The longitudinal trajectory of emotion regulation and associated neural activity in patients with bipolar disorder: A prospective fMRI study

Objectives Impaired emotion regulation is a key feature of bipolar disorder (BD) that presents during acute mood episodes and in remission. The neural correlates of voluntary emotion regulation seem to involve deficient prefrontal top-down regulation already at BD illness onset. However, the trajectory of aberrant neuronal activity during emotion regulation in BD is unclear. Methods We investigated neural activity during emotion regulation in response to aversive pictures from the International Affective Picture System in patients with recently diagnosed BD (n = 43) in full or partial remission and in healthy controls (HC) (n = 38) longitudinally at baseline and 16 months later. Results Patients with BD exhibited stable hypo-activity in the left dorsomedial prefrontal cortex (DMPFC) and right dorsolateral prefrontal cortex (DLPFC) and impaired emotion regulation compared to HC over the 16 months follow-up time. More DLPFC hypo-activity during emotion regulation correlated with less successful down-regulation (r = 0.16, p = 0.045), more subsyndromal depression (r = -0.18, p = 0.02) and more functional impairment (r = -0.24, p = 0.002), while more DMPFC hypo-activity correlated with less efficient emotion regulation (r = 0.16, p = 0.048). Finally, more DMPFC hypo-activity during emotion regulation at baseline was associated with an increased likelihood of subsequent relapse during the 16 months follow-up time (beta = -2.26, 95% CI [0.01; 0.99], p = 0.048). Conclusion The stable DLPFC and DMPFC hypo-activity during emotion regulation represents a neuronal trait-marker of persistent emotion regulation difficulties in BD. Hypo-activity in the DMPFC may contribute to greater risk of relapse.