Disease and state dependent neural markers in adolescents with BD. Understanding the neural bases of mania, depression and remission in a data fusion approach

Background Pediatric bipolar disorder (PBD) is a severe and disabling condition marked by alternating episodes of mania and depression, intermitted with periods of remission. A critical challenge in the field is to elucidate the neural mechanisms underlying these distinct mood states, as manic and depressive presentations reflect profoundly different clinical phenotypes. Despite their relevance, the functional and structural brain alterations associated with manic, depressed, and remitted states in PBD remain poorly understood. Method In this study, data on Resting-State Regional Homogeneity (ReHo) and grey matter concentration (GMC) were considered from 58 PBD patients and 21 healthy controls (HC), matched for age, gender, education, and IQ. The analysis was conducted using Parallel ICA, a multivariate data-driven approach that identifies joint patterns of covariation across resting-state functional and gray matter features. Results Among the nine RS-GM components identified, distinct disease- and state-dependent networks were detected. GM2, a cortico-limbic network, differentiated PBD from HC, suggesting a neural substrate of bipolar disorder independent of mood state. GM9, including the cingulate and the precuneus, distinguished manic from depressed states, while RS7, including the fusiform and occipital regions, was specific to depression compared to HC. RS1, including regions of the DMN, differentiated manic from remitted states. Conclusions These findings provide new fresh understanding on the common and separate functional and structural abnormalities displayed during mania, depression and remission phases in bipolar patients.