Factors Increasing Risk of Suicide after Traumatic Brain Injury: A State-of-the-Science Review of Military and Civilian Studies.

Primary Objective: Survey TBI literature to identify evidence of risk for post-injury suicide.Literature Selection: Search terms ((traumatic brain injury OR TBI) AND (suicidality OR suicidal behaviour OR suicidal ideation)) entered in PubMed, OVID Medline, PsychInfo, and Web of Science for papers published in print 01/01/1997 to 06/30/2019.Analysis of Literature: Authors screened abstracts, excluding duplicates and articles not meeting inclusion/exclusion criteria. Full papers were reviewed to make final exclusions. Data were extracted from 40 papers included co- and premorbid disorders, demographics, injury-related and psychological factors.Results: Persons with TBI have a higher risk for suicide than the general population. Reviewed articles reported comorbid depression and/or PTSD as risk factors for post-TBI suicide. Co- or premorbid substance misuse, sex, and sleep disturbance moderate risk. Quality of the literature was limited by sample size, the predominance of male participants, and inconsistency in reporting of findings.Conclusions: Comorbid depression and PTSD are significant post-TBI risk factors for suicide. Several variables combine to moderate or mediate TBI's connection with suicide. Civilian and military clinician cross-talk and consistent reporting of results from reproducible studies of post-TBI suicide risk factors could improve prevention and treatment efforts in veterans and civilians.

Vascular endothelial growth factor receptor-2 inhibition in experimental murine colitis.

BACKGROUND: In the setting of inflammatory bowel disease, inflammation is associated with a simultaneous increase in angiogenesis; moreover, elevated vascular endothelial growth factor (VEGF) levels implicate angiogenesis as a pathologic contributor to disease severity. We hypothesize that selectively inhibiting vascular endothelial growth factor receptor-2 (VEGFR2) in a model of murine colitis will reduce angiogenesis, resulting in decreased inflammation and disease severity, providing mechanistic insight into the role of pathologic angiogenesis in IBD. MATERIALS AND METHODS: In a dextran sodium sulfate model of murine colitis, anti-VEGFR2 monoclonal antibody (DC101) or placebo was administered. Clinical assessments followed by histologic and molecular tissue analysis were performed to quantify inflammation, microvessel density (MVD), VEGF and VEGFR2 gene expression, and phosphorylated mitogen-activated protein kinase protein expression. RESULTS: Weight loss began after d 6 with the treatment group demonstrating a more favorable percent weight change. Inflammation and MVD were similar between cohorts, both increasing in parallel toward a plateau. VEGF and VEGFR2 messenger RNA expression were not significantly different, but phosphorylated mitogen-activated protein kinase was elevated in the DC101 cohort (P = 0.03). CONCLUSIONS: Despite a more favorable weight change profile in the treated group, no difference was observed between cohorts regarding clinical disease severity. However, a parallel rise in inflammation and MVD was observed coinciding with weight loss, suggesting their relationship in IBD. VEGFR2 downstream signaling was significantly elevated in the treated cohort, possibly by VEGF-independent signal transduction. Early and effective inhibition of angiogenesis by limiting downstream VEGF signaling or targeting multiple angiogenic pathways may block angiogenesis, thereby reducing disease severity and provide evidence toward the mechanism and clinical benefit of antiangiogenics in the setting of IBD.