Connectomic Alterations Linked to Transdiagnostic Risk for Psychopathology at the Transition to Adolescence

Abstract

BACKGROUNDConvergent research identifies a general factor ("P factor") that confers transdiagnostic risk for psychopathology. However, brain functional connectivity patterns that underpin the P factor remain poorly understood, especially at the transition to adolescence when many serious mental disorders have their onset. OBJECTIVEIdentify a distributed connectome-wide neurosignature of the P factor and assess the generalizability of this neurosignature in held out samples. DESIGN, SETTING, AND PARTICIPANTSThis study used data from the full baseline wave of the Adolescent Brain and Cognitive Development (ABCD) national consortium study, a prospective, population-based study of 11,875 9- and 10-year olds. Data for this study were collected from September 1, 2016 to November 15, 2018 at 21 research sites across the United States. MAIN OUTCOMES AND MEASURESWe produced whole brain functional connectomes for 5,880 youth with high quality resting state scans. We then constructed a low rank basis set of 250 components that captures interindividual connectomic differences. Multi-level regression modeling was used to link these components to the P factor, and leave-one-site-out cross-validation was used to assess generalizability of P factor neurosignatures to held out subjects across 19 ABCD sites. RESULTSThe set of 250 connectomic components was highly statistically significantly related to the P factor, over and above nuisance covariates alone (ANOVA nested model comparison, incremental R-squared 6.05%, {chi}2(250) =412.1, p<4.6x10-10). In addition, two individual connectomic components were statistically significantly related to the P factor after Bonferroni correction for multiple comparisons (t(5511)= 4.8, p<1.4x10-06; t(5121)= 3.9, p<9.7x10-05). Functional connections linking control networks and default mode network were prominent in the P factor neurosignature. In leave-one-site-out cross-validation, the P factor neurosignature generalized to held out subjects (average correlation between actual and predicted P factor scores across 19 held out sites=0.13; pPERMUTATION<0.0001). Additionally, results remained significant after a number of robustness checks. CONCLUSIONS AND RELEVANCEThe general factor of psychopathology is associated with connectomic alterations involving control networks and default mode network. Brain imaging combined with network neuroscience can identify distributed and generalizable signatures of transdiagnostic risk for psychopathology during emerging adolescence.