American Journal of Medical Genetics Part B: Neuropsychiatric Genetics最新文献

Brasher, M. S., A. D. Grotzinger, N. P. Friedman, H. R. Smolker, and L. M. Evans. 2024. “Disentangling Differing Relationships Between Internalizing Disorders and Alcohol Use.” American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 195B: e32975. https://doi.org/10.1002/ajmg.b.32975.

In the originally published article, dbGaP phs001672 was not acknowledged properly.

The Acknowledgments section should have included the following: “The authors thank Million Veteran Program (MVP) staff, researchers, and volunteers, who have contributed to MVP, and especially participants who previously served their country in the military and now generously agreed to enroll in the study. (See https://www.research.va.gov/mvp/ for more details). The citation for MVP is Gaziano, J.M. et al. Million Veteran Program: A mega-biobank to study genetic influences on health and disease. J Clin Epidemiol 70, 214–23 (2016). This research is based on data from the Million Veteran Program, Office of Research and Development, Veterans Health Administration, and was supported by the Veterans Administration (VA) Million Veteran Program (MVP) award #000.”

The second sentence in the Methods section should read: “Internalizing phenotypes included the generalized anxiety disorder two item questionnaire (GAD-2) score from (Levey et al., 2020, summary statistics available through dbGaP phs001672), a meta-analysis of lifetime anxiety disorder from (Purves et al., 2020), and a meta-analysis of broad depression from (Howard et al., 2018).”

The Data Availability Statement should have included: “phs001672: Veterans Administration (VA) Million Veteran Program (MVP) Summary Results from Omics Studies.”

We apologize for this error.

People with mosaicism for trisomy 21 have been shown to exhibit many of the same phenotypic traits present in people with non-mosaic Down syndrome, but with varying symptom severity. However, the behavioral phenotype of people with mosaic Down syndrome (mDS) has not been well characterized. This study aimed to examine the prevalence of self-report and caregiver-report symptoms of depression and anxiety among a sample of 62 participants with mDS aged 12–46 and assess their association with the percentage of trisomy 21 in blood and/or buccal mucosa cells. The overall MANCOVA revealed a significant effect of trisomy on the set of internalizing scales, controlling for age and gender (p = 0.038, partial eta² = 0.22). However, follow-up univariate analyses showed that the initial significant effect of trisomy on fear (p = 0.049, partial eta² = 0.08) did not survive correction for multiple comparisons (adjusted p = 0.300). No other effects were significant. This study highlights the high occurrence of depression and anxiety symptoms in individuals with mDS and the need for routine assessment to optimize their care. It also demonstrates the ability of people with mDS to complete these evaluations, thereby supporting their inclusion in research studies/clinical trials.

Externalizing traits and behaviors are broadly defined by impairments in self-regulation and impulse control that typically begin in childhood and adolescence. Externalizing behaviors, traits, and symptoms span a range of traditional psychiatric diagnostic categories. In this study, we sought to generate an algorithm that could reliably identify transdiagnostic childhood-onset externalizing cases and controls within a university hospital electronic health record (EHR) database. Within the Vanderbilt University Medical Center (VUMC) EHR, our algorithm identified cases with a clinician-validated positive predictive value of 90% and controls with a negative predictive value of 88%. In individuals of genetically defined European ancestry (CEU-clustered; N_case = 487, N_control = 5638), case status was significantly associated with psychiatric comorbidity and with elevated externalizing polygenic scores (OR: 1.20; 95% CI: 1.09–1.33; p = 1.14 × 10⁻³; based on published genome-wide association data). To test whether our cohort definitions could be applied to generate novel genetic insights, we examined rare (allele frequency < 0.5%) copy number variation. An association (OR: 9.70; CI: 3.24–29.0) was identified in the CEU-clustered cohort on chromosome 2 (chr2: 45,408,678–45,551,530; duplication), although the statistical strength of this association was modest (p = 0.052). We also examined the role of an externalizing burden score based on the number of externalizing diagnoses present in cases and found similar results to our case–control analysis. This analysis identified several other statistically significant CNV region associations. This study provides a framework for identifying childhood externalizing case–control cohorts within an EHR. Future work should validate this framework within other health systems. A broadly applicable algorithm, like this one, may allow for detection of rare outcomes or outcomes in populations historically excluded from genomic research through meta-analysis of data across health care systems.

Anorexia nervosa (AN) is a psychiatric disorder with an estimated heritability of around 70%. Although the largest meta-analysis of genome-wide association studies on AN identified independent risk-conferring loci for the disorder, the molecular mechanisms underlying the genetic basis of AN remain to be elucidated. To investigate AN, we performed transcriptome profiling in peripheral blood mononuclear cells from 15 AN patients and 15 healthy controls. We validated our mean results in a mouse model of chronic food restriction, which mimics several aspects of AN. In this exploratory study, we identified 673 significantly differentially expressed genes in AN. Among these genes, we identified seven genes previously found to be dysregulated in IPSC-derived neurons from AN individuals and the Vanin-1 (Vnn1) gene, which appears to play an important role in the regulation of several metabolic pathways. We confirmed underexpression of Vnn1, particularly in the liver, in a mouse model of chronic food restriction. These results indicate that quantitative food restriction affects Vnn1 expression, suggesting that this gene may contribute to the anorexic phenotype in the chronic food restriction mouse model as well as in patients with AN. We believe that this report highlights promising candidate genes and gene pathways for AN, and although we did not obtain a significant result in the replication cohort, it identifies Vnn1 as a potential biomarker that may be used as a molecular target to predict and/or to understand AN.

Public stigma and prejudice toward people with psychiatric conditions is highly prevalent and damaging. Explanations for the origins of mental illness can influence attitudes toward people with these conditions. To date, studies exploring the effects of explanations for the origins of mental illness have focused on genetic or environmental explanations, and the impact of evidence-based multifactorial explanations for psychiatric illness on public attitudes remains unknown. Participants were recruited through Amazon Mechanical Turk to watch a 4-min video about the “mental illness jar model”—an evidence-based analogy that explains the complex interactions between genes and environment in the development of mental illness. Participants provided demographic information and completed questions regarding knowledge about the causes of mental illness, and the Prejudice towards People with Mental Illness (PPMI) scale both before and after watching the video. A total of 106 eligible participants completed the study. Watching the video had no significant effect on participants' knowledge about the causes of mental illness (p = 0.06), but there was a significant decrease in prejudicial attitudes toward mental illness (p = 0.0003), the effect size was small (−0.15). The use of this brief video (available at cogastudy.org) is a promising tool to decrease prejudicial attitudes toward mental illness that warrants further study.