Resting-state functional connectivity and spontaneous brain activity in early-onset bipolar disorder: A review of functional Magnetic Resonance Imaging studies

Background: Early-onset bipolar disorder (BD) is a complex psychiatric illness characterized by mood swings, irritability and functional impairments. To improve our understanding of the pathophysiology of the disorder, we collected the existing resting-state functional Magnetic Resonance Imaging (rs-fMRI) studies exploring resting-state functional connectivity (rs-FC) and spontaneous activity alterations in children and adolescents with BD. Methods: A search on PubMed, Web of Science and Scopus was conducted to identify all the relevant rs-fMRI investigations conducted in early-onset BD. A total of 14 studies employing different methodological approaches to explore rs-FC and spontaneous activity in early-onset BD were included (independent component analysis, n = 1; seed-based analysis, n = 7; amplitude of low frequency fluctuations analysis, n = 2; regional homogeneity analysis, n = 4). Results: Overall, the studies showed abnormalities within the Default Mode Network (DMN) and between the DMN and the Salience Network (SN). Moreover, widespread alterations in rs-FC and spontaneous brain activity within and between cortico-limbic structures, involving primarily the occipital and frontal lobes, amygdala, hippocampus, insula, thalamus and striatum were also reported. Limitations: The small sample sizes, the use of medications, the presence of comorbidities and the heterogeneity in methods hamper the integration of the study findings. Conclusions: Early-onset BD seems to be characterized by selective rs-FC and spontaneous activity dysfunctions in DMN and SN and in the cortico-limbic and cortico-striatal circuits, which could explain the emotive and cognitive deficits observed in this disabling psychiatric illness.