Free-Water Diffusion Magnetic Resonance Imaging Differentiates Suicidal Ideation From Suicide Attempt in Treatment-Resistant Depression.

BACKGROUND: Suicide attempt is highly prevalent in treatment-resistant depression (TRD); however, the neurobiological profile of suicidal ideation versus suicide attempt is unclear. Neuroimaging methods including diffusion magnetic resonance imaging-based free-water imaging may identify neural correlates underlying suicidal ideation and attempts in individuals with TRD. METHODS: Diffusion magnetic resonance imaging data were obtained from 64 male and female participants (mean age 44.5 ± 14.2 years), including 39 patients with TRD (n = 21 and lifetime history of suicidal ideation but no attempts [SI group]; n = 18 with lifetime history of suicide attempt [SA group]), and 25 age- and sex-matched healthy control participants. Depression and suicidal ideation severity were examined using clinician-rated and self-report measures. Whole-brain neuroimaging analysis was conducted using tract-based spatial statistics via FSL to identify differences in white matter microstructure in the SI versus SA groups and in patients versus control participants. RESULTS: Free-water imaging revealed elevated axial diffusivity and extracellular free water in fronto-thalamo-limbic white matter tracts of the SA group compared with the SI group. In a separate comparison, patients with TRD had widespread reductions in fractional anisotropy and axial diffusivity, as well as elevated radial diffusivity compared with control participants (thresholded p < .05, familywise error corrected). CONCLUSIONS: A unique neural signature consisting of elevated axial diffusivity and free water was identified in patients with TRD and suicide attempt history. Findings of reduced fractional anisotropy, axial diffusivity, and elevated radial diffusivity in patients versus control participants are consistent with previously published studies. Multimodal and prospective investigations are recommended to better understand biological correlates of suicide attempt in TRD.

Transforming the "SEAD": Evaluation of a Virtual Surgical Exploration and Discovery Program and its Effects on Career Decision-Making.

OBJECTIVE: The abrupt cessation of in-person education due to the COVID-19 pandemic has made it difficult for preclerkship students to explore a career in surgery. To supplement the lack of exposure, the Surgical Exploration and Discovery (SEAD) program was transitioned to an entirely virtual format. This study aims to describe the virtual SEAD program and evaluate its effectiveness as a career decision-making (CDM) intervention. DESIGN: The week-long program was delivered on Microsoft Teams, featured 11 surgical specialties, and comprised four activities: live demonstrations, virtual operating room observerships, career talks, and technical skills workshops. The program was evaluated using the four levels of the Kirkpatrick model: (1) reactions, (2) knowledge, (3) CDM behaviors - assessed using the Career Decision-making Difficulties Questionnaire (CDDQ) - and (4) results. The latter was indirectly assessed using CDDQ scores from an in-person SEAD program, where lower CDDQ scores indicate less difficulty with CDM. SETTING: Faculty of Medicine at the University of Ottawa in Ontario, Canada. PARTICIPANTS: Forty pre-clerkship students (27 first and 13 second year students) at the University of Ottawa RESULTS: Level 1: 97.5% of participants rated the program as good or very good. Live demonstration and technical skills workshops were the highest rated activities. Level 2: participants' scores on knowledge-based questions about a surgical career significantly increased following the program (pre: 9/25 vs post: 15/25, p = 0.008). Level 3: overall mean CDDQ scores (±SD) decreased difficulties with significantly following the program (pre: 45.6 ± 10.5 vs post: 38.8 ± 10.9, p < 0.001), which indicates decreased CDM difficulties. Level 4: Except for one sub-category, the difference in mean CDDQ scores between the virtual and in-person programs were not significantly different. CONCLUSION: The program received the positive reactions and significantly increased participants' knowledge. The change in CDDQ scores following the virtual program suggests it may reduce career decision-making difficulties in the short-term. In-person surgical exposure remains important; however, a hybrid model may be valuable in resource limited settings. WC: 300.

Assessment of Objective and Subjective Cognitive Function in Patients With Treatment-Resistant Depression Undergoing Repeated Ketamine Infusions.

BACKGROUND: Subanesthetic ketamine infusions can elicit rapid and sustained antidepressant effects, yet the potential cognitive impact of ketamine has not been thoroughly examined. This study measured changes in objective and subjective cognitive function following repeated ketamine treatment. METHODS: Thirty-eight patients with treatment-resistant depression were administered cognitive assessments before and after undergoing 7 i.v. ketamine infusions (0.5 mg/kg over 40 minutes) within a clinical trial examining the efficacy of single and repeated administrations. Depression severity and perceived concentration were evaluated with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptoms Self-Report. RESULTS: Twenty-three participants (60.5%) responded after repeated infusions (≥50% decrease in MADRS total scores). We measured significant improvements in several cognitive domains, including attention, working memory, verbal, and visuospatial memory (effect sizes ranging from Cohen d = 0.37-0.79). Cognitive changes were attributed to reduction in depressive symptoms except for improvement in verbal memory, which remained significant after adjustment for change in MADRS total score (P = .029, η p2 = 0.13). Only responders reported improvement in subjective cognitive function with repeated ketamine administration (MADRS item 6, P < .001, d = 2.00; Quick Inventory of Depressive Symptoms Self-Report item 10, P < .001, d = 1.36). CONCLUSION: A short course of repeated ketamine infusions did not impair neurocognitive function in patients with treatment-resistant depression. Further research is required to understand the potential mediating role of response and remission on improved cognitive function accompanying ketamine treatment as well as to examine longer-term safety outcomes. ClinicalTrials.gov identifier NCT01945047.

Sex Differences in Determinants of Suicide Risk Preceding Psychiatric Admission: An Electronic Medical Record Study.

Background: Individuals requiring inpatient psychiatric care represent a group at higher risk of progressing toward suicide attempt. Using electronic medical record (EMR) data collected from psychiatric inpatient admissions, the objective of this study was to identify sex differences in risk factors for suicide plans and/or attempts within the 30 days preceding hospital admission. Methods: Resident Assessment Instrument for Mental Health (RAI-MH) intake data were obtained for patients admitted to a Canadian tertiary-care hospital deemed a "threat or danger to self" during a 10-year period (2008-2018). Data was extracted for individuals categorized into three groups: non-suicidal (N = 568), presence of suicide plan (N = 178), and presence of suspected suicide attempt (N = 124) in the 30 days prior to hospital admission. Multivariate logistic regression models were used to examine determinants of suicide risk. Results: Across all models, diagnosis of depression was the strongest predictor of suicide plan and/or attempt (OR = 5.54, 95% CI = 3.71-8.27, p < 0.001). Comparing clinical symptoms between suicidal and non-suicidal groups at the time of admission, the largest effect sizes were found for hopelessness (p < 0.001, η2 = 0.11), and guilt or shame (p < 0.001, η2 = 0.09). Female sex was identified as a significant factor for elevated suicidal risk (OR = 1.56, 95% CI = 1.01-2.21, p = 0.01), thus we stratified the regression model by sex to identify specific risk factors for suicide plan and/or attempt for males and females. Among males, having no confidant (OR = 2.13, 95% CI = 1.19-3.80, p = 0.01), presence of recent stressors (OR = 1.95, 95% CI = 1.16-3.29, p = 0.01), and participation in social activities (OR = 1.67, 95% CI = 1.02-2.71, p = 0.04) were important predictors, while among females, younger age (OR = 0.96, 95% CI = 0.94-0.97, p < 0.001) increased odds of suicide plan and/or attempt. Conclusion: EMR-derived findings highlight different psychosocial and clinical determinants for males and females associated with suicide plan or attempt prior to psychiatric admission. Identifying precipitating factors that elevate imminent suicide risk may inform suicide prevention efforts for psychiatric inpatients.

The effects of intervening with physical activity in the early years (ages 3-5) on health-related quality of life: a secondary analysis of the Activity Begins in Childhood (ABC) trial.

PURPOSE: Limited research has measured the effect of physical activity (PA) interventions on health-related quality of life (HRQoL) among pre-school-aged children. This study evaluates the effect of the Activity Begins in Childhood (ABC) cluster-randomized controlled trial designed to increase PA in the ages 3-5 years on HRQoL. METHODS: This was a cluster-randomized controlled trial where the intervention group included PA education delivered to daycare providers only, or daycare providers and parents. In the current study, the two PA intervention groups were combined. The comparator group received standard daycare curriculum (COM). A total of 215 children were included (PA n = 161, COM n = 54). Parents completed the proxy Pediatric Quality of Life Inventory Generic Core Scale (PedsQL™ 4.0) to measure HRQoL at baseline and the end of the 6-month trial. HRQoL scores were analyzed as physical, psychosocial, and total domains. Baseline and 6-months measurements were compared for PA and COM groups, and mean changes in scores (95% confidence intervals) were measured using absolute values. RESULTS: No between-group differences were observed for the physical (p = 0.17), psychosocial (p = 0.95) or total scores (p = 0.20). Paired comparisons showed that only the PA group improved psychosocial- (PA mean difference = 2.18 (0.20, 4.15), p = 0.03; COM mean difference = 2.05 (- 1.03, 5.13), p = 0.19) and total-HRQoL scores (PA mean difference = 2.83 (1.83, 3.84), p < 0.001; COM mean difference = 0.19 (- 1.78, 2.16), p = 0.84) after 6 months. CONCLUSION: Although the within-PA group analysis showed an improvement in psychosocial and total HRQoL scores from baseline, no between-group differences were observed in the HRQoL over time among children aged 3-5 years.