Behavioral Epidemiology, Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Chemnitzer Str. 46, 01187 Dresden, Germany; Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
J Affect Disord. 2018 Jul;234:290-296. doi: 10.1016/j.jad.2018.02.060. Epub 2018 Mar 8.
The single nucleotide polymorphism rs4680 of the catechol-O-methyltransferase (COMT) gene has been implicated to be involved in the etiopathogenesis of panic. However, it remains unresolved whether rs4680 modifies the risk-association between early life stress and subsequent development of panic pathology.
The genotype of rs4680 was determined for n = 2242 adults with European ancestry from the Study of Health in Pomerania (SHIP, a regional longitudinal cohort study from northeastern Germany). Lifetime fearful spells, panic attacks and panic disorder were assessed according to DSM-IV in 2007-2010 (when participants were aged 29-89) using the Munich Composite International Diagnostic Interview (DIA-X/M-CIDI). Childhood adversities were assessed with the Childhood Trauma Questionnaire (CTQ).
Logistic regressions with interaction terms (adjusted for sex and age) revealed that rs4680 interacted with total childhood adversity, emotional abuse and physical abuse in predicting panic disorder: Respective childhood adversities predicted panic disorder in carriers of the Val/Met or Met/Met genotype, but not Val/Val genotype. Moreover, a 3-way interaction was found between rs4680, emotional abuse and sex in predicting panic attacks: Emotional abuse predicted panic attacks among male carriers of the Val/Val genotype and female carriers of the Val/Met or Met/Met genotype, but not among male carriers of the Val/Met or Met/Met genotype or female carriers of the Val/Val genotype.
Genotype data were derived by imputation. Childhood adversities and panic were assessed retrospectively.
Especially (female) carriers of the Val/Met or Met/Met genotype of rs4680 might profit from targeted early interventions to prevent the onset of panic after childhood adversities.
儿茶酚氧位甲基转移酶（COMT）基因的单核苷酸多态性 rs4680 与惊恐的发病机制有关。然而，它是否改变了早期生活压力与随后惊恐病理发展之间的风险关联仍未解决。
对来自德国东北部波罗的海研究（SHIP）的 2242 名具有欧洲血统的成年人的 rs4680 基因型进行了测定。2007-2010 年（参与者年龄为 29-89 岁），使用慕尼黑综合国际诊断访谈（DIA-X/M-CIDI），根据 DSM-IV 评估了终生惊恐发作、惊恐发作和惊恐障碍。使用童年创伤问卷（CTQ）评估儿童期逆境。
调整性别和年龄的逻辑回归分析显示，rs4680 与总童年逆境、情感虐待和身体虐待在预测惊恐障碍方面存在相互作用：相应的童年逆境预测 Val/Met 或 Met/Met 基因型携带者的惊恐障碍，但 Val/Val 基因型携带者则不然。此外，还发现 rs4680、情感虐待和性别在预测惊恐发作方面存在 3 种相互作用：情感虐待预测 Val/Val 基因型男性携带者和 Val/Met 或 Met/Met 基因型女性携带者的惊恐发作，但 Val/Met 或 Met/Met 基因型男性携带者或 Val/Val 基因型女性携带者则不然。
基因型数据是通过推断得出的。童年逆境和惊恐发作是回顾性评估的。
特别是 rs4680 的 Val/Met 或 Met/Met 基因型携带者（尤其是女性）可能受益于有针对性的早期干预，以防止儿童期逆境后惊恐发作的发生。
