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Mitochondrial DNA 3644T-->C mutation associated with bipolar disorder
Kae Munakata1, Masashi Tanaka, Kanako Mori
1Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Hirosawa 2-1, Wako, Saitama 351-0198, Japan.
Genomics
|November 10, 2004
Summary
A mitochondrial DNA mutation (3644T-->C) is linked to bipolar disorder risk. This mutation impairs mitochondrial complex I function, potentially increasing susceptibility to bipolar disorder and neurodegenerative diseases.
Area of Science:
- Genetics
- Neuroscience
- Mitochondrial Biology
Background:
- Mitochondrial dysfunction and mutant mitochondrial DNA (mtDNA) are implicated in bipolar disorder.
- Comorbidity between bipolar disorder and neurodegenerative diseases is frequently observed.
Purpose of the Study:
- To investigate the role of entire mitochondrial DNA (mtDNA) sequences in bipolar disorder patients with suspected mitochondrial disorders.
- To identify specific mtDNA mutations associated with bipolar disorder and assess their functional impact.
Main Methods:
- Sequencing of the entire mtDNA in six bipolar disorder subjects with comorbid symptoms.
- Genotyping of the 3644T-->C mutation in extended patient and control cohorts.
- Functional assessment using transmitochondrial cybrids to measure mitochondrial membrane potential and complex I activity.
Main Results:
- Several uncharacterized homoplasmic nonsynonymous mtDNA substitutions were identified.
- The 3644T-->C mutation was significantly associated with bipolar disorder (p = 0.007 in extended samples).
- This mutation reduced mitochondrial membrane potential and complex I activity in cybrid models.
Conclusions:
- The 3644T-->C mtDNA mutation, causing modest functional impairment of complex I, may increase the risk for bipolar disorder.
- The mutation's presence in Alzheimer's and Parkinson's disease patients suggests a potential role in neurodegeneration.
- Further research is warranted to elucidate the precise mechanisms linking this mutation to psychiatric and neurological disorders.