Konishi Yoshiaki, Tanii Hisashi, Otowa Takeshi, Sasaki Tsukasa, Tochigi Mamoru, Umekage Tadashi, Motomura Eishi, Shiroyama Takashi, Kaiya Hisanobu, Okazaki Yuji, Okada Motohiro
Department of Psychiatry, Division of Neuroscience, Graduate School of Medicine, Brain Science and Animal Model Research Center (BSAM), Mie University, Mie, Japan.
Department of Psychiatry, Division of Neuroscience, Graduate School of Medicine, Brain Science and Animal Model Research Center (BSAM), Mie University, Mie, Japan.
Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jun 3;51:119-25. doi: 10.1016/j.pnpbp.2014.01.020. Epub 2014 Feb 4.
Genetic and gender differences are among the factors that have a role in the etiology of panic disorder (PD). It is thought that PD is related to neurotransmitter pathways, such as brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT), both of which are involved in the regulation of the monoamine mechanism. We examined the interactions of BDNF, COMT and gender differences in terms of personality characteristics in PD. The subjects were 470 patients (178 men, 292 women) with a DSM-IV diagnosis of PD, and 458 healthy controls (195 men, 263 women). The subjects were further clinically characterized using the Revised NEO Personality Inventory (NEO-PI-R) and State-Trait Anxiety Inventory (STAI). COMT Val158Met polymorphisms (rs4680) and BDNF Val66Met (rs6265) polymorphisms were genotyped using allelic discrimination by a real-time PCR assay. A multivariate analysis of covariance (MANCOVA) was performed with STAI and NEO-PI-R scores as the dependent factor, gender and genotyping groups (BDNF and COMT) as fixed factors, and the covariate of age in the PD and healthy control groups. Post hoc MANCOVA tests were conducted to evaluate COMT × BDNF interactions. An interaction of BDNF × COMT × gender was confirmed in the PD group by MANCOVA on STAI scores and NEO-PI-R Neuroticism and Extraversion scores, whereas no association of such interactions was observed in the healthy controls. The anxiety sensitivity of the COMT Met+BDNF Val/Val carriers was higher than that of the COMT Val/Val+BDNF Val/Val carriers by post hoc MANCOVA. A significant BDNF × COMT × gender interaction was observed in the PD patients but not in the controls. Our findings partly demonstrated the involvement of a gene × gene × gender interaction in the pathogenesis of PD.
遗传和性别差异是惊恐障碍（PD）病因中的影响因素。人们认为PD与神经递质通路有关，如脑源性神经营养因子（BDNF）和儿茶酚-O-甲基转移酶（COMT），这两者都参与单胺机制的调节。我们从人格特征方面研究了BDNF、COMT与性别差异之间的相互作用。研究对象为470例符合DSM-IV诊断标准的PD患者（男性178例，女性292例）和458例健康对照者（男性195例，女性263例）。使用修订版的大五人格量表（NEO-PI-R）和状态-特质焦虑量表（STAI）对研究对象进行进一步的临床特征分析。采用实时荧光定量PCR等位基因分型法对COMT Val158Met多态性（rs4680）和BDNF Val66Met（rs6265）多态性进行基因分型。以STAI和NEO-PI-R评分作为因变量，性别和基因分型组（BDNF和COMT）作为固定因素，以PD组和健康对照组的年龄作为协变量，进行多变量协方差分析（MANCOVA）。进行事后MANCOVA检验以评估COMT×BDNF的相互作用。通过对STAI评分、NEO-PI-R神经质和外向性评分进行MANCOVA分析，在PD组中证实了BDNF×COMT×性别的相互作用，而在健康对照组中未观察到这种相互作用的关联。事后MANCOVA分析显示，COMT Met+BDNF Val/Val携带者的焦虑敏感性高于COMT Val/Val+BDNF Val/Val携带者。在PD患者中观察到显著的BDNF×COMT×性别相互作用，而在对照组中未观察到。我们的研究结果部分证明了基因×基因×性别相互作用参与了PD的发病机制。
