Faculty Bibliography

Iron deficits have been reported as a risk factor for psychotic spectrum disorders (PSD). However, examinations of brain iron in PSD remain limited. The current study employed quantitative MRI to examine iron content in several iron-rich subcortical structures in 49 young adult individuals with PSD (15 schizophrenia, 17 schizoaffective disorder, and 17 bipolar disorder with psychotic features) compared with 35 age-matched healthy controls (HC). A parametric approach based on a two-pool magnetization transfer model was applied to estimate longitudinal relaxation rate (R₁), which reflects both iron and myelin, and macromolecular proton fraction (MPF), which is specific to myelin. To describe iron content, a synthetic effective transverse relaxation rate (R₂*) was modeled using a linear fitting of R₁ and MPF. PSD patients compared to HC showed significantly reduced R₁ and synthetic R₂* across examined regions including the pallidum, ventral diencephalon, thalamus, and putamen areas. This finding was primarily driven by decreases in the subgroup with schizophrenia, followed by schizoaffective disorder. No significant group differences were noted for MPF between PSD and HC while for regional volume, significant reductions in patients were only observed in bilateral caudate, suggesting that R₁ and synthetic R₂* reductions in schizophrenia and schizoaffective patients likely reflect iron deficits that either occur independently or precede structural and myelin changes. Subcortical R₁ and synthetic R₂* were also found to be inversely related to positive symptoms within the PSD group and to schizotypal traits across the whole sample. These findings that decreased iron in subcortical regions are associated with PSD risk and symptomatology suggest that brain iron deficiencies may play a role in PSD pathology and warrant further study.

Importance/UNASSIGNED:Individuals with serious mental illness are at increased risk of severe COVID-19 infection. Several psychotropic medications have been identified as potential therapeutic agents to prevent or treat COVID-19 but have not been systematically examined in this population. Objective/UNASSIGNED:To evaluate the associations between the use of psychotropic medications and the risk of COVID-19 infection among adults with serious mental illness receiving long-term inpatient psychiatric treatment. Design, Setting, and Participants/UNASSIGNED:This retrospective cohort study assessed adults with serious mental illness hospitalized in a statewide psychiatric hospital system in New York between March 8 and July 1, 2020. The final date of follow-up was December 1, 2020. The study included 1958 consecutive adult inpatients with serious mental illness (affective or nonaffective psychoses) who received testing for SARS-CoV-2 by reverse transcriptase-polymerase chain reaction or antinucleocapsid antibodies and were continuously hospitalized from March 8 until medical discharge or July 1, 2020. Exposures/UNASSIGNED:Psychotropic medications prescribed prior to COVID-19 testing. Main Outcomes and Measures/UNASSIGNED:COVID-19 infection was the primary outcome, defined by a positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction or antibody test result. The secondary outcome was COVID-19-related death among patients with laboratory-confirmed infection. Results/UNASSIGNED:Of the 2087 adult inpatients with serious mental illness continuously hospitalized during the study period, 1958 (93.8%) underwent testing and were included in the study; 1442 (73.6%) were men, and the mean (SD) age was 51.4 (14.3) years. A total of 969 patients (49.5%) had laboratory-confirmed COVID-19 infection that occurred while they were hospitalized; of those, 38 (3.9%) died. The use of second-generation antipsychotic medications, as a class, was associated with decreased odds of infection (odds ratio [OR], 0.62; 95% CI, 0.45-0.86), whereas the use of mood stabilizers was associated with increased odds of infection (OR, 1.23; 95% CI, 1.03-1.47). In a multivariable model of individual medications, the use of paliperidone was associated with decreased odds of infection (OR, 0.59; 95% CI, 0.41-0.84), and the use of valproic acid was associated with increased odds of infection (OR, 1.39; 95% CI, 1.10-1.76). Clozapine use was associated with reduced odds of mortality in unadjusted analyses (unadjusted OR, 0.25; 95% CI, 0.10-0.62; fully adjusted OR, 0.43; 95% CI, 0.17-1.12). Conclusions and Relevance/UNASSIGNED:In this cohort study of adults hospitalized with serious mental illness, the use of second-generation antipsychotic medications was associated with decreased risk of COVID-19 infection, whereas the use of valproic acid was associated with increased risk. Further research is needed to assess the mechanisms that underlie these findings.

Individuals with schizophrenia show impairments in associative learning. One well-studied, quantifiable form of associative learning is Pavlovian fear conditioning. However, to date, studies of fear conditioning in schizophrenia have been inconclusive, possibly because they lacked sufficient power. To address this issue, we pooled data from four independent fear conditioning studies that included a total of 77 individuals with schizophrenia and 74 control subjects. Skin conductance responses (SCRs) to stimuli that were paired (the CS + ) or not paired (CS-) with an aversive, unconditioned stimulus were measured, and the success of acquisition of differential conditioning (the magnitude of CS + vs. CS- SCRs) and responses to CS + and CS- separately were assessed. We found that acquisition of differential conditioned fear responses was significantly lower in individuals with schizophrenia than in healthy controls (Cohen's d = 0.53). This effect was primarily related to a significantly higher response to the CS- stimulus in the schizophrenia compared to the control group. Moreover, the magnitude of this response to the CS- in the schizophrenia group was correlated with the severity of delusional ideation (p = 0.006). Other symptoms or antipsychotic dose were not associated with fear conditioning measures. In conclusion, individuals with schizophrenia who endorse delusional beliefs may be over-responsive to neutral stimuli during fear conditioning. This finding is consistent with prior models of abnormal associative learning in psychosis.

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.

D-amino acid oxidase activator (DAOA) gene, which plays a crucial role in the process of glutamatergic transmission and mitochondrial function, is frequently linked with the liability for schizophrenia. We aimed to investigate whether the variation of DAOA rs2391191 is associated with alterations in white matter integrity of first-episode schizophrenia (FES) patients; and whether it influences the association between white matter integrity, cognitive function and clinical symptoms of schizophrenia. Forty-six patients with FES and forty-nine healthy controls underwent DTI and were genotyped for DAOA rs2391191. Psychopathological assessments were performed by Brief Psychiatric Rating Scale (BPRS) and Scale for Assessment of Negative Symptoms (SANS). Cognitive function was assessed by MATRICS Consensus Cognitive Battery (MCCB). Schizophrenia patients presented lower fractional anisotropy (FA) and higher radial diffusivity (RD), mainly spreading over the corpus callosum and corona radiata compared with healthy controls. Compared with patients carrying G allele, patients with AA showed lower FA in the body of corpus callosum, and higher RD in the genu of corpus callosum, right superior and anterior corona radiata, and left posterior corona radiata. In patients carrying G allele, FA in body of corpus callosum was positively correlated with working memory, RD in genu of corpus callosum was negatively associated with the speed of processing, working memory, and the composite score of MCCB, while no significant correlations were found in AA homozygotes. In our study, patients with FES presented abnormal white matter integrity in corpus callosum and corona radiata. Furthermore, this abnormality was associated with the genetic variation of DAOA rs2391191, with AA homozygotes showing less white matter integrity in the corpus callosum. Our findings possibly provide further support to the evidence that DAOA regulates the process of glutamatergic neurotransmission and mitochondrial function in the pathophysiological mechanism of schizophrenia.

Reports an error in "Association of aripiprazole with reduced hippocampal atrophy during maintenance treatment of first-episode schizophrenia" by John Wang, Kamber L. Hart, Wei Qi, Babak A. Ardekani, Chenxiang Li, Julia Marx, Oliver Freudenreich, Corinne Cather, Daphne Holt, Iruma Bello, Erica D. Diminich, Yingying Tang, Michelle Worthington, Botao Zeng, Renrong Wu, Xiaoduo Fan, Jingping Zhao, Jijun Wang and Donald C. Goff (Journal of Clinical Psychopharmacology, 2021[May-Jun], Vol 41[3], 244-249). In the originally published article, there were errors in the affiliations for two authors. The correct affiliations are provided in the erratum and appear in this record. In addition, in the footnotes to Table 3, the words "Bonferroni correction" should have been deleted after the P value of 0.05. (The following abstract of the original article appeared in record 2021-44706-004). Purpose/Background: 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: 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: 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: 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. (PsycInfo Database Record (c) 2022 APA, all rights reserved)