Faculty Bibliography

Background: That PTSD is a heterogeneous condition is supported by both the failure to identify objective physiological measurements applicable to all who meet criteria for the disorder, and divergent responses associated with PTSD treatments.
Method(s): This study attempted to capitalize on biological diversity observed following epigenome-wide analysis in a well-characterized male veteran Discovery cohort (N=166) consisting of 83 PTSD+ and 83 PTSD- participants, to identify biologically relevant PTSD subtypes (biotypes) that might further improve molecular diagnosis and personalized treatment. Initial analysis revealed associations between DNA methylation (DNAm) profiles and 34 clinical features from which two epigenetically distinct biotypes - G1 and G2 - were derived.
Result(s): The findings were validated by examining participants (N=59) at a 3-year follow-up. Two other independent, cross-sectional veteran cohorts (N=54, and N=38, respectively), and a longitudinal active duty cohort (N = 133) were also used for validation of the initial biotypes. Interestingly, the biological pathways associated with the biotypes appeared to be regulated in opposite directions in comparison to controls. The impact of biotype-specific signal were evaluated in published DNAm markers, including an independent multi-omics biomarker developed using the same veteran cohort. Finally, we demonstrated filtering biotype-specific signal from a prior marker would result in a high-performance marker (AUC of 0.85).
Conclusion(s): The identification of two novel distinct epigenetic biotypes for PTSD may have future utility in understanding biological and clinical heterogeneity in PTSD and potential applications in treatment-matching and monitoring of clinical outcome. Supported By: This work was supported by funding from the U.S. Army Research Office, through award numbersW911NF-13-1-0376, W911NF-17-2-0086, W911NF-18-2-0056, by the Army Research Laboratory under grant number W911NF-17-1-0069, and from the U.S. Department of Defense under W81XWH-10-1-0021, W81XWH-09-2-0044, and W81XWH-14-1-0043. Keywords: Biotypes, Epigenetic Biomarkers, Subtype Diagnosis, DNA Methylation, PT

Veterans Health Administration (VA) Medical Centers provide excellent care for many veterans. However, there are a number of veterans who are ineligible or choose not to access mental health treatment at the VA. To meet the needs of those veterans and of military family members, private centers have emerged to fill in gaps where care is unavailable or scarce. This paper describes how one such center, the Steven A. Cohen Military Family Center at NYU Langone Health, partnered with the local VA hospital to give one veteran ineligible for free mental health services the care he desperately needed. The case demonstrates the transformative work that can take place when public-private partnerships are forged and evidence-based treatments can be provided in a flexible way. It also illustrates the complexity of many veterans' presentations, which in this case required the therapist to continually challenge her conceptualization as she and the patient navigated different phases of his treatment.

Military families face specific challenges related to military service, deployments, separations, and coming together. The process of reintegration back to civilian life can be challenged by posttraumatic stress and other readjustment difficulties that can affect not only the veteran but the family as a whole. Strengthening bonds and relationships is an important step in recovery. In this paper, the authors review the application of emotionally focused therapy to couples therapy with military couples and identify factors that can facilitate the therapeutic process with this unique population.

OBJECTIVE:The Fort Campbell Cohort study was designed to assess predeployment biological and behavioral markers and build predictive models to identify risk and resilience for posttraumatic stress disorder (PTSD) following deployment. This article addresses neurocognitive functioning variables as potential prospective predictors. METHOD/METHODS:In a sample of 403 soldiers, we examined whether PTSD symptom severity (using the PTSD Checklist) as well as posttraumatic stress trajectories could be prospectively predicted by measures of executive functioning (using two web-based tasks from WebNeuro) assessed predeployment. RESULTS:Controlling for age, gender, education, prior number of deployments, childhood trauma exposure, and PTSD symptom severity at Phase 1, linear regression models revealed that predeployment sustained attention and inhibitory control performance were significantly associated with postdeployment PTSD symptom severity. We also identified two posttraumatic stress trajectories utilizing latent growth mixture models. The "resilient" group consisted of 90.9% of the soldiers who exhibited stable low levels of PTSD symptoms from pre- to postdeployment. The "increasing" group consisted of 9.1% of the soldiers, who exhibited an increase in PTSD symptoms following deployment, crossing a threshold for diagnosis based on PTSD Checklist scores. Logistic regression models predicting trajectory revealed a similar pattern of findings as the linear regression models, in which predeployment sustained attention (95% CI of odds ratio: 1.0109, 1.0558) and inhibitory control (95% CI: 1.0011, 1.0074) performance were significantly associated with postdeployment PTSD trajectory. CONCLUSIONS:These findings have clinical implications for understanding the pathogenesis of PTSD and building preventative programs for military personnel. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Childhood maltreatment is highly prevalent and serves as a risk factor for mental and physical disorders. Self-reported childhood maltreatment appears heritable, but the specific genetic influences on this phenotype are largely unknown. The aims of this study were to (1) identify genetic variation associated with self-reported childhood maltreatment, (2) estimate SNP-based heritability (h²_snp), (3) assess predictive value of polygenic risk scores (PRS) for childhood maltreatment, and (4) quantify genetic overlap of childhood maltreatment with mental and physical health-related phenotypes, and condition the top hits from our analyses when such overlap is present. Genome-wide association analysis for childhood maltreatment was undertaken, using a discovery sample from the UK Biobank (UKBB) (n = 124,000) and a replication sample from the Psychiatric Genomics Consortium-posttraumatic stress disorder group (PGC-PTSD) (n = 26,290). h²_snp for childhood maltreatment and genetic correlations with mental/physical health traits were calculated using linkage disequilibrium score regression. PRS was calculated using PRSice and mtCOJO was used to perform conditional analysis. Two genome-wide significant loci associated with childhood maltreatment (rs142346759, p = 4.35 × 10^-8, FOXP1; rs10262462, p = 3.24 × 10^-8, FOXP2) were identified in the discovery dataset but were not replicated in PGC-PTSD. h²_snp for childhood maltreatment was ~6% and the PRS derived from the UKBB was significantly predictive of childhood maltreatment in PGC-PTSD (r²â€‰= 0.0025; p = 1.8 × 10^-15). The most significant genetic correlation of childhood maltreatment was with depressive symptoms (r_g = 0.70, p = 4.65 × 10^-40), although we show evidence that our top hits may be specific to childhood maltreatment. This is the first large-scale genetic study to identify specific variants associated with self-reported childhood maltreatment. Speculatively, FOXP genes might influence externalizing traits and so be relevant to childhood maltreatment. Alternatively, these variants may be associated with a greater likelihood of reporting maltreatment. A clearer understanding of the genetic relationships of childhood maltreatment, including particular abuse subtypes, with a range of phenotypes, may ultimately be useful in in developing targeted treatment and prevention strategies.

OBJECTIVE/UNASSIGNED:The authors sought to identify brain regions whose frequency-specific, orthogonalized resting-state EEG power envelope connectivity differs between combat veterans with posttraumatic stress disorder (PTSD) and healthy combat-exposed veterans, and to determine the behavioral correlates of connectomic differences. METHODS/UNASSIGNED:The authors first conducted a connectivity method validation study in healthy control subjects (N=36). They then conducted a two-site case-control study of veterans with and without PTSD who were deployed to Iraq and/or Afghanistan. Healthy individuals (N=95) and those meeting full or subthreshold criteria for PTSD (N=106) underwent 64-channel resting EEG (eyes open and closed), which was then source-localized and orthogonalized to mitigate effects of volume conduction. Correlation coefficients between band-limited source-space power envelopes of different regions of interest were then calculated and corrected for multiple comparisons. Post hoc correlations of connectomic abnormalities with clinical features and performance on cognitive tasks were conducted to investigate the relevance of the dysconnectivity findings. RESULTS/UNASSIGNED:Seventy-four brain region connections were significantly reduced in PTSD (all in the eyes-open condition and predominantly using the theta carrier frequency). Underconnectivity of the orbital and anterior middle frontal gyri were most prominent. Performance differences in the digit span task mapped onto connectivity between 25 of the 74 brain region pairs, including within-network connections in the dorsal attention, frontoparietal control, and ventral attention networks. CONCLUSIONS/UNASSIGNED:Robust PTSD-related abnormalities were evident in theta-band source-space orthogonalized power envelope connectivity, which furthermore related to cognitive deficits in these patients. These findings establish a clinically relevant connectomic profile of PTSD using a tool that facilitates the lower-cost clinical translation of network connectivity research.

INTRODUCTION/BACKGROUND:Current pharmacological treatments of post-traumatic stress disorder (PTSD) have limited efficacy. Although the diagnosis is based on psychopathological criteria, it is frequently accompanied by somatic comorbidities and perhaps "accelerated biological aging," suggesting widespread physical concomitants. Such physiological comorbidities may affect core PTSD symptoms but are rarely the focus of therapeutic trials. METHODS:To elucidate the potential involvement of metabolism, inflammation, and mitochondrial function in PTSD, we integrate findings and mechanistic models from the DOD-sponsored "Systems Biology of PTSD Study" with previous data on these topics. RESULTS:Data implicate inter-linked dysregulations in metabolism, inflammation, mitochondrial function, and perhaps the gut microbiome in PTSD. Several inadequately tested targets of pharmacological intervention are proposed, including insulin sensitizers, lipid regulators, anti-inflammatories, and mitochondrial biogenesis modulators. CONCLUSIONS:Systemic pathologies that are intricately involved in brain functioning and behavior may not only contribute to somatic comorbidities in PTSD, but may represent novel targets for treating core psychiatric symptoms.

Background/UNASSIGNED:United Nations (UN) personnel address a diverse range of political, social, and cultural crises throughout the world. Compared with other occupations routinely exposed to traumatic stress, there remains a paucity of research on mental health disorders and access to mental healthcare in this population. To fill this gap, personnel from UN agencies were surveyed for mental health disorders and mental healthcare utilization. Methods/UNASSIGNED:= 17 363) from 11 UN entities completed online measures of generalized anxiety disorder (GAD), major depressive disorder (MDD), posttraumatic stress disorder (PTSD), trauma exposure, mental healthcare usage, and socio-demographic information. Results/UNASSIGNED:Exposure to one or more traumatic events was reported by 36.2% of survey responders. Additionally, 17.9% screened positive for GAD, 22.8% for MDD, and 19.9% for PTSD. Employing multivariable logistic regressions, low job satisfaction, younger age (<35 years of age), greater length of employment, and trauma exposure on or off-duty was significantly associated with all the three disorders. Among individuals screening positive for a mental health disorder, 2.05% sought mental health treatment within and 10.01% outside the UN in the past year. Conclusions/UNASSIGNED:UN personnel appear to be at high risk for trauma exposure and screening positive for a mental health disorder, yet a small percentage screening positive for mental health disorders sought treatment. Despite the mental health gaps observed in this study, additional research is needed, as these data reflect a large sample of convenience and it cannot be determined if the findings are representative of the UN.