International Society for Traumatic Stress Studies

Biological/Medical Trauma


The ISTSS 34th Annual Meeting is the largest gathering of professionals dedicated to trauma treatment, education, research and prevention. There will be several workshops, symposia and expert trainings on biologial and physical aspects of trauma.

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Concurrent Session One: Symposium

Thursday, November 8 | 9:45 AM to 11:00 AM


Advancing Diagnostic Biological Markers for PTSD: Findings from DOD Systems Biology
 

Chair: Jett-Tilton, Marti, PhD;
Discussant: Marmar, Charles, MD

Approximately half the mental health burden in OIF/OEF veterans is attributed to Posttraumatic Stress Disorder (PTSD).  Management of PTSD is complicated by the overlapping symptoms of its comorbidities, the diagnostic reliance on self-report and time consuming psychological evaluation process. The purpose of this research is to facilitate an objective method of diagnosis, and advance development of experimental therapeutics. This symposium will present updated findings from DOD funded case-control studies of biological markers of PTSD. Study participants included male and female veterans deployed to Iraq or Afghanistan post-9/11 with and without PTSD, based on the Clinician Administered PTSD Scale for DSM-IV. Study procedures included a fasting blood draw (pre and post-dexamethasone), 24-hour urine collection, and self-report questionnaires. We compared 83 PTSD positive male cases (based on the Clinician Administered PTSD Scale for DSM-IV) with 83 PTSD negative male controls matched by age and ethnicity. We also included a validation cohort with 29 PTSD positive male cases and 40 male controls. New findings include genetic and epigenomic mechanisms relevant to PTSD, metabolic and glucocorticoid dysfunction in PTSD, and finally, integrating multi-omic signals of PTSD.
 

A Cohort Study of OIF/OEF Veterans: A Blood Integrative Molecular Assessment


Hammamieh, Rasha, PhD1; Gautam, Aarti, PhD2; Chakraborty, Nabarun, MBA3; Muhie, Seid, PhD4; Yang, Ruoting, PhD5; Donohue, Duncan, PhD6; Daigle, Bernie, PhD7; Yehuda, Rachel, PhD8; Marmar, Charles, MD9; Jett-Tilton, Marti, PhD2; Doyle III, Francis, PhD10; Flory, Janine, PhD11; Abu-Amara, Duna, MPH9; Petzold, Linda, Professor12; Zhang, Yuanyang, PhD12

1US Army Medical Research and Materiel Command, Ft. Detrick, Maryland, USA
2US Army CEHR, Fort Detrick, Maryland, USA
3U.S. Army, frederick, Maryland, USA
4National Institutes of Health, Bethesda, Maryland, USA
5US Army CEHR, Frederick, Maryland, USA
6US Army Research Institute of Environmental Medicine, Ft Detrick, Maryland, USA
7University of Memphis, Memphis, Tennessee, USA
8J. J. Peters Veterans Affairs Medical Center; Mount Sinai School of Medicine, Bronx, New York, USA
9New York University School of Medicine, New York, New York, USA
10Harvard University, Cambridge, Massachusetts, USA
11Mount Sinai School of Medicine/J.J. Peters VA Medical Center, New York, New York, USA
12University of California, Santa Barbara, Santa Barbara, California, USA


Management of PTSD is complicated by its comorbidities, and the diagnostic reliance on self-report and time consuming psychological evaluation. Molecular pathophysiology of PTSD could facilitate an unbiased biomarker-driven next-generation intervention strategy. Herein, we investigated the epigenomic consequences of combat elicited PTSD.

52 PTSD-positive male veterans were matched to 52 controls by age and ethnicity. Methylation status of DNA extracted from whole blood was assayed using high density arrays.

Results: We identified 3,600 unique differentially methylated genes, where nearly 85% were hypermethylated. Chromosomes 4 and 18 imprint many methylated probes, including those which control emotional and cognition process, and glucocorticoid deficiency. Interestingly, many genes facilitating telomere maintenance and insulin reception were hyper-methylated. Genes involved in memory consolidation, emotion/aggressive behavior, and perturbed circadian rhythm were preferentially hyper-methylated. An independent validation set of 31 PTSD+ /31 PTSD- veterans were used to confirm.

PTSD perturbed both the cellular and humoral immune system. Genes involved in several PTSD comorbidities, such as cardiomyopathy and poor insulin management, were also altered.  


Integrating Multi-Omic Signals of PTSD


Dean, Kelsey, PhD Candidate; Misganaw, Burook, PhD; Rajaram, Pramod, PhD; Doyle III, Francis, PhD
Harvard University, Cambridge, Massachusetts, USA

Diagnostic classifier trained on a given molecular type or modality have suboptimal performance owing to the inherent limitation in information content in a single molecular layer as well as technical and measurement errors associated with a given assay. One way to circumvent this limitation is to systematically combine individual single layer signatures into a multi-omics panel. We took molecular measurements (including DNA methylation, miRNAs, proteins, metabolites and single nucleotide polymorphism) from blood draws for OEF/OIF male veterans with combat experience. We trained single- and multi-omics classifiers on 83 PTSD cases and 83 (trauma exposed but healthy) controls. The multi-omics panel shows slight improvement over individual panels suggesting that the single-omic panels contain complementary biological signals. Validation studies were conducted on an independent cohort.


BDNF Mediates the Relationship between PTSD Status and Epigenetic Aging in Combat Veterans


Kang, Jee In, MD PhD1; Wolkowitz, Owen, MD2; Wu, Gwyneth, EdD1; Josine, Verhoeven, PhD3; Yang, Ruoting, PhD4; Hammamieh, Rasha, PhD5; Yehuda, Rachel, PhD6; Reus, Victor, MD7; Jett-Tilton, Marti, PhD8; Marmar, Charles, MD9; Mellon, Synthia, PhD, MPH10

1UCSF Department of Psychiatry, San Francisco, California, USA
2Academic Medical Center, San Francisco, California, USA
3VU University, Amsterdam,  Netherlands
4National Institutes of Health, Bethesda, Maryland, USA
5US Army Medical Research and Materiel Command, Ft. Detrick, Maryland, USA
6J. J. Peters Veterans Affairs Medical Center; Mount Sinai School of Medicine, Bronx, New York, USA
7University of California, San Francisco, San Francisco, California, USA
8US Army CEHR, Fort Detrick, Maryland, USA
9New York University School of Medicine, New York, New York, USA
10University of San Francisco, CA (USFCA), San Francisco, California, USA


Epigenetic DNA methylation age is a promising biomarker of cellular aging. The present study examined epigenetic age in combat veterans and the underlying mechanisms between PTSD status and epigenetic aging. Male veterans exposed to combat-related stress were grouped into those with (n = 106) and without (n = 108) PTSD. Epigenetic age assessed by Horvath’s method was determined from leukocyte DNA methylation assayed using Illumina 450K arrays. “Delta age” was defined as epigenetic age minus chronological age. Several biomarkers including serum BDNF were assessed. Epigenetic age was strongly associated with chronological age. Overall, epigenetic age acceleration was shown among veterans. Subjects with PTSD also showed accelerated delta age but significantly less than those without PTSD. Higher BDNF level was significantly associated with the presence of PTSD and lower delta age. Mediation analysis showed that BDNF significantly mediated the relationship between PTSD status and delta age, even in antidepressant-free subjects. Our findings implied that PTSD status may be associated with BDNF release as compensatory responses among combat-exposed people, leading to attenuation of epigenetic age acceleration. Longitudinal research in trauma-exposed people is needed to better understand the impact of trauma and PTSD and a role of BDNF on cellular aging. 


Metabolic and Glucocorticoid Dysfunction in PTSD: A Mechanistic Model


Flory, Janine, PhD1; Rajaram, Pramod, PhD2; Mellon, Synthia, PhD, MPH3; Wolkowitz, Owen, MD4; Yehuda, Rachel, PhD5; Marmar, Charles, MD6; Doyle III, Francis, PhD2

1James J Peters VAMC/Mount Sinai School of Medicine, Bronx, New York, USA
2Harvard University, Cambridge, Massachusetts, USA
3University of San Francisco, CA (USFCA), San Francisco, California, USA
4Academic Medical Center, San Francisco, California, USA
5J. J. Peters Veterans Affairs Medical Center; Mount Sinai School of Medicine, Bronx, New York, USA
6New York University School of Medicine, New York, New York, USA


Metabolic abnormalities have been observed in people with PTSD, including higher rates of metabolic syndrome, diabetes and insulin resistance.  Recently, we reported that combat veterans with PTSD showed evidence of higher anaerobic glycolysis, impairments in citric acid cycle functioning and amino acid metabolism, which could be attributed to mitochondrial dysfunction.  These results prompted an analysis of whether the co-occurrence of these metabolic abnormalities reflect independent problems or stem from an underlying regulatory deficiency in a sample of 166 male combat veterans; half of the sample developed PTSD following combat exposure. Metabolite concentration control coefficients for 350 model parameters were combined with results from glucocorticoid and standard clinical lab assays.  A correlational analysis followed with estimation of average causal effects using covariate balancing propensity score weighting.  A causal mediation hypothesis of hs-CRP, HOMA-IR, GGT and hypoxanthine as joint mediators for the effects of glucocorticoid sensitivity on metabolic profiles was tested using natural effect models.  Results indicate that the muscle-liver-adipose axis is most likely affected in PTSD, suggesting that greater glucocorticoid sensitivity as observed in PTSD might contribute to mitochondrial dysfunction and associated metabolic abnormalities.
 

Concurrent Session Three: Symposium

Thursday, November 8 | 3:00 PM to 4:15 PM


Advancing Neural Models of Posttraumatic Stress Disorder
 

Chair: Liddell, Belinda, PhD;
Discussant: Bryant, Richard, PhD

Research that sheds light on the neural mechanisms underpinning traumatic stress responses and psychopathology is critical to determining new treatment targets, particularly in vulnerable populations. This symposium will present four clinical research papers, each employing novel functional magnetic resonance imaging (fMRI) and cognitive neuroscience empirical methods to investigate the neural processes altered by trauma, PTSD and various interventions. The first paper presents new insights into the functioning of the cerebellum during resting state in PTSD. The second study examines the neural effects of attachment priming on the processing of negative visual cues in a cohort of trauma-exposed refugees, and whether these disrupted neural activation patterns are modulated by PTSD symptoms, attachment style and ongoing separation.  The third paper will present new findings related to a self-efficacy induction in combat-related PTSD, examining the impact on emotion regulation brain systems. The fourth study examines neural predictors of treatment response in military-veterans with PTSD, assigned to receive either prolonged exposure therapy (PE), sertraline medication (SERT), or the combination (PE+SERT), with a focus on emotion neural systems associated with symptom change across and within the treatment groups. These four studies highlight the potential of neuroimaging studies to contribute towards developing new treatment approaches, and advancing the neuroscience of PTSD.  
 

The Cerebellum after Trauma: Resting-state Functional Connectivity of the Cerebellum in Posttraumatic Stress Disorder and its Dissociative Subtype

 
Lanius, Ruth, MD, PhD1; Rabellino, Daniela, PhD1; Densmore, Maria, BSc2; Theberge, Jean, PhD3; McKinnon, Margaret, PhD4

1University of Western Ontario, London, Ontario, Canada
2University of Western Ontario, Depts of Psychiatry and Psychology, London, Ontario, Canada
3Lawson Health Research Institute, London, Ontario, Canada
4McMaster University, Hamilton, Ontario, Canada


Background: The cerebellum plays a critical role not only in motor function but also in affect regulation and cognition. Although several psychopathological disorders have been associated with overall cerebellar dysfunction, it remains unclear whether different regions of the cerebellum contribute uniquely to psychopathology. Methods: We compared seed-based resting-state functional connectivity of the anterior cerebellum (lobuleIV-V), of the posterior cerebellum (Crus I), and of the anterior vermis across posttraumatic stress disorder (PTSD; n = 65), its dissociative subtype (PTSD+DS; n = 37), and non-trauma-exposed healthy controls (HC; n = 47). Results: We observed decreased functional connectivity of the anterior cerebellum and anterior vermis with brain regions involved in multisensory integration and bodily self-consciousness in PTSD+DS as compared to PTSD and HC. Moreover, the PTSD+DS group showed increased functional connectivity of the posterior cerebellum with cortical areas related to emotion regulation as compared to PTSD. Conclusions: These findings underline not only the critical role of each cerebellar region examined in the psychopathology of PTSD but also demonstrate unique alterations in functional connectivity distinguishing the dissociative subtype of PTSD from PTSD.
 

Priming Attachment Modulates Neural Responses to Aversive Cues in Traumatized Refugees


Liddell, Belinda, PhD1; Den, Miriam, PhD, MRCPsych1; Malhi, Gin, PhD2; Felmingham, Kim, PhD3; Outhred, Tim, PhD2; Das, Pritha, PhD4; Nickerson, Angela, PhD1; Askovic, Mirjana, BSc Hons Psychology5; Coello, Mariano, BBSc, MPsych5; Aroche, Jorge, BBSc, MPsych5; Bryant, Richard, PhD6

1University of New South Wales, Sydney, NSW, Australia
2University of Sydney, St Leonards, NSW, Australia
3University of Melbourne, Melbourne, Victoria, Australia
4University of Sydney, Sydney, NSW, Australia
5South Western Sydney Area Health Service, Sydney, NSW, Australia
6University of New South Wales, Sydney, New South Wales, Australia


Any neural model of PTSD in refugees will need to account for the defining feature of being a refugee – separation from homeland, which includes severed connections with primary social attachments and fragmented social networks. How attachments can be restored to assist in promoting post-trauma recovery in refugees is unknown. In this study, 51 refugees with and without PTSD viewed a series of negative and neutral cues, which were primed by briefly presented attachment (vs non-attachment images) while undergoing functional magnetic resonance imaging (fMRI) scanning. In healthy refugees without psychopathology, attachment priming was associated with greater responsivity in dorsomedial prefrontal networks, suggesting enhanced neural engagement in emotion regulation processes. However, in refugees with PTSD, insecure attachment style or who were experiencing ongoing separation from primary social attachments, attachment priming failed to assist in regulating amygdala, insula and brainstem reactivity to negative cues. These findings suggest that treatment approaches need to be adapted to account for ongoing separation and attachment sensitivities in refugees, and that attachment activations may assist some refugees to manage strong emotional reactions more efficiently.  


Neural Circuitry Changes Associated with Enhancing Self-Efficacy in Combat Veterans with PTSD


Brown, Adam, PhD1; Titcombe, Roseann, MD PhD1; Chen, Jingyun, PhD1; Rahman, Nadia, BA2; Kouri, Nicole, BA3; Qian, Meng, PhD1; Bryant, Richard, PhD4; Marmar, Charles, MD1

1New York University School of Medicine, New York, New York, USA
2NYU School of Medicine/Bellevue Hospital, New York , New York, USA
3New York University School of Medicine, New York , New York, USA
4University of New South Wales, Sydney, New South Wales, Australia


PTSD is associated with maladaptive changes in self-identity such as low perceived self-efficacy. Low levels of self-efficacy are linked to PTSD onset and poor treatment outcome. The study aimed to determine whether increasing perceptions of self-efficacy in PTSD would be associated with changes in neural processing. Combat veterans (N=34) with PTSD were randomized to either a high self-efficacy (HSE) induction, in which they were asked to recall memories associated with successful coping, or a control condition before undergoing resting state fMRI scanning. Two global network measures in four neural circuits were examined. Participants in the HSE condition showed greater right-lateralized path length and decreased right-lateralized connectivity in the emotional regulation and executive function circuit. In addition, area under receiver operating characteristics curve (AUC) analyses found that average connectivity (.71) and path length (.70) moderately predicted HSE group membership. These findings provide further support for the importance of enhancing perceived control in PTSD, and doing so may engage neural targets that could guide the development of novel interventions. 
 

Activation in Pre-Ttreatment Emotion Modulation Circuitry is Associated with Treatment Response in PTSD


Duval, Elizabeth, PhD LP1; Sheynin, Jony, PhD1; King, Anthony, PhD2; Phan, Luan, MD3; Simon, Naomi, MD4; Martis, Brian, MD2; Porter, Katherine, PhD2; Norman, Sonya, PhD5; Stein, Murray, MD, MPH, FRCPC6; Rauch, Sheila, PhD, ABPP7; Liberzon, Israel, MD8

1The University of Michigan Health System, Ann Arbor, Michigan, USA
2VA Ann Arbor Healthcare System/ University of Michigan, Ann Arbor, Michigan, USA
3University of Illinois Chicago, Chicago, Illinois, USA
4Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
5National Center for PTSD, San Diego, California, USA
6University of California, San Diego, La Jolla, California, USA
7Emory University School of Medicine/Atlanta Veteran's Administration, Atlanta, Georgia, USA
8University of Michigan, Ann Arbor, Michigan, USA


Posttraumatic stress disorder (PTSD) has been associated with increased threat processing and decreased emotion modulation. We examined neural mechanisms underlying emotion processing and modulation, associated with treatment outcome in PTSD. Thirty six military veterans with PTSD were assigned to evidence-based treatment groups: Prolonged Exposure (N = 7), Sertraline (N = 14), and combined treatment (N = 15). Symptom assessment and MRI scanning occurred before and after treatment. The Shifted Attention Emotion Appraisal Task probed brain activation during implicit emotional processing, attention modulation of emotion, and emotion modulation by appraisal. Activation in the insula/IFG decreased from pre- to post-treatment during implicit emotional processing (t(35) = 2.08, p = .045) and modulation by appraisal (t(35) = 2.94, p = .006). During appraisal, brain activation at pre-treatment predicted change in PTSD symptoms across treatments (R2 = .28, F(7, 42) = 2.33, p = .04). Greater activation in insula/IFG (β = 2.03, p = .049) and vmPFC (β = 2.33, p = .025) before treatment was associated with symptom improvement over the course of treatment. These relationships remain after controlling for pre-treatment symptoms. These findings suggest that activation in emotion processing and modulation regions may predict treatment outcome in PTSD across psychotherapy and pharmacotherapy.
 

Concurrent Session Four: Symposium

Thursday, November 8 | 4:30 PM to 5:45 PM


From Basic Science to Psychotherapy: Sleep's Role in Extinction Learning and Trauma Memory Modification


Chair: Kleim, Birgit, PhD;
Discussant: Neylan, Thomas, MD

Sleep problems are a core feature of posttraumatic stress disorder (PTSD) and one of the most difficult symptoms to manage and modulate in treatment. Sleep disturbance is not only a negative outcome from PTSD, but may also contribute to its onset and to subsequent comorbidity. The role of sleep in processing trauma and subsequent emotional memories of a traumatic experience is thus a frontier topic in understanding adaptive and pathological adaptation to trauma and for advancing treatment. In this symposium, we will present recent data on (i) an animal model study on sex difference in REM sleep and fear conditioning (Kobayashi), (ii) sex differences in sleep after trauma (Felmingham), (iii) REM and NREM sleep in relation to fear conditioning, extinction, and extinction memory (Germain), (iv) the effect of REM sleep in naps after experimental trauma and the effect on intrusive reexperiencing (Kleim). Together, these presentations assign a key role for sleep in the development emotional memories, including sex differences in these processes, as well as in the development of PTSD. The results have implications for understanding pathways to PTSD, as well as for prevention and intervention science. 


Sex Differences in Roles of REM Sleep in Fear Memory Consolidation: A Mouse Model of Post-Trauma Sleep


Kobayashi, Ihori, PhD1; Hatcher, Mark, BS1; Boadi, Linda, MD1; Wilson, Camille, Undergraduate2; Polston, Eva, PhD1

1Howard University College of Medicine, Washington, District of Columbia, USA
2Howard University, Washington, District of Columbia, USA

Women are at greater risk than men for developing posttraumatic stress disorder (PTSD) after trauma exposure. Rapid-eye-movement (REM) sleep has been implicated in processing of emotional memories, and REM sleep fragmentation within a month of trauma has been associated with PTSD development in humans. However, recording sleep immediately after trauma has been challenging in humans, and animal models of sleep in PTSD have been tested only with males. To examine sex differences in roles of sleep in fear memory consolidation, we recorded electroencephalographic sleep in 7 male and 15 female C57BL/6 mice before and after fear conditioning. Mice received 15 footshocks after a 10-minute acclimatization period in a footshock chamber. Mice were returned to the chamber 9-13 days later for 10 minutes without footshocks. Percentage of freezing (freezing%) increased from the acclimatization to the context reexposure session in females (z=-3.30, p=.001), but not in males (z=-1.83, p=.07). In females, increased percentages of post-footshock REM sleep (REM%) in both active and inactive periods were associated with decreased freezing% (ρ=-.75 to -.60, p<.02). In males, REM% were not significantly correlated with freezing% (ρ=-.30 to .60, p>.29). Results suggest that REM sleep might hinder fear memory consolidation in females and that enhanced REM sleep may protect women against PTSD. 


Sex Specificity in Sleep, Emotional Memory and PTSD


Felmingham, Kim, PhD1; Schuez, Benjaimin, PhD2; O'Donnell, Meaghan, PhD3; Forbes, David, PhD3; Nickerson, Angela, PhD4; Creamer, Mark, PhD1; Silove, Derrick, MD PhD4; McFarlane, Alexander, MD5; Van Hooff, Miranda, BA (Hons), PhD5; Bryant, Richard, PhD6

1University of Melbourne, Melbourne, Victoria, Australia
2University of Bremen, Bremen, Bremen, Germany
3Phoenix Australia: Centre for Posttraumatic Mental Health: The University of Melbourne, Melbourne, Victoria, Australia
4University of New South Wales, Sydney, NSW, Australia
5The University of Adelaide, Adelaide, South Australia, Australia
6University of New South Wales, Sydney, New South Wales, Australia


This research examines sex specificity in sleep disturbances, emotional memory consolidation and in the risk of developing PTSD following trauma.  The current study presents a) longitudinal data identifying key predictors of PTSD developing following trauma, and b) experimental data examining the impact of sex and sleep quality on emotional memory processes. A longitudinal sample of 852 traumatic injury survivors were assessed at three and twelve months post-trauma with the Clinician Administered PTSD Scale.  Multigroup structural equation modelling revealed that acute re-experiencing symptoms were stronger predictors of PTSD symptoms at 12 months post-trauma in women compared to men.  Of the specific re-experiencing symptoms, post-trauma nightmares had a four-fold predictive strength of subsequent PTSD in women compared to men. In a second experimental study, 150 participants (50 with PTSD) completed an experimental memory task in which they viewed negative, neutral and positive IAPS images, sleep quality was examined using the Pittsburgh Sleep Quality Index and intrusive memories were recorded.  Sex was found to moderate the relationships between sleep quality and negative intrusive memories. These findings highlight the need to consider sex specific processes in key mechanisms underlying PTSD such as sleep and emotional memory consolidation.
 

The Role of REM Sleep in Trauma Memory Pathophysiology


Kleim, Birgit, PhD
University of Zurich, Zürich, ZH, Switzerland

Re-experiencing of emotional memories in form of intrusive memories is a hallmark PTSD symptom and thought to be related to dysfunctional encoding and subsequent lack of integration into existing autobiographical memory networks. Sleep is a key player in the integration of new memories. It may also, over the course of multiple nights, reactivate and consolidate memories and reduce distress. We previously demonstrated that sleep in the night after experimental trauma compared to wake led to fewer and less distressing intrusive emotional memories. The present study aimed to replicate these findings in a nap study in healthy females (N= 60) exposed to experimental trauma. We hypothesized that (i) a 90-minute nap is sufficient to produce a similar protective effect of sleep on intrusive memories and (ii) REM sleep is associated with reduction in intrusive memory distress. Results showed no difference between nap and wake groups in intrusions frequency and level of distress. However, presence of REM sleep during the nap determined frequency and distress of intrusive memories. Those with periods of REM sleep experienced fewer and less distressing intrusive trauma memories than those who did stay awake and those without REM sleep. Our findings indicate that a nap including REM sleep can play a protective role in intrusion formation and have implications for prevention science.
 

Do Theta Power and other Baseline REM Sleep Parameters predict Fear Conditioning, Extinction, and Extinction Recall in Healthy Adults?


Germain, Anne, PhD
University of Pittsburgh, Pittsburgh, Pennsylvania, USA

Acute and chronic changes in REM sleep theta activity and REM density following trauma exposure have been associated with vulnerability to stress-related psychiatric disorders. We investigated which pre-exposure, baseline REM sleep characteristics may predict or moderate the effect of sleep loss on fear conditioning, extinction learning, and extinction recall in healthy adults.  Healthy adults (n = 172; mean age 23.9 + 3.4 years; 95 women) completed a baseline overnight polysomnographic (PSG) study. On the following night, participants were randomized to a normal sleep (NS) condition, sleep restriction (SR), or sleep deprivation (SD).  Fear Conditioning and Extinction Learning occurred in the morning following Night 2. Extinction Recall was tested ~9 hours later. Theta activity and other REM sleep parameters were obtained on Night 1. Skin conductance response (SCR) indexed fear responses. Frontal theta activity during REM sleep did not independently or synergistically predict the effects of Group on Conditioning, Extinction, or Extinction Recall. REM density independently and positively predicted SCR Conditioning, regardless of sleep group (standardized beta coefficient = .20, t=2.57, p = 0.01). Only REM density was independently associated with enhanced discriminative learning during Conditioning. REM sleep changes following stress exposure may have better predictive power.
 

Concurrent Session Five: Symposium

Friday, November 9 | 9:45 AM to 11:00 AM


The Relationship between Trauma and Pain across Diverse Trauma-exposed Populations


Chair: Hellman, Natalie, BA;
Discussant: Hood, Caitlyn, BS

Pain often co-occurs in trauma survivors and persons with Posttraumatic Stress Disorder (PTSD), even though a substantial number of trauma survivors do not report a physical injury from the assault. Therefore, it does not appear that injuries sustained during the trauma are the primary mechanism for the development of pain and chronic pain. Limited research has examined how trauma impacts the development of chronic pain or alterations in pain sensitivity, with even less research examining at risk populations such as ethnic minorities. Four researchers present findings from self-report and experimental pain paradigms examining the relationship between pain and trauma exposure, and possible mechanisms for the development of persistent pain following a traumatic event. Interpersonal violence, sexual assault, PTSD from childhood sexual abuse, and PTSD in minority and low socioeconomic status populations will be evaluated separately and in combination. The course of pain and trauma, possible physiological and psychosocial etiological mechanisms, and the impact of PTSD symptoms will be discussed as possible risk or resiliency factors. Dr. Matt Morris will present longitudinal data examining predictors of pain outcomes in women recently exposed to interpersonal violence. Natalie Hellman will discuss data from the Oklahoma Study of Native American Pain Risk that uses experimental pain paradigms to study pain modulation in a sample of sexual assault survivors. Dr. Christian Schmahl will discuss how a sample of childhood sexual abuse survivors with PTSD, a trauma exposed group, and a control group responded to a stress induction paradigm and how pain sensitivity, dissociation ratings and heart rate variability differentiated the groups and their responses. Dr. Stevan Hobfoll will discuss how pain and PTSD interact among low income inner city women who identify as ethnic minorities, and how vulnerability factors support the conservation of resources theory of stress responses. Caitlyn Hood will serve as a discussant by time-keeping and providing brief introductions and the question-and-answer portion. Together, these speakers will discuss the course and potential etiological mechanisms of pain following trauma exposure.


Experimental Investigation of Stress Responsivity and Pain Sensitivity in CSA Survivors with and without PTSD


Rausch, Sophie, PhD Candidate1; Herzog, Julia, PhD Candidate1; Thome, Janine, PhD Candidate2; Niedtfeld, Inga, PhD1; Lis, Stefanie, PhD1; Kleindienst, Nikolaus, PhD2; Bohus, Martin, MD2; Schmahl, Christian, MD1

1Central Institute of Mental Health, Dept. of Psychosomatic Medicine, Mannheim, Germany, Mannheim, Baden-Württemberg, Germany
2Central Institute of Mental Health, Mannheim, Baden-Württemberg, Germany

Patients with PTSD following adverse childhood experiences (ACE) demonstrate alterations on a broad spectrum of variables related to stress and pain. To clarify the question whether these alterations are related to the diagnosis of PTSD or to ACE per se, we compared healthy women with a history of ACE (n=33), patients with PTSD related to ACE (n=33), and healthy controls (HC) with no history of ACE (n=32). We investigated i) indicators of  baseline stress levels (stress ratings, dissociation, heart rate, heart rate variability, and pain sensitivity) and ii) stress responses to a stress induction paradigm with respect to these indicators. At baseline, large effect sizes were found for the difference between the ACE and the PTSD group with respect to stress and dissociation ratings, heart rate, and heart rate variability, while effect sizes for the differences between ACE and HC were consistently small. In contrast, pain sensitivity was already significantly lower in the ACE group as compared to HC, with an additional smaller effect of PTSD in reducing pain sensitivity. Stress induction led to a further reduction of pain sensitivity in all three groups. These results suggest that psychophysiological measures of stress and dissociation are more dependent on the diagnosis of PTSD, while alterations of pain sensitivity can be related to the experience of ACE per se.


Pain Catastrophizing Adds to PTSD in African American Inner-City Women


Hobfoll, Stevan, PhD1; Gaffey, Allison, PhD2; Aranda, Frances, PhD MPH2; Burns, John, PhD2; Purim Shem Tov, Yanina, MD2

1Rush Medical College, Chicago, Illinois, USA
2Rush University Medical Center, Chicago, Illinois, USA

Although studies have found African-American women to be less susceptible to depression than White women, African-American women may endorse higher levels of PTSD symptoms. We tested a mediation model including hypothesized pathways between race, trauma, psychosocial vulnerability (i.e., pain  catastrophizing, anger, and social undermining), social support, and trauma-related psychopathology (i.e., symptoms of depression and PTSD) in a sample of inner-city women who presented to the Emergency Department (ED) with acute pain (N = 301; 60.1% African American/African-American). Despite comparable rates of traumatic experiences among the racial groups, African-American women reported higher PTSD symptoms, greater psychosocial vulnerability, and lower social support than other racial groups. Depression symptoms did not differ by race. In contrast, the hypothesized models, examined prospectively over a 3 month period, showed good fit, with psychosocial vulnerability, including pain catastrophizing)  mediating the pathway between race and PTSD. Social support did not mediate the effects of psychosocial vulnerability on PTSD symptoms. 
 

Exploring the Impact of Posttraumatic Negative Cognitions on Pain Outcomes in the Acute Aftermath of Interpersonal Violence


Morris, Matthew, PhD
Meharry Medical College, Nashville, Tennessee, USA

Persistent pain frequently co-occurs with trauma-related psychopathology even when the traumatic event does not involve physical injury, suggesting possible shared vulnerability factors. Cyberstalking - one type of interpersonal violence - is linked to a variety of negative mental and physical health outcomes; however, the extent to which cyberstalking is associated with pain outcomes has yet to be examined. The present longitudinal study examined the extent to which cognitive vulnerability factors for posttraumatic stress disorder (PTSD) were associated with changes in pain outcomes over and above the influence of posttraumatic stress and depressive symptoms. Outcomes were self-report affective and sensory pain intensity and pain-related interference measured at baseline assessment and again at one-, two-, and three-month follow-ups in 82 young adult women with recent exposure to cyberstalking. Multilevel models indicated that within-person increases in affective pain intensity were associated with higher posttraumatic stress and depressive symptoms but were not associated with negative cognitions. Both sensory pain intensity and pain-related interference were associated with more negative cognitions about the self. Results reveal persistent pain complaints in recent cyberstalking victims and suggest distinct psychological risk factors for pain intensity and interference.


Does Sexual Assault Disrupt Pain Modulation Circuitry?


Hellman, Natalie, BA1; Sturycz, Cassandra, BA1; Kuhn, Bethany, MA1; Lannon, Edward, MA1; Toledo, Tyler, BA1; Palit, Shreela, MA1; Huber, Felicitas, Dipl Psych2; DeMuth, Mara, BS1; Shadlow, Joanna, PhD1; Rhudy, Jamie, PhD1

1University of Tulsa, Tulsa, Oklahoma, USA
2University of Vienna, Tulsa, Oklahoma, USA

Sexual assault (SA) is associated with an increased risk for chronic pain. One possible mechanism for this relationship may be dysregulated pain modulation processes. This presentation reports data from two laboratory paradigms used to evaluate descending pain modulation circuitry in a diverse sample of currently pain-free female and male and survivors of SA versus a matched, comparison group of pain-free non-SA participants. One paradigm assessed emotional modulation of pain and the other assessed conditioned pain modulation (the ability for pain to inhibit other pain). Outcomes were pain report and a physiological correlate of pain signaling in the spinal cord (i.e., the nociceptive flexion reflex; NFR). Results using multilevel modeling indicated that SA survivors reported generally higher pain during testing and they failed to emotionally modulate pain signaling in the spinal cord. Further, the SA group displayed a disruption of conditioned pain modulation; specifically, pain signaling in the spinal cord was enhanced rather than inhibited in this group. Together, these results suggest that exposure to SA may disrupt pain modulation circuitry thus promoting central sensitization (amplification of pain signals within the central nervous system). This in turn may place SA survivors at risk for the future development of chronic pain.
 

Concurrent Session Six: Symposium

Friday, November 9 | 11:15 AM to 12:30 PM


Disturbed Sleep and PTSD Treatments: Examining Mechanisms and Outcomes


Chair: Neylan, Thomas, MD

There is evidence suggesting that disturbed sleep not only independently affects daytime functioning and worsens PTSD symptoms but may interfere with mechanisms involved with PTSD treatment such as emotion regulation and safety learning/extinction learning. Four clinical researchers will present findings on: (1) An outcome study of prolonged exposure (PE) followed by imagery rehearsal therapy for nightmares and cognitive behavioral therapy for insomnia (CBT-I); (2) The relationship between sleep and emotion regulation strategies in a large cohort of patients with and without PTSD; (3) REM sleep and safety learning/extinction learning in veterans with PTSD; (4) Pilot treatment data examining CBT-I prior to PE. Overall, results indicate that targeting sleep disturbance represents a logical method for enhancing mechanisms of emotion regulation and extinction learning involved with PTSD treatment.
 

Nightmare & Insomnia Treatment Efficacy Study (NITES): Results from Sequential PE and Sleep Interventions


Drummond, Sean, PhD
Monash University, San Diego, California, USA

Sleep difficulties are ubiquitous in PTSD, with 70-90% of individuals with PTSD reporting clinically significant insomnia and/or nightmares. Recent studies report limited benefit of evidence based PTSD interventions (i.e., PE, CPT) for sleep symptoms, though typically based on only a single self-report measure. If PE does not significantly improve sleep, administering sleep interventions after PE could result in better overall improvement in PTSD severity. This study examined a) the impact of PE on objective and subjective assessments of sleep; and b) the benefit of adding evidence based sleep interventions onto the end of PE. Forty-five veterans with PTSD and sleep difficulties received 12 sessions of PE over 6 weeks. A subset of 15 veterans were then randomized to either sleep (IRT+CBT-Insomnia) or Supportive Care Therapy (SCT) interventions for 12 sessions. PE significantly improved PTSD severity. Of 17 subjective and objective sleep measures, only 4 showed significant improvements after PE, but none were within the normal range at Posttreatment. Compared to SCT, IRT+CBT-Insomnia significantly improved nightmare intensity and sleep efficiency. Sleep interventions also lead to non-significant improvement in CAPS and PCL, with medium effect sizes. Overall, these data suggest sleep should be addressed specifically and independently of daytime PTSD interventions.


Sleep Quality is Associated with Emotion Regulation Processes in Veterans with and without PTSD: Results from the Mind Your Heart Study


Straus, Laura, PhD; Neylan, Thomas, MD; Cohen, Beth, MD, MAS
San Francisco VA Medical Center and UCSF, San Francisco, California, USA

Previous research has shown relationships between sleep quality and emotion regulation processes, though this has not been well examined in clinical populations. We examined the relationship between sleep quality and emotion regulation in a large cohort of veterans with and without posttraumatic stress disorder (PTSD; n=705). We used the Emotion Regulation Questionnaire (ERQ) to assess two different emotion regulation strategies: suppression and reappraisal. Sleep quality was assessed using the global sleep quality item from the Pittsburgh Sleep Quality Index (PSQI), and PTSD was assessed with the Clinician Administered PTSD Scale (CAPS) using DSM-IV-TR criteria. After adjusting for age, sex, and ethnicity, linear regression showed poor sleep quality was associated with increased emotional suppression (B=.557, p<.001) and decreased reappraisal (B=-.359, p=.017). These relationships remained even when adding current PTSD diagnosis in the model (B=.322, p=.008 for suppression; B=-.387, p=.017 for reappraisal). These results suggest poor sleep quality is associated with increased emotional suppression and decreased reappraisal even when accounting for PTSD diagnosis. Future studies should examine the mechanisms by which poor sleep is associated with these emotion regulation strategies, and how these constructs are related to PTSD symptoms and/or treatment response.
 

REM Sleep and Safety Signal Learning in Posttraumatic Stress Disorder

 
Straus, Laura, PhD1; Norman, Sonya, PhD2; Risbrough, Victoria, PhD3; Acheson, Dean, PhD3; Drummond, Sean, PhD4

1San Francisco VA Medical Center and UCSF, San Francisco, California, USA
2National Center for PTSD, San Diego, California, USA
3University of California, San Diego; Center of Excellence for Stress and Mental Health, VASDHS, La Jolla, California, USA
4Monash University, San Diego, California, USA


Fear conditioning plays an important mechanistic role in PTSD, and extinction learning and safety learning are critical for recovery. Sleep, particularly REM sleep, is linked to improved safety learning and enhanced extinction in animal models and healthy humans. This study examined the relationship between REM sleep, safety signal learning, and extinction processes in veterans with PTSD (n=13). Laboratory polysomnography was used to measure REM sleep for three nights. During three consecutive days, veterans underwent 1) fear conditioning and safety learning, 2) extinction learning, and 3) a recall session. All testing sessions involved presentation of threat (CS+) and safety (CS-) signals; startle EMG was used to characterize fear response to both cues. Veterans who underwent safety learning more quickly on the first day of testing showed more efficient REM sleep that night (r=.607, p=.028). Veterans with more REM sleep on the last night showed more rapid safety re-learning on the last day of testing (r=.688, p=.009). Results suggest REM sleep was associated with both initial safety learning and subsequent safety re-learning, which provides additional evidence that REM sleep could play a mechanistic role in the maintenance of PTSD and may be a modifiable biological process to target in treatment of PTSD.


A Pilot Study Examining Cognitive Behavioral Therapy for Insomnia Integrated with Prolonged Exposure


Colvonen, Peter, PhD1; Drummond, Sean, PhD2; Gehrman, Philip, PhD3; Angkaw, Abigail, PhD4; Norman, Sonya, PhD1

1VA San Diego Healthcare System, San Diego, California, USA
2Monash University, San Diego, California, USA
3University of Pennsylvania, Philadelphia, Pennsylvania, USA
4National Center for PTSD, VA San Diego, UCSD, San Diego, California, USA


Insomnia not only independently affects daytime functioning and worsens PTSD symptoms but also may interfere with response to prolonged exposure (PE) through impaired emotional processing, cognitive functioning, and safety learning/extinction learning. Although cognitive behavioral therapy for insomnia (CBT-I) is an effective intervention for insomnia, it has not been examined in conjunction with PE. This presentation reviews the rationale for integrated treatment, describes the key elements of an integrated CBT-I and PE (2NITE) protocol, and presents pilot data from 12 treatment seeking veterans with PTSD and insomnia. Measures include assessments of PTSD, quality of life, and objective/subjective measures of sleep. Client satisfaction for the 2NITE protocol was high (mean score of 29.66 out of 32 points). On average, there were statistically and clinically meaningful changes in all measures, including a 20.16 point decrease in PCL, a 11.75 point reduction in the insomnia severity index, an 11% increase in sleep efficiency, and 51 minute increase in total sleep time using actigraphy. Cohen’s d effect sizes ranged from 1.3 to 2.4. Among individuals with insomnia and PTSD, addressing insomnia integrated with PE represents a logical, innovative, and empirically-informed method for augmenting existing treatments and optimizing global outcomes that justifies further investigation.
 

Concurrent Session Seven: Symposium

Friday, November 9 | 3:00 PM to 04:15 PM


Trauma from Childhood to Adulthood: The Impact of Timing of Trauma on Neurobiological Response


Chair: Felmingham, Kim, PhD;
Discussant: Schmahl, Christian, MD

There has been recent recognition that the impact of trauma exposure on neurobiological processes may be particularly powerful during critical sensitive periods of development, yet the issue of critical sensitive periods of trauma exposure has received relatively little investigation in the PTSD field.  This symposium brings together cutting-edge neurobiological research which examines the impact of timing of trauma, and the type of trauma on neurobiological processes across development.  This symposium will include the presentation of findings from longitudinal structural and functional neuroimaging data, and event-related potential data analysed in relation the type and timing of trauma exposure from childhood, through adolescence to adulthood.  Functional neuroimaging and event-related potential data will be presented from various paradigms, including emotional face processing, emotional stroop, and emotional response inhibition tasks.  An emphasis will be on various machine learning analytic approaches to explore the neurobiological data in relation to the timing of trauma exposure.
 

Are there Effects of Childhood and Adolescent Maltreatment on Brain Volume and Function during Sensitive Time Periods?


Herzog, Julia, PhD Candidate1; Thome, Janine, PhD Candidate2; Bohus, Martin, MD2; Lis, Stefanie, PhD1; Schmahl, Christian, MD1

1Central Institute of Mental Health, Dept. of Psychosomatic Medicine, Mannheim, Germany, Mannheim, Baden-Württemberg, Germany
2Central Institute of Mental Health, Mannheim, Baden-Württemberg, Germany

Deleterious effects of adverse childhood experiences (ACE) on brain volume are widely reported. Yet, there is an upcoming interest in the type and timing of ACE, as first evidence points to differential effects on brain volume and function. In a sample with a history of ACE, with (N=42) and without (N = 26) PTSD, we assessed exposure to ACE from age 3 up to 17 using the Maltreatment and Abuse Chronology of Exposure interview (MACE). Covariations of MACE severity at different ages with brain volume was calculated by applying conditional random forest regression. Emotion processing was measured with an Emotional Stroop Task and a Sternberg working memory task (EWMT).
Bilateral amygdala volume were best predicted by maltreatment at age 13, while right amygdala volume was additionally predicted by maltreatment at age 10. With respect to the right hippocampal volume, best prediction was found by MACE severity at age 10, 11, and 13. Crucially, trauma type modulated this effect, as neglect severity was more important during this sensitive period
The present investigation confirms previous findings on the relationship between brain volume and ACE during sensitive periods. Preliminary results on the relationship between type and timing of ACE and neurobiological responses to emotional stimuli will be presented.


Differential Effects of Exposure to Specific Traumatic Events versus Ongoing Traumatic Neighborhood Violence on Brain Structure and Function in Children


van Rooij, Sanne, PhD; Stevens, Jennifer, PhD; Smith, Ryan, MD; Ely, Timothy, BSc; Jovanovic, Tanja, PhD
Emory University School of Medicine, Atlanta, Georgia, USA

Childhood trauma is a major risk factor for the development of PTSD. Retrospective MRI studies have shown negative effects on brain structure and function. Here we assess the effects of exposure to specific traumatic events as well as ongoing traumatic neighborhood violence on brain structure and function in 43 children (8-14 y/o) recruited through an ongoing study in a vulnerable, highly traumatized, African-American population.

Exposure to specific traumatic events was assessed with the TESI. Traumatic violence exposure was measured with the VEX-R. Functional and structural MRI scans were collected. Freesurfer v5.3 was used to assess bilateral hippocampal volume (N=43). An emotional Go/NoGo fMRI task was used to measure response inhibition in the amygdala, hippocampus and vmPFC (N=27).

Traumatic events (TESI) correlated negatively with hippocampal volume (r=-.37, p=.016), but not with fMRI measures. On the other hand, violence exposure (VEX-R) did not correlate with hippocampal volume, but positively correlated with amygdala (r=.47, p=.019), hippocampal (r=.50, p=.013), and vmPFC activation (r=.41, p=.045) during response inhibition.

These findings suggest that exposure to specific traumatic events negatively impact hippocampal structure, whereas exposure to ongoing traumatic neighborhood violence may result in functional brain changes representing an adaptive response.

Abnormal Development of Amygdala-salience Network Connectivity during Emotion Processing in Pediatric Post-traumatic Stress Disorder

Keding, Taylor, BSc; Herringa, Ryan, MD PhD
University of Wisconsin-Madison, Madison, Wisconsin, USA

Pediatric post-traumatic stress disorder (PTSD) has been characterized by abnormalities in amygdala functional development cross-sectionally. However, little is known about its longitudinal development in afflicted youth. In this naturalistic, longitudinal study, we examined developmental changes in amygdala functional connectivity in 23 youth with PTSD (ages 8-18 at baseline) compared to 21 non-traumatized, typically-developing (TD) youth, matched for age and sex. All youth underwent trauma and psychiatric screens and fMRI during implicit emotional face processing at initial evaluation and one-year follow-up. In multiple group x time interactions, right centromedial and superficial nuclei showed abnormal coupling with the dorsal anterior cingulate cortex and anterior insula, key nodes in the salience network. In all cases, PTSD youth showed increased connectivity between scans, while TD youth showed decreased or no change in connectivity. These findings represent the first known longitudinal investigation of task-based functional connectivity in PTSD youth and indicate abnormal development of amygdala coupling with the salience network. This may serve as a neural basis for increased importance of facial affect in threat/safety discrimination after trauma-exposure, which typically decreases during adolescence. 


Using Machine Learning to Discriminate the Impact of Timing of Childhood Trauma on Deployment Related Neurocognitive Functioning in a Military Sample


Miller, Lisa, PhD Student1; Hogendoorn, Hinze, PhD1; Forbes, David, PhD2; Simmons, Julian, PhD3; McFarlane, Alexander, MD4; Van Hooff, Miranda, BA (Hons), PhD4; Whittle, Sarah, PhD5; Lawrence-Wood, Ellie, BSc Hons Psychology6; Felmingham, Kim, PhD5

1University of Melbourne, Parkville, Victoria, Australia
2Phoenix Australia: Centre for Posttraumatic Mental Health: The University of Melbourne, Carlton, Victoria, Australia
3University of Melbourne, Carlton, Victoria, Australia
4The University of Adelaide, Adelaide, South Australia, Australia
5University of Melbourne, Melbourne, Victoria, Australia
6Adelaide University, Adelaide , South Australia, Australia


Within the military, an increase in childhood trauma coupled with high combat exposure has been linked to increased post-traumatic stress symptoms (PTSS). However not all military personnel follow the same trajectory of PTSS across deployment. One explanation for differences in PTSS may be the timing of trauma. Vulnerability of the right hippocampus, right amygdala and prefrontal cortex, brain regions known to be associated with PTSS, has been linked to trauma occurring at specific ages in late childhood and adolescence. We applied multivariate pattern analysis (MVPA) to timeseries electroencephalogram (EEG) recordings from an emotional face paradigm collected on a sample of over 200 Australian military personnel before and after deployment. We found MVPA distinguished traumatised from non-traumatised groups, with strongest accuracy for classification of traumas occurring before 10 and 15-17 years of age. Early- and mid-range EEG timepoints were selected for trauma occurring before 10 years suggesting trauma at this age may affect early selective attention and perceptual processing of emotional faces. In contrast, late EEG timepoints were selected for trauma occurring between 15-17 years of age, suggesting trauma at this time may affect cognitive processing of emotional faces only. These findings will be discussed in relation to PTSS before and after deployment.  
 

Concurrent Session Eight: Symposium

Friday, November 9 | 4:30 PM to 05:45 PM


The Effects of Trauma on Social Emotional Processing and Responding: Implications for Social Impairment


Chair: Crum, Kathleen, PhD;
Discussant: Kmett Danielson, Carla, PhD
 

Clinical researchers will present findings from neural, physiological, behavioral, and report-based investigations of how trauma impacts social interactions and impairment across the lifespan. Findings indicate that trauma-related social impairment may take on several forms, including difficulty interpreting others’ emotions and strained parent-child relationships, and that neural and physiological factors may underlie post-trauma social impairment. The first talk discusses parallels between adult social threat reactivity (startle response) and trauma reactivity. The second talk highlights the differential impact of abuse subtypes on youth neural functioning in brain regions critical to processing and regulating social emotions. The third talk links trauma to child callous-unemotional traits, as well as social-cognitive and physiological dysregulation that may impair social interactions. Finally, the fourth talk characterizes associations between trauma, substance use, and caregiver-child relationships. To facilitate translation into clinical settings, findings will be discussed in the context of real-world social interactions and relationships. Considering the varied clinical presentations of social impairment following trauma, as well as factors contributing to these presentations across the lifespan, is critically important to case conceptualization/ treatment planning.
 

The Impact of Parental Trauma Exposure and Child Social Impairment Among Substance-Using Parents


Moreland, Angela, PhD1; Crum, Kathleen, PhD2; Newman, Carla, LMSW1

1Medical University of South Carolina, Charleston, South Carolina, USA
2National Crime Victims Research and Treatment Center/MUSC, Charleston, South Carolina, USA

Literature has linked child social impairment, including elevated disruptive behavior and anxiety, as well as decreased coping skills, to both parental substance use (Bornovalova et al., 2010; Bountress & Chassin, 2015) and parent trauma (Landoldt et al., 2005). Although up to 96% of substance users report experiencing at least one traumatic experience in their lifetimes (Lawson et al., 2013), studies have not examined the child social impairment among parents who report overlapping trauma and substance use. The current study fills this gap by examining the link between parent trauma exposure and child social impairment among a sample of 52 parents enrolled in a substance use treatment program. Of these parents, 70% reported experiencing at least one traumatic experience in their lifetime. Results utilizing multiple regression indicated that, in substance using parents, increased trauma exposure was significantly linked to child social impairment, including increased disruptive behavior and general anxiety, as well as decreased coping competence. Further, this link was similar across various types of substance use. Overall, findings highlight the impact of parent traumatic stress on child social impairment in a high-risk sample of substance using parents. Clinical implications and recommendations will be discussed in relation to the results.


Beyond Trauma: Defensive Reactivity to Social Threat in PTSD


Sege, Christopher, PhD1; McTeague, Lisa, PhD1; Bradley, Margaret, PhD2; Lang, Peter, PhD2

1Medical University of South Carolina, Charleston, South Carolina, USA
2University of Florida, Gainesville, Florida, USA

While frontline posttraumatic stress disorder treatments often focus on hyper-reactivity to trauma as a primary target, impaired social functioning is often also a core feature. Here, we present translational research on biological concomitants of social threat reactivity in PTSD. Research builds on similar work examining trauma-specific reactivity with a lab-based imagery task; here, we present peripheral/ reflex physiology data collected from single-trauma PTSD (n=22), multi-trauma PTSD (n=27), and control (n=76) subjects who imagined social threat, social reward, and neutral situations. In presenting various data aspects, we first discuss evidence for parallel social and trauma reactivity deficits – that is, social threat reactivity is exaggerated in focally fearful (i.e., single-trauma) PTSD cases, and blunted in broadly distressed (i.e., multi-trauma) cases. Next, we consider analyses of social reward that test if deficits are specific to threat or instead affect general emotional processing. Finally, we present analyses of dimensional social anxiety in our principal PTSD sample, with evidence that social anxiety increases with PTSD symptomatology and might mediate reactivity disruptions. Results are discussed in terms of broad response deficits that might underlie PTSD impairment, with implications for emotion-focused treatment and for capturing cross-case heterogeneity.


Linking Child Trauma to Callous-Unemotional Traits: Perceptions of and Responses to Other Children’s Distress


Crum, Kathleen, PhD1; Aloi, Joseph, BS2; Comer, Jonathan, PhD3; Musser, Erica, PhD3; Moreland, Angela, PhD4; Chou, Tommy, MA5; Flores, Christina, BA3; Lorenzo, Michelle, BA3

1National Crime Victims Research and Treatment Center/MUSC, Charleston, South Carolina, USA
2University of Nebraska Medical Center, Boys Town, Nebraska, USA
3Florida International University, Miami, Florida, USA
4Medical University of South Carolina, Charleston, South Carolina, USA
5Oakland University, Miami, Florida, USA


Child trauma may be linked to callous-unemotional traits (CU)—a form of psychopathology related to severe, lasting social impairment, and characterized by lack of caring for others and lack of guilt. Youth with trauma and CU may have unique physiological and behavioral profiles. Children aged 7-13 (N=45) completed laboratory tasks and questionnaires to assess whether trauma, CU, and their interaction predict 1) perceptions of peer emotions while experimentally manipulating distress-cue salience, 2) parasympathetic arousal (resting respiratory sinus arrhythmia; RSARest). As peer distress salience increased, trauma predicted decreased ratings of peer fear among non-CU youth, and increased ratings among CU youth. Trauma was associated with increased RSARest among non-CU youth; RSARest among CU youth was similar to non-CU youth with trauma. Findings indicate CU modulates the link between trauma and perceptions of peer emotions, and non-CU youth with trauma show dysregulated parasympathetic arousal similar to CU youth (regardless of trauma). Data support that trauma is linked to physiological dysregulation. Recruiting “top-down” emotion regulation strategies to reduce autonomic arousal and improve perceptions of peer emotions may be a useful intervention target for CU youth and youth with trauma, and RSARest may help identify physiological profiles in these populations.


Differential Developmental Impacts of Different Subtypes of Abuse and Neglect on Systems Engaged in Task Performance and Emotional Responding


Blair, Karina, PhD
Boys Town National Research Hospital, Boys Town, Nebraska, USA

Maltreatment exposure has been associated with detrimental outcomes. However, recent literature suggests that two different forms of maltreatment, abuse (physical, emotional and sexual) versus neglect (physical and emotional), may have differential developmental impacts. Further, different subtypes of abuse and neglect may differentially impact brain development. However, little work has directly addressed this issue. Youth in a residential care facility and the surrounding community (N=117) who had experienced varying prior maltreatment levels performed the affective Stroop task during fMRI. Greater levels of prior abuse were associated with disrupted recruitment of regions implicated in top-down attentional control, including superior frontal cortex and posterior cingulate cortex. In contrast, greater levels of neglect were associated with disrupted recruitment of anterior insula cortex (implicated in attentional processing) in the context of threatening distracters. Further, different abuse subtypes—emotional and sexual abuse—were associated with specific disruptions. Findings demonstrate the adverse developmental impacts of both abuse and neglect and reveal their developmental specificity for systems engaged in task performance and emotional responding. Data indicate that different abuse subtypes are important in future research specifications and treatment considerations.
 

Concurrent Session Nine: Symposium

Saturday, November 10 | 9:45 AM to 11:00 AM


Tackling Ongoing Violence with Narrative Exposure: Primary Insights from Individual and Community Levels in Eastern DR Congo and Brazil Involving Epigenetic and Psychological Measures


Chair: Köbach, Anke, PhD, MSc

Scholars have recently begun to examine the relationship between violence and endemic mental health problems around the globe (Slutkin, 2017). Importantly, trauma exposure not only produces mental illness but also increases violence (Elbert et al., 2018). It therefore significantly contributes to armed conflict, criminality, and familial violence. Indeed, violence still remains one of the most elemental parts of the human condition and the scope of it is exponential to trauma exposure itself. War, criminality, child abuse, child terrorism and torture continue to occur on a mass scale. Violence reduction usually involves reliance on military and peacekeeping missions on the international level, or the involvement of local police and justice systems within the national / community level. Neither address mental health issues underlying the violence. Criminal reconviction rates are over 50% within the following 3 years (Fazel & Wolf, 2015), and in armed conflicts, only 18% of 140 conflicts since 1945 have reached a peaceful settlement (Glassmyer & Sambanis, 2008).

With these challenges in mind, our research focuses on people’s experiences of violence, both as perpetrators and victims, the adaptive and maladaptive psychological and epigenetic consequences of both of these scenarios and how these can be addressed by means of psychological interventions like Narrative Exposure Therapy (NET; Schauer et al., 2011) and its variants.

We will start this symposium by introducing a broad epigenetic signature presented in trauma exposed individuals and derive theoretic implications and opportunities for research. From there, we will turn to our clinical trials and present findings from two different settings: Goma, Eastern DR Congo and Rio de Janeiro/Brazil. Both settings have been affected by ongoing severe forms of violence and have in common a  scarcity of mental health services. Here, NET can be used to fill the gap as a specialized trauma therapy which can be delivered in non-medical settings by trained counsellors.  During our therapeutic work biographic narratives of collective relevance are produced. In the final presentation we consider how these may be used to reflect back and challenge the cycles of violence at the community level, and present primary data about the feasibility of such an intervention. 
 

The Broad Epigenetic Signature of Trauma-Related Mental Burden


Nätt, Daniel, PhD1; Serpeloni, Fernanda, PhD2; Köbach, Anke, PhD, MSc3; Elbert, Thomas, PhD4

1Linkoping University, Linkoping, SE, Sweden
2University of Konstanz, Department of Psychology; Clinical and Neuropsychology, konstanz, DE, Germany
3University of Konstanz, Department of Psychology; Clinical and Neuropsychology, Konstanz, Baden Württemberg, Germany
4University of Konstanz & vivo international, Konstanz, Germany, Germany


Previous research has shown that trauma alters epigenetic marks like DNA-methylation, and that these changes could be involved in the etiology of the psychopathologies that may follow (Ryan et al., 2016). However, while it has been proposed that epigenetic changes could be used as biomarkers for trauma and mental disorders, so far no test has reached the clinic. One possible reason for this is the low reproducibility of single candidate discoveries, such as changes in specific genes. Accordingly, we and others have shown that epigenetic changes associated with stress and psychiatric vulnerability is less specific in nature, mimicking the effects seen in biological aging (Nätt et al., 2015; Nätt and Thorsell, 2016). Our results therefore suggest that methods that take into account multiple genomic regions are essential if we are to obtain reliable evidence needed to infer implications for clinical practice. Here, we will present ongoing studies on trauma exposed populations in Brazil, Central Africa, Germany and Sweden, where we focus on the broad epigenetic signatures of trauma-related mental impact. We will present novel bioinformatic methods, which applied on genome-scale DNA-methylation profiles, allow us to model multiple epigenetic changes following trauma, resulting in novel biomarkers like stress-induced methylome reshuffling and epigenetic age acceleration.


Treatment of Traumatised Ex-combatants and Perpetrators Using NET – a RCT in Eastern DR Congo


Robjant, Katy, Clinical Psychologist1; Chibashimba, Amani, MA2; Schmitt, Sabine, MSc3; Köbach, Anke, PhD, MSc4; Elbert, Thomas, PhD5

1University of Konstanz & Vivo International, Konstanz, Baden Württemberg, Germany
2University of Konstanz & Vivo International, Konstanz, BW, Germany
3Konstanz University, Konstanz, Baden-Württemberg , Germany
4University of Konstanz, Department of Psychology; Clinical and Neuropsychology, Konstanz, Baden Württemberg, Germany
5University of Konstanz & vivo international, Konstanz, Germany, Germany


In post-conflict settings, and particularly in DR Congo, high PTSD rates and increased levels of aggression are found in both male and female traumatized offenders. Unless treated for their trauma and aggression, they remain at risk of perpetrating ongoing violence, both by re-joining armed groups, and also as civilians within the community and family. In previous trials with samples of ex-combatants and street children, Narrative Exposure Therapy for Forensic Offender Rehabilitation (FORNET) produced positive results for the reduction of PTSD whereas the findings with regards to aggression were more difficult to interpret (e.g. Köbach et al., 2015). In this trial, we further developed the group therapy component of the intervention in order to target the ongoing violence perpetrated within this group in the community. We will present a randomized controlled trial demonstrating the efficiency of FORNET compared to a waitlist control group.  Clinical variables of PTSD, appetitive aggression, and depression as well as social variables of current aggressive behaviour, social acknowledgement and guilt were investigated at 3 and/or 6 months follow up. The treatments were delivered by trained Congolese personnel.
 

Efficiency of NET in a Pilot Study in Rio de Janeiro, Brazil


Serpeloni, Fernanda, PhD1; Köbach, Anke, PhD, MSc2; Schauer, Maggie, PhD3; Assis, Simone, Prof Dr4

1University of Konstanz, Department of Psychology; Clinical and Neuropsychology, konstanz, DE, Germany
2University of Konstanz, Department of Psychology; Clinical and Neuropsychology, Konstanz, Baden Württemberg, Germany
3University of Konstanz & vivo international, Konstanz, Germany, Germany
4
Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil

In Brazil approximately 11,4 million citizens live in so-called favelas. These areas are characterized by decreased governmental control, high levels of violence and poverty. Previous research has repeatedly demonstrated that those exposed to community violence like frequent and constant exposure to the use of guns, knives, drugs, and random acts of violence are at higher risk of developing trauma-related mental problems, especially PTSD. However there is a lack of specialized treatment for individuals suffering from PTSD in these regions. In the present study, we integrated NET into the services provided by local health centres and evaluated its efficacy in reducing trauma-related symptoms compared to a waitlist control group. Brazilian mental health workers were trained in NET and closely supervised by NET experts. At baseline and 3 month follow up, we assessed PTSD, depression, substance use disorders, and social acknowledgement. Here, we will present primary results of this pilot trial implementing NET into public health structures in a Latin American country and consider the feasibility of implementing this approach at a larger scale.


Breaking the Cycle of Violence with Facts derived from NET


Schmitt, Sabine, MSc1; Robjant, Katy, Clinical Psychologist2; Chibashimba, Amani, MA3; Elbert, Thomas, PhD4; Kaiser, Elisabeth, PhD5; Köbach, Anke, PhD, MSc6

1Konstanz University, Konstanz, Baden-Württemberg , Germany
2University of Konstanz & Vivo International, Konstanz, Baden Württemberg, Germany
3University of Konstanz & Vivo International, Konstanz, BW, Germany
4University of Konstanz & vivo international, Konstanz, Germany, Germany
5vivo international, Konstanz, Baden-Württemberg, Germany
6University of Konstanz, Department of Psychology; Clinical and Neuropsychology, Konstanz, Baden Württemberg, Germany


In our therapeutic work with NET delivered to survivors and perpetrators of organised violence, torture and armed conflict, full biographical testimonies are produced as part of the therapy. These narratives, which document the life events and experiences of clinical cases, provide profound insight into the psychic experience of our clients. At the same time, they have political, ethical and human rights implications and are of collective interest. Whilst communities are aware that these events take place, the traumatizing details remain largely hidden.  The community’s collective memory therefore lacks information about the destructive nature of violence and prevents empathic reactions in consequence to conflict peaks. As a result, in Eastern DR Congo, survivors are frequently stigmatised and excluded. The presentation will briefly introduce how these testimonies are obtained, followed by a presentation of extracts of narratives from diverse client populations at different stages of the therapeutic process. Finally, the development, delivery and first results of a feasibility trial involving the therapeutic use of the narratives within groups at the community level will be presented. 
 

Concurrent Session Ten: Symposium

Saturday, November 10 | 11:15 AM to 12:30 PM


Evaluation of DBT-PTSD and Cognitive Processing Therapy for Patients with Complex PTSD after Childhood Abuse: a Multicenter RCT


Chair: Bohus, Martin, MD;
Discussant: Resick, Patricia, PhD, ABPP

Dialectical behavior therapy for complex posttraumatic stress disorder (DBT-PTSD) is specifically tailored to treat complex PTSD in adult survivors of childhood abuse. The program is designed as a multicomponent treatment, merging DBT principles, trauma-specific cognitive and exposure based techniques, compassion focused interventions, and behavioral change concepts. Recent data of a first RCT have shown good feasibility and large effect sizes under residantial conditions. In order to test the program under outpatient conditions we designed a German multicenter RCT, comparing 40 sessions DBT-PTSD with 40 sessions CPT. We included 200 female subjects, meeting criteria for PTSD after childhood abuse and a minimum of minimum 3 BPD crieria, including criterion 6 (severe problems with emotion dysregulation). The symposium will i) give an overview on principles and structure on the newly developed DBT-PTSD program. ii) provide the psychometric outcome data of the RCT, including preliminary moderator and mediator analyses; iii) present the differential impact of both treatment arms on social behavior under real life conditions, as assessed with ambulatory monitoring tools; and iv) provide the differential analysis of changes in emotion regulation under fMRI conditions after DBT-PTSD and CPT. 
 

Basics and Principles of DBT-PTSD - a Modular Treatment Approach for Complex PTSD after Childhood Abuse


Bohus, Martin, MD
Central Institute of Mental Health, Mannheim, Baden-Württemberg, Germany

DBT - PTSD is based on rules and principles of DBT, merging trauma-focussed cognitive and exposure based techniques, compassionate focused therapy, radical acceptance and behaviour change. The program is applicable for a wide range of patients experiencing complex PTSD including strong dissociative symptomatology, chronic suicidality, and ongoing self-harm. This is reflected by its modular multi-component architecture, which allows sufficient flexibility to cover both complex psychopathology and crises within a principle-based structure. The program comprises 3 treatment phases. In Phase I patients receive psychoeducation and learn to identify their individual escape and avoidance strategies from trauma-related primary. Based on these individualized functional analyses, they learn to use specific DBT skills in order control these behaviours. Phase II focusses on cognitive and exposure-based interventions (skills-assisted exposure). In Phase III patients work on radical acceptance of trauma-related facts. DBT-PTSD was first examined in a randomized controlled trial under residential conditions. Data revealed large effect sizes (d=1.4) and extremely low drop put rates. Of particular importance seems that neither the severity of borderline personality disorder nor the number of self-harm behaviour at the beginning of the therapy had negatively affected treatment outcome.
 

Neural Correlates of Emotional-cognitive Interaction before and after DBT-PTSD


Herzog, Julia, PhD Candidate1; niedtfeld, inga, PhD1; Rausch, Sophie, PhD Candidate1; Thome, Janine, PhD Candidate2; Steil, Regina, PhD3; Bohus, Martin, MD2; Priebe, Kathlen, MSc1; Schmahl, Christian, MD1

1Central Institute of Mental Health, Dept. of Psychosomatic Medicine, Mannheim, Germany, Mannheim, Baden-Württemberg, Germany
2Central Institute of Mental Health, Mannheim, Baden-Württemberg, Germany
3Goethe-University, Frankfurt, Hessia, Germany


Functional neuroimaging studies (fMRI) in PTSD suggest hypoactivation of inhibition-related prefrontal regions , leading to increased activation in limbic areas, such as the amygdala and insula. However, results are rare regarding patients with complex PTSD after adverse childhood experiences (ACE). We investigated differences in inhibition-related prefrontal networks associated with cognitive control as well as emotion-processing networks (amygdala, insula). Using fMRI, we examined neural activity in 28 female patients with cPTSD, 28 female trauma-exposed controls (TCs) and 28 female non-trauma-exposed healthy controls (HCs) with an emotional Stroop Task and an emotional working memory task (EWMT) before and after DBT-PTSD. Patients with cPTSD displayed significantly greater Stroop interference with trauma-related words (slower reaction times and increased errors) compared to the other conditions and compared to the TC and HC groups. Moreover, patients with cPTSD showed increased activation in the context of trauma-related words in brain regions associated with cognitive control (dlPFC, ventromedial PFC, dorsal ACC) compared to both control groups. In the EWMT, the cPTSD group exhibited diminished rostral ACC activation during the presentation of negative distractors compared to the HC group.  First results of the longitudinal study will be presented.
 

DBT-PTSD as Compared to Cognitive Processing Therapy for Childhood Abuse Related PTSD and Comorbid Emotion Regulation Difficulties – a Randomized Controlled Trial (the RELEASE Study)


Steil, Regina, PhD1; Priebe, Kathlen, MSc2; Fydrich, Thomas, PhD3; Hahn, Christopher, MSc4; Kleindienst, Nikolaus, PhD5; Ludaescher, Petra, PhD2; Mueller-Engelmann, Meike, PhD1; Bohus, Martin, MD5

1Goethe-University, Frankfurt, Hessia, Germany
2Central Institute of Mental Health, Dept. of Psychosomatic Medicine, Mannheim, Germany, Mannheim, Baden-Württemberg, Germany
3Humboldt-University Berlin, Germany , Berlin, Berlin, Germany
4Central Institute of Mental Health, Dept. of Psychosomatic Medicine, Mannheim, Germany, Mannheim, Germany, Germany
5Central Institute of Mental Health, Mannheim, Baden-Württemberg, Germany


Dialectical behavior therapy for posttraumatic stress disorder (DBT-PTSD), which is tailored to treat adults with PTSD and emotion regulation difficulties, has already demonstrated its efficacy in an inpatient setting. It combines elements of DBT with novel trauma-focused cognitive behavioral interventions. To investigate the effects of DBT-PTSD as compared to Cognitive Processing Therapy as state of the art PTSD treatment on posttraumatic symptoms as well as secondary outcomes such as dissociation, depression, global functioning and symptoms of borderline personality disorder in an outpatient treatment setting, we treated 98 vs. 95 female patients suffering from PTSD following childhood abuse plus difficulties in emotion regulation within a mutli-site randomized controlled clinical trial. The CAPS and PCL-5 were used as primary outcomes. Assessments were administered pretreatment, post-treatment and at 3 months follow up. Improvement was significant for all outcomes, with large pretreatment to follow-up effect sizes for the patient sample according to protocol. The outcomes suggest significant treatment effects on primary and secondary outcomes for both treatments investigated, with significant advantages for DBT-PTSD over CPT, particularly for patients with comorbid BPS. 
 

Relating e-Diary Captured Stress-induced Dissociation and Affective Instability to Treatment Outcome in the RELEASE Study


Ebner-Priemer, Ulrich, PhD1; Santangelo, Philip, PhD1; Friedmann, Franziska, MA PhD Student2; Priebe, Kathlen, MSc3; Fydrich, Thomas, PhD4; Steil, Regina, PhD5; Bohus, Martin, MD6

1Karlsruhe Institute of Technology, Karlsruhe, Baden-Wuerttemberg, Germany
2 Humboldt-University Berlin, Berlin, Berlin, Germany
3Central Institute of Mental Health, Dept. of Psychosomatic Medicine, Mannheim, Germany, Mannheim, Baden-Württemberg, Germany
4Humboldt-University Berlin, Germany , Berlin, Berlin, Germany
5Goethe-University, Frankfurt, Hessia, Germany
6Central Institute of Mental Health, Mannheim, Baden-Württemberg, Germany


Electronic diaries are ideally suited to examine dynamic psychopathological processes in participants’ daily life and come with the promise of higher effect sizes in treatment studies, as real time assessment are less prone to retrospective biases. We used e-diaries to assess affective instability and stress-induced dissociative experience in all participants of the RELEASE study. Affective instability was chosen, because it was defined as an inclusion criterion. Stress-induced dissociative experience has been shown to influence treatment outcome. This study aimed at relating stress-induced dissociation and affective instability to treatment outcome. In the RELEASE study, 200 patients with PTSD took part in an e-diary assessment three times over the course of the treatment program (pre, midterm, post). We used a high sampling frequency approach (i.e., brief assessments in 30 minute intervals) to assess momentary dissociative disturbances, stress, and affective states during 12 hours per day on two consecutive days. Using multilevel modelling, both momentary mechanisms (stress-induced dissociation and affective instability) show significant treatment effects. Analysing the influence of momentary stress-induced dissociation on treatment outcome is still ongoing. E-diaries seem to be a promising methodology to capture daily life symptomatology in treatment studies.