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脑源性神经营养因子(BDNF)和儿茶酚-O-甲基转移酶(COMT)等位基因,但不是载脂蛋白 E(APOE)等位基因,与耐药性癫痫的精神症状有关。

BDNF and COMT, but not APOE, alleles are associated with psychiatric symptoms in refractory epilepsy.

机构信息

Cleveland Clinic Lerner College of Medicine, Cleveland, OH, United States of America.

Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America.

出版信息

Epilepsy Behav. 2019 May;94:131-136. doi: 10.1016/j.yebeh.2019.02.032. Epub 2019 Mar 22.

Abstract

OBJECTIVE

The objective of this study was to determine whether three common genetic polymorphisms [apolipoprotein (APOE) ε4 (rs42938 and rs7412), brain derived neurotrophic factor (BDNF) Met (rs6265), and catechol-O-methyltransferase (COMT) Val (rs4680)] are associated with increased psychiatric symptomatology in individuals with pharmacoresistant epilepsy.

METHODS

One hundred forty-eight adults (M = 38 years; 53% female) with refractory epilepsy completed self-report measures of mood, anxiety, and/or personality/psychopathology. Mann-Whitney U, t-tests, and Fisher's exact tests were used to determine if APOE4, BDNF Val66Met, or COMT Val158Met are associated with increased psychiatric symptomatology in people with epilepsy.

RESULTS

As a group, BDNF Met carriers reported greater symptoms of depression on the Personality Assessment Inventory (PAI) than those without a Met allele (p = 0.004); COMT Val carriers reported greater symptoms on the PAI Schizophrenia (p = 0.007), Antisocial Features (p = 0.04), and Alcohol Problems (p = 0.03) scales than noncarriers. On the individual level, a significantly greater proportion of BDNF Met carriers demonstrated elevated PAI Depression scores compared to those without a Met allele (p = 0.046). There was also a larger proportion of COMT Val carriers with elevated PAI Anxiety scores as compared to those without a Val allele (p = 0.036).

SIGNIFICANCE

This retrospective cross-sectional study provides preliminary evidence for a genetic basis of psychiatric comorbidities in epilepsy and suggests that BDNF and COMT may play an important role in the pathophysiology of mental health problems in this vulnerable population.

摘要

目的

本研究旨在确定三种常见的遗传多态性(载脂蛋白(APOE)ε4(rs42938 和 rs7412)、脑源性神经营养因子(BDNF)Met(rs6265)和儿茶酚-O-甲基转移酶(COMT)Val(rs4680))是否与药物难治性癫痫患者的精神症状增加有关。

方法

148 名成年(M=38 岁;53%为女性)药物难治性癫痫患者完成了情绪、焦虑和/或人格/精神病理学的自我报告量表。采用 Mann-Whitney U 检验、t 检验和 Fisher 确切检验来确定 APOE4、BDNF Val66Met 或 COMT Val158Met 是否与癫痫患者的精神症状增加有关。

结果

作为一个整体,BDNF Met 携带者在人格评估量表(PAI)上报告的抑郁症状比没有 Met 等位基因的人更严重(p=0.004);COMT Val 携带者在 PAI 分裂症(p=0.007)、反社会特征(p=0.04)和酒精问题(p=0.03)量表上的症状比非携带者更严重。在个体水平上,与没有 Met 等位基因的人相比,BDNF Met 携带者表现出更高的 PAI 抑郁评分的比例显著更高(p=0.046)。COMT Val 携带者中 PAI 焦虑评分升高的比例也明显高于无 Val 等位基因的携带者(p=0.036)。

意义

这项回顾性横断面研究为癫痫的精神共病存在遗传基础提供了初步证据,并表明 BDNF 和 COMT 可能在这一弱势群体的心理健康问题的病理生理学中发挥重要作用。

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