Resting-state fMRI signals in offspring of parents with bipolar disorder at the high-risk and ultra-high-risk stages and their relations with cognitive function

Bipolar disorder (BD) has been associated with dysfunctional resting-state brain functioning. However, it is still not known whether the aberrant functioning occurs and predict cognitive functioning before illness onset. We examined the resting-state regional and network dysfunctioning, and their correlates with neurocognitive performance, in the high-risk (HR) and ultra-high-risk (UHR) stages of bipolar disorder. Using amplitude of low-frequency fluctuations (ALFF), region homogeneity (ReHo) and hypothesis-driven region-of-interest (ROI)-based connectivity, we examined resting-state fMRI data of 8- to 25-year-old healthy offspring (HR, n = 28) and offspring with subthreshold syndromes (UHR, n = 22) of a BD parent, and age-matched healthy controls without any personal or family psychopathology (HC, n = 46). Participants' neurocognitive profiles were assessed using the MATRICS Consensus Cognitive Battery (MCCB). ALFF signals in the left putamen and right rolandic operculum were lower in the HR group compared to the HC group. In contrast, ALFF signals were increased in the UHR group in the right middle pars orbitalis of the inferior frontal gyrus, right calcarine sulcus and right cerebellum. Connectivities between the right amygdala and left inferior temporal gyrus, between the left hippocampus and inferior occipital gyrus, and between the left hippocampus and middle pars orbitalis gyrus were decreased in the HR group compared to the HC group. In UHR versus HC group, connectivity between the right amygdala and the left hippocampus and left insula was increased, and connectivity between the left hippocampus and the left insula and the cerebellum was also increased. Among cognitive measures, processing speed was positively correlated with ALFF signals in the left putamen in the HR offspring. In the UHR offspring, processing speed, attention, and verbal learning/memory were positively correlated with the functional connectivity between the left hippocampus and cerebellum. Offspring of parents with BD in the HR and UHR stages show largely non-overlapping patterns of atypical resting-state signals and functional connectivity that predicted cognitive functioning, possibly reflecting inherited abnormalities and/or complimentary reactions.