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Mol Neuropsychiatry. 2018 Feb;3(3):157-169. doi: 10.1159/000484348. Epub 2017 Nov 30.

Mitochondrial Complex I Deficiency in Schizophrenia and Bipolar Disorder and Medication Influence.

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Functional Genomics Laboratory, Department of Psychiatry & Human Behavior, University of California, Irvine, CA, USA.
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Department of Psychiatry, Weill Cornell Medical College, Ithaca, NJ, USA.
HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
MBNI, University of Michigan, Ann Arbor, MI, USA.
Department of Psychiatry & Human Behavior, University of California, Irvine, CA, USA.


Subjects with schizophrenia (SZ) and bipolar disorder (BD) show decreased protein and transcript levels for mitochondrial complex I. In vitro results suggest antipsychotic and antidepressant drugs may be responsible. We measured complex I activity in BD, SZ, and controls and presence of antipsychotic and antidepressant medications, mitochondrial DNA (mtDNA) copy number, and the mtDNA "common deletion" in the brain. Complex I activity in the prefrontal cortex was decreased by 45% in SZ compared to controls (p = 0.02), while no significant difference was found in BD. Complex I activity was significantly decreased (p = 0.01) in pooled cases (SZ and BD) that had detectable psychotropic medications and drugs compared to pooled cases with no detectable levels. Subjects with age at onset in their teens and psychotropic medications showed decreased (p < 0.05) complex I activity compared to subjects with an adult age at onset. Both SZ and BD groups displayed significant increases (p < 0.05) in mtDNA copy number compared to controls; however, common deletion burden was not altered. Complex I deficiency is found in SZ brain tissue, and psychotropic medications may play a role in mitochondrial dysfunction. Studies of medication-free first-episode psychosis patients are needed to elucidate whether mitochondrial pathophysiology occurs independent of medication effects.


Antidepressant drug; Antipsychotic drug; Complex I activity; Mitochondria; Mitochondrial DNA common deletion; Prefrontal cortex; Schizophrenia; mtDNA copy number

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