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

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.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).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.The small sample sizes, the use of medications, the presence of comorbidities and the heterogeneity in methods hamper the integration of the study findings.Early-onset BD seems to be characterized by selective rs-FC and spontaneous activity dysfunctions in DMN and SN as well as in the cortico-limbic and cortico-striatal circuits, which could explain the emotive and cognitive deficits observed in this disabling psychiatric illness.