Objective: Mood disorders have been associated with lateralized brain dysfunction, on the left-side for depression and right-side for mania. Consistently, asymmetry of cortical excitability, as measured by transcranial magnetic stimulation (TMS) has been reported. Here, we reviewed and summarized work assessing such measures bilaterally in mood disorders.

Methods: We performed a systematic review and extracted data to perform meta-analyses of interhemispheric asymmetry of motor cortex excitability, assessed with TMS, across different mood disorders and in healthy subjects. Additionally, potential predictors of interhemispheric asymmetry were explored.

Results: Asymmetry of resting motor threshold (MT) among healthy volunteers was significant, favoring lower right relative to left-hemisphere excitability. MT was also significantly asymmetric in major depressive disorder (MDD), but with lower excitability of the left -hemisphere, when compared to the right, no longer observed in recovered patients. Findings on intracortical facilitation were similar. The few trials including bipolar depression revealed similar trends for imbalance, but with lower right hemisphere excitability, relative to the left.

Conclusions: There is interhemispheric asymmetry of motor cortical excitability in MDD, with lower excitability on left when compared to right-side. Interhemispheric asymmetry, with lower right relative to left-sided excitability, was found for bipolar depression and was also suggested for healthy volunteers, in a pattern that is clearly distinct from MDD.

Significance: Mood disorders display asymmetric motor cortical excitability that is distinct from that found in healthy volunteers, supporting the presence of lateralized brain dysfunction in these disorders.