The Impact of Lithium on Brain Function in Bipolar Disorder: An Updated Review of Functional Magnetic Resonance Imaging Studies

Lithium remains a gold standard treatment for bipolar disorder (BD), and functional magnetic resonance imaging (fMRI) studies have contributed to clarifying its impact on neural circuitries in affected individuals. However, the specific neurobiological mechanisms through which lithium exerts its effects on brain function are not fully understood. In this review, we aimed to summarize the results of recent fMRI studies evaluating the impact of lithium on brain functional activity and connectivity in patients diagnosed with BD. We performed a literature search of available sources found in the PubMed database reported in English since 2016, when the last available review on this topic was published. Five fMRI studies in resting-state condition and six studies performed during the execution of emotional tasks met the inclusion criteria. Overall, the available evidence supports normalizing effects of lithium on brain activity and connectivity. Most of these studies reported a normalization in prefrontal regions and interconnected areas involved in emotion regulation and processing, regardless of the task employed. Importantly, lithium treatment showed distinct patterns of activity/connectivity changes compared with other treatments. Finally, lithium modulation of neural circuitries was found to be associated with clinical improvement in BD. These results are consistent with the hypothesis that selective abnormalities in neural circuitries supporting emotion processing and regulation improve during lithium treatment in BD. However, the heterogeneity of the examined studies regarding study design, sample selection, and analysis methods might limit the generalizability of the findings and lead to difficulties in comparing the results. Therefore, in future studies, larger cohorts and homogeneous experimental tasks are needed to further corroborate these findings.