Mittal Kirti, Gonçalves Vanessa F, Harripaul Ricardo, Cuperfain Ari B, Rollins Brandi, Tiwari Arun K, Zai Clement C, Maciukiewicz Malgorzata, Müller Daniel J, Vawter Marquis P, Kennedy James L
Neurogenetics Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, ON, Canada.
Neurogenetics Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, ON, Canada.
Schizophr Res. 2017 Sep;187:67-73. doi: 10.1016/j.schres.2017.06.046. Epub 2017 Jul 8.
Antipsychotic Induced Weight Gain (AIWG) is a common and severe side effect of many antipsychotic medications. Mitochondria play a vital role for whole-body energy homeostasis and there is increasing evidence that antipsychotics modulate mitochondrial function. This study aimed to examine the role of variants in nuclear-encoded mitochondrial genes and the mitochondrial DNA (mtDNA) in conferring risk for AIWG. We selected 168 European-Caucasian individuals from the CATIE sample based upon meeting criteria of multiple weight measures while taking selected antipsychotics (risperidone, quetiapine or olanzapine). We tested the association of 670 nuclear-encoded mitochondrial genes with weight change (%) using MAGMA software. Thirty of these genes showed nominally significant P-values (<0.05). We were able to replicate the association of three genes, CLPB, PARL, and ACAD10, with weight change (%) in an independent prospectively assessed AIWG sample. We analyzed mtDNA variants in a subset of 74 of these individuals using next-generation sequencing. No common or rare mtDNA variants were found to be significantly associated with weight change (%) in our sample. Additionally, analysis of mitochondrial haplogroups showed no association with weight change (%). In conclusion, our findings suggest nuclear-encoded mitochondrial genes play a role in AIWG. Replication in larger sample is required to validate our initial report of mtDNA variants in AIWG.
抗精神病药物所致体重增加（AIWG）是许多抗精神病药物常见且严重的副作用。线粒体在全身能量稳态中起着至关重要的作用，并且越来越多的证据表明抗精神病药物会调节线粒体功能。本研究旨在探讨核编码线粒体基因和线粒体DNA（mtDNA）变异在赋予AIWG风险中的作用。我们根据在服用选定抗精神病药物（利培酮、喹硫平或奥氮平）时符合多次体重测量标准，从CATIE样本中选取了168名欧洲白种人个体。我们使用MAGMA软件测试了670个核编码线粒体基因与体重变化（%）的关联。其中30个基因显示出名义上显著的P值（<0.05）。我们能够在一个独立的前瞻性评估的AIWG样本中重复三个基因CLPB、PARL和ACAD10与体重变化（%）的关联。我们使用下一代测序分析了这些个体中的74个子集的mtDNA变异。在我们的样本中未发现常见或罕见的mtDNA变异与体重变化（%）有显著关联。此外，线粒体单倍群分析显示与体重变化（%）无关联。总之，我们的研究结果表明核编码线粒体基因在AIWG中起作用。需要在更大的样本中进行重复验证我们关于AIWG中mtDNA变异的初步报告。
