors, such as education,in preparation of U.S. service members for future
global engagements.

22

11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Calbrain is Reduced in PTSD Orbitofrontal Cortex in Parallelwith Reductions in Dendritic Spine Density
Authors

study, we investigated gene expression of calbrain(CABP1), a neuron-specific calcium channel synaptic protein. Specifically, calbrain is a calmodulin“antagonist” at the C-terminal domain of L-type
calcium channels like CACNA1C.

Keith A. Young, PhD1, Lynn D. Selemon, PhD2,Dianne A. Cruz, PhD3, Douglas E. Williamson, PhD3

Affiliations

1. VA Center of Excellence for Research on
Returning War Veterans at Central Texas Veterans
Heath Care System and Texas A&M Health
Science Center, Temple, TX, USA.
2. Department of Neurobiology, Yale University
School of Medicine, New Haven, CT, USA.
3. Duke University School of Medicine andDurham VA Medical Center, Durham, NC, USA.

Method: FKBP5 and calbrain gene expression andmodified Golgi dendritic spine counts in PTSD frozen brain from OFC were performed in 8 PTSD and
8 normal controls.
Results: Calbrain was significantly reduced in PTSD
(P<0.05) and was directly correlated with mushroom
spine density (r=0.56, P<0.05).

ABSTRACT

Conclusion: The data suggest that mushroom spine
density reduction in PTSD is accompanied by areduction in Calbrain gene expression. Calbrain
may represent a class of synaptic elements found inmature mushroom-type spines. Elevated levels of
FKBP5 could signify an up-regulation of FKBP5 inareas of neurons preserved in PTSD. Alternatively,
since FKBP5 is expressed in astrocytes as well as
neurons, the signal could represent an astrocytic
response to neuronal stress and loss of dendritic
spines. The data are consistent with observations ofstress effects on cortical synaptic structure in animalmodels, observations of premature senescence in peripheral organs in PTSD, and activation of intracellular pathways shared with neuroimmune responses
in the CNS.

Background: The orbitofrontal cortex (OFC, BA11)
plays an important role in the management ofemotional learning and for linking this learning withvisceromotor responding. As outlined by Ongur andPrice (2000), the OFC integrates information fromthe cortex, amygdala and mediodorsal thalamus andprovides output to the striatum and brainstem/hypothalamus, modulating the autonomic nervous system and the HPA axis. We previously examined therelationship between dendritic OFC spine densities
and FKBP5 gene expression in PTSD and normal
controls (n=8/8). ANCOVA revealed that PTSD
cases had a significantly elevated density of stubby
spines and a trend for a reduction in mushroom
spine density, with an inverse correlation between
FKBP5 gene expression and mushroom/overall
spine density (Young et al., 2015). In the present

2311th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Genetic Risk Mechanisms of Post-Traumatic Stress
Disorder in Human Brain
Authors

Methods: We performed and analyzed DNA andRNA sequencing and DNA-methylation-microarraydatasets to derive eQTL and meQTL associations innormal dorsolateral prefrontal cortex (N=320). We
analyzed amygdala RNA sequencing data from theGTEx (Genotype to Tissue Expression) Consortium(N=67). We employed an fMRI paradigm to test
the association between SNP genotype and amygdala response to fearful stimuli in normal controls(N=195).

Rahul Bharadwaj, PhD1, Andrew Jaffe, PhD1, Qiang
Chen, PhD1, Amy Deep, MS, BS1, Aaron Goldman,
MS, BS1, Michelle Mighdoll, MS, BS1, John Cotoia,
BS1, JooHeon Shin, PhD1, Anand Mattay, MD, PhD1,
Daniel Weinberger, MD, PhD1, Joel Kleinman, MD,
PhD1.

Affiliations

1. Lieber Institute for Brain Development, Johns
Hopkins Medical Campus, Baltimore, MD, USA.

Results: We report significant eQTL associations between PTSD risk SNP rs363276 and two
genes: SLC18A2 (P= 7.13X10-11)* and PDZD8(P=6.32X10-24)*, with the PTSD risk allele ‘T’ associated with significantly lower levels of gene expression for both. These associations were independently
confirmed in the amygdala from the GTEX dataset.
Rs363276 risk allele carriers also showed a significantly increased response in the amygdala (pFWE= .029) during an emotional face-matching task inhealthy volunteers and were additionally associated with DNA-methylation levels in the SLC18A2PDZD8 genetic locus.

ABSTRACT

Background: There is a limited understanding of themolecular and functional biology associated with
PTSD in human brain. Efforts thus far to identify
differences in postmortem human brains between
controls and PTSD subjects may be confoundedby ante mortem substance abuse and/or treatment
effect. Recent findings of genetic variants associated with PTSD risk by many groups, including thePsychiatric Genomics Consortium PosttraumaticStress Disorder Workgroup, have opened research
avenues to identify the underlying biological mechanisms for PTSD in the human brain. We present
preliminary findings of multiple phenotype associations including gene expression, DNA-methylation,and functional-neuroimaging for a ‘candidate’ PTSD
risk SNP rs363276 (P=2.1X10-5), in normal humanbrains. These findings are currently being evaluatedin PTSD brains in the next part of our approach todissect mechanisms of genetic risk for PTSD.

Conclusion: Our preliminary findings are the firststeps of an approach to identify transcript mechanisms by which genetic variants potentially increaserisk for PTSD.
* Linear regression, where the p-value is based on
the Wald (T) statistic, which is slope of the genotype
effect on expression over its standard error.

24

11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Transcriptional Effects of Radiation and GT3 Radioprotection
on the Rhesus Macaque Brain, and Anatomical Subregions
Associated with the Fronto-Limbic System
Authors

sus were irradiated with at least 5.8 Gy. Seven brain
regions (Amygdala, Orbital Frontal Cortex, Anterior
Cingulate Cortex, Area 25, Insular Cortex, Hippocampus, and Entorhinal Cortex) were harvested per
Rhesus (n = 70). mRNA was extracted and sequenced
using Illumina GAIIx. Published mRNA sequencing
from unirradiated Rhesus brains were added to thiscohort (Dalgard et al. 2015 Brain Research). mRNA
sequencing data were computationally processed to
produce Rhesus genomic alignments and to quantify
gene expression. Differentially expressed genes were
calculated using SAM and unsupervised clusters weregenerated through ConsensusClusterPlus (Wilkerson
et al. 2010 Bioinformatics).

Jerez A. Te, PhD1,2, Matthew D. Wilkerson, PhD1,2,
Kadharbatcha S. Saleem, PhD3, Vijay K. Singh, PhD4,
Clifton L. Dalgard, PhD1,2,5, Gauthaman Sukumar,
MS1,2, David M. Jacobowitz, PhD5, Harvey B. Pollard,
MD, PhD1,2,5

Affiliations

1. The American Genome Center, Uniformed
Services University of the Health Sciences,
Bethesda, MD, USA
2. Collaborative Health Initiative Research Program(CHIRP), Uniformed Services University of the
Health Sciences, Bethesda, MD, USA
3. National Institute of Mental Health, National
Institutes of Health, Bethesda, MD, USA
4. Department of Pharmacology and Molecular
Therapeutics, Armed Forces Radiobiological
Institute (AFRRI), Uniformed Services Universityof the Health Sciences, Bethesda, MD, USA
5. Department of Anatomy, Physiology andGenetics, Uniformed Services University of the
Health Sciences, Bethesda, MD, USA

Results: The effect of radiation upon the Rhesus
brain was evident by the number of genes that wereboth up-regulated (8,090, including RTN4R) anddown-regulated (617, including COX7AI). Amongvehicle-treated and irradiated Rhesus, different regions
had dys-regulated genes associated with pathways
relating to brain function and diseases. GT3 radioprotection had a large transcriptional effect including
overexpression of defense, immune, and inflammatory response pathways and genes such as GABRB1.
Analyzing our data for region-specific transcriptional
responses to radioprotection, we found the anterior cingulate cortex had an appreciable number of
uniquely expressed genes.

ABSTRACT

Background/Objective: Developing biomedical
strategies to prevent, mitigate, treat, and assess healthconsequences from exposure to ionizing radiation
is important for countermeasures against radiation.
Gamma-tocotrienol (GT3) is a candidate radioprotectant that counteracts radiation-induced injury.
mRNA expression profiling of healthy, irradiated,
and radioprotected irradiated nonhuman primate
brains may identify biomarkers of exposure andidentify dys-regulated molecular pathways.
Method: Method: Five Rhesus macaque were treatedwith GT3; 5 Rhesus received a vehicle. Ten Rhe-

Conclusions: We have identified a diverse array of individual gene and pathway modulations in the Rhesus
brain that are a consequence of radiation exposureand that are modulated by a promising radioprotectant, GT3. These results provide a foundation for
exposure-biomarker and therapeutic target discovery
directly relevant to man.
25

11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Continuing Education Credit
PhysiciansSocial Workers

This live activity, Amygdala, Stress and PTSD Conference on April 19, 2016 has been reviewed and isacceptable for up to 5.25 prescribed credits by theAmerican Academy of Family Physicians. Physicians
should claim only the credit commensurate with theextent of their participation in the activity.

The Department of Social Work, Walter Reed National Military Medical Center, maintains responsibility for this program and has been granted automatic authorization from the Maryland Board ofSocial Work Examiners to offer 5.0 category I CEU
credits for this professional training activity. 2.0hours of CEU credit will be given for the morning
session and 3.0 hours of CEU credit will be given
for the afternoon session. No credit will be provided
for partial session attendance. On the day of theconference, participants must submit an evaluation
sheet for each session to receive CE credit and document their attendance for each session via sign-in
and sign-out rosters.

Psychologists

The Department of Psychology, Walter Reed National Military Medical Center, is approved by theAmerican Psychological Association to sponsor
continuing education for psychologists. The Department of Psychology, Walter Reed National Military
Medical Center, maintains responsibility for thisprogram and its contents. 5.0 hours of CE credit
will be given for full attendance at the conference.
2.0 hours of CE credit will be given for the morning
session and 3.0 hours of CE credit will be given for
the afternoon session. No credit will be provided
for partial session attendance. On the day of theconference, participants must submit an evaluation
sheet for each session to receive CE credit and document their attendance for each session via sign-in
and sign-out rosters.

NursesWe regret we are unable to offer CEUs for nurses in2016.

Psychologists and Social Workers attending the conference will be
required to complete an evaluation form in order to receive
continuing education credit.
Questions? Please visit the Continuing Education tablelocated in the lobby.

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11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Notes

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11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

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11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Notes

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11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Notes

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11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Notes

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11th Annual Amygdala, Stress and PTSD Conference: The Effects of Stress and Loss

Center for the Study of Traumatic Stress
Department of Psychiatry
Uniformed Services University
4301 Jones Bridge Road, Bethesda, MD 20814
contact@amygdalaptsdconference.org
www.CSTSonline.org
www.facebook.com/USU.CSTS
www.twitter.com/CSTS_USU
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