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Published on: May 15, 2020
Validating mitochondrial electron transport chain content in individuals at clinical high risk for psychosis
Abbie Wu1, Tania Da Silva2, Maya Jacobson2
1Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.
Abstract:
Altered mitochondrial electron transport chain function has been implicated in the pathophysiology and etiology of schizophrenia. To date, our previously published study (i.e. first cohort) is still the only study to demonstrate that mitochondrial electron transport chain is not altered in white blood cells from individuals at clinical high risk for psychosis. Here, we aimed to replicate our previous findings with an independent set of samples and validate the levels of mitochondrial complex I-V content in individuals at clinical high risk for psychosis. We demonstrated that the second cohort (i.e. validation cohort) expressed similar results as the first cohort. We combined the first cohort study with the second cohort and once more validated a lack of differential levels in mitochondrial complex I-V content between the two groups. In addition, we were able to validate a correlation between complex III content and prodromal negative symptom severity when the two cohorts studies were combined. Additionally, a correlation between complex V content and prodromal disorganization symptom severity was found when the two cohorts were combined. In conclusion, our results showed that dysfunction of the mitochondrial electron transport chain is not detected in peripheral blood mononuclear cells of individuals in the putative prodromal stage of schizophrenia.
Insights
Mitochondrial electron transport chain (ETC) function is not altered in individuals at clinical high risk for psychosis. This study validated no ETC dysfunction in peripheral blood cells, but found correlations between specific ETC complexes and symptom severity.
Area of Science:
- Neuroscience
- Cellular Biology
- Psychiatry
Background:
- Mitochondrial electron transport chain (ETC) dysfunction is hypothesized to contribute to schizophrenia's development.
- Previous research indicated no ETC alterations in white blood cells of individuals at clinical high risk for psychosis.
Purpose of the Study:
- To replicate and validate findings of unaltered mitochondrial complex I-V content in a new cohort of individuals at clinical high risk for psychosis.
- To investigate correlations between mitochondrial complex levels and psychosis prodrome symptoms.
Main Methods:
- Analysis of mitochondrial complex I-V content in peripheral blood mononuclear cells from two independent cohorts of individuals at clinical high risk for psychosis.
- Statistical analysis to compare complex levels between groups and correlate with symptom severity.
Main Results:
- Replication of the initial finding: no significant differences in mitochondrial complex I-V content were observed in the validation cohort.
- Combined analysis of both cohorts confirmed the lack of differential mitochondrial complex levels.
- Identified significant correlations between mitochondrial complex III and negative symptoms, and complex V and disorganization symptoms.
Conclusions:
- Mitochondrial electron transport chain dysfunction is not a detectable feature in the peripheral blood of individuals in the prodromal stage of schizophrenia.
- While overall ETC function appears intact, specific complex levels may correlate with certain symptom domains in early psychosis.
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