Transcriptional profiling of mitochondria associated genes in prefrontal cortex of subjects with major depressive disorder

Abstract

Objectives: Recent evidences suggest that mitochondrial dysfunction maybe involved in the pathophysiology of major depressive disorder (MDD); however, the role of mitochondrial genes in this disorder has not been studied systematically. In the present study, we profiled expression of mitochondrial genes in dorsolateral prefrontal cortex (dlPFC) of MDD and non-psychiatric control subjects.

Methods: Human mitochondrial RT² profile PCR array plates were used to examine differentially expressed genes in dlPFC of 11 MDD and 11 control subjects. Differentially expressed genes were validated independently by qRT-PCR. Biological relevance of differentially expressed genes was analysed by gene ontology (GO) and ingenuity pathways analysis (IPA).

Results: We found that 16 genes were differentially expressed in the MDD group compared with control group. Among them, three genes were downregulated and 13 genes upregulated. None of these genes were affected by confounding variables, such as age, post-mortem interval, brain pH, and antidepressant toxicology. Seven differentially expressed genes were successfully validated in MDD subjects. GO and IPA analyses identified several new regulatory networks associated with mitochondrial dysfunctions in MDD.

Conclusions: Our findings suggest abnormal mitochondrial systems in the brain of MDD subjects which could be involved in the etiopathogenesis of this disorder.

Keywords:

• Expression
• gene network
• major depression
• dorsolateral prefrontal cortex
• mitochondrial genes

Acknowledgements

We sincerely thank the Maryland Brain Collection for providing post-mortem brain samples.

Statement of interest

None to declare.

Funding information

This research was supported by grants from National Institute of Mental Health (R01MH082802, R01MH100616 and R01MH101980) to Dr Yogesh Dwivedi.