Written by: Giselli Scaini
The “mitochondrial hypothesis” suggests that bipolar disorder is triggered, in part, via dysfunction of the cell’s powerhouses. This can be intimately linked to a wide range of processes associated with treatment outcomes and disease progression or severity, including inflammation, oxidative stress, stress response systems, and accelerated aging(1). Across all areas of medicine, mitochondrial research is on the rise due to recent recognition of nonenergetic roles of these organelles, suggesting a new paradigm where multiple mechanisms cooperate to translate abnormal mitochondrial function into the pathophysiology of several diseases (2). Within each cell, the mitochondrial network is continually reshaping itself to adapt to environmental, metabolic, and neuroendocrine stressors and stress mediators. Reshaping of mitochondrial networks is referred to as mitochondrial quality control within scientific research, allowing the mitochondria to respond to damage and reshape themselves, resulting in a healthy pool of mitochondria (3) .
Researchers from the Translational Psychiatry Program at the University of Texas Health Science Center at Houston (UTHealth) are studying how changes in the mitochondrial quality control can contribute to bipolar disorder. We have evidence that some patients with bipolar disorder show impairment in the processes responsible for keeping the quality of mitochondria. This is due to an increase in the mitochondrial fragmentation, a decrease in proteins responsible to the selective, and efficient removal damaged mitochondria, followed by apoptosis activation. Moreover, we found a link between the severity of bipolar disorder and issues with the mitochondria function. When the severity of manic and depressive symptoms increased, the changes in the mitochondrial quality control related proteins rose as well. Our study also highlighted the significant correlation between mitochondrial alterations with a decrease in functional status (4, 5).
Among other areas of research, our department focused on better understanding the role of mitochondrial dysfunction in psychiatric disorders by studying blood samples from volunteers and post-mortem brain tissues of deceased patients after consent from the next-of-kin. We hope that our studies will help to identify the mechanical reasons for the mitochondrial alterations in bipolar disorder and contribute to the identification of clinically-relevant targets for the development of novel treatments.
Giselli Scaini, PhD, is a Postdoctoral Research Fellow in the Department of Psychiatry and Behavioral Sciences at McGovern Medical School at UTHealth. Her research focuses on the complex interactions of cellular and molecular mechanism related to mitochondrial function with brain alterations and memory impairments associated with bipolar disorder.
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- Scaini G, Barichello T, Fries GR, Kennon EA, Andrews T, Nix BR, Zunta-Soares G, Valvassori SS, Soares JC, Quevedo J. TSPO upregulation in bipolar disorder and concomitant downregulation of mitophagic proteins and NLRP3 inflammasome activation. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2018. doi: 10.1038/s41386-018-0293-4. PubMed PMID: 30575805.
- Scaini G, Fries GR, Valvassori SS, Zeni CP, Zunta-Soares G, Berk M, Soares JC, Quevedo J. Perturbations in the apoptotic pathway and mitochondrial network dynamics in peripheral blood mononuclear cells from bipolar disorder patients. Transl Psychiatry. 2017;7(5):e1111. doi: 10.1038/tp.2017.83. PubMed PMID: 28463235; PMCID: PMC5534951.