Cortico-limbic interactions and carotid atherosclerotic burden during chronic stress exposure.

BACKGROUND AND AIMS: Chronic stress associates with cardiovascular disease, but mechanisms remain incompletely defined. Advanced imaging was used to identify stress-related neural imaging phenotypes associated with atherosclerosis. METHODS: Twenty-seven individuals with post-traumatic stress disorder (PTSD), 45 trauma-exposed controls without PTSD, and 22 healthy controls underwent 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). Atherosclerotic inflammation and burden were assessed using 18F-FDG PET (as maximal target-to-background ratio, TBR max) and MRI, respectively. Inflammation was assessed using high-sensitivity C-reactive protein (hsCRP) and leucopoietic imaging (18F-FDG PET uptake in spleen and bone marrow). Stress-associated neural network activity (SNA) was assessed on 18F-FDG PET as amygdala relative to ventromedial prefrontal cortex (vmPFC) activity. MRI diffusion tensor imaging assessed the axonal integrity (AI) of the uncinate fasciculus (major white matter tract connecting vmPFC and amygdala). RESULTS: Median age was 37 years old and 54% of participants were female. There were no significant differences in atherosclerotic inflammation between participants with PTSD and controls; adjusted mean difference in TBR max (95% confidence interval) of the aorta 0.020 (-0.098, 0.138), and of the carotids 0.014 (-0.091, 0.119). Participants with PTSD had higher hsCRP, spleen activity, and aorta atherosclerotic burden (normalized wall index). Participants with PTSD also had higher SNA and lower AI. Across the cohort, carotid atherosclerotic burden (standard deviation of wall thickness) associated positively with SNA and negatively with AI independent of Framingham risk score. CONCLUSIONS: In this study of limited size, participants with PTSD did not have higher atherosclerotic inflammation than controls. Notably, impaired cortico-limbic interactions (higher amygdala relative to vmPFC activity or disruption of their intercommunication) associated with carotid atherosclerotic burden. Larger studies are needed to refine these findings.

Circulating PACAP levels are associated with altered imaging measures of entorhinal cortex neurite density in posttraumatic stress disorder.

Introduction: Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates plasticity in brain systems underlying arousal and memory and is associated with posttraumatic stress disorder (PTSD). Research in animal models suggests that PACAP modulates entorhinal cortex (EC) input to the hippocampus, contributing to impaired contextual fear conditioning. In PTSD, PACAP is associated with higher activity of the amygdala to threat stimuli and lower functional connectivity of the amygdala and hippocampus. However, PACAP-affiliated structural alterations of these regions have not been investigated in PTSD. Here, we examined whether peripheral PACAP levels were associated with neuronal morphology of the amygdala and hippocampus (primary analyses), and EC (secondary) using Neurite Orientation Dispersion and Density Imaging.Methods: Sixty-four (44 female) adults (19 to 54 years old) with DSM-5 Criterion A trauma exposure completed the Clinician-Administered PTSD Scale (CAPS-5), a blood draw, and magnetic resonance imaging. PACAP38 radioimmunoassay was performed and T1-weighted and multi-shell diffusion-weighted images were acquired. Neurite Density Index (NDI) and Orientation Dispersion Index (ODI) were quantified in the amygdala, hippocampus, and EC. CAPS-5 total score and anxious arousal score were used to test for clinical associations with brain structure.Results: Higher PACAP levels were associated with greater EC NDI (ß = 0.0099, q = 0.032) and lower EC ODI (ß = -0.0073, q = 0.047), and not hippocampal or amygdala measures. Neither EC NDI nor ODI was associated with clinical measures.Conclusions: Circulating PACAP levels were associated with altered neuronal density of the EC but not the hippocampus or amygdala. These findings strengthen evidence that PACAP may impact arousal-associated memory circuits in PTSD.

PACAP was associated with altered entorhinal cortex neurite density in PTSD.PACAP was not associated with altered neurite density in amygdala or hippocampus.PACAP may impact arousal-associated memory circuits.

A prospective study on EEG default mode network associated with subsequent posttraumatic stress disorder following sexual assault.

This study aimed to explore the predictors of posttraumatic stress disorder (PTSD) in women who have recently experienced sexual assault, by examining psychological and neurophysiological factors using a prospective design with resting-state electroencephalogram (EEG) functional connectivity. The study enrolled 33 women who had been recently traumatized by sexual assault and conducted assessments within a month of the trauma. These survivors were evaluated for PTSD three months later and were classified into two groups: PTSD positive (n = 12) and PTSD negative (n = 21). They were compared to two control groups comprising women who had not experienced any extremely traumatic events: 25 with depression and 25 healthy controls. The evaluation focused on resting-state EEG functional connectivity within default mode network (DMN) using small-worldness (SW), based on graph theory. We also assessed self-reported levels of depression, anxiety, anger, and executive functions. The findings indicated that survivors who developed PTSD three months post-trauma exhibited higher anxiety levels and reduced DMN SW in the beta 3 frequency, compared to those who did not develop PTSD. Contrary to expectations, survivors without PTSD showed decreased executive functioning and lower prefrontal centrality compared to those with PTSD. This study underscores the importance of early assessment and intervention for sexual assault survivors at risk of developing PTSD.

Less is more: Smaller hippocampal subfield volumes predict greater improvements in posttraumatic stress disorder symptoms over 2 years.

Posttraumatic stress disorder (PTSD) is a heterogeneous disorder, and symptom severity varies over time. Neurobiological factors that predict PTSD symptoms and their chronicity remain unclear. This study investigated whether the volume of the hippocampus and its subfields, particularly cornu ammonis (CA) 1, CA3, and dentate gyrus, are associated with current PTSD symptoms and whether they predict PTSD symptom changes over 2 years. We examined clinical and structural magnetic resonance imaging measures from 252 trauma-exposed post-9/11 veterans (159 with Time 1 PTSD diagnosis) during assessments approximately 2 years apart. Automated hippocampal subfield segmentation was performed with FreeSurfer Version 7.1, producing 19 bilateral subfields. PTSD symptoms were measured at each assessment using the Clinician-Administered PTSD Scale-IV (CAPS). All models included total intracranial volume as a covariate. First, similar to previous reports, we showed that smaller overall hippocampal volume was associated with greater PTSD symptom severity at Time 1. Notably, when examining regions of interest (CA1, CA3, dentate gyrus), we found that smaller Time 1 hippocampal volumes in the bilateral CA1-body and CA2/3-body predicted decreased PTSD symptom severity at Time 2. These findings were not accounted for by combat exposure or treatment history. Additionally, both Time 1 CA1-body and CA2/3-body volume showed unique associations with changes in avoidance/numbing, but not with changes in reexperiencing or hyperarousal symptoms. This supports a more complex and nuanced relationship between hippocampal structure and PTSD symptoms, where during the posttrauma years bigger may not always mean better, and suggests that the CA1-body and CA2/3-body are important factors in the maintenance of PTSD symptoms. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Hippocampus, amygdala, and insula activation in response to romantic relationship dissolution stimuli: A case-case-control fMRI study on emerging adult students.

BACKGROUND: Romantic relationship dissolutions (RRDs) are associated with posttraumatic stress symptoms (PTSS). Functional magnetic resonance imaging in RRD studies indicate overlapping neural activation similar to posttraumatic stress disorder. These studies combine real and hypothetical rejection, and lack contextual information and control and/or comparison groups exposed to non-RRD or DSM-5 defined traumatic events. AIM: We investigated blood oxygen level dependent (BOLD) activation in the hippocampus, amygdala, and insula of participants with RRDs compared with other traumatic or non-trauma stressors. METHODS: Emerging adults (mean age = 21.54 years; female = 74.7 %) who experienced an RRD (n = 36), DSM-5 defined trauma (physical and/or sexual assault: n = 15), or a non-RRD or DSM-5 stressor (n = 28) completed PTSS, depression, childhood trauma, lifetime trauma exposure, and attachment measures. We used a general and customised version of the International Affective Picture System to investigate responses to index-trauma-related stimuli. We used mixed linear models to assess between-group differences, and ANOVAs and Spearman's correlations to analyse factors associated with BOLD activation. RESULTS: BOLD activity increased between index-trauma stimuli as compared to neutral stimuli in the hippocampus and amygdala, with no significant difference between the DSM-5 Trauma and RRD groups. Childhood adversity, sexual orientation, and attachment style were associated with BOLD activation changes. Breakup characteristics (e.g., initiator status) were associated with increased BOLD activation in the hippocampus and amygdala, in the RRD group. CONCLUSION: RRDs should be considered as potentially traumatic events. Breakup characteristics are risk factors for experiencing RRDs as traumatic. LIMITATION: Future studies should consider more diverse representation across sex, ethnicity, and sexual orientation.

Brain morphological changes and functional neuroanatomy related to cognitive and emotional distractors during working memory maintenance in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is associated with abnormalities in the processing and regulation of emotion as well as cognitive deficits. This study evaluated the differential brain activation patterns associated with cognitive and emotional distractors during working memory (WM) maintenance for human faces between patients with PTSD and healthy controls (HCs) and assessed the relationship between changes in the activation patterns by the opposing effects of distraction types and gray matter volume (GMV). Twenty-two patients with PTSD and twenty-two HCs underwent T1-weighted magnetic resonance imaging (MRI) and event-related functional MRI (fMRI), respectively. Event-related fMRI data were recorded while subjects performed a delayed-response WM task with human face and trauma-related distractors. Compared to the HCs, the patients with PTSD showed significantly reduced GMV of the inferior frontal gyrus (IFG) (p < 0.05, FWE-corrected). For the human face distractor trial, the patients showed significantly decreased activities in the superior frontal gyrus and IFG compared with HCs (p < 0.05, FWE-corrected). The patients showed lower accuracy scores and slower reaction times for the face recognition task with trauma-related distractors compared with HCs as well as significantly increased brain activity in the STG during the trauma-related distractor trial was observed (p < 0.05, FWE-corrected). Such differential brain activation patterns associated with the effects of distraction in PTSD patients may be linked to neural mechanisms associated with impairments in both cognitive control for confusable distractors and the ability to control emotional distraction.

Traumatic Brain Injury and Post-Traumatic Stress Disorder and Their Influence on Development and Pattern of Alzheimer's Disease Pathology in Later Life.

Background: Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are potential risk factors for the development of dementia including Alzheimer's disease (AD) in later life. The findings of studies investigating this question are inconsistent though. Objective: To investigate if these inconsistencies are caused by the existence of subgroups with different vulnerability for AD pathology and if these subgroups are characterized by atypical tau load/atrophy pattern. Methods: The MRI and PET data of 89 subjects with or without previous TBI and/or PTSD from the DoD ADNI database were used to calculate an age-corrected gray matter tau mismatch metric (ageN-T mismatch-score and matrix) for each subject. This metric provides a measure to what degree regional tau accumulation drives regional gray matter atrophy (matrix) and can be used to calculate a summary score (score) reflecting the severity of AD pathology in an individual. Results: The ageN-T mismatch summary score was positively correlated with whole brain beta-amyloid load and general cognitive function but not with PTSD or TBI severity. Hierarchical cluster analysis identified five different spatial patterns of tau-gray matter interactions. These clusters reflected the different stages of the typical AD tau progression pattern. None was exclusively associated with PTSD and/or TBI. Conclusions: These findings suggest that a) although subsets of patients with PTSD and/or TBI develop AD-pathology, a history of TBI or PTSD alone or both is not associated with a significantly higher risk to develop AD pathology in later life. b) remote TBI or PTSD do not modify the typical AD pathology distribution pattern.

Functional connectivity alterations in PTSD patients with suicidal ideation.

Post-traumatic stress disorder (PTSD) is a highly prevalent psychological disorder characterized by intense feelings of fear or helplessness after experiencing a traumatic event. PTSD is highly comorbid with mood disorders and patients are at increased risk for suicide. The present study aimed to identify neural connectivity alterations associated with suicidal ideation (SI) in PTSD patients by using resting-state functional magnetic resonance imaging. Voxel-to-voxel intrinsic connectivity was compared between PTSD patients with no (N-SI; N = 26) and high (H-SI; N = 7) SI. Region-to-voxel functional connectivity analysis was performed to identify the regions that contributed to intrinsic connectivity changes. H-SI patients had increased connectivity to various brain regions representing the central executive network, salience network, and default mode network in the frontal, temporal, and occipital lobes as well as subcortical structures involved in executive and limbic functioning, and motor systems. These results suggest SI is associated with large network-level alterations in PTSD patients and is not the result of neuronal abnormalities in any one specific area.

Biomarkers associated with cognitive impairment in post-traumatic stress disorder: A systematic review of current evidence.

OBJECTIVE: This systematic review aimed at synthesizing current evidence on biomarkers associated with cognitive impairment (CI) in Post-Traumatic Stress Disorder (PTSD). METHODS: A systematic literature search was conducted for studies assessing biomarkers associated with CI in PTSD. RESULTS: Of the 10,149 titles screened, 8 studies met our inclusion criteria. In a single longitudinal study, MRI volumes, Aß and tau accumulation were not associated with CI in PTSD. Studies on structural imaging reported no significant association between morphological changes and CI. Two studies on diffusion neuroimaging showed abnormalities in white matter tracts which were cross-sectionally associated with CI in PTSD. Similarly, lower resting-state functional connectivity in neocortical networks, and elevated tau in the neocortex were also cross sectionally associated with CI. Two single studies on biochemical biomarkers showed that sixteen novel plasma proteins and lower BDNF, indicative of genetic vulnerabilities associated with neural and synaptic dysfunctions commonly observed in neurodegeneration, were cross-sectionally associated with CI in PTSD. Overall, evidence is of low quality. CONCLUSIONS: Longitudinal research utilizing large representative samples of trauma exposed populations are needed to establish the utility of specific biomarkers in monitoring cognitive decline in PTSD.

Multilayer analysis of dynamic network reconfiguration in pediatric posttraumatic stress disorder.

Neuroimage studies have reported functional connectome abnormalities in posttraumatic stress disorder (PTSD), especially in adults. However, these studies often treated the brain as a static network, and time-variance of connectome topology in pediatric posttraumatic stress disorder remain unclear. To explore case-control differences in dynamic connectome topology, resting-state functional magnetic resonance imaging data were acquired from 24 treatment-naïve non-comorbid pediatric posttraumatic stress disorder patients and 24 demographically matched trauma-exposed non-posttraumatic stress disorder controls. A graph-theoretic analysis was applied to construct time-varying modular structure of whole-brain networks by maximizing the multilayer modularity. Network switching rate at the global, subnetwork, and nodal levels were calculated and compared between posttraumatic stress disorder and trauma-exposed non-posttraumatic stress disorder groups, and their associations with posttraumatic stress disorder symptom severity and sex interactions were explored. At the global level, individuals with posttraumatic stress disorder exhibited significantly lower network switching rates compared to trauma-exposed non-posttraumatic stress disorder controls. This difference was mainly involved in default-mode and dorsal attention subnetworks, as well as in inferior temporal and parietal brain nodes. Posttraumatic stress disorder symptom severity was negatively correlated with switching rate in the global network and default mode network. No significant differences were observed in the interaction between diagnosis and sex/age. Pediatric posttraumatic stress disorder is associated with dynamic reconfiguration of brain networks, which may provide insights into the biological basis of this disorder.

Effects of a dissociative drug on fronto-limbic resting-state functional connectivity in individuals with posttraumatic stress disorder: a randomized controlled pilot study.

RATIONALE: A subanesthetic dose of ketamine, a non-competitive N-methyl-D-aspartate glutamate receptor (NMDAR) antagonist, elicits dissociation in individuals with posttraumatic stress disorder (PTSD), who also often suffer from chronic dissociative symptoms in daily life. These debilitating symptoms have not only been linked to worse PTSD trajectories, but also to increased resting-state functional connectivity (RSFC) between medial prefrontal cortex (mPFC) and amygdala, supporting the conceptualization of dissociation as emotion overmodulation. Yet, as studies were observational, causal evidence is lacking. OBJECTIVES: The present randomized controlled pilot study examines the effect of ketamine, a dissociative drug, on RSFC between mPFC subregions and amygdala in individuals with PTSD. METHODS: Twenty-six individuals with PTSD received either ketamine (0.5mg/kg; n = 12) or the control drug midazolam (0.045mg/kg; n = 14) during functional magnetic resonance imaging (fMRI). RSFC between amygdala and mPFC subregions, i.e., ventromedial PFC (vmPFC), dorsomedial PFC (dmPFC) and anterior-medial PFC (amPFC), was assessed at baseline and during intravenous drug infusion. RESULTS: Contrary to pre-registered predictions, ketamine did not promote a greater increase in RSFC between amygdala and mPFC subregions from baseline to infusion compared to midazolam. Instead, ketamine elicited a stronger transient decrease in vmPFC-amygdala RSFC compared to midazolam. CONCLUSIONS: A dissociative drug did not increase fronto-limbic RSFC in individuals with PTSD. These preliminary experimental findings contrast with prior correlative findings and call for further exploration and, potentially, a more differentiated view on the neurobiological underpinning of dissociative phenomena in PTSD.

Sensory alterations in post-traumatic stress disorder.

PTSD is characterized by difficulties in accurately evaluating the threat value of sensory stimuli. While the role of canonical fear and threat neural circuitry in this ability has been well studied, recent lines of evidence suggest a need to include more emphasis on sensory processing in the conceptualization of PTSD symptomology. Specifically, studies have demonstrated a strong association between variability in sensory processing regions and the severity of PTSD symptoms. In this review, we summarize recent findings that underscore the importance of sensory processing in PTSD, in addition to the structural and functional characteristics of associated sensory brain regions. First, we discuss the link between PTSD and various behavioral aspects of sensory processing. This is followed by a discussion of recent findings that link PTSD to variability in the structure of both gray and white matter in sensory brain regions. We then delve into how brain activity (measured with task-based and resting-state functional imaging) in sensory regions informs our understanding of PTSD symptomology.

Neuroimaging in Adolescents: Post-Traumatic Stress Disorder and Risk for Substance Use Disorders.

Trauma in childhood and adolescence has long-term negative consequences in brain development and behavior and increases the risk for psychiatric disorders. Among them, post-traumatic stress disorder (PTSD) during adolescence illustrates the connection between trauma and substance misuse, as adolescents may utilize substances to cope with PTSD. Drug misuse may in turn lead to neuroadaptations in learning processes that facilitate the consolidation of traumatic memories that perpetuate PTSD. This reflects, apart from common genetic and epigenetic modifications, overlapping neurocircuitry engagement triggered by stress and drug misuse that includes structural and functional changes in limbic brain regions and the salience, default-mode, and frontoparietal networks. Effective strategies to prevent PTSD are needed to limit the negative consequences associated with the later development of a substance use disorder (SUD). In this review, we will examine the link between PTSD and SUDs, along with the resulting effects on memory, focusing on the connection between the development of an SUD in individuals who struggled with PTSD in adolescence. Neuroimaging has emerged as a powerful tool to provide insight into the brain mechanisms underlying the connection of PTSD in adolescence and the development of SUDs.

White matter predictors of PTSD: Testing different machine learning models in a sample of Black American women.

BACKGROUND: Machine learning neuroimaging studies of posttraumatic stress disorder (PTSD) show promise for identifying neurobiological signatures of PTSD. However, studies to date, have largely evaluated a single machine learning approach, and few studies have examined white matter microstructure as a predictor of PTSD. Further, individuals from minoritized racial groups, specifically, Black individuals, who experience disproportionate trauma frequency, and have relatively higher rates of PTSD, have been underrepresented in these studies. We used four different machine learning models to test white matter microstructure classifiers of PTSD in a sample of trauma-exposed Black American women with and without PTSD. METHOD: Participants included 45 Black women with PTSD and 89 trauma-exposed controls recruited from an ongoing trauma study. Current PTSD presence was estimated using the Clinician-Administered PTSD Scale. Average fractional anisotropy of 53 white matter tracts served as input features. Additional exploratory analysis incorporated estimates of interpersonal and structural racism exposure. Classification models included linear support vector machine, radial basis function support vector machine, multilayer perceptron, and random forest. RESULTS: Performance varied notably between models. With white matter features along, linear support vector machine demonstrated the best model fit and reached an average AUC = 0.643. Inclusion of estimates of exposure to racism increased linear support vector machine performance (AUC = 0.808). CONCLUSIONS: White matter microstructure had limited ability to predict PTSD presence in this sample. These results may indicate that the relationship between white matter microstructure and PTSD may be nuanced across race and gender spectrums.

Distinct pre-COVID brain structural signatures in COVID-19-related post-traumatic stress symptoms and post-traumatic growth.

Post-traumatic stress symptoms and post-traumatic growth are common co-occurring psychological responses following exposure to traumatic events (such as COVID-19 pandemic), their mutual relationship remains unclear. To explore this relationship, structural magnetic resonance imaging data were acquired from 115 general college students before the COVID-19 pandemic, and follow-up post-traumatic stress symptoms and post-traumatic growth measurements were collected during the pandemic. Voxel-based morphometry was conducted and individual structural covariance networks based on gray matter volume were further analyzed using graph theory and partial least squares correlation. Behavioral correlation found no significant relationship between post-traumatic stress symptoms and post-traumatic growth. Voxel-based morphometry analyses showed that post-traumatic stress symptoms were positively correlated with gray matter volume in medial prefrontal cortex/dorsal anterior cingulate cortex, and post-traumatic growth was negatively correlated with gray matter volume in left dorsolateral prefrontal cortex. Structural covariance network analyses found that post-traumatic stress symptoms were negatively correlated with the local efficiency and clustering coefficient of the network. Moreover, partial least squares correlation showed that post-traumatic stress symptoms were correlated with pronounced nodal properties patterns in default mode, sensory and motor regions, and a marginal correlation of post-traumatic growth with a nodal property pattern in emotion regulation-related regions. This study advances our understanding of the neurobiological substrates of post-traumatic stress symptoms and post-traumatic growth, and suggests that they may have different neuroanatomical features.

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.

Functional brain changes after alternative pharmacological interventions in posttraumatic stress disorder: A systematic review of clinical trials.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a complex and heterogeneous mental health condition that can develop after exposure to a traumatic event. Clinical trials have used alternative pharmacological agents to treat PTSD, but their associated neural correlates remain unclear. The present systematic review aims to summarize the changes in brain function associated with the use of these alternative pharmacological agents in PTSD. METHODS: Clinical trials using functional magnetic resonance imaging, either at rest or during the performance of tasks, were included if they compared the effects of alternative pharmacological agents between PTSD patients and either trauma-exposed controls or never-exposed healthy controls. RESULTS: Sixteen studies were included, of which 11 used intranasal oxytocin, 2 used hydrocortisone, and 3 used delta-9-tetrahydrocannabinol (THC). Oxytocin administration was associated with the normalization of functional connectivity between the ventromedial prefrontal cortex and amygdala as well as enhanced the function of brain regions specifically involved in emotion processing (e.g., amygdala), working memory (e.g., dorsolateral prefrontal cortex), and reward (e.g., putamen). Hydrocortisone did not influence brain function at rest or during the performance of an autobiographical memory task, whereas THC was associated with the reduction of the amygdala and increased medial prefrontal cortex activation. CONCLUSIONS: This systematic review identified preliminary evidence for normalizing brain function after the use of alternative pharmacological agents. Importantly, sex-specific differences were noted, in particular when using oxytocin, that will require further investigation.

Posttraumatic Stress and Traumatic Brain Injury: Cognition, Behavior, and Neuroimaging Markers in Vietnam Veterans.

BACKGROUND: Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are common in Veterans and linked to behavioral disturbances, increased risk of cognitive decline, and Alzheimer's disease. OBJECTIVE: We studied the synergistic effects of PTSD and TBI on behavioral, cognitive, and neuroimaging measures in Vietnam war Veterans. METHODS: Data were acquired at baseline and after about one-year from male Veterans categorized into: PTSD, TBI, PTSD+TBI, and Veteran controls without PTSD or TBI. We applied manual tractography to examine white matter microstructure of three fiber tracts: uncinate fasciculus (N = 91), cingulum (N = 87), and inferior longitudinal fasciculus (N = 95). ANCOVAs were used to compare Veterans' baseline behavioral and cognitive functioning (N = 285), white matter microstructure, amyloid-ß (N = 230), and tau PET (N = 120). Additional ANCOVAs examined scores' differences from baseline to follow-up. RESULTS: Veterans with PTSD and PTSD+TBI, but not Veterans with TBI only, exhibited poorer behavioral and cognitive functioning at baseline than controls. The groups did not differ in baseline white matter, amyloid-ß, or tau, nor in behavioral and cognitive functioning, and tau accumulation change. Progression of white matter abnormalities of the uncinate fasciculus in Veterans with PTSD compared to controls was observed; analyses in TBI and PTSD+TBI were not run due to insufficient sample size. CONCLUSIONS: PTSD and PTSD+TBI negatively affect behavioral and cognitive functioning, while TBI does not contribute independently. Whether progressive decline in uncinate fasciculus microstructure in Veterans with PTSD might account for cognitive decline should be further studied. Findings did not support an association between PTSD, TBI, and Alzheimer's disease pathology based on amyloid and tau PET.

Persistence of post-traumatic stress disorder in Chinese Shidu parents is associated with combined gray and white matter abnormalities.

Post-traumatic stress disorder (PTSD) is one of the most common mental health disorders among Shidu parents. Identification of gray and white matter differences between persistence of PTSD (P-PTSD) and remission of PTSD (R-PTSD) is crucial to determine their prognosis. A total of 37 Shidu parents with PTSD were followed for five years. Surface-based morphometry and diffusion tensor imaging were carried out to analyze the differences in gray and white matter between P-PTSD and R-PTSD. Finally, 30 patients with PTSD were enrolled, including 12 with P-PTSD and 18 with R-PTSD. Compared with patients with R-PTSD, patients with P-PTSD exhibited lower fractional anisotropy (FA) in Cluster 1 (including body of the corpus callosum, superior longitudinal fasciculus, corticospinal tract) and Cluster 2 (including inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, splenium of the corpus callosum) in the left cerebral hemisphere and higher cortical thickness in the right lateral occipital cortex (LOC). In patients with P-PTSD, FA values of Cluster 2 were negatively correlated with cortical thickness of the right LOC. These results suggest that among Shidu parents, differences were observed in gray and white matter between P-PTSD and R-PTSD. Moreover, some certain gray and white matter abnormalities were often present simultaneously in P-PTSD.

Hypothalamus volume mediates the association between adverse childhood experience and PTSD development after adulthood trauma.

The hypothalamus is critical for regulation of the hypothalamic-pituitary-adrenal (HPA) axis and response to stress. Adverse childhood experience (ACE) can affect brain structure, which may contribute to development of posttraumatic stress disorder (PTSD) after subsequent adult trauma. It is unclear, however, if ACE history is particularly associated with aspects of hypothalamic structure which contribute to development of PTSD. To address this issue, the present study longitudinally assessed hypothalamic volumes and their associations with ACE and early post-trauma stress symptoms in subjects who did or did not develop PTSD during 12 months after adult trauma. 109 subjects (18-60 years, F/M = 75/34) completed the PTSD Checklist (PCL) questionnaire for post-trauma stress symptoms, the Childhood Trauma Questionnaire (CTQ) for ACE assessment, and an initial MRI brain scan for hypothalamic volume measurement, within 2 weeks after adult trauma. At post-trauma 12 months, subjects underwent a subsequent PTSD diagnosis interview using the Clinician-Administered PTSD Scale (CAPS), and a follow-up MRI scan. Left and right hypothalamus volumes at 2 weeks after adult trauma negatively correlated with CTQ scores. Right hypothalamus volume at this early time mediated an association between ACE and PTSD symptoms 12 months later. Right hypothalamus volumes also remained persistently smaller from 2 weeks to 12 months after trauma in survivors who developed PTSD. These results suggest that smaller right hypothalamus volume may be related to ACE history in ways that contribute to PTSD development after trauma in adulthood.