Traumatic brain injury (TBI), mental health conditions (e.g., posttraumatic stress disorder [PTSD]), and vascular comorbidities (e.g., hypertension, diabetes) are highly prevalent in the Veteran population and may exacerbate age-related changes to cerebral white matter (WM). Our study examined (1) relationships between health conditions—TBI history, PTSD, and vascular risk—and cerebral WM micro- and macrostructure, and (2) associations between WM measures and cognition.

We analyzed diffusion tensor images from 183 older male Veterans (mean age = 69.18; SD = 3.61) with (n = 95) and without (n = 88) a history of TBI using tractography. Generalized linear models examined associations between health conditions and diffusion metrics. Total WM hyperintensity (WMH) volume was calculated from fluid-attenuated inversion recovery images. Robust regression examined associations between health conditions and WMH volume. Finally, elastic net regularized regression examined associations between WM measures and cognitive performance.

Veterans with and without TBI did not differ in severity of PTSD or vascular risk (p’s >0.05). TBI history, PTSD, and vascular risk were independently associated with poorer WM microstructural organization (p’s <0.5, corrected), however the effects of vascular risk were more numerous and widespread. Vascular risk was positively associated with WMH volume (p = 0.004, β=0.200, R2 = 0.034). Higher WMH volume predicted poorer processing speed (R2 = 0.052).

Relative to TBI history and PTSD, vascular risk may be more robustly associated with WM micro- and macrostructure. Furthermore, greater WMH burden is associated with poorer processing speed. Our study supports the importance of vascular health interventions in mitigating negative brain aging outcomes in Veterans.

Research indicates that Veterans with a history of traumatic brain injury (TBI) are at increased risk for dementia. Although the precise mechanisms underlying this relationship are poorly understood, remote TBI may exacerbate normal age-related changes to cerebral white matter (WM) and result in cognitive decline. However, Veterans commonly experience a constellation of mental (e.g., post-traumatic stress disorder [PTSD] and depression) and vascular (e.g., diabetes, hypertension, obesity) health conditions that have also been implicated in pathologic cerebral WM and cognitive aging trajectories. Therefore, the present study sought to (1) clarify the effects of remote TBI within the context of PTSD, depression, and vascular risk on WM micro- and macrostructure, and (2) explore if WM integrity is associated with cognition in a sample of Vietnam-Era Veterans.

The sample consisted of 195 male Veterans ages 60-80 (mean age=69.3) enrolled in the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative (DoD-ADNI) study. 102 Veterans met criteria for TBI by sustaining a head-injury that resulted in a loss of consciousness, alteration of consciousness, or post-traumatic amnesia. Current and/or lifetime PTSD was designated by scores >30 on the Clinician-Administered PTSD Scale. The Geriatric Depression Scale was used as a continuous measure of depression. A vascular risk score (0-3) was calculated based on diabetes, hypertension, and obesity (BMI >30 kg/m2). An executive functioning composite was created by averaging sample-specific z-scores for Trail Making Tests (A and B), with higher scores indicating worse performance. Voxelwise analysis of WM microstructure (fractional anisotropy [FA]) was conducted with Tract-Based Spatial Statistics (TBSS), using non-parametric permutation testing with threshold-free cluster enhancement. SPM’s Lesion Segmentation Tool was used to investigate WM macrostructure (WM hyperintensity [WMH] volume). Lesion probability maps were masked to restrict WMH volume calculations to WM. Robust regression using M-estimation and predictive R2 calculated using 10-fold cross-validation examined WMH volume, predictor, and cognitive associations. Age was a covariate in all WM analyses, and education was a covariate in all cognitive analyses.

TBSS analysis revealed widespread, significant negative relationships between vascular risk and FA across numerous WM tracts (p’s<0.05). These associations remained significant after adjusting for TBI history, PTSD, and depression. TBSS identified significant positive relationships between executive functioning performance and FA across similar brain regions (p’s<0.05). Robust regressions revealed that vascular risk significantly predicted WMH volume (p=0.006; ß=0.161; R2=0.093), whereas TBI history, PTSD, and depression did not (p’s=0.107-0.166; ß's=-0.089-0.101). WMH volume significantly predicted executive functioning (p=0.002; ß=0.216; R2=0.105), whereas TBI history, PTSD, depression, and vascular risk did not (p’s=0.123-0.888; ß's=-0.012-0.125).

Our results suggest that vascular health, relative to remote TBI, PTSD, and depression, may be more robustly associated with cerebral WM micro- and macrostructure in older Veterans. Furthermore, poorer WM integrity is associated with poorer cognitive performance. These findings underscore the importance of vascular health interventions in preventing negative brain and cognitive aging outcomes in Veterans, independent of TBI history. Future studies might leverage other neuroimaging modalities (e.g., functional MRI) to further investigate the effects of vascular health on aging in Veterans with a history of TBI.

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Catheter ablation is a safe and effective therapy for the treatment of supraventricular tachycardia in children. Current improvements in technology have allowed progressive reduction in radiation exposure associated with the procedure. To assess the impact of three-dimensional mapping, we compared acute procedural results collected from the Catheter Ablation with Reduction or Elimination of Fluoroscopy registry to published results from the Prospective Assessment after Pediatric Cardiac Ablation study.

Inclusion and exclusion criteria from the Prospective Assessment after Pediatric Cardiac Ablation study were used as guidelines to select patient data from the Catheter Ablation with Reduction or Elimination of Fluoroscopy registry to compare acute procedural outcomes between cohorts. Outcomes assessed include procedural and fluoroscopy exposure times, success rates of procedure, and complications.

In 786 ablation procedures, targeting 498 accessory pathways and 288 atrioventricular nodal reentrant tachycardia substrates, average procedural time (156.5 versus 206.7 minutes, p < 0.01), and fluoroscopy time (1.2 versus 38.3 minutes, p < 0.01) were significantly shorter in the study group. Success rates for the various substrates were similar except for manifest accessory pathways which had a significantly higher success rate in the study group (96.4% versus 93.0%, p < 0.01). Major complication rates were significantly lower in the study group (0.3% versus 1.6%, p < 0.01).

In a large, multicentre study, three-dimensional systems show favourable improvements in clinical outcomes in children undergoing catheter ablation of supraventricular tachycardia compared to the traditional fluoroscopic approach. Further improvements are anticipated as technology advances.

Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.

We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.

In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).

AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.