Identifying biomarkers associated with the diagnosis and illness progression of mood disorders

Despite decades of extensive genetic and pharmacological research, the pathophysiology of Bipolar disorder (BD) remains elusive. Consequently, a growing number of studies are focusing on the molecular biology underlying BD, and some consistencies with respect to possible mechanisms of action have emerged, including: (1) altered cerebral energy metabolism; (2) decreased expression of the mitochondrial electron transport chain (mETC), complexes I-V subunits in prefrontal cortex, hippocampus and lymphocytes; (3) increased protein oxidation in the prefrontal cortex and serum; (4) higher levels of lipid peroxidation in the cingulte cortex and serum; (5) increased levels of DNA oxidative damage in hippocampus and lymphocytes; (6) alteration in the balance between anti-inflammatory/ pro-inflammatory cytokines; and (7) decreased levels of brain derived neurotrophic factor (BDNF) in the hippocampus and serum. These findings highlight the fact that oxidative damage and neurotrophic factors are present in both the brain and periphery, and suggest that oxidative stress and BDNF could be potential biomarkers for mood disorder. Dr. Ana Andreazza is working as part of a collaborative network in Canada, Brazil, Australia and Portugal, that is studying a large sample size of patients with mood disorders (bipolar disorder and depression), in order to determine whether mitochondrial dysfunction, oxidative stress markers, cytokines and BDNF levels may be used as biomarkers of progressive illness. As a secondary objective of their studies, Dr. Andreazza and colleagues will correlate their findings on the oxidative stress with cognitive impairment, accelerated aging (i.e. telomere shortening), and decreased levels of neurotrophic factors. In addition to identifying biomarkers that may be used to follow progressive illness, the results of this work may represent significant therapeutic targets. In the larger picture, the discovery of biomarkers for mood disorders and their incorporation into clinical decision-making could dramatically change the future of mental health care.