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.

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.

Instrumented Balance Error Scoring System in Children and Adolescents-A Cross Sectional Study.

Background: The Balance Error Scoring System (BESS) is a commonly used method for clinically evaluating balance after traumatic brain injury. The utilization of force plates, characterized by their cost-effectiveness and portability, facilitates the integration of instrumentation into the BESS protocol. Despite the enhanced precision associated with instrumented measures, there remains a need to determine the clinical significance and feasibility of such measures within pediatric cohorts. Objective: To report a comprehensive set of posturographic measures obtained during instrumented BESS and to examine the concurrent validity, reliability, and feasibility of instrumented BESS in the pediatric point of care setting. Methods: Thirty-seven participants (18 female; aged 13.32 ± 3.31 years) performed BESS while standing on a force plate to simultaneously compute stabilometric measures (instrumented BESS). Ellipse area (EA), path length (PL), and sway velocity (VM) were obtained for each of the six BESS positions and compared with the respective BESS scores. Additionally, the effects of sex and age were explored. A second BESS repetition was performed to evaluate the test-retest reliability. Feedback questionnaires were handed out after testing to evaluate the feasibility of the proposed protocol. Results: The BESS total score was 20.81 ± 6.28. While there was no statistically significant age or sex dependency in the BESS results, instrumented posturography demonstrated an age dependency in EA, VM, and PL. The one-leg stance on a soft surface resulted in the highest BESS score (8.38 ± 1.76), EA (218.78 cm2 ± 168.65), PL (4386.91 mm ± 1859.00), and VM (21.93 mm/s ± 9.29). The Spearman's coefficient displayed moderate to high correlations between the EA (rs = 0.429-0.770, p = 0.001-0.009), PL (rs = 0.451-0.809, p = 0.001-0.006), and VM (rs = 0.451-0.809, p = 0.001-0.006) when compared with the BESS scores for all testing positions, except for the one-leg stance on a soft surface. The BESS total score significantly correlated during the first and second repetition (rs = 0.734, p ≤ 0.001), as did errors during the different testing positions (rs = 0.489-0.799, p ≤ 0.001-0.002), except during the two-legged stance on a soft surface. VM and PL correlated significantly in all testing positions (rs = 0.465-0.675, p ≤ 0.001-0.004; (rs = 0.465-0.675, p ≤ 0.001-0.004), as did EA for all positions except for the two-legged stance on a soft surface (rs = 0.392-0.581, p ≤ 0.001-0.016). A total of 92% of participants stated that the instructions for the testing procedure were very well-explained, while 78% of participants enjoyed the balance testing, and 61% of participants could not decide whether the testing was easy or hard to perform. Conclusions: Instrumented posturography may complement clinical assessment in investigating postural control in children and adolescents. While the BESS score only allows for the consideration of a total score approximating postural control, instrumented posturography offers several parameters representing the responsiveness and magnitude of body sway as well as a more differentiated analysis of movement trajectory. Concise instrumented posturography protocols should be developed to augment neuropediatric assessments in cases where a deficiency in postural control is suspected, potentially stemming from disruptions in the processing of visual, proprioceptive, and/or vestibular information.

Symptoms of mental disorders and oral contraception use: A systematic review and meta-analysis.

Worldwide, over 150 million adolescent and adult women use oral contraceptives (OC). An association between OC-use and the emergence of symptoms of mental disorders has been suggested. This systematic review and meta-analysis provide an overview of published research regarding symptoms of mental disorders in association with OC-use, factoring the influence of OC types, age of first-use, duration of OC-intake, and previous diagnoses of mental disorders. A systematic literature search was conducted between June-July 2022. 22 studies were included. While most found no significant OC-use effects on mental symptoms, some hinted at OCs as a potential risk. The existing evidence regarding the potential link between progestin-only OC-use and an elevated risk of mental symptoms in comparison to combined OC-use remains inconclusive. However, due to emerging indications suggesting that the formulation of OC might play a role in mental health outcomes, this topic warrants further investigation. Moreover, indications of an increased risk for depressive symptoms in adolescent OC-users should be noted. Hence, while general population effects seem unlikely, they cannot be completely disregarded. The decision on OC-use should depend on the patient's medical history and should be re-evaluated regularly.

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.

Adverse Outcome Following Mild Traumatic Brain Injury Is Associated with Microstructure Alterations at the Gray and White Matter Boundary.

The gray matter/white matter (GM/WM) boundary of the brain is vulnerable to shear strain associated with mild traumatic brain injury (mTBI). It is, however, unknown whether GM/WM microstructure is associated with long-term outcomes following mTBI. The diffusion and structural MRI data of 278 participants between 18 and 65 years of age with and without military background from the Department of Defense INTRuST study were analyzed. Fractional anisotropy (FA) was extracted at the GM/WM boundary across the brain and for each lobe. Additionally, two conventional analytic approaches were used: whole-brain deep WM FA (TBSS) and whole-brain cortical thickness (FreeSurfer). ANCOVAs were applied to assess differences between the mTBI cohort (n = 147) and the comparison cohort (n = 131). Associations between imaging features and post-concussive symptom severity, and functional and cognitive impairment were investigated using partial correlations while controlling for mental health comorbidities that are particularly common among military cohorts and were present in both the mTBI and comparison group. Findings revealed significantly lower whole-brain and lobe-specific GM/WM boundary FA (p < 0.011), and deep WM FA (p = 0.001) in the mTBI cohort. Whole-brain and lobe-specific GM/WM boundary FA was significantly negatively correlated with post-concussive symptoms (p < 0.039), functional (p < 0.016), and cognitive impairment (p < 0.049). Deep WM FA was associated with functional impairment (p = 0.002). Finally, no significant difference was observed in cortical thickness, nor between cortical thickness and outcome (p > 0.05). Findings from this study suggest that microstructural alterations at the GM/WM boundary may be sensitive markers of adverse long-term outcomes following mTBI.

Psychometric Properties of the German Version of the Quality of Life after Brain Injury Scale for Kids and Adolescents (QOLIBRI-KID/ADO) Using Item Response Theory Framework: Results from the Pilot Study.

Health-related quality of life (HRQOL) is an important indicator for recovery after pediatric TBI. To date, there are a few questionnaires available for assessing generic HRQOL in children and adolescents, but there are not yet any TBI-specific measures of HRQOL that are applicable to pediatric populations. The aim of the present study was to examine psychometric characteristics of the newly developed Quality of Life After Brain Injury Scale for Kids and Adolescents (QOLIBRI-KID/ADO) questionnaire capturing TBI-specific HRQOL in children and adolescents using an item response theory (IRT) framework. Children (8-12 years; n = 152) and adolescents (13-17 years; n = 148) participated in the study. The final version of the QOLIBRI-KID/ADO, comprising 35 items forming 6 scales, was investigated using the partial credit model (PCM). A scale-wise examination for unidimensionality, monotonicity, item infit and outfit, person homogeneity, and local independency was conducted. The questionnaire widely fulfilled the predefined assumptions, with a few restrictions. The newly developed QOLIBRI-KID/ADO instrument shows at least satisfactory psychometric properties according to the results of both classical test theoretical and IRT analyses. Further evidence of its applicability should be explored in the ongoing validation study by performing multidimensional IRT analyses.

A Multidimensional Approach to Assessing Factors Impacting Health-Related Quality of Life after Pediatric Traumatic Brain Injury.

In the field of pediatric traumatic brain injury (TBI), relationships between pre-injury and injury-related characteristics and post-TBI outcomes (functional recovery, post-concussion depression, anxiety) and their impact on disease-specific health-related quality of life (HRQoL) are under-investigated. Here, a multidimensional conceptual model was tested using a structural equation model (SEM). The final SEM evaluates the associations between these four latent variables. We retrospectively investigated 152 children (8-12 years) and 148 adolescents (13-17 years) after TBI at the recruiting clinics or online. The final SEM displayed a fair goodness-of-fit (SRMR = 0.09, RMSEA = 0.08 with 90% CI [0.068, 0.085], GFI = 0.87, CFI = 0.83), explaining 39% of the variance across the four latent variables and 45% of the variance in HRQoL in particular. The relationships between pre-injury and post-injury outcomes and between post-injury outcomes and TBI-specific HRQoL were moderately strong. Especially, pre-injury characteristics (children's age, sensory, cognitive, or physical impairments, neurological and chronic diseases, and parental education) may aggravate post-injury outcomes, which in turn may influence TBI-specific HRQoL negatively. Thus, the SEM comprises potential risk factors for developing negative post-injury outcomes, impacting TBI-specific HRQoL. Our findings may assist healthcare providers and parents in the management, therapy, rehabilitation, and care of pediatric individuals after TBI.

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.

White Matter Microstructure Is Associated with Serum Neuroactive Steroids and Psychological Functioning.

Military service members are at increased risk for mental health issues, and comorbidity with mild traumatic brain injury (mTBI) is common. Largely overlapping symptoms between conditions suggest a shared pathophysiology. The present work investigates the associations among white matter microstructure, psychological functioning, and serum neuroactive steroids that are part of the stress-response system. Diffusion-weighted brain imaging was acquired from 163 participants (with and without military affiliation) and free-water-corrected fractional anisotropy (FAT) was extracted. Associations between serum neurosteroid levels of allopregnanolone (ALLO) and pregnenolone (PREGNE), psychological functioning, and whole-brain white matter microstructure were assessed using regression models. Moderation models tested the effect of mTBI and comorbid post-traumatic stress disorder (PTSD) and mTBI on these associations. ALLO is associated with whole-brain white matter FAT (ß = 0.24, t = 3.05, p = 0.006). This association is significantly modulated by PTSD+mTBI comorbidity (ß = 0.00, t = 2.50, p = 0.027), although an mTBI diagnosis alone did not significantly impact this association (p = 0.088). There was no significant association between PREGNE and FAT (p = 0.380). Importantly, lower FAT is associated with poor psychological functioning (ß = -0.19, t = -2.35, p = 0.020). This study provides novel insight into a potential common pathophysiological mechanism of neurosteroid dysregulation underlying the high risk for mental health issues in military service members. Further, comorbidity of PTSD and mTBI may bring the compensatory effects of the brain's stress response to their limit. Future research is needed to investigate whether neurosteroid regulation may be a promising tool for restoring brain health and improving psychological functioning.

Association of War Zone-Related Stress With Alterations in Limbic Gray Matter Microstructure.

Importance: Military service members returning from theaters of war are at increased risk for mental illness, but despite high prevalence and substantial individual and societal burden, the underlying pathomechanisms remain largely unknown. Exposure to high levels of emotional stress in theaters of war and mild traumatic brain injury (mTBI) are presumed factors associated with risk for the development of mental disorders. Objective: To investigate (1) whether war zone-related stress is associated with microstructural alterations in limbic gray matter (GM) independent of mental disorders common in this population, (2) whether associations between war zone-related stress and limbic GM microstructure are modulated by a history of mTBI, and (3) whether alterations in limbic GM microstructure are associated with neuropsychological functioning. Design, Setting, and Participants: This cohort study was part of the TRACTS (Translational Research Center for TBI and Stress Disorders) study, which took place in 2010 to 2014 at the Veterans Affair Rehabilitation Research and Development TBI National Network Research Center. Participants included male veterans (aged 18-65 years) with available diffusion tensor imaging data enrolled in the TRACTS study. Data analysis was performed between December 2017 to September 2021. Exposures: The Deployment Risk and Resilience Inventory (DRRI) was used to measure exposure to war zone-related stress. The Boston Assessment of TBI-Lifetime was used to assess history of mTBI. Stroop Inhibition (Stroop-IN) and Inhibition/Switching (Stroop-IS) Total Error Scaled Scores were used to assess executive or attentional control functions. Main Outcomes and Measures: Diffusion characteristics (fractional anisotropy of tissue [FAT]) of 16 limbic and paralimbic GM regions and measures of functional outcome. Results: Among 384 male veterans recruited, 168 (mean [SD] age, 31.4 [7.4] years) were analyzed. Greater war zone-related stress was associated with lower FAT in the cingulate (DRRI-combat left: P = .002, partial r = -0.289; DRRI-combat right: P = .02, partial r = -0.216; DRRI-aftermath left: P = .004, partial r = -0.281; DRRI-aftermath right: P = .02, partial r = -0.219), orbitofrontal (DRRI-combat left medial orbitofrontal cortex: P = .02, partial r = -0.222; DRRI-combat right medial orbitofrontal cortex: P = .005, partial r = -0.256; DRRI-aftermath left medial orbitofrontal cortex: P = .02, partial r = -0.214; DRRI-aftermath right medial orbitofrontal cortex: P = .005, partial r = -0.260; DRRI-aftermath right lateral orbitofrontal cortex: P = .03, partial r = -0.196), and parahippocampal (DRRI-aftermath right: P = .03, partial r = -0.191) gyrus, as well as with higher FAT in the amygdala-hippocampus complex (DRRI-combat: P = .005, partial r = 0.254; DRRI-aftermath: P = .02, partial r = 0.223). Lower FAT in the cingulate-orbitofrontal gyri was associated with impaired response inhibition (Stroop-IS left cingulate: P < .001, partial r = -0.440; Stroop-IS right cingulate: P < .001, partial r = -0.372; Stroop-IS left medial orbitofrontal cortex: P < .001, partial r = -0.304; Stroop-IS right medial orbitofrontal cortex: P < .001, partial r = -0.340; Stroop-IN left cingulate: P < .001, partial r = -0.421; Stroop-IN right cingulate: P < .001, partial r = -0.300; Stroop-IN left medial orbitofrontal cortex: P = .01, partial r = -0.223; Stroop-IN right medial orbitofrontal cortex: P < .001, partial r = -0.343), whereas higher FAT in the mesial temporal regions was associated with improved short-term memory and processing speed (left amygdala-hippocampus complex: P < .001, partial r = -0.574; right amygdala-hippocampus complex: P < .001, partial r = 0.645; short-term memory left amygdala-hippocampus complex: P < .001, partial r = 0.570; short-term memory right amygdala-hippocampus complex: P < .001, partial r = 0.633). A history of mTBI did not modulate the association between war zone-related stress and GM diffusion. Conclusions and Relevance: This study revealed an association between war zone-related stress and alteration of limbic GM microstructure, which was associated with cognitive functioning. These results suggest that altered limbic GM microstructure may underlie the deleterious outcomes of war zone-related stress on brain health. Military service members may benefit from early therapeutic interventions after deployment to a war zone.

Psychometric Properties of the German Version of the Rivermead Post-Concussion Symptoms Questionnaire in Adolescents after Traumatic Brain Injury and Their Proxies.

The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) assesses post-concussion symptoms (PCS) after traumatic brain injury (TBI). The current study examines the applicability of self-report and proxy versions of the German RPQ in adolescents (13-17 years) after TBI. We investigated reliability and validity on the total and scale score level. Construct validity was investigated by correlations with the Post-Concussion Symptoms Inventory (PCSI-SR13), Generalized Anxiety Disorder Scale 7 (GAD-7), and Patient Health Questionnaire 9 (PHQ-9) and by hypothesis testing regarding individuals' characteristics. Intraclass correlation coefficients (ICC) assessed adolescent-proxy agreement. In total, 148 adolescents after TBI and 147 proxies completed the RPQ. Cronbach's α (0.81-0.91) and McDonald's ω (0.84-0.95) indicated good internal consistency. The three-factor structure outperformed the unidimensional model. The RPQ was strongly correlated with the PCSI-SR13 (self-report: r = 0.80; proxy: r = 0.75) and moderately-strongly with GAD-7 and PHQ-9 (self-report: r = 0.36, r = 0.35; proxy: r = 0.53, r = 0.62). Adolescent-proxy agreement was fair (ICC [2,1] = 0.44, CI95% [0.41, 0.47]). Overall, both self-report and proxy assessment forms of the German RPQ are suitable for application in adolescents after TBI. As proxy ratings tend to underestimate PCS, self-reports are preferable for evaluations. Only if a patient is unable to answer, a proxy should be used as a surrogate.

Biopsychosocial risk factors of persistent fatigue after acute infection: A systematic review to inform interventions.

OBJECTIVES: Fatigue is a prevalent and debilitating symptom, preceded by an acute infectious episode in some patients. This systematic review aimed to identify risk factors for the development of persistent fatigue after an acute infection, to develop an evidence-based working model of post-infectious fatigue. METHODS: Electronic databases (Medline, PsycINFO and EMBASE) were searched, from inception to March 2016, for studies which investigated biopsychosocial risk factors of on-going fatigue after an acute infection. Inclusion criteria were: prospective design; biological, psychological or social risk factors; standardised measure of post-infectious fatigue (self-report scales or clinical diagnosis). Studies were excluded if the sample had a pre-existing medical condition, infection was conceptualised as 'vaccination' or they were intervention trials. A narrative synthesis was performed. RESULTS: Eighty-one full texts were screened, of which seventeen were included in the review. Over half included glandular fever populations. Other infections included dengue fever, 'general'/'viral' and Q-fever. Risk factors were summarised under biological, social, behavioural, cognitive and emotional subthemes. Patients' cognitive and behavioural responses to the acute illness, and pre-infection or baseline distress and fatigue were the most consistent risk factors for post-infectious fatigue. CONCLUSION: An empirical summary model is provided, highlighting the risk factors most consistently associated with persistent fatigue. The components of the model, the possible interaction of risk factors and implications for understanding the fatigue trajectory and informing preventative treatments are discussed.