Rare copy number variation in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10-8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q < 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further.

Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis.

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.

Cohort profile: the Ohio Army National Guard Mental Health Initiative (OHARNG-MHI).

PURPOSE: Rates of mental disorders in the United States military have increased in recent years. National Guard members may be particularly at risk for mental disorders, given their dual role as citizen-soldiers and their increased involvement in combat deployments during recent conflicts. The Ohio Army National Guard Mental Health Initiative (OHARNG-MHI) was launched to assess the prevalence, incidence, and potential causes and consequences of mental disorders in this unique population. METHODS: OHARNG-MHI is a decade-long dynamic cohort study that followed over 3,000 National Guard members yearly through structured telephone interviews. RESULTS: Findings thus far have applied a pre-, peri-, post-deployment framework, identifying factors throughout the life course associated with mental disorders, including childhood events and more recent events, both during and outside of deployment. An estimated 61% of participants had at least one mental disorder in their lifetime, the majority of which initiated prior to military service. Psychiatric comorbidity was common, as were alcohol use and stressful events. Latent class growth analyses revealed four distinct trajectory paths of both posttraumatic stress and depression symptoms across four years. Only 37% of soldiers with probable past-year mental disorders accessed mental health services in the subsequent year, with substance use disorders least likely to be treated. CONCLUSION: Strengths of this study include a large number of follow-up interviews, detailed data on both military and non-military experiences, and a clinical assessment subsample that assessed the validity of the telephone screening instruments. Findings, methods, and procedures of the study are discussed, and collaborations are welcome.

Associations between resting-state functional connectivity and treatment response in a randomized clinical trial for posttraumatic stress disorder.

BACKGROUND: Alterations in resting-state functional connectivity (rsFC) have been reported in posttraumatic stress disorder (PTSD). Here, we examined pre- and post-treatment rsFC during a randomized clinical trial to characterize alterations and examine predictors of treatment response. METHODS: Sixty-four combat veterans with PTSD were randomly assigned to prolonged exposure (PE) plus placebo, sertraline plus enhanced medication management, or PE plus sertraline. Symptom assessment and resting-state functional magnetic resonance imaging (fMRI) scans occurred before and after treatment. Twenty-nine trauma-exposed combat veterans without PTSD served as a control group at intake. Seed-based and region of interest (ROI)-to-ROI connectivities, as well as an exploratory connectome-based approach were used to analyze rsFC patterns. Based on previously reported findings, analyses focused on Salience Network (SN) and Default-Mode Network (DMN). RESULTS: At intake, patients with PTSD showed greater DMN-dorsal attention network (DAN) connectivity (between ventromedial prefrontal cortex and superior parietal lobule; family-wise error corrected p = .011), greater SN-DAN connectivity (between insula and middle frontal gyrus; corrected p = .003), and a negative correlation between re-experiencing symptoms and within-DMN connectivity (between posterior cingulate cortex (PCC) and middle temporal gyrus; corrected p < .001). We also found preliminary evidence for associations between rsFC and treatment response. Specifically, high responders (≥50% PTSD symptom improvement), compared with low responders, had greater SN-DMN segregation (i.e., less pre-treatment amygdala-PCC connectivity; p = .011) and lower pre-treatment global centrality (p = .042). CONCLUSIONS: Our findings suggest neural abnormalities in PTSD and may inform future research examining neural biomarkers of PTSD treatment response.

Neural function during emotion processing and modulation associated with treatment response in a randomized clinical trial for posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with exaggerated threat processing and deficits in emotion modulation circuitry. It remains unknown how neural circuits are associated with response to evidence-based treatments for PTSD. METHOD: We examined associations between PTSD symptoms and indicators of neural response in key emotion processing and modulation regions. Fifty-six military Veterans with PTSD were randomly assigned to one of three evidence-based treatments (prolonged exposure, sertraline, and PE plus sertraline) in a randomized clinical trial ("PROGrESS"; 2018, Contemp Clin Trials, 64, 128-138). Twenty-seven combat-exposed controls (CCs) served as a comparison group at pretreatment. Before and after PTSD treatment, functional magnetic resonance imaging was used to assess brain activation and connectivity during the validated Shifted Attention Emotion Appraisal Task (2003, J Neurosci, 23, 5627-5633; 2013, Biol Psychiatry, 73, 1045-1053). RESULTS: Greater activation in emotion processing (anterior insula) and modulation (prefrontal cortex) regions and increased connectivity between attentional control (dorsolateral prefrontal cortex and superior parietal cortex) and emotion processing (amygdala) regions, at pretreatment, were associated with subsequent PTSD symptom improvement. CONCLUSIONS: This study is one of the first to examine task-based activation and functional connectivity in a PTSD treatment trial, and provides evidence to suggest that activation in and connectivity between emotion processing and modulation regions are important predictors of treatment response.

Prenatal intimate partner violence exposure predicts infant biobehavioral regulation: Moderation by the brain-derived neurotrophic factor (BDNF) gene.

The ability to regulate stress is a critical developmental milestone of early childhood that involves a set of interconnected behavioral and physiological processes and is influenced by genetic and environmental stimuli. Prenatal exposure to traumatic stress and trauma, including intimate partner violence (IPV), increases risk for offspring biobehavioral regulation problems during childhood and adolescence. Although individual differences in susceptibility to prenatal stress have been largely unexplored, a handful of studies suggest children with specific genetic characteristics are most vulnerable to prenatal stress. We evaluated the brain-derived neurotrophic factor Val66Met gene (BDNF) as a moderator of the effect of prenatal IPV exposure on infant temperamental and cortisol regulation in response to a psychosocial challenge. Ninety-nine mother-infant dyads recruited from the community were assessed when infants (51% female) were 11 to 14 months. Maternal reports of IPV during pregnancy and infant temperament were obtained, and infant saliva was collected for genotyping and to assess cortisol reactivity (before and after the Strange Situation Task). Significant genetic moderation effects were found. Among infants with the BDNF Met allele, prenatal IPV predicted worse temperamental regulation and mobilization of the cortisol response, while controlling for infant postnatal exposure to IPV, other maternal traumatic experiences, and infant sex. However, prenatal IPV exposure was not associated with temperamental or cortisol outcomes among infant carriers of the Val/Val genotype. Findings are discussed in relation to prenatal programming and biological susceptibility to stress.

Behavioral and neural correlates of disrupted orienting attention in posttraumatic stress disorder.

Prior work has revealed that posttraumatic stress disorder (PTSD) is associated with altered (a) attentional performance and (b) resting-state functional connectivity (rsFC) in brain networks linked to attention. Here, we sought to characterize and link these behavioral and brain-based alterations in the context of Posner and Peterson's tripartite model of attention. Male military veterans with PTSD (N = 49; all deployed to Iraq or Afghanistan) and healthy age-and-gender-matched community controls (N = 26) completed the Attention Network Task. A subset of these individuals (36 PTSD and 21 controls) also underwent functional magnetic resonance imaging (fMRI) to assess rsFC. The behavioral measures revealed that the PTSD group was impaired at disengaging spatial attention, relative to the control group. FMRI measures further revealed that, relative to the control group, the PTSD group exhibited greater rsFC between the salience network and (a) the default mode network, (b) the dorsal attention network, and (c) the ventral attention network. Moreover, problems with disengaging spatial attention increased the rsFC between the networks above in the control group, but not in the PTSD group. The present findings link PTSD to both altered orienting of spatial attention and altered relationships between spatial orienting and functional connectivity involving the salience network. Interventions that target orienting and disengaging spatial attention may be a new avenue for PTSD research.

Childhood Cumulative Risk Exposure and Adult Amygdala Volume and Function.

Considerable work indicates that early cumulative risk exposure is aversive to human development, but very little research has examined the neurological underpinnings of these robust findings. This study investigates amygdala volume and reactivity to facial stimuli among adults (mean 23.7 years of age, n = 54) as a function of cumulative risk exposure during childhood (9 and 13 years of age). In addition, we test to determine whether expected cumulative risk elevations in amygdala volume would mediate functional reactivity of the amygdala during socioemotional processing. Risks included substandard housing quality, noise, crowding, family turmoil, child separation from family, and violence. Total and left hemisphere adult amygdala volumes were positively related to cumulative risk exposure during childhood. The links between childhood cumulative risk exposure and elevated amygdala responses to emotionally neutral facial stimuli in adulthood were mediated by the corresponding amygdala volumes. Cumulative risk exposure in later adolescence (17 years of age), however, was unrelated to subsequent adult amygdala volume or function. Physical and socioemotional risk exposures early in life appear to alter amygdala development, rendering adults more reactive to ambiguous stimuli such as neutral faces. These stress-related differences in childhood amygdala development might contribute to the well-documented psychological distress as a function of early risk exposure.

ALTERED DEFAULT MODE NETWORK (DMN) RESTING STATE FUNCTIONAL CONNECTIVITY FOLLOWING A MINDFULNESS-BASED EXPOSURE THERAPY FOR POSTTRAUMATIC STRESS DISORDER (PTSD) IN COMBAT VETERANS OF AFGHANISTAN AND IRAQ.

BACKGROUND: Recent studies suggest that mindfulness may be an effective component for posttraumatic stress disorder (PTSD) treatment. Mindfulness involves practice in volitional shifting of attention from "mind wandering" to present-moment attention to sensations, and cultivating acceptance. We examined potential neural correlates of mindfulness training using a novel group therapy (mindfulness-based exposure therapy (MBET)) in combat veterans with PTSD deployed to Afghanistan (OEF) and/or Iraq (OIF). METHODS: Twenty-three male OEF/OIF combat veterans with PTSD were treated with a mindfulness-based intervention (N = 14) or an active control group therapy (present-centered group therapy (PCGT), N = 9). Pre-post therapy functional magnetic resonance imaging (fMRI, 3 T) examined resting-state functional connectivity (rsFC) in default mode network (DMN) using posterior cingulate cortex (PCC) and ventral medial prefrontal cortex (vmPFC) seeds, and salience network (SN) with anatomical amygdala seeds. PTSD symptoms were assessed at pre- and posttherapy with Clinician Administered PTSD Scale (CAPS). RESULTS: Patients treated with MBET had reduced PTSD symptoms (effect size d = 0.92) but effect was not significantly different from PCGT (d = 0.46). Increased DMN rsFC (PCC seed) with dorsolateral dorsolateral prefrontal cortex (DLPFC) regions and dorsal anterior cingulate cortex (ACC) regions associated with executive control was seen following MBET. A group × time interaction found MBET showed increased connectivity with DLPFC and dorsal ACC following therapy; PCC-DLPFC connectivity was correlated with improvement in PTSD avoidant and hyperarousal symptoms. CONCLUSIONS: Increased connectivity between DMN and executive control regions following mindfulness training could underlie increased capacity for volitional shifting of attention. The increased PCC-DLPFC rsFC following MBET was related to PTSD symptom improvement, pointing to a potential therapeutic mechanism of mindfulness-based therapies.

Impaired contextual modulation of memories in PTSD: an fMRI and psychophysiological study of extinction retention and fear renewal.

Post-traumatic stress disorder (PTSD) patients display pervasive fear memories, expressed indiscriminately. Proposed mechanisms include enhanced fear learning and impaired extinction or extinction recall. Documented extinction recall deficits and failure to use safety signals could result from general failure to use contextual information, a hippocampus-dependent process. This can be probed by adding a renewal phase to standard conditioning and extinction paradigms. Human subjects with PTSD and combat controls were conditioned (skin conductance response), extinguished, and tested for extinction retention and renewal in a scanner (fMRI). Fear conditioning (light paired with shock) occurred in one context, followed by extinction in another, to create danger and safety contexts. The next day, the extinguished conditioned stimulus (CS+E) was re-presented to assess extinction recall (safety context) and fear renewal (danger context). PTSD patients showed impaired extinction recall, with increased skin conductance and heightened amygdala activity to the extinguished CS+ in the safety context. However, they also showed impaired fear renewal; in the danger context, they had less skin conductance response to CS+E and lower activity in amygdala and ventral-medial prefrontal cortex compared with combat controls. Control subjects displayed appropriate contextual modulation of memory recall, with extinction (safety) memory prevailing in the safety context, and fear memory prevailing in the danger context. PTSD patients could not use safety context to sustain suppression of extinguished fear memory, but they also less effectively used danger context to enhance fear. They did not display globally enhanced fear expression, but rather showed a globally diminished capacity to use contextual information to modulate fear expression.

Presurgical Psychological and Neuroendocrine Predictors of Psychiatric Morbidity After Major Vascular Surgery: A Prospective Longitudinal Study.

OBJECTIVES: Major life stressors, including major surgeries, are often followed by psychiatric symptoms and disorders. Prior retrospective work found abdominal aortic aneurysm (AAA) repair is followed by increased psychiatric morbidity, which may adversely influence physical and functional recovery. Identifying risk factors before surgery, such as dysregulation in stress response systems, might be useful in improving preventative intervention. METHODS: Two hundred sixteen patients receiving open AAA or aortofemoral bypass surgeries, endovascular AAA repair, or nonsurgical AAA treatment were recruited from two vascular surgery services. Psychiatric symptoms and salivary cortisol measures (waking, 4 PM, and 11 PM, before and after low-dose dexamethasone) were obtained at intake and 3- and 9-month follow-ups. RESULTS: After open surgeries, 18% of patients had new psychiatric disorders, compared with 4% of patients receiving endovascular AAA repair or nonsurgical treatment (odds ratio = 6.0, 95% confidence interval = 1.6-22.1, p = .007). Having a history of major depression predicted the onset of new disorders in surgical patients. Presurgical cortisol levels were associated with both baseline (r = 0.23, p < .05) and 9-month (r = 0.32, p < .01) psychiatric symptoms (cortisol B = 1.0, standard error = 0.48, p < .05, in repeated-measures mixed model). CONCLUSIONS: Open AAA repair surgery is prospectively linked to the development of psychiatric morbidity, and history of depression elevates risk. Cortisol measures before surgery are associated with current and future psychological functioning, suggesting potential neurobiological mechanisms that may contribute to vulnerability. These results can help identify surgical patients at risk and point to potential targets for risk reduction interventions.

Biological and symptom changes in posttraumatic stress disorder treatment: a randomized clinical trial.

BACKGROUND: Understanding cognitive and biological mechanisms of PTSD treatment can help refine treatments and increase rates of response. METHODS: Thirty-six veterans with PTSD were randomly assigned to receive Prolonged exposure therapy (PE) or Present-Centered therapy (PCT). We examined symptoms, trauma-related cognitions, and two indices of HPA axis function (cortisol awakening response and cortisol response to a script-driven imagery task). RESULTS: Thirty veterans started treatment and 26 completed. PE resulted in significantly more symptom reduction than PCT (P = .008). High treatment responders collapsed across treatments showed nominally higher cortisol levels measured at pretreatment 30 min after trauma script exposure compared to low responders (P = .08). At midtreatment, high treatment responders showed higher cortisol levels throughout the imagery task (Ps = .03-.04). There were no differences between high and low treatment responders at posttreatment. Thoughts of incompetence (F (1.6, 35.8) = 16.8, P = .000) and a dangerous world (F (1.3, 29.9) = 8.2, P = .004) significantly improved over time in high treatment responders but showed no change in low responders. Script-associated cortisol response prior to treatment and reductions in thoughts of incompetence accounted for 83% of the variance in reductions in PTSD severity with PE. CONCLUSIONS: Both increased cortisol response to personal trauma script prior to PTSD therapy and reductions in cognitive symptoms of PTSD were significantly and uniquely related to reductions in the core symptoms of PTSD in PE. However, contrary to our hypotheses, cortisol measures were not related to cognitive changes.

A pilot study of group mindfulness-based cognitive therapy (MBCT) for combat veterans with posttraumatic stress disorder (PTSD).

BACKGROUND: "Mindfulness-based" interventions show promise for stress reduction in general medical conditions, and initial evidence suggests that they are accepted in trauma-exposed individuals. Mindfulness-based cognitive therapy (MBCT) shows substantial efficacy for prevention of depression relapse, but it has been less studied in anxiety disorders. This study investigated the feasibility, acceptability, and clinical outcomes of an MBCT group intervention adapted for combat posttraumatic stress disorder (PTSD). METHODS: Consecutive patients seeking treatment for chronic PTSD at a VA outpatient clinic were enrolled in 8-week MBCT groups, modified for PTSD (four groups, n = 20) or brief treatment-as-usual (TAU) comparison group interventions (three groups, n = 17). Pre and posttherapy psychological assessments with clinician administered PTSD scale (CAPS) were performed with all patients, and self-report measures (PTSD diagnostic scale, PDS, and posttraumatic cognitions inventory, PTCI) were administered in the MBCT group. RESULTS: Intent to treat analyses showed significant improvement in PTSD (CAPS (t(19) = 4.8, P < .001)) in the MBCT condition but not the TAU conditions, and a significant Condition × Time interaction (F[1,35] = 16.4, P < .005). MBCT completers (n = 15, 75%) showed good compliance with assigned homework exercises, and significant and clinically meaningful improvement in PTSD symptom severity on posttreatment assessment in CAPS and PDS (particularly in avoidance/numbing symptoms), and reduced PTSD-relevant cognitions in PTCI (self blame). CONCLUSIONS: These data suggest group MBCT as an acceptable brief intervention/adjunctive therapy for combat PTSD, with potential for reducing avoidance symptom cluster and PTSD cognitions. Further studies are needed to examine efficacy in a randomized controlled design and to identify factors influencing acceptability and efficacy.

DNA methylation GrimAge acceleration in US military veterans with PTSD.

Epigenetic alterations in DNA methylation might mediate gene expression effects of trauma underlying PTSD symptoms, or effects of PTSD on related health problems. PTSD is associated with all-cause morbidity and premature mortality, suggesting accelerated biological aging. We measured genome-wide DNA methylation (Illumina MethylationEPIC BeadChip) in whole blood in a treatment study for combat-related PTSD - "PROGrESS", a multisite RCT comparing sertraline plus enhanced medication management (SERT + EMM), prolonged exposure (PE) therapy plus placebo (PE + PLB), and the combination (SERT + PE). DNA methylation was measured in 140 US military veterans who served in Iraq and/or Afghanistan (112 current PTSD cases enrolled in a PTSD treatment study and 28 veterans without PTSD history controls), and also 59 non-trauma exposed controls at baseline posttreatment (24 weeks after baseline). Increased DNA methylation GrimAge acceleration (p = 8.8e-09) was observed in patients with PTSD compared to a pooled control group (trauma exposed and non-trauma exposed), suggesting a higher risk of premature mortality in those with PTSD. There was no difference in GrimAge acceleration between combat trauma and non-trauma exposed controls. No treatment-related changes in GrimAge acceleration were found in within-subject comparisons of PTSD patients pre- to post-treatment.

Neural dysregulation in posttraumatic stress disorder: evidence for disrupted equilibrium between salience and default mode brain networks.

OBJECTIVE: Convergent research demonstrates disrupted attention and heightened threat sensitivity in posttraumatic stress disorder (PTSD). This might be linked to aberrations in large-scale networks subserving the detection of salient stimuli (i.e., the salience network [SN]) and stimulus-independent, internally focused thought (i.e., the default mode network [DMN]). METHODS: Resting-state brain activity was measured in returning veterans with and without PTSD (n = 15 in each group) and in healthy community controls (n = 15). Correlation coefficients were calculated between the time course of seed regions in key SN and DMN regions and all other voxels of the brain. RESULTS: Compared with control groups, participants with PTSD showed reduced functional connectivity within the DMN (between DMN seeds and other DMN regions) including the rostral anterior cingulate cortex/ventromedial prefrontal cortex (z = 3.31; p = .005, corrected) and increased connectivity within the SN (between insula seeds and other SN regions) including the amygdala (z = 3.03; p = .01, corrected). Participants with PTSD also demonstrated increased cross-network connectivity. DMN seeds exhibited elevated connectivity with SN regions including the insula (z = 3.06; p = .03, corrected), and SN seeds exhibited elevated connectivity with DMN regions including the hippocampus (z = 3.10; p = .048, corrected). CONCLUSIONS: During resting-state scanning, participants with PTSD showed reduced coupling within the DMN, greater coupling within the SN, and increased coupling between the DMN and the SN. Our findings suggest a relative dominance of threat-sensitive circuitry in PTSD, even in task-free conditions. Disequilibrium between large-scale networks subserving salience detection versus internally focused thought may be associated with PTSD pathophysiology.

Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder.

BACKGROUND: Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have shown hyperactivation in emotion-related regions, including the amygdala and insula, and hypoactivation in emotion-regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure. METHODS: Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD. RESULTS: Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with PTSD showed greater positive connectivity between the amygdala and insula, reduced positive connectivity between the amygdala and hippocampus, and reduced anticorrelation between the amygdala and dorsal ACC and rostral ACC. LIMITATIONS: Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non-combat related PTSD. CONCLUSION: These results demonstrate that studies of functional connectivity during resting state can discern aberrant patterns of coupling within emotion circuits and suggest a possible brain basis for emotion-processing and emotion-regulation deficits in individuals with PTSD.

Oxytocin receptor gene, post-traumatic stress disorder and dissociation in a community sample of European American women.

The aims of this study were: (a) to examine associations of oxytocin receptor gene (OXTR) single nucleotide polymorphisms (SNPs) with post-traumatic stress disorder (PTSD) and dissociative symptoms and (b) to investigate gene-environment (G × E) interaction with childhood maltreatment. Salivary DNA samples from 228 women of European ancestry were analysed. Two SNPs, rs237895 and rs237897, were associated with dissociative symptoms but not PTSD diagnosis. Another SNP (rs2254298) was associated with dissociation when interacting with history of childhood maltreatment. These results contribute to theorising and evidence suggesting that the oxytocin system and its genetics may be associated with risk for dissociation among European American women, including those with maltreatment history. Replication with larger patient samples, including men and other ancestry groups, is needed.

Stressful life events and trajectories of depression symptoms in a U.S. military cohort.

Depression is a common mental disorder that may comprise distinct, underlying symptom patterns over time. Associations between stressful life events throughout the civilian lifecourse-including during childhood-and adult depression have been documented in many populations, but are less commonly assessed in military samples. We identified different trajectories of depression symptoms across four years in a military cohort using latent class growth analysis, and investigated the relationship between these trajectories and two domains of civilian life experiences: childhood adversity (e.g., being mistreated during childhood) and more proximal stressful experiences (e.g., divorce). A four-group depression model was identified, including a symptom-free group (62%), an increasing symptom group (13%), a decreasing symptom group (16%), and a "chronic" symptom group (9%). Compared to the symptom-free group, soldiers with childhood adversity were more likely to be in the chronic depression, decreasing, and increasing symptom groups. Time-varying adult stressors had the largest effect on depression symptoms for the increasing symptom group compared to other groups, particularly in the last two years of follow-up. This study indicates the importance of considering events from throughout the lifecourse-not only those from deployment-when studying the mental health of servicemembers.

Interdependent self-construal predicts increased gray matter volume of scene processing regions in the brain.

Interdependent self-construal (SC) is thought to lead to a more holistic cognitive style that emphasizes the processing of the background scene of a focal object. At present, little is known about whether the structural properties of the brain might underlie this functional relationship. Here, we examined the gray matter (GM) volume of three cortical regions involved in scene processing -- a cornerstone of contextual processing. Study 1 tested 78 European American non-student adults and found that interdependent (vs. independent) SC predicts higher GM volume in the parahippocampal place area (PPA), one of the three target regions. Testing both European American and East Asian college students (total N = 126), Study 2 replicated this association. Moreover, the GM volume of all the three target regions was greater for East Asians than for European Americans. Our findings suggest that there is a structural neural underpinning for the cultural variation in cognitive style.