Brain structural abnormalities of the associative striatum in adolescents and young adults at genetic high-risk of schizophrenia: Implications for illness endophenotypes.

OBJECTIVE: Dysfunction in cortico-striatal circuitry represents a core component of the pathophysiology in schizophrenia (SZ) but its potential as a candidate endophenotype of the illness is often confounded by neuroleptic medication. METHODS: Accordingly, 26 adolescent and young adult participants at genetic high-risk for schizophrenia, but who were asymptomatic and neuroleptic naïve, and 28 age-matched controls underwent 1.5T structural magnetic resonance imaging of the striatum, manually parcellated into limbic (LST), associative (AST), and sensorimotor (SMST) functional subregions. RESULTS: In relation to their age peers, participants at genetic high-risk for schizophrenia showed overall lower striatal gray matter volume with their most pronounced loss, bilaterally in the AST, but not the LST or SMST. Neuropsychological testing revealed reduced executive functioning for genetically at-risk participants, although the groups did not differ significantly in overall intelligence or oral reading. For controls but not for at-genetic high-risk participants, stronger executive functioning correlated with increased bilateral AST volume. CONCLUSIONS: Reduced bilateral AST volume in genetic high-risk adolescents and young adults, accompanied by heritable loss of higher cognitive brain-behavior relationships, might serve as a useful endophenotype of SZ.

Network analysis of mild traumatic brain injury, persistent neurobehavioral and psychiatric symptoms, and functional disability among recent-era United States veterans.

Recent-era U.S. veterans are clinically complex, with a high prevalence of co-occurring mild traumatic brain injury (mTBI), psychiatric conditions, and behavioral dysfunction. The current study examined the direct and indirect associations between mTBI and persistent neurobehavioral, psychiatric, and functional disability symptoms among recent-era U.S. veterans and service members (n = 648). We evaluated the postconcussive syndrome (PCS) potential causal model with two network analysis modeling approaches. Separate analyses were conducted for military mTBI and lifetime mTBI. An exploratory factor analysis was conducted to limit topological overlap in the network analysis. The most influential symptoms (i.e., the unique variables most strongly associated with the rest of the network) in the military mTBI network were behavioral disengagement, expected influence (EI) = 1.10; cognitive difficulties, EI = 1.08; agitation/irritability, EI = 1.05; and PTSD-related reexperiencing and avoidance symptoms, EI = 0.98. After accounting for other symptoms, mTBI was only minimally informative, EI = 0.34. Additionally, military mTBI did not moderate the association between symptoms or the overall connectivity of the network. The results for lifetime mTBI were consistent with those for military mTBI. The present analyses identified a variety of behavioral, cognitive, and emotional symptoms that play an important role in understanding comorbidity and daily functioning among recent-era U.S. veterans. Associations between cumulative mTBI that occurred in civilian or military settings were indirect and relatively small in magnitude. The current results add to a growing literature raising doubts about the PCS model.

The impact of interpersonal early life trauma on cardio-metabolic health in post-9/11 veterans.

OBJECTIVE: This study examined the impact of early life trauma (ELT) on cardio-metabolic health in veterans from post-9/11 conflicts who experience significant stress from deployment and reintegration. METHOD: Three hundred thirty-seven veterans from the Translational Research Center for Traumatic Brain Injury and Stress Disorders study underwent physiological assessments, including blood pressure and waist circumference. Fasting blood samples were collected to measure metabolic syndrome (MetS; cholesterol/triglycerides/glucose). ELT history was determined using the Traumatic Life Events Questionnaire. Posttraumatic stress disorder (PTSD) symptoms were assessed using the Clinician-Administered PTSD Scale. Logistic regression models examined the association of ELT and MetS diagnostic criteria while controlling for confounders. RESULTS: The adjusted logistic regression showed a significant relationship between interpersonal ELT (IP ELT) and risk of MetS, with IP ELT having an approximately 3-fold increase in the risk of cardio- metabolic syndrome compared with those with no trauma (odds ratio [OR] = 3.06, p < .05). IP ELT was associated with over a 2-fold increased risk of elevated triglycerides compared with those with no trauma (OR = 2.06, p < .05). PTSD symptoms also explained in part the IP-ELT/MetS relationship. Veterans with any ELT were significantly more likely to meet for a current diagnosis of PTSD. CONCLUSIONS: Our findings suggest that veterans with IP ELT are more likely to meet MetS and PTSD diagnostic criteria than veterans without IP ELT. This is concerning considering the young age of the sample and stresses the importance of an integrated and holistic approach in the assessment of physical and mental health in returning veterans. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Comprehensive analysis of the predictors of neurobehavioral symptom reporting in veterans.

OBJECTIVE: This study assessed the strength of military-related concussion-, psychological-, and behavioral-related measures to predict neurobehavioral symptom (NBS) reporting in order to help clarify the extent to which persistent NBS reflect lingering effects of concussion vs other psychological/behavioral factors among veterans. METHODS: Baseline analysis included 351 consecutively enrolled veterans in the Translational Research Center for Traumatic Brain Injury and Stress Disorders longitudinal cohort study. One hundred eighty-six returned for a follow-up evaluation averaging 24 months post baseline. The Neurobehavioral Symptom Inventory (NSI) was used to measure NBS reporting. Predictor variables included diagnosis of military-related mild traumatic brain injury (M-mTBI), psychological measures, including posttraumatic stress disorder, mood, anxiety, and substance abuse disorders, and behavioral measures, including self-reported current pain and sleep impairment. Hierarchical and multivariable regression analyses examined the relationships between the predictor variables and NSI scores. The k-fold cross-validation assessed generalizability and validity of the regressions. RESULTS: Baseline analysis revealed that psychological and behavioral conditions independently accounted for 42.5% of variance in the NSI total score compared to 1.5% for M-mTBI after controlling for psychological and behavioral conditions. Prospective analysis revealed that M-mTBI at baseline did not significantly predict NSI score at follow-up, while psychological and behavioral measures at baseline independently accounted for 24.5% of NSI variance. Posttraumatic stress disorder was the most consistent predictor. Cross-validation analyses supported generalizability of the results. CONCLUSIONS: Psychological and behavioral-related measures are strong predictors of persistent NBS reporting in veterans, while M-mTBI is negligible. NBS more likely reflect influential comorbidities as opposed to brain injury, per se.

Verbal Memory Deficits in OEF/OIF/OND Veterans Exposed to Blasts at Close Range.

OBJECTIVES: This study investigated the relationship between close proximity to detonated blast munitions and cognitive functioning in OEF/OIF/OND Veterans. METHODS: A total of 333 participants completed a comprehensive evaluation that included assessment of neuropsychological functions, psychiatric diagnoses and history of military and non-military brain injury. Participants were assigned to a Close-Range Blast Exposure (CBE) or Non-Close-Range Blast Exposure (nonCBE) group based on whether they had reported being exposed to at least one blast within 10 meters. RESULTS: Groups were compared on principal component scores representing the domains of memory, verbal fluency, and complex attention (empirically derived from a battery of standardized cognitive tests), after adjusting for age, education, PTSD diagnosis, sleep quality, substance abuse disorder, and pain. The CBE group showed poorer performance on the memory component. Rates of clinical impairment were significantly higher in the CBE group on select CVLT-II indices. Exploratory analyses examined the effects of concussion and multiple blasts on test performance and revealed that number of lifetime concussions did not contribute to memory performance. However, accumulating blast exposures at distances greater than 10 meters did contribute to poorer performance. CONCLUSIONS: Close proximity to detonated blast munitions may impact memory, and Veterans exposed to close-range blast are more likely to demonstrate clinically meaningful deficits. These findings were observed after statistically adjusting for comorbid factors. Results suggest that proximity to blast should be considered when assessing for memory deficits in returning Veterans. Comorbid psychiatric factors may not entirely account for cognitive difficulties. (JINS, 2018, 24, 466-475).

Feasibility of a Skills-Based Group Reintegration Workshop for OEF/OIF Veterans: STEP-Home.

OBJECTIVE: To evaluate the feasibility of a newly developed reintegration workshop for Operation Iraqi Freedom/Operation Enduring Freedom (OEF/OIF) Veterans that is based on an evidence-based rehabilitation program shown to be effective in treating mild traumatic brain injury-related symptoms in civilians. Underutilization and resistance to mental health treatment remain a significant problem for OEF/OIF Veterans. Innovative, integrative, transdiagnostic, and acceptable interventions are needed, particularly for this heterogeneous group. PARTICIPANTS: Eighty-four OEF/OIF/Operation New Dawn Veterans (74 male and 10 female)-mean age = 35; standard deviation = 7.4. SETTING: VA Healthcare System. INTERVENTION: A 12-week, 2-hour/wk, group skills-based workshop with individual skill building to assist all OEF/OIF Veterans (with and without psychiatric and/or traumatic brain injury) in reintegration after military service. MAIN MEASURES: Primary outcomes were feasibility measures including treatment fidelity, acceptability, tolerability/adherence, and treatment-related skill acquisition. Secondary outcomes were interest and engagement in future treatment and reintegration status. RESULTS: Veterans' enrollment, adherence, and attrition data indicated that Short-Term Executive Plus adapted for Veteran civilian reintegration (STEP-Home) was acceptable and tolerable. Pre-/postintervention differences in attention, problem-solving, and emotional regulation skills demonstrated treatment-related skills acquisition. Secondary outcome data demonstrated Veterans who were hesitant to participate in mental health treatments before enrollment were more open to treatment engagement after STEP-Home, and reintegration status improved. CONCLUSIONS: This study demonstrated that the STEP-Home workshop is feasible in OEF/OIF Veterans and changes in treatment-related skill acquisition and reintegration status were observed. STEP-Home has potential to facilitate readjustment and serves as a gateway to additional, critically needed Veterans Administration services.