Brain functional effects of psychopharmacological treatments in bipolar disorder

Functional magnetic resonance imaging (fMRI) studies have contributed to the understanding of bipolar disorder. However the effect of medication on brain activation remains poorly understood. We conducted an extensive literature review on PubMed and ScienceDirect to investigate the influence of medication in fMRI studies, including both longitudinal and cross-sectional studies, which aimed at assessing this influence. Although we reported all reviewed studies, we gave greater emphasis to studies with the most robust methodology. One hundred and forty studies matched our inclusion criteria and forty-seven studies demonstrated an effect of pharmacological treatment on fMRI blood oxygen level dependent (BOLD) signal in adults and children with bipolar disorder. Out of these studies, nineteen were longitudinal. Most of cross-sectional studies suffered from methodological bias, due to post-hoc analyses performed on a limited number of patients and did not find any effect of medication. However, both longitudinal and cross-sectional studies showing an impact of treatment tend to suggest that medication prescribed to patients with bipolar disorder mostly influenced brain activation in prefrontal regions, when measured by tasks involving emotional regulation and processing as well as non-emotional cognitive tasks. FMRI promises to elucidate potential new biomarkers in bipolar disorder and could be used to evaluate the effect of new therapeutic compounds. Further research is needed to disentangle the effect of medication and the influence of the changes in mood state on brain activation in patients with bipolar disorder.