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与精神分裂症和双相情感障碍遗传易感性相关的人格:与儿茶酚-O-甲基转移酶(COMT)缬氨酸108/158蛋氨酸多态性的差异关联

Personality in relation to genetic liability for schizophrenia and bipolar disorder: differential associations with the COMT Val 108/158 Met polymorphism.

作者信息

Silberschmidt Amy L, Sponheim Scott R

机构信息

Veterans Affairs Medical Center, Minneapolis, Minnesota 55417, United States.

出版信息

Schizophr Res. 2008 Mar;100(1-3):316-24. doi: 10.1016/j.schres.2007.12.467. Epub 2008 Jan 16.

Abstract

Schizophrenia and bipolar disorder may share aspects of genetic etiology. Evidence supports the Val 108/158 Met polymorphism of the Catechol-o-Methyltransferase (COMT) gene as potentially contributing to the etiology of both disorders. To determine whether the COMT gene is associated with personality traits related to genetic risk for either schizophrenia or bipolar disorder, we examined dimensions of personality psychopathology in biological relatives of individuals with the disorders. Specifically, we contrasted personality characteristics of first-degree relatives of people with schizophrenia, first-degree relatives of people with bipolar-I disorder, and nonpsychiatric control participants using scores from the Dimensional Assessment of Personality Pathology-Brief Questionnaire (DAPP-BQ). We also characterized the COMT Val 108/158 Met polymorphism of subjects. Compared to controls, relatives of schizophrenia patients scored lower on stimulus seeking and higher on restrictive expression and social avoidance. Compared to relatives of bipolar patients, relatives of schizophrenia patients had lower scores on narcissism, rejectionality (i.e., rejection of ideas of others), stimulus seeking, passive-aggressive oppositionality, and self-harm. The subset of relatives of schizophrenia patients who were COMT val homozygotes exhibited lower scores on narcissism, rejectionality, and stimulus seeking than met homozygote relatives of schizophrenia patients and control participants. Although relatives of bipolar patients showed scale elevations consistent with emotional dysregulation, the scores failed to be associated with the Val 108/158 Met polymorphism. Abnormally low narcissism and rejectionality in val homozygote relatives of schizophrenia patients suggests that the val allele of the COMT polymorphism may be associated with an underdeveloped self-concept phenomenologically similar to made volition and passivity experiences comprising first-rank symptoms of schizophrenia.

摘要

精神分裂症和双相情感障碍可能在遗传病因方面存在共同之处。有证据支持儿茶酚-O-甲基转移酶(COMT)基因的Val 108/158 Met多态性可能对这两种疾病的病因有影响。为了确定COMT基因是否与精神分裂症或双相情感障碍的遗传风险相关的人格特质有关,我们研究了患有这些疾病个体的生物学亲属的人格精神病理学维度。具体而言,我们使用《人格病理学维度评估-简短问卷》(DAPP-BQ)的得分,对比了精神分裂症患者的一级亲属、双相I型障碍患者的一级亲属以及非精神科对照参与者的人格特征。我们还对受试者的COMT Val 108/158 Met多态性进行了特征分析。与对照组相比,精神分裂症患者的亲属在寻求刺激方面得分较低,在限制性表达和社交回避方面得分较高。与双相情感障碍患者的亲属相比,精神分裂症患者的亲属在自恋、拒绝性(即拒绝他人观点)、寻求刺激、被动攻击型对立性和自我伤害方面得分较低。精神分裂症患者中COMT val纯合子的亲属子集在自恋、拒绝性和寻求刺激方面的得分低于精神分裂症患者的met纯合子亲属和对照参与者。尽管双相情感障碍患者的亲属表现出与情绪调节障碍一致的量表升高,但这些得分与Val 108/158 Met多态性无关。精神分裂症患者val纯合子亲属中异常低的自恋和拒绝性表明,COMT多态性的val等位基因可能与自我概念发展不足有关,从现象学角度来看,类似于构成精神分裂症一级症状的意志减退和被动体验。

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