The number of women in the United States that experience blows to the head during assaults by intimate partners is substantial. The number of head blows that result in a traumatic brain injury (TBI) is virtually unknown, but estimates far exceed numbers of TBI in parallel populations (e.g., blast exposure, accidents, sports) combined. Research on the impact of TBI on post-traumatic stress disorder (PTSD) in survivors of intimate partner violence (IPV) is sparse. This methodology paper describes the comprehensive, multi-method approach used by a multi-disciplinary team of investigators from several different fields of expertise to assess the interaction of psychiatric, cognitive, psychological, and physical conditions that result from IPV. Using state-of-the-art instruments, a comprehensive assessment of lifetime trauma exposure, lifetime history of TBI, psychiatric history, and a full assessment of current cognitive, neuropsychological and biomedical function was conducted with 51 female survivors of IPV who screened positive for PTSD. This multi-method assessment included clinician-administered diagnostic interviews modified to specifically assess the sequelae of IPV, standardized self-report surveys, neuropsychological tests, structural, diffusion, and functional neuroimaging and blood-based biomarkers. The specific details and full report of the results of the full study are beyond the scope of this methodology paper. Descriptive characteristics of the complex clinical presentation observed in this unique sample are described. The sample reported high rates of trauma exposure across the lifespan and 80% met full criteria for current PTSD. Women also reported high rates of lifetime subconcussive head injury (88.2%) and TBI (52.9%) from various etiologies (35.3% secondary to IPV). Descriptive findings from the methodological protocol described here have begun to reveal information that will advance our understanding of the impact of subconcussive head injury and TBI on recovery from mental injury among IPV survivors.

The volume of subcortical structures represents a reliable, quantitative, and objective phenotype that captures genetic effects, environmental effects such as trauma, and disease effects such as posttraumatic stress disorder (PTSD). Trauma and PTSD represent potent exposures that may interact with genetic markers to influence brain structure and function. Genetic variants, associated with subcortical volumes in two large normative discovery samples, were used to compute polygenic scores (PGS) for the volume of seven subcortical structures. These were applied to a target sample enriched for childhood trauma and PTSD. Subcortical volume PGS from the discovery sample were strongly associated in our trauma/PTSD enriched sample (n = 7580) with respective subcortical volumes of the hippocampus (p = 1.10 × 10(-20)), thalamus (p = 7.46 × 10(-10)), caudate (p = 1.97 × 10(-18)), putamen (p = 1.7 × 10(-12)), and nucleus accumbens (p = 1.99 × 10(-7)). We found a significant association between the hippocampal volume PGS and hippocampal volume in control subjects from our sample, but was absent in individuals with PTSD (GxE; (beta = -0.10, p = 0.027)). This significant GxE (PGS × PTSD) relationship persisted (p  1 × 10(-19)) in four out of five threshold peaks (0.024, 0.133, 0.487, 0.730, and 0.889) used to calculate hippocampal volume PGSs. We detected similar GxE (G × ChildTrauma) relationships in the amygdala for exposure to childhood trauma (rs4702973; p = 2.16 × 10(-7)) or PTSD (rs10861272; p = 1.78 × 10(-6)) in the CHST11 gene. The hippocampus and amygdala are pivotal brain structures in mediating PTSD symptomatology. Trauma exposure and PTSD modulate the effect of polygenic markers on hippocampal volume (GxE) and the amygdala volume PGS is associated with PTSD risk, which supports the role of amygdala volume as a risk factor for PTSD.

Elevated serum C-reactive protein (CRP) and possessing an APOE ε4 allele are two of the most prominent risk factors for cognitive and neurological dysfunction in older adults, but little is known about the unique or cumulative effects of these risk factors in young-to-middle-aged adults. To further characterize these potential relationships, measures of cognition and microstructural white matter integrity were examined using data from a sample of 329 post-9/11 war veterans that was collected as part of a comprehensive evaluation that included assessment of neuropsychological functioning, MRI scanning, psychiatric diagnoses, health screening, markers of inflammation, and APOE genotypes. Hierarchical linear regression analyses revealed the CRP and APOE ε4 interaction was associated with global cognition (β = -0.633), executive functioning (β = -0.566), and global fractional anisotropy (β = -0.470), such that elevated CRP was associated with worse cognition and white matter integrity in APOE ε4 carriers. Diffusion tensor imaging (DTI) was used to determine if CRP × APOE ε4 presence was associated with regionally specific fractional anisotropy in white matter tracts. Tract-based spatial statistics revealed CRP × APOE ε4 presence was associated with fractional anisotropy in the corpus callosum, right superior longitudinal fasciculus, right posterior corona radiata, as well as the bilateral anterior and superior corona radiatas. This suggests that APOE ε4 carriers may be uniquely vulnerable to the potentially negative impact of elevated systematic inflammation to cognition and microstructural white matter integrity.

Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symptoms and blood pressure genetics to continuous blood pressure levels. We harnessed the power of the Psychiatric Genomics Consortium-PTSD Physical Health Working Group and investigated these associations across 11 studies of 72,224 trauma-exposed individuals of European (n = 70,870) and African (n = 1,354) ancestry. Genetic contributions to blood pressure were modeled via polygenic scores (PGS) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that were derived from a prior trans-ethnic blood pressure genome-wide association study (GWAS). Results of trans-ethnic meta-analyses revealed significant main effects of the PGS on blood pressure levels [SBP: β = 2.83, standard error (SE) = 0.06, p 1E-20; DBP: β = 1.32, SE = 0.04, p 1E-20]. Significant main effects of PTSD symptoms were also detected for SBP and DBP in trans-ethnic meta-analyses, though there was significant heterogeneity in these results. When including data from the largest contributing study - United Kingdom Biobank - PTSD symptoms were negatively associated with SBP levels (β = -1.46, SE = 0.44, p = 9.8E-4) and positively associated with DBP levels (β = 0.70, SE = 0.26, p = 8.1E-3). However, when excluding the United Kingdom Biobank cohort in trans-ethnic meta-analyses, there was a nominally significant positive association between PTSD symptoms and SBP levels (β = 2.81, SE = 1.13, p = 0.01); no significant association was observed for DBP (β = 0.43, SE = 0.78, p = 0.58). Blood pressure PGS did not significantly moderate the associations between PTSD symptoms and blood pressure levels in meta-analyses. Additional research is needed to better understand the extent to which PTSD is associated with high blood pressure and how genetic as well as contextual factors may play a role in influencing cardiovascular risk.

Posttraumatic Stress Disorder (PTSD) symptomatology disrupts inhibitory control during sustained attention. However, PTSD-related inhibitory control deficits are partially ameliorated when punishments and rewards are administered based on task performance, which suggests motivational processes contribute to these deficits. Additionally, PTSD may also impair error-related cognitive control following inhibitory control failures as measured by post-error slowing (PES). However, it remains unclear if motivational processes also contribute to impaired error-related cognitive control in PTSD. Using an incentivized sustained attention paradigm in two independent samples of post-9/11 veterans, we characterized PTSD-related differences in PES during both non-motivated conditions (no task-based incentives) and motivated conditions (task-based rewards and punishments). In Study 1 (n = 139), PTSD symptom severity was modestly associated with smaller PES in the non-motivated condition, whereas no PTSD-related association was observed in the motivated condition. In Study 2 (n = 35), we replicated and extended these results by using fMRI to characterize modulation of the triple network system comprised of the Salience Network (SN), Frontoparietal Control Network (FPCN), and Default Mode Network (DMN). In the non-motivated condition, PTSD symptom severity was associated with non-specific SN and FPCN hyperactivation during both failed and successful inhibitory control. In the motivated condition, PTSD symptom severity was associated with greater focal activation of both the SN and Superior Parietal Lobule cluster (an FPCN node) during punished inhibitory control failures and weaker SN-FPCN connectivity during rewarded inhibitory control successes. Together, these results suggest that dysregulated motivational processes in PTSD may contribute to impaired error-related cognitive control. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.

OBJECTIVE: Survivors of intimate partner violence (IPV) report significant trauma histories, high rates of posttraumatic stress disorder (PTSD), head injuries and comorbid disorders, and multiple barriers to treatment that often preclude the regular attendance and engagement required in typical therapy protocols. The significant challenges faced by IPV survivors needing treatment may be ameliorated by condensing effective treatments for PTSD, such as cognitive processing therapy (CPT), in an accelerated delivery timeline. METHOD: Using a multiple subject, single case design of six matched pairs of 12 female IPV survivors, we preliminarily tested the relative effectiveness of individual massed CPT delivered over 5 days (mCPT) as compared with standard CPT (sCPT) delivery in women IPV survivors. Assessments included full psychiatric diagnostic interviews, clinical interviews assessing trauma history and head injury prior to treatment, symptom monitoring during treatment, and full repeat assessments at 1 month and 3 months following treatment. RESULTS: No treatment group effect was found for PTSD severity between mCPT and sCPT among intention-to-treat, F(1, 10) = .01, p = .93. Both mCPT and sCPT were associated with significant improvement in PTSD, F(2, 20) = 45.05, p .001, ds = 1.32-2.38). CONCLUSION: Overall, findings indicate mCPT appears effective in reducing psychological symptoms for women IPV survivors and suggest that condensed treatment is both palatable and feasible. Accelerated treatment delivery in this population may provide a necessary lifeline for women with IPV-related PTSD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Posttraumatic stress disorder (PTSD) is characterized by intrusive thoughts, avoidance, negative alterations in cognitions and mood, and arousal symptoms that adversely affect mental and physical health. Recent evidence links changes in DNA methylation of CpG cites to PTSD. Since clusters of proximal CpGs share similar methylation signatures, identification of PTSD-associated differentially methylated regions (DMRs) may elucidate the pathways defining differential risk and resilience of PTSD. Here we aimed to identify epigenetic differences associated with PTSD. DNA methylation data profiled from blood samples using the MethylationEPIC BeadChip were used to perform a DMR analysis in 187 PTSD cases and 367 trauma-exposed controls from the Grady Trauma Project (GTP). DMRs were assessed with R package bumphunter. We identified two regions that associate with PTSD after multiple test correction. These regions were in the gene body of HLA-DPB1 and in the promoter of SPATC1L. The DMR in HLA-DPB1 was associated with PTSD in an independent cohort. Both DMRs included CpGs whose methylation associated with nearby sequence variation (meQTL) and that associated with expression of their respective genes (eQTM). This study supports an emerging literature linking PTSD risk to genetic and epigenetic variation in the HLA region.