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Schizophr Res. 2017 Sep;187:67-73. doi: 10.1016/j.schres.2017.06.046. Epub 2017 Jul 8.

A comprehensive analysis of mitochondrial genes variants and their association with antipsychotic-induced weight gain.

Author information

1
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.
2
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. Electronic address: Vanessa.Goncalves@camh.ca.
3
Institute of Medical Sciences, University of Toronto, ON, Canada; Molecular Neuropsychiatry & Development (MiND) Lab, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
4
Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.

Abstract

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.

KEYWORDS:

Antipsychotic-induced weight gain; Mitochondria; Mitochondrial DNA variants; Next generation sequencing; Nuclear-encoded mitochondrial genes; Schizophrenia

PMID:
28693754
PMCID:
PMC5660917
DOI:
10.1016/j.schres.2017.06.046
[Indexed for MEDLINE]
Free PMC Article

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