双相情感障碍中抗精神病药物的使用：临床与基因组相关性——梅奥诊所双相情感障碍生物样本库研究

Antipsychotic Use in Bipolar Disorder: Clinical and Genomic Correlates- A Mayo Clinic Bipolar Disorder Biobank Study.

作者信息

Singh Balwinder, Ho Ada Man-Choi, Coombes Brandon J, Romo-Nava Francisco, Bond David J, Veldic Marin, Pendegraft Richard S, Batzler Anthony, Cuellar-Barboza Alfredo B, Gardea-Reséndez Manuel, Prieto Miguel L, Ozerdem Aysegul, McElroy Susan L, Biernacka Joanna M, Frye Mark A

机构信息

Mayo Clinic.

Lindner Center of HOPE.

出版信息

Res Sq. 2025 Aug 5:rs.3.rs-7274612. doi: 10.21203/rs.3.rs-7274612/v1.

DOI:10.21203/rs.3.rs-7274612/v1

PMID:40799747

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12340913/

Abstract

BACKGROUND

Responsiveness to mood-stabilizing pharmacotherapy varies in bipolar disorder (BD). We investigated clinical correlates of second-generation antipsychotic (SGA) treatment response and conducted the first genome-wide association study (GWAS), including exploratory polygenic scores (PGS), of SGA pharmacogenomic treatment response in BD.

METHODS

Treatment response was quantified using the Alda scale, and GWAS was performed using Alda-A score, controlling for sex, genotyping batch, and the genomic principal components.

RESULTS

The cohort included 2,159 adults with BD (1,416 BD-I, 691 BD-II, 51 schizoaffective BD), mean age 41.8 years, 62% female, 84% white, and 14% Hispanic. Nearly half (48%) were treated with SGAs. Current SGA users were younger (41.2±14.7 vs. 42.5±15.3 years, =0.040), more likely to be Hispanic (14% vs. 11%, =0.047), had a higher body mass index (BMI; 30.4±7.6 vs. 29.5±7.1 kg/m, =0.005). Lifetime comorbidity patterns for current SGA users include higher rates of manic psychosis (29% vs. 17%, <0.001) and eating disorders - Anorexia Nervosa (7% vs. 4%, =0.003), Bulimia Nervosa (7% vs. 4%, =0.003), and Binge Eating Disorder (14% vs. 11%, =0.030). We detected a genome-wide significant association between SGA Alda-A scores and variants (top variant: rs202127418, =-2.998, =4.96E-08). However, SGA response was not significantly associated with PGS for schizophrenia, BD, and major depression (FDR>0.05).

CONCLUSIONS

SGAs are frequently utilized as mood stabilizers in patients with BD and are associated with manic psychosis and eating disorders. variants may predict SGA response, but larger, more diverse cohorts are needed for validation.

摘要

背景

双相情感障碍（BD）患者对心境稳定剂药物治疗的反应各不相同。我们研究了第二代抗精神病药物（SGA）治疗反应的临床相关因素，并开展了第一项全基因组关联研究（GWAS），包括对BD中SGA药物基因组治疗反应的探索性多基因评分（PGS）。

方法

使用阿尔达量表对治疗反应进行量化，并使用阿尔达-A评分进行GWAS，对性别、基因分型批次和基因组主成分进行控制。

结果

该队列包括2159名患有BD的成年人（1416例BD-I型、691例BD-II型、51例精神分裂症性BD），平均年龄41.8岁，62%为女性，84%为白人，14%为西班牙裔。近一半（48%）接受了SGA治疗。目前使用SGA的患者更年轻（41.2±14.7岁对42.5±15.3岁，P=0.040），更可能是西班牙裔（14%对11%，P=0.047），体重指数（BMI）更高（30.4±7.6对29.5±7.1kg/m²，P=0.005）。目前使用SGA的患者终生共病模式包括更高的躁狂性精神病发生率（29%对17%，P<0.001）和饮食失调——神经性厌食症（7%对4%，P=0.003）、神经性贪食症（7%对4%，P=0.003）和暴饮暴食症（14%对11%，P=0.030）。我们在SGA阿尔达-A评分与[具体基因]变体之间检测到全基因组显著关联（顶级变体：rs202127418，β=-2.998，P=4.96E-08）。然而，SGA反应与精神分裂症、BD和重度抑郁症的PGS无显著关联（FDR>0.05）。