Faculty Bibliography

Importance/UNASSIGNED:Heterogeneous evidence exists for the association between COVID-19 and the clinical outcomes of patients with mental health disorders. It remains unknown whether patients with COVID-19 and mental health disorders are at increased risk of mortality and should thus be targeted as a high-risk population for severe forms of COVID-19. Objective/UNASSIGNED:To determine whether patients with mental health disorders were at increased risk of COVID-19 mortality compared with patients without mental health disorders. Data Sources/UNASSIGNED:For this systematic review and meta-analysis, MEDLINE, Web of Science, and Google Scholar were searched from inception to February 12, 2021. Bibliographies were also searched, and the corresponding authors were directly contacted. The search paradigm was based on the following combination: (mental, major[MeSH terms]) AND (COVID-19 mortality[MeSH terms]). To ensure exhaustivity, the term mental was replaced by psychiatric, schizophrenia, psychotic, bipolar disorder, mood disorders, major depressive disorder, anxiety disorder, personality disorder, eating disorder, alcohol abuse, alcohol misuse, substance abuse, and substance misuse. Study Selection/UNASSIGNED:Eligible studies were population-based cohort studies of all patients with identified COVID-19 exploring the association between mental health disorders and mortality. Data Extraction and Synthesis/UNASSIGNED:Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used for abstracting data and assessing data quality and validity. This systematic review is registered with PROSPERO. Main Outcomes and Measures/UNASSIGNED:Pooled crude and adjusted odds ratios (ORs) for the association of mental health disorders with mortality were calculated using a 3-level random-effects (study/country) approach with a hierarchical structure to assess effect size dependency. Results/UNASSIGNED:In total, 16 population-based cohort studies (data from medico-administrative health or electronic/medical records databases) across 7 countries (1 from Denmark, 2 from France, 1 from Israel, 3 from South Korea, 1 from Spain, 1 from the UK, and 7 from the US) and 19 086 patients with mental health disorders were included. The studies covered December 2019 to July 2020, were of good quality, and no publication bias was identified. COVID-19 mortality was associated with an increased risk among patients with mental health disorders compared with patients without mental health disorders according to both pooled crude OR (1.75 [95% CI, 1.40-2.20]; P < .05) and adjusted OR (1.38 [95% CI, 1.15-1.65]; P < .05). The patients with severe mental health disorders had the highest ORs for risk of mortality (crude OR: 2.26 [95% CI, 1.18-4.31]; adjusted OR: 1.67 [95% CI, 1.02-2.73]). Conclusions and Relevance/UNASSIGNED:In this systematic review and meta-analysis of 16 observational studies in 7 countries, mental health disorders were associated with increased COVID-19-related mortality. Thus, patients with mental health disorders should have been targeted as a high-risk population for severe forms of COVID-19, requiring enhanced preventive and disease management strategies. Future studies should more accurately evaluate the risk for patients with each mental health disorder. However, the highest risk seemed to be found in studies including individuals with schizophrenia and/or bipolar disorders.

Myelin abnormalities have been reported in schizophrenia spectrum disorders (SSD) in white matter. However, in vivo examinations of cortical myeloarchitecture in SSD, especially those using quantitative measures, are limited. Here, we employed macromolecular proton fraction (MPF) obtained from quantitative magnetization transfer imaging to characterize intracortical myelin organization in 30 SSD patients versus 34 healthy control (HC) participants. We constructed cortical myelin profiles by extracting MPF values at various cortical depths and quantified their shape using a nonlinearity index (NLI). To delineate the association of illness duration with myelin changes, SSD patients were further divided into 3 duration groups. Between-group comparisons revealed reduced NLI in the SSD group with the longest illness duration (>5.5 years) compared with HC predominantly in bilateral prefrontal areas. Within the SSD group, cortical NLI decreased with disease duration and was positively associated with a measure of spatial working memory capacity as well as with cortical thickness (CT). Layer-specific analyses suggested that NLI decreases in the long-duration SSD group may arise in part from significantly increased MPF values in the midcortical layers. The current study reveals cortical myelin profile changes in SSD with illness progression, which may reflect an abnormal compensatory mechanism of the disorder.

PURPOSE/BACKGROUND/OBJECTIVE:Hippocampal volume loss in early schizophrenia has been linked with markers of inflammation and oxidative stress, and with less response of negative symptoms. Aripiprazole has been reported to preserve hippocampal volume and to reduce inflammation. METHODS/PROCEDURES/UNASSIGNED:Study 1 was a 12-month multicenter randomized placebo-controlled trial of citalopram added to clinician-determined second-generation antipsychotic medication in 95 patients with first-episode schizophrenia (FES), 19 of whom received aripiprazole. We compared participants taking aripiprazole with those on other antipsychotics to determine whether those on aripiprazole had less hippocampal volume loss. We also examined peripheral biomarker data from medication-naive patients with schizophrenia receiving 8 weeks of antipsychotic treatment (n = 24) to see whether markers of inflammation and oxidative stress that previously predicted hippocampal volume differed between aripiprazole (n = 9) and other antipsychotics (study 2). FINDINGS/RESULTS/UNASSIGNED:Aripiprazole was associated with a mean increase in hippocampal volume of 0.35% (SD, 0.80%) compared with a 0.53% decrease (SD, 1.2%) with other antipsychotics during the first year of maintenance treatment in patients with FES. This difference was significant after adjusting for age, sex, citalopram treatment, and baseline Brief Psychiatric Rating Scale score (B = 0.0079, P = 0.03). Aripiprazole was also associated with reduced concentrations of the inflammatory cytokines interleukin-8 and tumor necrosis factor (P < 0.01) during the first 8 weeks of treatment in medication-naive patients with FES. IMPLICATIONS/CONCLUSIONS/UNASSIGNED:These results suggest that aripiprazole may protect against hippocampal atrophy via an anti-inflammatory mechanism, but these results require replication in larger, randomized trials, and the clinical relevance of hippocampal volume loss is not established.

Hippocampal volume loss is prominent in first episode schizophrenia (FES) and has been associated with poor clinical outcomes and with BDNF genotype; antidepressants are believed to reverse hippocampal volume loss via release of BDNF. In a 12-month, placebo-controlled add-on trial of the antidepressant, citalopram, during the maintenance phase of FES, negative symptoms were improved with citalopram. We now report results of structural brain imaging at baseline and 6 months in 63 FES patients (34 in citalopram group) from the trial to assess whether protection against hippocampal volume loss contributed to improved negative symptoms with citalopram. Hippocampal volumetric integrity (HVI) did not change significantly in the citalopram or placebo group and did not differ between treatment groups, whereas citalopram was associated with greater volume loss of the right CA1 subfield. Change in cortical thickness was associated with SANS change in 4 regions (left rostral anterior cingulate, right frontal pole, right cuneus, and right transverse temporal) but none differed between treatment groups. Our findings suggest that minimal hippocampal volume loss occurs after stabilization on antipsychotic treatment and that citalopram's potential benefit for negative symptoms is unlikely to result from protection against hippocampal volume loss or cortical thinning.