Non-invasive Brain Stimulation Normalizes Dopaminergic Transmission in the Frontostriatal Circuit to Alleviate Depression With Metabolic Disorders.

Brief Summary

Depression and metabolic disorder (MetD) are two of the most common and debilitating disorders worldwide, occurring with significant rates of comorbidity. This is a major clinical challenge as the outcomes of both conditions are worsened. Studies have uncovered that depression and metabolic disorder are associated with chronic, low-grade inflammation. In brain circuit level, patients with depression are characterized with aberrant frontostriatal (FS) circuit connectivity and reduced activity level that also associated with metabolic comorbidity. In neurotransmitter level, the dopaminergic pathway, that could be feedback regulated by immune and metabolic factors, has long been known to involve in emotional and metabolic homeostasis. More importantly, this dopamine (DA) input is critical to shaping the FS circuit-level dynamic connectivity and plasticity. Therefore, this study hypothesizes that inflammatory and metabolic dysregulations on DA transmission link to the aberrant FS function that cause mood and metabolic syndromes. To clarify the underlying mechanisms, 90 patients who meet the DSM-5 diagnostic criteria of major depressive episode in either major depressive disorder or bipolar disorder are planned to be recruit. FS functional connectivity and activation, before and after receiving 10 Hz repetitive transcranial magnetic stimulation (rTMS) to left dorsolateral prefrontal cortex will be measured. Then systemically analyze participants' clinical symptomology, neurocognitive function, inflammation and metabolic status. Possible correlations between indices, the effects of rTMS and differences between groups will be tested. Results could provide a chance for further understanding the pathophysiology of depression with MetD and comparing between unipolar and bipolar depression, and developing brain circuit based non-invasive brain stimulation personalized treatment for depression with MetD to achieve a better outcome.

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