Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup.

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

Can Listening to a Verbal Trauma Report Induce Intrusions? - Replication of a Randomized Trial.

Recent evidence suggests that indirect verbal exposure to traumatic events can be sufficient to cause intrusions and other posttraumatic stress symptoms. In this study, we used a verbal trauma report to experimentally induce intrusions and a tactile task to manipulate the putative processes underlying intrusion development. Our findings indicate that the verbal report indeed induced intrusive recall. Moreover, the verbal report induced negative mood, state anxiety, and state dissociation, with mood and state dissociation predicting intrusion development. Additionally, the tactile task interfered with intrusion formation as indicated by the primary diary measure, but not the retrospective self-report. However, these results await further replication as this and previous trials suffered from limited statistical power. The findings support the reports by trauma therapists who experience secondary traumatization. They also challenge the assumption that all intrusions develop bottom-up from low-level sensory input via sensory representations. Future studies should explore differential processes for intrusion development based on their modality.

Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium.

BACKGROUND: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. METHODS: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. RESULTS: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. CONCLUSION: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

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.

The Clinician-Administered Dissociative States Scale (CADSS): Validation of the German Version.

The Clinician-Administered Dissociative States Scale (CADSS) is a structured clinical interview to assess state dissociation rated by clinicians. The current study aimed to validate the German version of CADSS by comparing it to the established self-report measures for dissociation and exploring its underlying factor structure. Severity of within-session state dissociation was assessed directly following a standard psychotherapy session in a trauma-exposed patient sample (N= 105; 81.9% female). Internal consistency, convergent validity with other dissociation measures, and the factorial structure of the instrument were analyzed. The German version exhibited excellent internal consistency (Cronbach's α = .94) and correlated significantly with self-report measures of state dissociation (r = .86) and trait dissociation (r = .77) indicative of high convergent validity. Exploratory factor analysis revealed a three-factor solution with the factors (1) Depersonalization/Derealization, (2) Identity Confusion/Alteration, and (3) Amnesia. Results support the CADSS as a useful instrument to assess state dissociation, conceptualized as a multidimensional construct, in clinical practice.

Did domestic violence really increase in the early phase of the COVID-19 pandemic? Results of an interview-based observational study.

Objectives: The COVID-19 lockdown may lead to rising numbers of domestic violence (DV), especially among previously victimized individuals. The aim of this study was to investigate the development and influential factors of DV during the early COVID-19 lockdown. Methods: In this telephone-based study, previous participants with (n = 34) and without (n = 33) DV completed questionnaires on DV, attachment and COVID-19 related stressors. Development of DV and influential factors were investigated with repeated measures ANOVAs and linear regression models. Results: Individuals with prior DV reported significantly higher DV than previously not affected individuals. However, a statistically significant decrease of DV was found in the group with prior DV. Past DV, childlessness and insecure attachment, but not COVID-19 related stressors predicted current DV. Conclusions: In light of an insecure attachment style lockdown measures may have led to a temporary relationship stabilization. However, a reassessment is necessary to evaluate whether this stabilization was a short-time trend only.

Allocentric spatial memory performance predicts intrusive memory severity in posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is characterized by distressing trauma-related memories. According to the dual representation theory, intrusive memories arise from strengthened egocentric encoding and a poor contextual encoding, with spatial context requiring allocentric processing. Contextualization of mental imagery is proposed to be formed hierarchically through the ventral visual stream (VVS) to the hippocampal formation. Here, we tested this notion by investigating whether neuronal aberrations in structures of the VVS or in the hippocampus, as well as allocentric memory performance are associated with intrusive memory severity. METHODS: The sample comprised 33 women with PTSD due to childhood trauma. Allocentric memory performance was measured with the virtual Town Square Task and T1-weighted images acquired on a 3T Siemens Scanner. Intrusive memories were evoked by presenting an audio script describing parts of their trauma (script-driven imagery). RESULTS: Using hierarchical linear regression analysis, we found a significant association between lower intrusive memory severity and higher allocentric spatial memory, controlling for age, working memory, and general visuospatial ability. No significant association was found between cortical thickness of VVS structures, hippocampal volume and intrusive memory severity. Post hoc exploratory analyses revealed a negative correlation between years since index trauma and left hippocampal volume. LIMITATIONS: Our results are based on correlational analyses, causality cannot be inferred. CONCLUSION: This study supports the dual representation theory, which emphasizes the role of allocentric spatial memory for the contextualization of mental imagery in PTSD. Clinical implications are discussed.

Experiencing and Witnessing Patient Violence - an Occupational Risk for Outpatient Therapists?

Violence against therapists by their clients are a common occurrence across clinical settings and may have a lasting impact on the clinician's professional and personal functioning. In spite of this, no study to date has looked at the frequency of trauma-induced symptoms in psychotherapists. Using a sample of N = 917 psychotherapists across Germany, Austria, and Switzerland, we analyzed the frequency and sequelae of patient attacks suffered or witnessed by therapists. More than half (51.3%) of the sample reported having been the victim or witness of patient attacks or threats of violence in their career. Among the affected therapists, 27.7% reported posttraumatic symptoms lasting longer than four weeks and 2.7% presented symptoms amounting to a full-PTSD diagnosis. Thus, while the frequency of attacks and trauma-induced symptoms were considerable, estimated PTSD rates were rather low. The findings suggest that practitioners should be conscious of client violence being an occupational risk and that it is advisable to have protective measures in place.

[Effectiveness of Psychoanalytic Psychotherapy for Children and Adolescents with Severe Anxiety Psychopathology in a Naturalistic Treatment Setting]. / Wirksamkeit analytischer Psychotherapie bei Kindern und Jugendlichen mit klinischen Angstsyndromen im naturalistischen Behandlungssetting.

Effectiveness of Psychoanalytic Psychotherapy for Children and Adolescents with Severe Anxiety Psychopathology in a Naturalistic Treatment Setting The aim of the study was to evaluate naturalistic out-patient psychoanalytic youth psychotherapy in Germany. The study was a partly controlled effectiveness trial. While the first treatment interval (25 sessions, 6.13 months) was compared with a wait-list control group (5 supportive sessions, 2.94 months), the effects of long-term psychoanalytical treatment were analyzed using a time-series design. 86 children and adolescents (aged 4 to 21 years) and their parents who entered psychoanalytic therapy in private practices participated in this study. The wait-list control group comprised 35 patients. Questionnaires were administered at the beginning and the end of treatment, as well as 6 and 12 month follow-up (FU). Patients received on average 94.04 therapy sessions (range 8 to 300) over 25.70 months. Data analyses were carried out with multilevel mixed linear models on the intention-to-treat (ITT) sample. The patients in the intervention group reported moderate symptom improvements at the end of therapy (d = .57), these effects are stable at the 1-year follow-up and increase from the patient perspective (d = .80). When comparing the first therapy interval with the (minimal treatment) wait-list control group, both groups improved significantly with small effect sizes and no significant group differences. The results suggest that long-term psychoanalytic therapy is successful in alleviating anxiety pathology and improving quality of life for youth with anxiety disorders, and that improvements remain stable across a 1-year follow-up period.

White matter network alterations in patients with depersonalization/derealization disorder.

BACKGROUND: Depersonalization/derealization disorder (DPD) is a chronic and distressing condition characterized by detachment from oneself and/or the external world. Neuroimaging studies have associated DPD with structural and functional alterations in a variety of distinct brain regions. Such local neuronal changes might be mediated by altered interregional white matter connections. However, to our knowledge, no research on network characteristics in this patient population exists to date. METHODS: We explored the structural connectome in 23 individuals with DPD and 23 matched, healthy controls by applying graph theory to diffusion tensor imaging data. Mean interregional fractional anisotropy (FA) was used to define the network weights. Group differences were assessed using network-based statistics and a link-based controlling procedure. RESULTS: Our main finding refers to lower FA values within left temporal and right temporoparietal regions in individuals with DPD than in healthy controls when using a link-based controlling procedure. These links were also associated with dissociative symptom severity and could not be explained by anxiety or depression scores. Using network-based statistics, no significant results emerged. However, we found a trend for 1 subnetwork that may support the model of frontolimbic dysbalance suggested to underlie DPD symptomatology. LIMITATIONS: To ensure ecological validity, patients with certain comorbidities or psychotropic medication were included in the study. Confirmatory replications are necessary to corroborate the results of this explorative investigation. CONCLUSION: In patients with DPD, the structural connectivity between brain regions crucial for multimodal integration and emotion regulation may be altered. Aberrations in fibre tract communication seem to be not solely a secondary effect of local grey matter volume loss, but may present a primary pathophysiology in patients with DPD.

White matter network alterations in patients with depersonalization/derealization disorder.

BACKGROUND: Depersonalization/derealization disorder (DPD) is a chronic and distressing condition characterized by detachment from oneself and/or the external world. Neuroimaging studies have associated DPD with structural and functional alterations in a variety of distinct brain regions. Such local neuronal changes might be mediated by altered interregional white matter connections. However, to our knowledge, no research on network characteristics in this patient population exists to date. METHODS: We explored the structural connectome in 23 individuals with DPD and 23 matched, healthy controls by applying graph theory to diffusion tensor imaging data. Mean interregional fractional anisotropy (FA) was used to define the network weights. Group differences were assessed using network-based statistics and a link-based controlling procedure. RESULTS: Our main finding refers to lower FA values within left temporal and right temporoparietal regions in individuals with DPD than in healthy controls when using a link-based controlling procedure. These links were also associated with dissociative symptom severity and could not be explained by anxiety or depression scores. Using network-based statistics, no significant results emerged. However, we found a trend for 1 subnetwork that may support the model of frontolimbic dysbalance suggested to underlie DPD symptomatology. LIMITATIONS: To ensure ecological validity, patients with certain comorbidities or psychotropic medication were included in the study. Confirmatory replications are necessary to corroborate the results of this explorative investigation. CONCLUSION: In patients with DPD, the structural connectivity between brain regions crucial for multimodal integration and emotion regulation may be altered. Aberrations in fibre tract communication seem to be not solely a secondary effect of local grey matter volume loss, but may present a primary pathophysiology in patients with DPD.

Prevalence of and Risk Factors for Secondary Traumatization in Interpreters for Refugees: A Cross-Sectional Study.

BACKGROUND: A substantial proportion of refugees, fleeing persecution, torture, and war, are estimated to suffer from psychological traumatization. After being sheltered in reception centers, the refugees come in close contact with different occupational groups, e.g., physicians, social workers, and interpreters. Previous studies ascertained that such interpreters themselves often suffer from primary psychological traumatization. Moreover, through translating refugees' potentially traumatic depictions, the interpreters are in danger of developing a so-called secondary traumatization. OBJECTIVE: The present study aimed (1) to analyze the prevalence rates of primary traumatization in interpreters, (2) to assess the prevalence of secondary traumatization, depression, anxiety, and stress symptoms, (3) to examine the association between secondary traumatization symptoms and resilience factors in terms of sense of coherence, social support, and attachment style, and (4) to test whether these resilience factors mediate the relationship between primary and secondary traumatization. METHODS: Participating interpreters (n = 64) were assessed for past exposure to potentially traumatic events as well as symptoms of posttraumatic stress disorder (PTSD), secondary traumatization, depressive symptoms, anxiety, and subjective stress levels. Furthermore, we conducted psychometric surveys to measure interpreters' sense of coherence, degree of social support, and attachment style as potential predictors. RESULTS: (1) 9% of the interpreters fulfilled all criteria for PTSD and a further 33% had subclinical PTSD; (2) a secondary traumatization was present in 21% of the examined interpreters - of these, 6% showed very high total scores indicating a severe secondary traumatization; furthermore, we found higher scores for depression, anxiety, and stress as compared to representative population samples, especially for females; (3) a present sense of coherence, an existing social support network, and a secure or preoccupied attachment style correlated significantly with low scores for secondary traumatization; and (4) a significant correlation emerged between primary and secondary traumatization (r = 0.595, p < 0.001); a mediation analysis revealed that this effect is partially mediated by secure attachment. CONCLUSION: A substantial proportion of interpreters working with refugees suffer from primary as well as secondary traumatization. However, high scores for sense of coherence and social support, male gender, and especially a secure attachment style were identified as resilience factors for secondary traumatization. The results may have implications for the selection, training, and supervision of interpreters.

Psychoanalytic Psychotherapy for Children and Adolescents with Severe Externalising Psychopathology: An Effectiveness Trial.

OBJECTIVES: This partly waitlist-controlled prospective field study aimed to evaluate the effectiveness of psychoanalytic psychotherapy for children and adolescents with severe externalising symptoms. Externalising symptoms are associated with diagnoses of conduct disorders, hyperkinetic disorders, and disorders of social functioning. METHODS: Participants were 93 children and adolescents in psychoanalytic therapy with a diagnosed psychiatric disorder with externalising symptomatology (intervention group: n = 65; minimal supportive treatment/waitlist control group: n = 28). Data was collected from parents and patients (≥ 11 years) at beginning/end of treatment, 6- and 12-month follow-up. The effects of long-term psychoanalytical treatment were analysed using a longitudinal design. RESULTS: At the end of therapy, externalising symptoms were significantly reduced rated by both parents and patients (parent-rated: d = .69, patient-rated: d = .63). This effect was stable at the 1-year follow-up (parent-rated: d = .77, patient-rated: d = .68). About 70% of the patients may be considered as recovered or improved by the end of therapy. CONCLUSIONS: Psychoanalytic therapy may be successful in alleviating psychiatric disorders with externalising symptoms with effects stable at the 1-year follow-up.

Grey matter alterations in patients with depersonalization disorder: a voxel-based morphometry study.

BACKGROUND: To our knowledge, no whole brain investigation of morphological aberrations in dissociative disorder is available to date. Previous region-of-interest studies focused exclusively on amygdalar, hippocampal and parahippocampal grey matter volumes and did not include patients with depersonalization disorder (DPD). We therefore carried out an explorative whole brain study on structural brain aberrations in patients with DPD. METHODS: We acquired whole brain, structural MRI data for patients with DPD and healthy controls. Voxel-based morphometry was carried out to test for group differences, and correlations with symptom severity scores were computed for grey matter volume. RESULTS: Our study included 25 patients with DPD and 23 controls. Patients exhibited volume reductions in the right caudate, right thalamus and right cuneus as well as volume increases in the left dorsomedial prefrontal cortex and right somatosensory region that are not a direct function of anxiety or depression symptoms. LIMITATIONS: To ensure ecological validity, we included patients with comorbid disorders and patients taking psychotropic medication. CONCLUSION: The results of this first whole brain investigation of grey matter volume in patients with a dissociative disorder identified structural alterations in regions subserving the emergence of conscious perception. It remains unknown if these alterations are best understood as risk factors for or results of the disorder.

Behavioural and neural correlates of self-focused emotion regulation in social anxiety disorder.

BACKGROUND: In healthy individuals, voluntary modification of self-relevance has proven effective in regulating subjective emotional experience as well as physiologic responses evoked by emotive stimuli. As social anxiety disorder (SAD) is characterized by both altered emotional and self-related processing, we tested if emotion regulation through self-focused reappraisal is effective in individuals with SAD. METHODS: While undergoing 3 T functional magnetic resonance imaging, individuals with SAD and matched healthy controls either passively viewed neutral and aversive pictures or actively increased or decreased their negative emotional experience through the modification of self-relevance or personal distance to aversive pictures. Participants rated all pictures with regard to the intensity of elicited emotions and self-relatedness. RESULTS: We included 21 individuals with SAD and 23 controls in our study. Individuals with SAD reported significantly stronger emotional intensity across conditions and showed a nonsignificant tendency to judge pictures as more self-related than controls. Compared with controls, individuals with SAD showed an overactivation in bilateral temporoparietal regions and in the posterior midcingulate cortex during the passive viewing of aversive compared with neutral pictures. During instructed emotion regulation, activation patterns normalized and no significant group differences were detected. LIMITATIONS: As no positive pictures were presented, results might be limited to the regulation of negative emotion. CONCLUSION: During passive viewing of aversive images, individuals with SAD showed evidence of neural hyperreactivity that may be interpreted as increased bodily self-consciousness and heightened perspective-taking. During voluntary increase and decrease of negative emotional intensity, group differences disappeared, suggesting self-focused reappraisal as a successful emotion regulation strategy for individuals with SAD.

Childhood Maltreatment and Revictimization: A Systematic Literature Review.

There is established evidence that childhood/adolescent victimization is associated with victimization in adulthood although the underlying mechanisms are not still clear. The current study aimed to systematically review empirical studies examining potential psychological factors linking childhood maltreatment to victimization in adulthood and the gaps in the literature. Following PRISMA protocol, 71 original studies consisting of a total sample of n = 31,633 subjects were analyzed. Symptom severity for various trauma-related disorders, dissociation, emotion dysregulation, and risky sexual behaviors emerged as potential predictors of revictimization. While these potential risk factors mediate the relationship between childhood maltreatment and adulthood victimization, evidence for additional factors such as social support, attachment styles, maladaptive schemas, and risk detection is very limited. Addressing these intrapersonal risk factors, found by prior studies, in interventions and preventive programs might decrease the probability of revictimization. The interactions between the identified risk factors have not been studied well yet. Hence, more research on mediating risk factors of revictimization is needed.

Self-regulatory Sex Motives Scale in Online Dating: Exploratory Factor Analysis and Internal Consistency.

Risky sex behavior is common among online dating users. Understanding the motives behind risky sex behavior might help identify suitable targets for prevention. We developed the Self-regulatory Sex Motives Scale in Online Dating (SSOD) to assess sex motives for casual sex in online dating users. This study evaluated the psychometric properties of the SSOD and examined the relationship between sex motives indexed by the SSOD and risky sex behavior. The new scale showed high internal consistency. Exploratory factor analysis suggested a one-factor solution. Sex motives were related to a higher frequency of having sex on the first date.

Differential constellations of dissociative symptoms and their association with childhood trauma - a latent profile analysis.

Background: While several studies documented a positive correlation between childhood maltreatment severity and dissociation severity, it is currently unknown whether specific dissociative symptoms cluster together among individuals with childhood trauma histories ranging from none to severe.Objective: We aimed to explore symptom constellations across the whole spectrum of dissociative processing from patients with severe dissociative disorders to healthy controls and relate these to maltreatment severity and sociodemographic characteristics.Methods: We employed latent profile analysis to explore symptom profiles based on five subscales, measuring absorption, depersonalization, derealization, somatoform and identity alteration, based on the 20 items of the German short version of the Dissociative Experiences Scale-II (Fragebogen zu Dissoziativen Symptomen-20) in a large aggregate sample (n = 3,128) overrepresenting patients with trauma-related disorders. We then related these profiles to maltreatment severity as measured by the five subscales of the Childhood Trauma Questionnaire as well as sociodemographic characteristics.Results: Based on the five FDS subscales, six clusters differentiated by symptom severity, but not symptom constellations, were identified. Somatoform dissociation varied in accordance with the remaining symptom clusters. The cluster with the highest overall symptom severity entailed nearly all subjects diagnosed with Dissociative Identity Disorder and was characterized by extreme levels of childhood maltreatment. Both abuse and neglect were predictive of cluster membership throughout.Conclusions: The higher the severity of dissociative processing in a cluster, the more subjects reported high severity and multiplicity of childhood maltreatment. However, some subjects remain resilient to the development of dissociative processing although they experience extreme childhood maltreatment.

Dissociative symptoms, including identity alterations, are closely related to the severity of experienced childhood abuse.Somatoform dissociation occurs on all levels of overall dissociation severity.Some subjects with a history extreme childhood maltreatment do not develop dissociative symptoms, while some subjects with extreme dissociative symptoms do not report any childhood maltreatment.

Examining the association between posttraumatic stress disorder and disruptions in cortical networks identified using data-driven methods.

Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD patients and 1124 trauma-exposed controls without PTSD. We used regression analyses to investigate associations between CT within SCNs and PTSD diagnosis (with and without accounting for the potential confounding effect of trauma type) and symptom severity in the full sample. We performed additional regression analyses in subsets of the data to examine associations between SCNs and comorbid depression, childhood trauma severity, and alcohol abuse. NMF identified 20 unbiased SCNs, which aligned closely with functionally defined brain networks. PTSD diagnosis was most strongly associated with diminished CT in SCNs that encompassed the bilateral superior frontal cortex, motor cortex, insular cortex, orbitofrontal cortex, medial occipital cortex, anterior cingulate cortex, and posterior cingulate cortex. CT in these networks was significantly negatively correlated with PTSD symptom severity. Collectively, these findings suggest that PTSD diagnosis is associated with widespread reductions in CT, particularly within prefrontal regulatory regions and broader emotion and sensory processing cortical regions.

White matter integrity and its relationship to PTSD and childhood trauma--a systematic review and meta-analysis.

Recent reviews and meta-analyses reported structural gray matter changes in patients suffering from adult-onset posttraumatic stress disorder (PTSD) and in subjects with and without PTSD who experienced childhood trauma. However, it remains unclear if such structural changes are also affecting the white matter. The aim of this systematic review is to provide a comprehensive overview of all empirical investigations measuring white matter integrity in populations affected by PTSD and/or childhood trauma. To this end, results from different methodological approaches were included. Twenty-five articles are reviewed of which 10 pertained to pediatric PTSD and the effects of childhood trauma measured during childhood, seven to the effects of childhood trauma measured during adulthood, and eight to adult-onset PTSD. Overall, reductions in white matter volume were reported more often than increases in these populations. However, the heterogeneity of the exact locations indicates only a weak overlap across published studies. In addition, a meta-analysis was carried out on seven whole-brain diffusion tensor imaging (DTI) studies in adults. Significant clusters of both increases and decreases were identified in various structures, most notably the cingulum and the superior longitudinal fasciculus. Future research directions are discussed.