Bousman Chad A, Katalinic Natalie, Martin Donel M, Smith Deidre J, Ingram Anna, Dowling Nathan, Ng Chee, Loo Colleen K
From the *Department of Psychiatry, The University of Melbourne, Melbourne; †School of Psychiatry, University of New South Wales; ‡Black Dog Institute, School of Psychiatry, University of New South Wales, Sydney and §Melbourne School of Psychological Sciences, The University of Melbourne, Melbourne, Australia.
J ECT. 2015 Jun;31(2):129-35. doi: 10.1097/YCT.0000000000000170.
The aim of this study was to explore the main and interaction effects of the COMT Val158Met, DRD2 C957T, BDNF Val66Met, and APOE polymorphisms on treatment efficacy and cognitive side effects of electroconvulsive therapy (ECT).
A total of 117 adult inpatients with a diagnosis of major depressive disorder recruited from 3 hospitals were administered the Montgomery-Äsberg Depression Rating Scale and a cognitive battery assessing global cognition, anterograde memory, executive function, speed and concentration, as well as retrograde memory at baseline and after ECT treatment.
DRD2 C957T heterozygotes had 3.7 (95% confidence interval, 1.13-12.25; P = 0.032) greater odds of remission compared with CC homozygotes. Among the men, COMT Val/Val carriers had greater depressive symptom reduction compared with Met/Met carriers (Montgomery-Äsberg Depression Rating Scale percentage of reduction, 76% vs 35%; P = 0.020) but not among the women (P = 0.903) after ECT. For cognitive outcomes, an interaction effect on anterograde memory was observed between the DRD2 and BDNF polymorphisms (P = 0.016), in which carriers of the DRD2 TT and BDNF Val/Val genotypes had significantly less decline in anterograde performance than those that carried the TC and Met-allele (P = 0.001) or CC and Met-allele (P = 0.003) genotypes. However, no results withstood correction for multiple comparisons.
These observations provide preliminary evidence supporting an association between common functional genotypic variation and ECT efficacy as well as anterograde memory side effects after ECT. Validation of these findings is required before firm conclusions can be made and clinical utility can be assessed.
本研究旨在探讨儿茶酚-O-甲基转移酶（COMT）基因Val158Met、多巴胺D2受体（DRD2）基因C957T、脑源性神经营养因子（BDNF）基因Val66Met和载脂蛋白E（APOE）基因多态性对电休克治疗（ECT）疗效及认知副作用的主要和交互作用。
从3家医院招募了117例诊断为重度抑郁症的成年住院患者，在基线期及ECT治疗后，对其进行蒙哥马利-Åsberg抑郁量表评定以及认知功能测试，评估整体认知、顺行性记忆、执行功能、速度与注意力，以及逆行性记忆。
与CC纯合子相比，DRD2基因C957T杂合子缓解几率高3.7倍（95%置信区间，1.13 - 12.25；P = 0.032）。在男性中，ECT治疗后，COMT基因Val/Val携带者较Met/Met携带者抑郁症状减轻更明显（蒙哥马利-Åsberg抑郁量表减分百分比，76%对35%；P = 0.020），但在女性中无此差异（P = 0.903）。对于认知结果，观察到DRD2基因和BDNF基因多态性对顺行性记忆存在交互作用（P = 0.016），其中DRD2基因TT型和BDNF基因Val/Val基因型携带者顺行性记忆功能下降显著低于携带TC和Met等位基因（P = 0.001）或CC和Met等位基因（P = 0.003）基因型者。然而，没有结果能经得起多重比较校正。
这些观察结果提供了初步证据，支持常见功能基因变异与ECT疗效以及ECT后顺行性记忆副作用之间存在关联。在得出确切结论并评估临床实用性之前，需要对这些发现进行验证。
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