Social trauma engages lateral septum circuitry to occlude social reward.

In humans, traumatic social experiences can contribute to psychiatric disorders1. It is suggested that social trauma impairs brain reward function such that social behaviour is no longer rewarding, leading to severe social avoidance2,3. In rodents, the chronic social defeat stress (CSDS) model has been used to understand the neurobiology underlying stress susceptibility versus resilience following social trauma, yet little is known regarding its impact on social reward4,5. Here we show that, following CSDS, a subset of male and female mice, termed susceptible (SUS), avoid social interaction with non-aggressive, same-sex juvenile C57BL/6J mice and do not develop context-dependent social reward following encounters with them. Non-social stressors have no effect on social reward in either sex. Next, using whole-brain Fos mapping, in vivo Ca2+ imaging and whole-cell recordings, we identified a population of stress/threat-responsive lateral septum neurotensin (NTLS) neurons that are activated by juvenile social interactions only in SUS mice, but not in resilient or unstressed control mice. Optogenetic or chemogenetic manipulation of NTLS neurons and their downstream connections modulates social interaction and social reward. Together, these data suggest that previously rewarding social targets are possibly perceived as social threats in SUS mice, resulting from hyperactive NTLS neurons that occlude social reward processing.

Increased medial prefrontal cortical thickness and resilience to traumatic experiences in North Korean refugees.

Little is known regarding structural brain changes in traumatized refugees and the association with psychopathology. In the present study, the cortical thickness in North Korean refugees and the association with psychological symptoms were explored. North Korean refugees with lifetime post-traumatic stress disorder (PTSD group, n = 27), trauma-exposed North Korean refugees without lifetime PTSD (trauma-exposed control (TEC) group, n = 23), and healthy South Korean controls without traumatic experiences (HC group, n = 51) completed questionnaires assessing depression, anxiety, somatization, and PTSD symptoms. The cortical thickness was measured by magnetic resonance imaging (MRI) using FreeSurfer. Age- and sex-adjusted cortical thickness of the right medial prefrontal cortex (mPFC) was greater in the TEC group than in the HC group. However, significant differences were not observed between the PTSD and HC groups. Increased right mPFC thickness was significantly correlated with less anxiety and somatization after controlling for age and sex in the TEC group, but not in the PTSD or HC groups. North Korean refugees who did not develop PTSD after trauma showed increased right mPFC thickness, which was associated with less severe psychiatric symptoms. These findings indicate that increased mPFC thickness might have helped to reduce PTSD and psychiatric symptoms after trauma, and likely reflects resilience achieved by potentially enhancing emotional regulation in the mPFC.

Hippocampal volume varies with acute posttraumatic stress symptoms following medical trauma.

The hippocampus and amygdala play an important role in the pathophysiology of posttraumatic stress disorder (PTSD). In fact, chronic PTSD has been consistently linked to reductions in hippocampal and amygdala volume. However, the acute impact posttraumatic stress has on the volume of these brain regions has received limited attention. Determining the acute impact posttraumatic stress has on brain volume may improve our understanding of the development of PTSD. Therefore, the present study recruited participants acutely (i.e., ∼1-month posttrauma) following trauma exposure and examined the relationship between brain volume (assessed at ∼1-month posttrauma) and posttraumatic stress symptoms (assessed at ∼1 and >3-months posttrauma) to determine whether brain volume was associated with acute posttraumatic stress symptom expression. Twenty-one trauma-exposed (TE) patients and 19 nontrauma-exposed (NTE) controls were recruited for the present study. Brain volume was assessed by structural magnetic resonance imaging completed during the ∼1-month assessment. Left hippocampal volumes were smaller in TE than NTE participants. Among TE participants, bilateral hippocampal volumes decreased as the number of days posttrauma increased. Further, bilateral hippocampal volumes varied negatively with the severity of posttraumatic stress symptoms at ∼1-month posttrauma. The present findings suggest that there is a progressive decrease in hippocampal volume acutely (e.g., within approximately 1 month) following trauma exposure, and demonstrates that acutely assessed hippocampal volumes vary with posttraumatic stress symptom expression. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Alterations in hippocampal subfield and amygdala subregion volumes in posttraumatic subjects with and without posttraumatic stress disorder.

The hippocampus and amygdala are important structures in the posttraumatic stress disorder (PTSD); however, the exact relationship between these structures and stress or PTSD remains unclear. Moreover, they consist of several functionally distinct subfields/subregions that may serve different roles in the neuropathophysiology of PTSD. Here we present a subregional profile of the hippocampus and amygdala in 145 survivors of a major earthquake and 56 non-traumatized healthy controls (HCs). We found that the bilateral hippocampus and left amygdala were significantly smaller in survivors than in HCs, and there was no difference between survivors with (n = 69) and without PTSD (trauma-exposed controls [TCs], n = 76). Analyses revealed similar results in most subfields/subregions, except that the right hippocampal body (in a head-body-tail segmentation scheme), right presubiculum, and left amygdala medial nuclei (Me) were significantly larger in PTSD patients than in TCs but smaller than in HCs. Larger hippocampal body were associated with the time since trauma in PTSD patients. The volume of the right cortical nucleus (Co) was negatively correlated with the severity of symptoms in the PTSD group but positively correlated with the same measurement in the TC group. This correlation between symptom severity and Co volume was significantly different between the PTSD and TCs. Together, we demonstrated that generalized smaller volumes in the hippocampus and amygdala were more likely to be trauma-related than PTSD-specific, and their subfields/subregions were distinctively affected. Notably, larger left Me, right hippocampal body and presubiculum were PTSD-specific; these could be preexisting factors for PTSD or reflect rapid posttraumatic reshaping.

Psychological trauma in different mechanisms of traumatic injury: A hospital-based cross-sectional study.

BACKGROUND: Psychological distress following traumatic injury can influence the patient health, well-being and quality of life; however, this impact may partly vary according to the type and severity of injury. We aimed to study the predominant distress causing cluster and individual symptoms of Post-Traumatic Stress Disorders (PTSD) at the clinical and subthreshold level in patients with traumatic injuries, based on the mechanism of injury (MOI). METHODS: A hospital based cross-sectional study was conducted at a Level 1 Trauma Center utilizing PTSD Checklist to diagnose PTSD after one month of the traumatic event. All patients suffering from psychological distresses were assessed by a clinical psychologist in the trauma section. PTSD diagnostic criteria from DSM-5 were used to classify the patients. The inclusion criteria comprised of adult trauma patients who were directly involved in traumatic injuries and admitted under the Trauma Surgery services for a minimum of one day; have ability to provide written informed consent and can be assessed with the PCL-5 checklist after 4 weeks post-injury. RESULTS: Two hundred patients completed PCL-5 checklist, of them 26 (13.0%) were positive for PTSD and 174 (87%) had subthreshold scores. The mean age of participants was 34.4±11.8 years and males constituted 90.5%. Road traffic injury (RTI) was most the frequent injury mechanism (59%). PTSD positive patients with RTI, fall of heavy objects, pedestrian injury and assaults had highest average scores on clusters of negative alterations in mood and cognitions (16.9, 18.0, 18.5, 17.0 respectively), followed by hyperarousal. Symptom of always being on the guard and having repeated unwanted or disturbing memories of the incident, was reported by nearly 100% PTSD positive patients. Patients with subthreshold scores also reported distressing symptoms on all four clusters of PTSD. CONCLUSIONS: Patients with different MOI showed a broad range of psychological problems with respect to symptom clusters. Negative alteration in mood and cognition followed by hyperarousal caused higher level of distress in patients post traumatic injuries. Subthreshold symptoms of PTSD are more common and deserve more attention.

Cortical Thickness in Dutch Police Officers: An Examination of Factors Associated with Resilience.

Previous neuroimaging studies on resilience have generally compared resilience and psychopathology after stress exposure, which does not allow for conclusions regarding correlates specific to resilience. The aim of the present study was to investigate resilience-specific correlates in cortical thickness and/or cortical surface area and their correlations with psychometric measurements, using a three-group design that included a non-trauma-exposed control group in order to disentangle effects related to resilience from those related to psychopathology. Structural magnetic resonance imaging scans were acquired from 82 Dutch police officers. Participants were categorized into resilient (n = 31; trauma exposure, no psychopathology), vulnerable (n = 32; trauma exposure, psychopathology), and control groups (n = 19; no trauma exposure, no psychopathology). Specific regions of interest (ROIs) were identified based on previous studies that found the rostral and caudal anterior cingulate cortex (ACC) to be implicated in trauma-related psychopathology. Cortical thickness and surface area of the ROIs-the rostral and caudal ACC-and of the whole brain were examined. No significant differences in cortical thickness or surface area were found between the resilient group and other groups in the ROI and whole-brain analyses. Thus, the results of the present study provide no evidence of an association between resilience to traumatic stress and measures of thickness and surface area in cortical regions of the brain in a sample of Dutch police officers.

Interactions of OXTR rs53576 and emotional trauma on hippocampal volumes and perceived social support in adolescent girls.

Oxytocin (OXT) is a neuropeptide involved in social behaviour and is sensitive to environmental influences to alter individual vulnerability or resilience to stress resulting in both negative and positive outcomes. The effects of the OXT receptor (OXTR) single nucleotide polymorphism (SNP) rs53576 on hippocampal and amygdala structure and functions in adults are differentially associated with susceptibility to adversity and social behaviours, but this evidence is lacking in healthy adolescents. Adolescence is a developmental period characterised by neurobiological and psychosocial changes resulting in higher susceptibility to mood disorders, particularly among girls. As the brain is highly plastic at this stage, to understand psychosocial and emotional development, clarity of the interactions between rs53576 and adversity on hippocampal and amygdala volumes and social behaviours is needed. In this study, we investigated the interactions between rs53576 and emotional trauma (ET) exposure on hippocampal and amygdala volumes of adolescent girls, and associations with parenting style, perceived social support and bullying behaviour. Based on an unbiased and corrected analytical approach, we found smaller left hippocampal volumes in higher (hET) compared to minimally (mET) exposed AA homozygotes, but no differences in G allele carriers nor in the amygdala. Within the mET AA group, larger volumes were associated with peer perceived social support, but in their hET counterparts, smaller volumes were associated with familial perceived social support. This evidence supports an important role for the hippocampus in social behaviours but extends current knowledge to suggest that hippocampal social behavioural features are contextually dependent on rs53576.

Dysfunctional neuroplasticity in newly arrived Middle Eastern refugees in the U.S.: Association with environmental exposures and mental health symptoms.

BACKGROUND: Psychological war trauma among displaced refugees is an established risk factor for mental health disorders, especially post-traumatic stress disorder (PTSD). Persons with trauma-induced disorders have heightened neuroplastic restructuring of limbic brain circuits (e.g., amygdala and hippocampus), which are critical factors in the pathophysiology of PTSD. Civilians in war are exposed to both psychological trauma and environmental hazards, such as metals. Little is known about the possible mental health impact from such environmental exposures, alone or in combination with trauma. It is of special interest to determine whether war exposures contribute to dysfunctional neuroplasticity; that is, an adverse outcome from sustained stress contributing to mental health disorders. The current study examined Middle Eastern refugees in the United States to determine the relationships among pre-displacement trauma and environmental exposures, brain derived neurotrophic growth factor (BDNF) and nerve growth factor (NGF)-two neurotrophins reported to mediate neuroplasticity responses to stress-related exposures-and mental health. METHODS: Middle Eastern refugees (n = 64; 33 men, 31 women) from Syria (n = 40) or Iraq (n = 24) were assessed 1 month after arrival to Michigan, US. Participants were interviewed in Arabic using a semi-structured survey to assess pre-displacement trauma and environmental exposure, PTSD, depression, anxiety, and self-rated mental health. Whole blood was collected, and concentrations of six heavy metals as well as BDNF and NGF levels were determined. Because these two neurotrophins have similar functions in neuroplasticity, we combined them to create a neuroplasticity index. Linear regression tested whether psychosocial trauma, environmental exposures and biomarkers were associated with mental health symptoms. FINDINGS: The neuroplasticity index was associated with PTSD (standardized beta, ß = 0.25, p < 0.05), depression (0.26, < 0.05) and anxiety (0.32, < 0.01) after controlling for pre-displacement trauma exposures. In addition, pre-displacement environmental exposure was associated with PTSD (0.28, < 0.05) and anxiety (0.32, < 0.05). Syrian refugees and female gender were associated with higher scores on depression (0.25, < 0.05; 0.30, < 0.05) and anxiety scales (0.35, < 0.01; 0.27, < 0.05), and worse on self-rated mental health (0.32, < 0.05; 0.34, < 0.05). In bivariate analysis, the neuroplasticity index was related to blood lead levels (r = 0.40; p < 0.01). CONCLUSIONS: The current study confirms the adverse effects of war trauma on mental health. Higher levels of biomarkers of neuroplasticity correlated with worse mental health and higher blood lead levels. Higher neurotrophin levels in refugees might indicate dysfunctional neuroplasticity with increased consolidation of adverse war memories in the limbic system. Such a process may contribute to psychiatric symptoms. Further research is needed to clarify the pathobiological mechanisms linking war trauma and environmental exposures to adverse mental health.

Hippocampal and parahippocampal volumes vary by sex and traumatic life events in children

Background: Childhood trauma is reliably associated with smaller hippocampal volume in adults; however, this finding has not been shown in children, and even less is known about how sex and trauma interact to affect limbic structural development in children. Methods: Typically developing children aged 9 to 15 years who completed a trauma history questionnaire and structural T1-weighted MRI were included in this study (n = 172; 85 female, 87 male). All children who reported 4 or more traumas (n = 36) composed the high trauma group, and all children who reported 3 or fewer traumas (n = 136) composed the low trauma group. Using multivariate analysis of covariance, we compared FreeSurfer-derived structural MRI volumes (normalized by total intracranial volume) of the amygdalar, hippocampal and parahippocampal regions by sex and trauma level, controlling for age and study site. Results: We found a significant sex × trauma interaction, such that girls with high trauma had greater volumes than boys with high trauma. Follow-up analyses indicated significantly increased volumes for girls and generally decreased volumes for boys, specifically in the hippocampal and parahippocampalregions for the high trauma group; we observed no sex differences in the low trauma group. We noted no interaction effect for the amygdalae. Limitations: We assessed a community sample and did not include a clinical sample. We did not collect data about the ages at which children experienced trauma. Conclusion: Results revealed that psychological trauma affects brain development differently in girls and boys. These findings need to be followed longitudinally to elucidate how structural differences progress and contribute to well-known sex disparities in psychopathology.

Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells.

Empirical and anecdotal evidence has associated stress with accelerated hair greying (formation of unpigmented hairs)1,2, but so far there has been little scientific validation of this link. Here we report that, in mice, acute stress leads to hair greying through the fast depletion of melanocyte stem cells. Using a combination of adrenalectomy, denervation, chemogenetics3,4, cell ablation and knockout of the adrenergic receptor specifically in melanocyte stem cells, we find that the stress-induced loss of melanocyte stem cells is independent of immune attack or adrenal stress hormones. Instead, hair greying results from activation of the sympathetic nerves that innervate the melanocyte stem-cell niche. Under conditions of stress, the activation of these sympathetic nerves leads to burst release of the neurotransmitter noradrenaline (also known as norepinephrine). This causes quiescent melanocyte stem cells to proliferate rapidly, and is followed by their differentiation, migration and permanent depletion from the niche. Transient suppression of the proliferation of melanocyte stem cells prevents stress-induced hair greying. Our study demonstrates that neuronal activity that is induced by acute stress can drive a rapid and permanent loss of somatic stem cells, and illustrates an example in which the maintenance of somatic stem cells is directly influenced by the overall physiological state of the organism.

Structural brain differences predict early traumatic memory processing.

Intrusive memories are a key symptom of post-traumatic stress disorder (PTSD). They emerge early after trauma exposure and are predictive for PTSD development. There is a high relevance in evaluating the neurobiological mechanisms of early stages of intrusive symptom development to provide a further understanding of PTSD. In the present study, we explore structural differences in healthy young female subjects preceding experimental trauma exposure and their relationship to early intrusive memory development using a traumatic film paradigm. With voxel-based morphometry, we demonstrate that smaller insular volume was associated with an increased number of early intrusive film memories. Moreover, larger lingual gyrus/cerebellar and inferior frontal gyrus/precentral gyrus volumes were also related to an increased number of early intrusive film memories. Our results identify unique brain areas associated with early experimental trauma memory processing and highlight the necessity of evaluating early symptom stages relevant for personalized PTSD prevention and treatment.

Childhood trauma and hippocampal subfield volumes in first-episode schizophrenia and healthy controls.

Childhood trauma and schizophrenia are both associated with neuroanatomical abnormalities in the hippocampus, a stress-sensitive structure vulnerable to developmental insults. However, few studies have evaluated the effects of childhood trauma exposure on hippocampal morphometry in minimally treated first-episode schizophrenia patients. Here we aim to investigate the associations of childhood trauma with hippocampal subfield volumes in a cohort of antipsychotic-naive or minimally treated first-episode schizophrenia spectrum disorder patients and matched controls. 79 patients with first-episode schizophrenia spectrum disorder and 82 matched controls completed the childhood trauma questionnaire and underwent MRI assessment. Hippocampal subfields were reconstructed using FreeSurfer 6.0. We considered inter-correlations between the various subfields, by entering them as dependent variables into a multivariate analysis of co-variance (MANCOVA), modeling for interactions between diagnosis, childhood trauma total score and gender while controlling for substance use, scanner sequence and age. MANCOVA revealed a significant interaction between sex, childhood trauma total scores and diagnosis across hippocampal sub-regions (p = 0.012). Bonferroni corrected post-hoc analysis revealed a significant sex*diagnosis*childhood trauma score interaction for the hippocampal fissure (F(1,161) = 9.485,p = .002). Hippocampal fissure size showed a positive relationship with CA structures as well as whole hippocampal size in the larger sample. Findings from the present study suggest that childhood trauma exposure exerts illness-specific effects on hippocampal structures in female patients with first-episode schizophrenia, consistent with increased stress sensitivity in this group.

Structural connectivity and risk for anhedonia after trauma: A prospective study and replication.

Anhedonia emerges in some people after psychological trauma, reflected by a loss of interest, diminished affect, and detachment. Structural abnormalities in specific neural pathways at the time of trauma may influence the development of these posttraumatic anhedonia (PTA) symptoms. In this prospective study, we determined whether white matter connectivity at around one month post-trauma predicts PTA and other PTSD symptoms at six months post-trauma. Thirty men and women aged 19-62 were recruited from the emergency department of a Level I trauma center. Participants received diffusion tensor imaging at approximately one month post-trauma and clinical assessments at one and six months post-trauma. Probabilistic tractography was used to examine connectivity of select pathways. A replication sample (N = 57) in an independent, cross-sectional dataset of traumatized women was similarly analyzed. Logistic regression results indicated that, after accounting for early PTSD symptoms (at one month) and other clinical risk factors, the integrity of the uncinate fasciculus (UF) uniquely predicted the presence of PTA at six months post-trauma (Beta = -225.6, p < .05). Together, these factors contributed to 76% of the variance in PTA. Integrity of the UF also predicted re-experiencing PTSD symptoms at six months post-trauma. These results were supported in our replication analyses. Our findings indicate that the integrity of the UF around 1 month post-trauma affects vulnerability for the development of anhedonic PTSD symptoms as well as re-experiencing symptoms. Connectivity of this amygdala-ventromedial prefrontal pathway appears to be a salient predictor of anhedonia, above and beyond clinical risk factors.

The left dorsolateral prefrontal cortex volume is reduced in adults reporting childhood trauma independent of depression diagnosis.

Both major depressive disorder (MDD) and childhood trauma have been linked with brain structural changes. As childhood trauma is more highly prevalent in MDD patients, previous morphometric findings in MDD therefore might have been confounded by childhood trauma. This study aimed to differentiate the impact of childhood trauma from the influence of MDD diagnosis on gray matter volume (GMV). Seventy-eight subjects were recruited into four study groups (n = 16, MDD patients with childhood trauma exposures, CTE/MDD; n = 14, MDD patients without CTE, non-CTE/MDD; n = 24, healthy controls with CTE, CTE/HC; and n = 24, HCs without CTE, non-CTE/HC). All participants underwent high-resolution structural magnetic resonance scans. Voxel-based morphometry was used to investigate GM alterations, and a 2 × 2 analysis of variance was performed to identify the main effects of diagnosis, childhood trauma, and their interactions. The main effects of diagnosis displayed abnormal GMV located in the left superior parietal lobule (MDD < HC) and right middle occipital gyrus (MDD > HC). While the left dorsolateral prefrontal cortex (DLPFC) volume revealed a significant main effect of childhood trauma, as shown by decreased GMV of the left DLPFC in subjects with CTE, regardless of diagnosis. A negative correlation was also found between the left DLPFC volume and emotional neglect in individuals reporting CTE. The present findings suggest that decreased GMV of the left DLPFC is a function of childhood trauma rather than MDD, which may represent the biological risk for developing MDD.

Childhood Trauma Associated White Matter Abnormalities in First-Episode Schizophrenia.

Schizophrenia is associated with brain connection irregularities within and between brain regions. Childhood trauma increases the risk of schizophrenia suggesting that the relationships between childhood trauma and brain connectivity requires further investigation. Here, we examine the relationship between childhood trauma (as measured by the Childhood Trauma Questionnaire) and fractional anisotropy (FA) in 54 minimally treated first-episode schizophrenia (FES) patients and 51 community matched controls. Patients who experienced high levels of trauma had significantly lower FA in the inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and inferior fronto-occipital fasciculus (IFOF) compared with controls who experienced high levels of childhood trauma. A history of childhood sexual abuse in patients was associated with lower FA in the IFOF, ILF, SLF, and forceps major compared with patients without a history of sexual abuse. However, patients who had experienced childhood emotional neglect had higher FA in the right SLF compared to patients with low levels of emotional neglect. Our findings highlight altered cortico-limbic circuitry in FES patients compared with controls and differential effects of childhood emotional neglect and sexual abuse on white matter in patients. Although stress-related white matter (WM) pathways appear to be involved in both schizophrenia and otherwise healthy controls previously exposed to childhood trauma, the pattern of disruption of WM integrity in FES patients appears to be distinct.

Regional Prefrontal Resting-State Functional Connectivity in Posttraumatic Stress Disorder.

BACKGROUND: Prefrontal subregions, including the ventromedial prefrontal cortex (PFC), dorsomedial PFC, and dorsolateral PFC (DLPFC), are differentially implicated in the pathophysiology of posttraumatic stress disorder (PTSD), though few existing studies have examined subregional differences in resting-state functional connectivity (rsFC). We hypothesized that PTSD would involve weaker positive rsFC between ventromedial PFC, dorsomedial PFC, and other default mode network regions and increased negative rsFC between DLPFC and posterior default mode network regions. Additionally, we hypothesized that prefrontal regions exhibiting group differences in rsFC would be characterized by alterations in cortical thickness. METHODS: Participants included 36 healthy control subjects, 30 trauma-exposed control subjects, and 21 individuals with current DSM-IV PTSD resulting from community-acquired trauma. Participants completed the Clinician Administered PTSD Scale, questionnaires (Childhood Trauma Questionnaire, Adverse Childhood Events, Life Events Checklist, Beck Depression Inventory), structural neuroimaging, and resting-state functional magnetic resonance imaging. rsFC of DLPFC, ventromedial PFC, and dorsomedial PFC seeds was evaluated in SPM12 and CONN. Cortical thickness for regions with significant rsFC findings was assessed using FreeSurfer. RESULTS: Relative to both healthy control and trauma-exposed control subjects, individuals with PTSD showed increased negative rsFC between the DLPFC and a region of precuneus. This finding was associated with increased overall symptom severity but not with trauma load or childhood trauma exposure. Greater negative DLPFC-precuneus connectivity was associated with greater bilateral precuneus thickness. CONCLUSIONS: Given participation of precuneus subregions in the central executive network, increased anticorrelation between right DLPFC and precuneus in this sample may reflect increased opposition between anterior and posterior central executive network hubs in PTSD.

Reduced local segregation of single-subject gray matter networks in adult PTSD.

To psychoradiologically investigate the topological organization of single-subject gray matter networks in patients with PTSD. Eighty-nine adult PTSD patients and 88 trauma-exposed controls (TEC) underwent a structural T1 magnetic resonance imaging scan. The single-subject brain structural networks were constructed based on gray matter similarity of 90 brain regions. The area under the curve (AUC) of each network metric was calculated and both global and nodal network properties were measured in graph theory analysis. We used nonparametric permutation tests to identify group differences in topological metrics. Relationships between brain network measures and clinical symptom severity were analyzed in the PTSD group. Compared with TEC, brain networks of PTSD patients were characterized by decreased clustering coefficient (Cp ) (p = .04) and local efficiency (Eloc ) (p = .04). Locally, patients with PTSD exhibited altered nodal centrality involving medial superior frontal (mSFG), inferior orbital frontal (iOFG), superior parietal (SPG), middle frontal (MFG), angular, and para-hippocampal gyri (p < .05, corrected). A negative correlation between the segregation (Cp ) of gray matter and functional networks was found in PTSD patients but not the TEC group. Analyses of topological brain gray matter networks indicate a more randomly organized brain network in PTSD. The reduced segregation in gray matter networks and its negative relation with increased segregation in the functional network indicate an inverse relation between gray matter and functional changes. The present psychoradiological findings may reflect a compensatory increase in functional network segregation following a loss of segregation in gray matter networks.

Psychological and neural correlates of embitterment in old age.

OBJECTIVE: Posttraumatic embitterment disorder (PTED) comprises a stress-related response to a negative life event that violates the belief system of the individual. Characteristic symptoms involve repeated intrusive thoughts, emotional arousal when reminded of the event, and decreases in well-being. METHOD: Within the scope of the present study, embitterment was treated as a continuous rather than categorical concept, and we investigated its psychological and brain structural correlates in a sample of healthy older adults. RESULTS: We found a negative association between the PTED self-rating score and self-reported well-being, life satisfaction, and future time perspective and a positive association with loneliness, perceived stress, chronic strain, and external control beliefs. We found no significant association between embitterment and brain regions that have been associated with stress exposure and posttraumatic stress disorder (PTSD)-hippocampus and the medial prefrontal cortex. This may emphasize the fundamental difference between PTED and PTSD. In a whole-brain analysis, we found a positive correlation between embitterment and gray matter volume in the precuneus and white matter volume in the bilateral uncinate fasciculus. CONCLUSIONS: The precuneus and uncinate fasciculus are brain regions that have been related to episodic memory retrieval, matching well to the symptoms of intrusive thoughts and an overwhelming preoccupation with the event that caused the PTED. Further longitudinal research is needed to unravel whether these structural correlates represent preconditions or rather the consequence of embitterment. (PsycINFO Database Record

Genome-wide association study of subcortical brain volume in PTSD cases and trauma-exposed controls.

Depending on the traumatic event, a significant fraction of trauma survivors subsequently develop PTSD. The additional variability in PTSD risk is expected to arise from genetic susceptibility. Unfortunately, several genome-wide association studies (GWAS) have failed to identify a consistent genetic marker for PTSD. The heritability of intermediate phenotypes such as regional brain volumes is often 80% or higher. We conducted a GWAS of subcortical brain volumes in a sample of recent military veteran trauma survivors (n = 157), grouped into PTSD (n = 66) and non-PTSD controls (n = 91). Covariates included PTSD diagnosis, sex, intracranial volume, ancestry, childhood trauma, SNP×PTSD diagnosis, and SNP×childhood trauma. We identified several genetic markers in high linkage disequilibrium (LD) with rs9373240 (p = 2.0 × 10-7, FDR q = 0.0375) that were associated with caudate volume. We also observed a significant interaction between rs9373240 and childhood trauma (p-values = 0.0007-0.002), whereby increased trauma exposure produced a stronger association between SNPs and increased caudate volume. We identified several SNPs in high LD with rs34043524, which is downstream of the TRAM1L1 gene that were associated with right lateral ventricular volume (p = 1.73 × 10-7; FDR q = 0.032) and were also associated with lifetime alcohol abuse or dependence (p = 2.49 × 10-7; FDR q = 0.0375). Finally, we identified several SNPs in high LD with rs13140180 (p = 2.58 × 10-7; FDR q = .0016), an intergenic region on chromosome 4, and several SNPs in the TMPRSS15 associated with right nucleus accumbens volume (p = 2.58 × 10-7; FDR q = 0.017). Both TRAM1L1 and TMPRSS15 have been previously implicated in neuronal function. Key results survived genome-wide multiple-testing correction in our sample. Leveraging neuroimaging phenotypes may offer a shortcut, relative to clinical phenotypes, in mapping the genetic architecture and neurobiological pathways of PTSD.

Sex Differences in Trauma-Related Psychopathology: a Critical Review of Neuroimaging Literature (2014-2017).

PURPOSE OF REVIEW: Sex differences in the epidemiology and clinical presentation of trauma-related psychopathology have long been documented. Multiple underlying mechanisms have been examined, both psychosocial and biological. Among the most promising biological mechanisms are neural substrates of trauma-related psychopathology that have been uncovered in recent years. RECENT FINDINGS: Neuroimaging studies of sex-related heterogeneity published over the past 3 years (2014-2017) demonstrate an interaction between sex and type, timing, and load of trauma exposure. These studies suggest that, for males, early trauma exposure may involve a loss of gray matter in the limbic system, including the prefrontal cortex (PFC), amygdala, and hippocampus, and an over-activity and increased connectivity of salience hubs, and particularly dorsal anterior cingulate cortex (dACC). For females, however, early trauma exposure may involve overactive and possibly an enlarged amygdala, as well as decreased connectivity of salience hubs such as the dACC. Underlying mechanisms may include interaction with several endocrine systems and result in differential neural response to naturally occurring and added endocrine ligands, as well as sex-specific genetic and epigenetic risk and resilience factors. This complex interaction between multiple biological systems may be associated with sex-specific behavioral patterns, in turn associated with trauma-related psychopathology. While substantial number of published studies present preliminary evidence for neural mechanisms of sex-specific posttraumatic responses, there is a paucity of research directly designed to examine sex as a biological factor in trauma-related psychopathology. Specific foci for future studies aiming to bridge current gaps in the literature are discussed.