Resting state functional connectivity in women with bipolar disorder during clinical remission

Periods of euthymia in bipolar disorder (BD) serve as a valuable time to study trait-based pathophysiology. The use of resting state functional connectivity (Rs-FC) can aid in the understanding of BD pathophysiology free of task or mood state biases. The present study investigated two unexplored areas of Rs-FC research in bipolar remission: (i) Rs-FC in women, controlling for the potential influence of premenstrual symptoms, and (ii) the use of both independent component analysis (ICA) and seed-based analysis (SBA) to investigate Rs-FC.

We investigated Rs-FC of the default mode network, meso-paralimbic network and fronto-parietal network in a sample of 32 euthymic women with BD and 36 age-matched controls during the mid-follicular phase of their menstrual cycle. Rs-FC was assessed with ICA and SBA using the posterior cingulate cortex (PCC), amygdala and dorsolateral prefrontal cortex (dlPFC) as seed points for their respective resting state networks.

In BD, compared to controls, SBAs revealed increased coupling between the PCC and the angular gyrus (P=.002, false discovery rate [FDR]-corrected) and between the right dlPFC and the brainstem (P=.03, FDR-corrected). In BD only, PCC-angular gyrus coupling was correlated with anxiety symptoms. Group differences in Rs-FC using ICA did not survive multiple comparisons.

Negative findings from whole-brain ICA Rs-FC may reflect a state of clinical remission in BD. Heightened activation between the PCC and the angular gyrus and between the dlPFC and the brainstem may reflect (i) an abnormal trait integration of affective information during clinical remission and/or (ii) an adaptive compensatory mechanism required for clinical stabilization.