Metabolic syndrome is associated with reduced default mode network functional connectivity in young post-9/11 Veterans.

Metabolic syndrome is a collection of health factors that increases risk for cardiovascular disease. A condition of aging, metabolic syndrome is associated with reduced brain network integrity, including functional connectivity alterations among the default mode, regions vulnerable to neurodegeneration. Prevalence of metabolic syndrome is elevated in younger populations including post-9/11 Veterans and individuals with posttraumatic stress disorder, but it is unclear whether metabolic syndrome affects brain function in earlier adulthood. Identifying early effects of metabolic syndrome on brain network integrity is critical, as these impacts could contribute to increased risk for cognitive disorders later in life for Veterans. The current study examined whether metabolic syndrome and its individual components were associated with default mode functional connectivity. We also explored the contribution of posttraumatic stress disorder and traumatic brain injury on these metabolic syndrome-brain relationships. Post-9/11 Veterans with combat deployment history (95 with and 325 without metabolic syndrome) underwent functional magnetic resonance imaging to capture seed-based resting-state functional connectivity within the default mode. The metabolic syndrome group demonstrated reduced positive functional connectivity between the posterior cingulate cortex seed and the bilateral superior frontal gyrus. Data-driven analyses demonstrated that metabolic syndrome components, particularly cholesterol and central adiposity, were associated with widespread reductions in default mode network connectivity. Functional connectivity was also reduced in participants with metabolic syndrome but without current posttraumatic stress disorder diagnosis and with traumatic brain injury history. These results suggest that metabolic syndrome disrupts resting-state functional connectivity decades earlier than prior work has shown.

Blood-based DNA methylation and exposure risk scores predict PTSD with high accuracy in military and civilian cohorts.

BACKGROUND: Incorporating genomic data into risk prediction has become an increasingly popular approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not. METHODS: Elastic Net was used to develop three risk score models using a discovery dataset (n = 1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip. The first risk score, exposure and methylation risk score (eMRS) used cumulative and childhood trauma exposure and DNAm variables; the second, methylation-only risk score (MoRS) was based solely on DNAm data; the third, methylation-only risk scores with adjusted exposure variables (MoRSAE) utilized DNAm data adjusted for the two exposure variables. The potential of these risk scores to predict future PTSD based on pre-deployment data was also assessed. External validation of risk scores was conducted in four independent cohorts. RESULTS: The eMRS model showed the highest accuracy (92%), precision (91%), recall (87%), and f1-score (89%) in classifying PTSD using 3730 features. While still highly accurate, the MoRS (accuracy = 89%) using 3728 features and MoRSAE (accuracy = 84%) using 4150 features showed a decline in classification power. eMRS significantly predicted PTSD in one of the four independent cohorts, the BEAR cohort (beta = 0.6839, p=0.006), but not in the remaining three cohorts. Pre-deployment risk scores from all models (eMRS, beta = 1.92; MoRS, beta = 1.99 and MoRSAE, beta = 1.77) displayed a significant (p < 0.001) predictive power for post-deployment PTSD. CONCLUSION: The inclusion of exposure variables adds to the predictive power of MRS. Classification-based MRS may be useful in predicting risk of future PTSD in populations with anticipated trauma exposure. As more data become available, including additional molecular, environmental, and psychosocial factors in these scores may enhance their accuracy in predicting PTSD and, relatedly, improve their performance in independent cohorts.

Association between metabolic syndrome and white matter integrity in young and mid-age post-9/11 adult Veterans.

Metabolic syndrome has been associated with reduced brain white matter integrity in older individuals. However, less is known about how metabolic syndrome might impact white matter integrity in younger populations. This study examined metabolic syndrome-related global and regional white matter integrity differences in a sample of 537 post-9/11 Veterans. Metabolic syndrome was defined as ≥3 factors of: increased waist circumference, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension, and high fasting glucose. T1 and diffusion weighted 3 T MRI scans were processed using the FreeSurfer image analysis suite and FSL Diffusion Toolbox. Atlas-based regions of interest were determined from a combination of the Johns Hopkins University atlas and a Tract-Based Spatial Statistics-based FreeSurfer WMPARC white matter skeleton atlas. Analyses revealed individuals with metabolic syndrome (n = 132) had significantly lower global fractional anisotropy than those without metabolic syndrome (n = 405), and lower high-density lipoprotein cholesterol levels was the only metabolic syndrome factor significantly related to lower global fractional anisotropy levels. Lobe-specific analyses revealed individuals with metabolic syndrome had decreased fractional anisotropy in frontal white matter regions compared with those without metabolic syndrome. These findings indicate metabolic syndrome is prevalent in this sample of younger Veterans and is related to reduced frontal white matter integrity. Early intervention for metabolic syndrome may help alleviate adverse metabolic syndrome-related brain and cognitive effects with age.

Poor sleep and decreased cortical thickness in veterans with mild traumatic brain injury and post-traumatic stress disorder.

BACKGROUND: Poor sleep quality has been associated with changes in brain volume among veterans, particularly those who have experienced mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). This study sought to investigate (1) whether poor sleep quality is associated with decreased cortical thickness in Iraq and Afghanistan war veterans, and (2) whether these associations differ topographically depending on the presence or absence of mTBI and PTSD. METHODS: A sample of 440 post-9/11 era U.S. veterans enrolled in the Translational Research Center for Traumatic Brain Injury and Stress Disorders study at VA Boston, MA from 2010 to 2022 was included in the study. We examined the relationship between sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI), and cortical thickness in veterans with mTBI (n = 57), PTSD (n = 110), comorbid mTBI and PTSD (n = 129), and neither PTSD nor mTBI (n = 144). To determine the topographical relationship between subjective sleep quality and cortical thickness in each diagnostic group, we employed a General Linear Model (GLM) at each vertex on the cortical mantle. The extent of topographical overlap between the resulting statistical maps was assessed using Dice coefficients. RESULTS: There were no significant associations between PSQI and cortical thickness in the group without PTSD or mTBI (n = 144) or in the PTSD-only group (n = 110). In the mTBI-only group (n = 57), lower sleep quality was significantly associated with reduced thickness bilaterally in frontal, cingulate, and precuneus regions, as well as in the right parietal and temporal regions (ß = -0.0137, P < 0.0005). In the comorbid mTBI and PTSD group (n = 129), significant associations were observed bilaterally in frontal, precentral, and precuneus regions, in the left cingulate and the right parietal regions (ß = -0.0094, P < 0.0005). Interaction analysis revealed that there was a stronger relationship between poor sleep quality and decreased cortical thickness in individuals with mTBI (n = 186) compared to those without mTBI (n = 254) specifically in the frontal and cingulate regions (ß = -0.0077, P < 0.0005). CONCLUSIONS: This study demonstrates a significant relationship between poor sleep quality and lower cortical thickness primarily within frontal regions among individuals with both isolated mTBI or comorbid diagnoses of mTBI and PTSD. Thus, if directionality is established in longitudinal and interventional studies, it may be crucial to consider addressing sleep in the treatment of veterans who have sustained mTBI.

Negative global metacognitive biases are associated with depressive and posttraumatic stress disorder symptoms and improve with targeted or game-based cognitive training.

OBJECTIVE: Metacognition is disrupted in several clinical populations. One aspect of metacognition, global metacognitive bias (difference between objective and self-reported abilities), has shown to be particularly relevant to clinical functioning. However, previous studies of global metacognitive biases in populations with elevated depressive/posttraumatic stress disorder (PTSD) symptoms have not measured objective and self-reported abilities relative to normative samples, limiting the quantification of biases. Additionally, few studies have examined whether cognitive interventions can improve metacognitive biases or how this relates to depressive/PTSD symptom severity. METHOD: A total of 84 participants with mild traumatic brain injury (77% veterans) performed PTSD and depression assessments along with self-reported and objective measures of global cognition. Age-adjusted norm-based z scores were used for self-reported and objective cognition, and bias was calculated by subtracting objective minus self-report scores. Participants then received 13 weeks of targeted cognitive training or entertainment games training (both providing performance feedback). Participants were assessed at baseline, immediately posttraining, and 3 months posttraining. RESULTS: We found large negative metacognitive biases in those with clinically significant severity of depressive symptoms (z score difference = -1.77), PTSD symptoms (-1.47), and depressive + PTSD symptoms (-2.29). Metacognitive biases improved after both targeted and entertainment training and was associated with reductions in depressive/PTSD symptom severity (r = -.41/-.42, respectively), led by the entertainment training group (r = -.54/-.46, respectively). CONCLUSIONS: These findings show that clinically significant severity of depressive/PTSD symptoms is associated with substantial negative global metacognitive biases and preliminarily suggests that cognitive training may improve these biases and depressive/PTSD symptom severity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Epigenome-wide association studies identify novel DNA methylation sites associated with PTSD: A meta-analysis of 23 military and civilian cohorts.

Background: The occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, the impact of trauma, or the sequelae of PTSD itself. These effects include differences in DNA methylation (DNAm), an important form of epigenetic gene regulation, at multiple CpG loci across the genome. Moreover, these effects can be shared or specific to both central and peripheral tissues. Here, we aim to identify blood DNAm differences associated with PTSD and characterize the underlying biological mechanisms by examining the extent to which they mirror associations across multiple brain regions. Methods: As the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup, we conducted the largest cross-sectional meta-analysis of epigenome-wide association studies (EWASs) of PTSD to date, involving 5077 participants (2156 PTSD cases and 2921 trauma-exposed controls) from 23 civilian and military studies. PTSD diagnosis assessments were harmonized following the standardized guidelines established by the PGC-PTSD Workgroup. DNAm was assayed from blood using either Illumina HumanMethylation450 or MethylationEPIC (850K) BeadChips. A common QC pipeline was applied. Within each cohort, DNA methylation was regressed on PTSD, sex (if applicable), age, blood cell proportions, and ancestry. An inverse variance-weighted meta-analysis was performed. We conducted replication analyses in tissue from multiple brain regions, neuronal nuclei, and a cellular model of prolonged stress. Results: We identified 11 CpG sites associated with PTSD in the overall meta-analysis (1.44e-09 < p < 5.30e-08), as well as 14 associated in analyses of specific strata (military vs civilian cohort, sex, and ancestry), including CpGs in AHRR and CDC42BPB. Many of these loci exhibit blood-brain correlation in methylation levels and cross-tissue associations with PTSD in multiple brain regions. Methylation at most CpGs correlated with their annotated gene expression levels. Conclusions: This study identifies 11 PTSD-associated CpGs, also leverages data from postmortem brain samples, GWAS, and genome-wide expression data to interpret the biology underlying these associations and prioritize genes whose regulation differs in those with PTSD.

Intimate partner violence perpetration among veterans: associations with neuropsychiatric symptoms and limbic microstructure.

Background: Intimate partner violence (IPV) perpetration is highly prevalent among veterans. Suggested risk factors of IPV perpetration include combat exposure, post-traumatic stress disorder (PTSD), depression, alcohol use, and mild traumatic brain injury (mTBI). While the underlying brain pathophysiological characteristics associated with IPV perpetration remain largely unknown, previous studies have linked aggression and violence to alterations of the limbic system. Here, we investigate whether IPV perpetration is associated with limbic microstructural abnormalities in military veterans. Further, we test the effect of potential risk factors (i.e., PTSD, depression, substance use disorder, mTBI, and war zone-related stress) on the prevalence of IPV perpetration. Methods: Structural and diffusion-weighted magnetic resonance imaging (dMRI) data were acquired from 49 male veterans of the Iraq and Afghanistan wars (Operation Enduring Freedom/Operation Iraqi Freedom; OEF/OIF) of the Translational Research Center for TBI and Stress Disorders (TRACTS) study. IPV perpetration was assessed using the psychological aggression and physical assault sub-scales of the Revised Conflict Tactics Scales (CTS2). Odds ratios were calculated to assess the likelihood of IPV perpetration in veterans with either of the following diagnoses: PTSD, depression, substance use disorder, or mTBI. Fractional anisotropy tissue (FA) measures were calculated for limbic gray matter structures (amygdala-hippocampus complex, cingulate, parahippocampal gyrus, entorhinal cortex). Partial correlations were calculated between IPV perpetration, neuropsychiatric symptoms, and FA. Results: Veterans with a diagnosis of PTSD, depression, substance use disorder, or mTBI had higher odds of perpetrating IPV. Greater war zone-related stress, and symptom severity of PTSD, depression, and mTBI were significantly associated with IPV perpetration. CTS2 (psychological aggression), a measure of IPV perpetration, was associated with higher FA in the right amygdala-hippocampus complex (r = 0.400, p = 0.005). Conclusion: Veterans with psychiatric disorders and/or mTBI exhibit higher odds of engaging in IPV perpetration. Further, the more severe the symptoms of PTSD, depression, or TBI, and the greater the war zone-related stress, the greater the frequency of IPV perpetration. Moreover, we report a significant association between psychological aggression against an intimate partner and microstructural alterations in the right amygdala-hippocampus complex. These findings suggest the possibility of a structural brain correlate underlying IPV perpetration that requires further research.

Neurocognitive and psychiatric outcomes associated with postacute COVID-19 infection without severe medical complication: a meta-analysis.

BACKGROUND: Cognitive symptoms are often reported by those with a history of COVID-19 infection. No comprehensive meta-analysis of neurocognitive outcomes related to COVID-19 exists despite the influx of studies after the COVID-19 pandemic. This study meta-analysed observational research comparing cross-sectional neurocognitive outcomes in adults with COVID-19 (without severe medical/psychiatric comorbidity) to healthy controls (HCs) or norm-referenced data. METHODS: Data were extracted from 54 studies published between January 2020 and June 2023. Hedges' g was used to index effect sizes, which were pooled using random-effects modelling. Moderating variables were investigated using meta-regression and subgroup analyses. RESULTS: Omnibus meta-analysis of 696 effect sizes extracted across 54 studies (COVID-19 n=6676, HC/norm-reference n=12 986; average time since infection=~6 months) yielded a small but significant effect indicating patients with COVID-19 performed slightly worse than HCs on cognitive measures (g=-0.36; 95% CI=-0.45 to -0.28), with high heterogeneity (Q=242.30, p<0.001, τ=0.26). Significant within-domain effects was yielded by cognitive screener (g=-0.55; 95% CI=-0.75 to -0.36), processing speed (g=-0.44; 95% CI=-0.57 to -0.32), global cognition (g=-0.40; 95% CI=-0.71 to -0.09), simple/complex attention (g=-0.38; 95% CI=-0.46 to -0.29), learning/memory (g=-0.34; 95% CI=-0.46 to -0.22), language (g=-0.34; 95% CI=-0.45 to -0.24) and executive function (g=-0.32; 95% CI=-0.43 to -0.21); but not motor (g=-0.40; 95% CI=-0.89 to 0.10), visuospatial/construction (g=-0.09; 95% CI=-0.23 to 0.05) and orientation (g=-0.02; 95% CI=-0.17 to 0.14). COVID-19 samples with elevated depression, anxiety, fatigue and disease severity yielded larger effects. CONCLUSION: Mild cognitive deficits are associated with COVID-19 infection, especially as detected by cognitive screeners and processing speed tasks. We failed to observe clinically meaningful cognitive impairments (as measured by standard neuropsychological instruments) in people with COVID-19 without severe medical or psychiatric comorbidities.

Posttraumatic survivor guilt is associated with white matter microstructure alterations.

BACKGROUND: Military veterans with posttraumatic stress disorder (PTSD) commonly experience posttraumatic guilt. Guilt over commission or omission evolves when responsibility is assumed for an unfortunate outcome (e.g., the death of a fellow combatant). Survivor guilt is a state of intense emotional distress experienced by the weight of knowing that one survived while others did not. METHODS: This study of the Translational Research Center for TBI and Stress Disorders (TRACTS) analyzed structural and diffusion-weighted magnetic resonance imaging data from 132 male Iraq/Afghanistan veterans with PTSD. The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) was employed to classify guilt. Thirty (22.7 %) veterans experienced guilt over acts of commission or omission, 34 (25.8 %) experienced survivor guilt, and 68 (51.5 %) had no posttraumatic guilt. White matter microstructure (fractional anisotropy, FA), cortical thickness, and cortical volume were compared between veterans with guilt over acts of commission or omission, veterans with survivor guilt, and veterans without guilt. RESULTS: Veterans with survivor guilt had significantly lower white matter FA compared to veterans who did not experience guilt (p < .001), affecting several regions of major white matter fiber bundles. There were no significant differences in white matter FA, cortical thickness, or volumes between veterans with guilt over acts of commission or omission and veterans without guilt (p > .050). LIMITATIONS: This cross-sectional study with exclusively male veterans precludes inferences of causality between the studied variables and generalizability to the larger veteran population that includes women. CONCLUSION: Survivor guilt may be a particularly impactful form of posttraumatic guilt that requires specific treatment efforts targeting brain health.

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).

Association of mild traumatic brain injury, post-traumatic stress disorder, and other comorbidities on photosensitivity.

SIGNIFICANCE: Photosensitivity is common after mild traumatic brain injury. However, this study demonstrates that photosensitivity is also impacted by common comorbidities that often occur with mild traumatic brain injury. Understanding how physical and psychological traumas impact photosensitivity can help improve provider care to trauma survivors and guide novel therapeutic interventions. PURPOSE: This study aimed to characterize the association between mild traumatic brain injury and common comorbidities on photosensitivity in post-9/11 veterans. METHODS: Existing data from the Translational Research Center for TBI and Stress Disorders cohort study were analyzed including traumatic brain injury history and post-traumatic stress disorder clinical diagnostic interviews; sleep quality, anxiety, and depression symptoms self-report questionnaires; and photosensitivity severity self-report from the Neurobehavioral Symptom Inventory. Analysis of covariance and multiple ordinal regression models were used to assess associations between mild traumatic brain injury and common comorbidities with photosensitivity severity. RESULTS: Six hundred forty-one post-9/11 veterans were included in this study. An initial analysis showed that both mild traumatic brain injury and current post-traumatic stress disorder diagnosis were independently associated with higher photosensitivity ratings compared with veterans without either condition, with no interaction observed between these two conditions. Results of the ordinal regression models demonstrated positive associations between degree of photosensitivity and the number of mild traumatic brain injuries during military service and current post-traumatic stress disorder symptom severity, particularly hyperarousal symptoms, even when controlling for other factors. In addition, the degree of sleep disturbances and current anxiety symptoms were both positively associated with photosensitivity ratings, whereas depression symptoms, age, and sex were not. CONCLUSIONS: Repetitive mild traumatic brain injury, post-traumatic stress disorder, anxiety, and sleep disturbances were all found to significantly impact photosensitivity severity and are therefore important clinical factors that eye care providers should consider when managing veterans with a history of deployment-related trauma reporting photosensitivity symptoms.

Blood-based DNA methylation and exposure risk scores predict PTSD with high accuracy in military and civilian cohorts.

Background: Incorporating genomic data into risk prediction has become an increasingly useful approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not. Methods: Elastic Net was used to develop three risk score models using a discovery dataset (n = 1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip. The first risk score, exposure and methylation risk score (eMRS) used cumulative and childhood trauma exposure and DNAm variables; the second, methylation-only risk score (MoRS) was based solely on DNAm data; the third, methylation-only risk scores with adjusted exposure variables (MoRSAE) utilized DNAm data adjusted for the two exposure variables. The potential of these risk scores to predict future PTSD based on pre-deployment data was also assessed. External validation of risk scores was conducted in four independent cohorts. Results: The eMRS model showed the highest accuracy (92%), precision (91%), recall (87%), and f1-score (89%) in classifying PTSD using 3730 features. While still highly accurate, the MoRS (accuracy = 89%) using 3728 features and MoRSAE (accuracy = 84%) using 4150 features showed a decline in classification power. eMRS significantly predicted PTSD in one of the four independent cohorts, the BEAR cohort (beta = 0.6839, p-0.003), but not in the remaining three cohorts. Pre-deployment risk scores from all models (eMRS, beta = 1.92; MoRS, beta = 1.99 and MoRSAE, beta = 1.77) displayed a significant (p < 0.001) predictive power for post-deployment PTSD. Conclusion: Results, especially those from the eMRS, reinforce earlier findings that methylation and trauma are interconnected and can be leveraged to increase the correct classification of those with vs. without PTSD. Moreover, our models can potentially be a valuable tool in predicting the future risk of developing PTSD. As more data become available, including additional molecular, environmental, and psychosocial factors in these scores may enhance their accuracy in predicting the condition and, relatedly, improve their performance in independent cohorts.

Importance of validity testing in psychiatric assessment: evidence from a sample of multimorbid post-9/11 veterans.

OBJECTIVE: Performance validity (PVTs) and symptom validity tests (SVTs) are necessary components of neuropsychological testing to identify suboptimal performances and response bias that may impact diagnosis and treatment. The current study examined the clinical and functional characteristics of veterans who failed PVTs and the relationship between PVT and SVT failures. METHOD: Five hundred and sixteen post-9/11 veterans participated in clinical interviews, neuropsychological testing, and several validity measures. RESULTS: Veterans who failed 2+ PVTs performed significantly worse than veterans who failed one PVT in verbal memory (Cohen's d = .60-.69), processing speed (Cohen's d = .68), working memory (Cohen's d = .98), and visual memory (Cohen's d = .88-1.10). Individuals with 2+ PVT failures had greater posttraumatic stress (PTS; ß = 0.16; p = .0002), and worse self-reported depression (ß = 0.17; p = .0001), anxiety (ß = 0.15; p = .0007), sleep (ß = 0.10; p = .0233), and functional outcomes (ß = 0.15; p = .0009) compared to veterans who passed PVTs. 7.8% veterans failed the SVT (Validity-10; ≥19 cutoff); Multiple PVT failures were significantly associated with Validity-10 failure at the ≥19 and ≥23 cutoffs (p's < .0012). The Validity-10 had moderate correspondence in predicting 2+ PVTs failures (AUC = 0.83; 95% CI = 0.76, 0.91). CONCLUSION: PVT failures are associated with psychiatric factors, but not traumatic brain injury (TBI). PVT failures predict SVT failure and vice versa. Standard care should include SVTs and PVTs in all clinical assessments, not just neuropsychological assessments, particularly in clinically complex populations.

Inhibitory control and alcohol use history predict changes in posttraumatic stress disorder symptoms.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with significant disability and can become chronic. Predictors of PTSD symptom changes over time, especially in those with a PTSD diagnosis, remain incompletely characterized. METHOD: In the present study, we examined 187 post-9/11 veterans (Mage = 32.8 years, 87% male) diagnosed with PTSD who performed two extensive clinical and cognitive evaluations approximately 2 years apart. RESULTS: We found that greater PTSD symptom reductions over time were related to lower lifetime drinking history and better baseline inhibitory control ability (Color-Word Inhibition and Inhibition/Switching), though not performance on other executive function tasks. Further, groups with reliably Improved, Worsened, or Chronic PTSD symptoms demonstrated significant differences in baseline inhibitory control and lifetime drinking history, with marked drinking differences starting in the early-to-mid 20s. We also found that PTSD symptom changes showed little-to-no associations with changes in inhibitory control or alcohol consumption. CONCLUSIONS: Together, these findings suggest that, in those diagnosed with PTSD, inhibitory control and alcohol use history reflect relatively stable risk/resiliency factors predictive of PTSD chronicity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Semantic Priming from Uncued Distractors in Alzheimer's Disease.

RESEARCH QUESTION: Are semantic impairments in Alzheimer's disease (AD) partially due to deficits in spatial attention? METHODS AND RESULTS: In a target detection task, both older adults (OAs) and AD individuals were facilitated by valid spatial cues, but only OAs were impaired by invalid cues compared to neutral. In a reading task, spatial cues validly or invalidly cued the location of pictures, which were related or unrelated to subsequent, centrally presented, words. OAs showed semantic priming only after valid cues, whereas AD individuals showed priming after valid and invalid cues. DISCUSSION: Failure to inhibit uncued locations results in processing of potentially distracting semantic information in AD.

Neurobiological and genetic correlates of the dissociative subtype of posttraumatic stress disorder.

Approximately 10%-30% of individuals with posttraumatic stress disorder (PTSD) exhibit a dissociative subtype of the condition defined by symptoms of depersonalization and derealization. This study examined the psychometric evidence for the dissociative subtype of PTSD in a sample of young, primarily male post-9/11-era Veterans (n = 374 at baseline and n = 163 at follow-up) and evaluated its biological correlates with respect to resting state functional connectivity (default mode network [DMN]; n = 275), brain morphology (hippocampal subfield volume and cortical thickness; n = 280), neurocognitive functioning (n = 337), and genetic variation (n = 193). Multivariate analyses of PTSD and dissociation items suggested a class structure was superior to dimensional and hybrid ones, with 7.5% of the sample comprising the dissociative class; this group showed stability over 1.5 years. Covarying for age, sex, and PTSD severity, linear regression models revealed that derealization/depersonalization severity was associated with: decreased DMN connectivity between bilateral posterior cingulate cortex and right isthmus (p = .015; adjusted-p [padj] = .097); increased bilateral whole hippocampal, hippocampal head, and molecular layer head volume (p = .010-.034; padj = .032-.053); worse self-monitoring (p = .018; padj = .079); and a candidate genetic variant (rs263232) in the adenylyl cyclase 8 gene (p = .026), previously associated with dissociation. Results converged on biological structures and systems implicated in sensory integration, the neural representation of spatial awareness, and stress-related spatial learning and memory, suggesting possible mechanisms underlying the dissociative subtype of PTSD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Sleep Quality Disturbances Are Associated with White Matter Alterations in Veterans with Post-Traumatic Stress Disorder and Mild Traumatic Brain Injury.

Sleep disturbances are strongly associated with mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI have been linked to alterations in white matter (WM) microstructure, but whether poor sleep quality has a compounding effect on WM remains largely unknown. We evaluated sleep and diffusion magnetic resonance imaging (dMRI) data from 180 male post-9/11 veterans diagnosed with (1) PTSD (n = 38), (2) mTBI (n = 25), (3) comorbid PTSD+mTBI (n = 94), and (4) a control group with neither PTSD nor mTBI (n = 23). We compared sleep quality (Pittsburgh Sleep Quality Index, PSQI) between groups using ANCOVAs and calculated regression and mediation models to assess associations between PTSD, mTBI, sleep quality, and WM. Veterans with PTSD and comorbid PTSD+mTBI reported poorer sleep quality than those with mTBI or no history of PTSD or mTBI (p = 0.012 to <0.001). Poor sleep quality was associated with abnormal WM microstructure in veterans with comorbid PTSD+mTBI (p < 0.001). Most importantly, poor sleep quality fully mediated the association between greater PTSD symptom severity and impaired WM microstructure (p < 0.001). Our findings highlight the significant impact of sleep disturbances on brain health in veterans with PTSD+mTBI, calling for sleep-targeted interventions.

The Impact of Blast Exposure-With or Without Traumatic Brain Injury-on Metabolic Abnormalities in Post-9/11 Veterans.

OBJECTIVE: The primary aim included explorations of: (1) the associations between the history of blast exposure (BE), close blast exposure (CBE), and blast-related traumatic brain injury (bTBI) and metabolic abnormality; and (2) the potential mediating effect of comorbid psychological and somatic conditions on these associations. The secondary aim explored the association of dose-response impact of BE, CBE, and bTBI and metabolic abnormality. SETTING: Data were collected by the Translational Research Center for TBI and Stress Disorders (TRACTS). PARTICIPANTS: Post-9/11 veterans from the TRACTS baseline sample who had conflict-zone deployment experience ( N = 734). DESIGN: Cross-sectional secondary data analysis. We computed relative risks (RRs) and 95% CI using modified Poisson regression. We quantified the impact of co-occurring psychological and somatic conditions on this association using mediation analyses. MAIN MEASURES: Exposures included BE (<100 m), CBE (<10 m), and bTBI. Metabolic abnormality outcomes included (1) overweight/obesity (defined by abnormal waist-hip ratio [WHR] and abnormal waist circumference [WC]); (2) glucose dysregulation; and (3) meeting criteria for cardiometabolic syndrome (defined by guidelines). RESULTS: The sample was majority male (91%) and White (68%), with a mean age of 34.6 years (SD = 8.99). Most participants had 1 or more BE (83%); 48% experienced 1 or more CBE. Overweight/obesity was highly prevalent in the sample (51% had abnormal WHR and 60% abnormal WC). There was no significant direct or indirect association between BE, CBE, and bTBI and metabolic abnormalities (RRs: 0.70-1.51; P 's > .05). CONCLUSION: Future research is needed to investigate the association of BE with metabolic abnormalities with larger, more targeted sample selection, and longer follow-up. Effective and sustainable weight management and metabolic health prevention interventions for this veteran cohort are needed.

Genetic Risk for Alzheimer Disease and Plasma Tau Are Associated With Accelerated Parietal Cortex Thickness Change in Middle-Aged Adults.

Background and Objectives: Neuroimaging and biomarker studies in Alzheimer disease (AD) have shown well-characterized patterns of cortical thinning and altered biomarker concentrations of tau and ß-amyloid (Aß). However, earlier identification of AD has great potential to advance clinical care and determine candidates for drug trials. The extent to which AD risk markers relate to cortical thinning patterns in midlife is unknown. The first objective of this study was to examine cortical thickness change associated with genetic risk for AD among middle-aged military veterans. The second objective was to determine the relationship between plasma tau and Aß and change in brain cortical thickness among veterans stratified by genetic risk for AD. Methods: Participants consisted of post-9/11 veterans (N = 155) who were consecutively enrolled in the Translational Research Center for TBI and Stress Disorders prospective longitudinal cohort and were assessed for mild traumatic brain injury (TBI) and posttraumatic disorder (PTSD). Genome-wide polygenic risk scores (PRSs) for AD were calculated using summary results from the International Genomics of Alzheimer's Disease Project. T-tau and Aß40 and Aß42 plasma assays were run using Simoa technology. Whole-brain MRI cortical thickness change estimates were obtained using the longitudinal stream of FreeSurfer. Follow-up moderation analyses examined the AD PRS × plasma interaction on change in cortical thickness in AD-vulnerable regions. Results: Higher AD PRS, signifying greater genetic risk for AD, was associated with accelerated cortical thickness change in a right hemisphere inferior parietal cortex cluster that included the supramarginal gyrus, angular gyrus, and intraparietal sulcus. Higher tau, but not Aß42/40 ratio, was associated with greater cortical thickness change among those with higher AD PRS. Mild TBI and PTSD were not associated with cortical thickness change. Discussion: Plasma tau, particularly when combined with genetic stratification for AD risk, can be a useful indicator of brain change in midlife. Accelerated inferior parietal cortex changes in midlife may be an important factor to consider as a marker of AD-related brain alterations.

Changes in Mild Neurocognitive Disorder Status in Mobility Limited Older Primary Care Patients: Implications for Rehabilitative Care.

OBJECTIVE: The aim of the study is to identify potential rehabilitative treatment targets associated with participants' annual cognitive status. DESIGN: A cohort study patients with self-reported mobility limitation who completed neuropsychological, physical performance testing, and questionnaires at baseline to 2-year follow-up were categorized into three groups (persistently cognitively normal, nonpersistent mild neurocognitive disorder, and persistently mild neurocognitive disorder) based on their annual cognitive status using baseline, years 1 and 2 performance on Hopkins Verbal Learning, Trail Making, and Digit Symbol Substitution Tests. Repeated measures multinomial regression analysis was used to examine the differences between groups and associated characteristics. RESULTS: Study included 349 participants (mean age, 76 ± 7) with 57% of participants were persistently cognitively normal, 16% persistently mild neurocognitive disorder, and 27% nonpersistent mild neurocognitive disorder over 2 yrs of follow-up. Faster gait speed (relative risk reduction, 0.64-0.89) was associated with risk reduction and increase in depressive symptoms (relative risk reduction, 1.09-1.12) was associated with greater risk of being classified into the nonpersistent or persistently mild neurocognitive disorder compared with persistently cognitively normal. CONCLUSIONS: Variability across cognitive status over time was observed. Gait speed and depressive symptoms were modifiable risk factors associated with nonpersistent and persistent mild neurocognitive disorder status. This study reinforces the potential benefit of multifaceted rehabilitation for preventing and treating older adults with mobility and/or cognitive problems.