Brain Functional Connectome Defines a Transdiagnostic Dimension Shared by Cognitive Function and Psychopathology in Preadolescents

Background: Cognitive function and general psychopathology are two important classes of human behavior dimensions that are individually related to mental disorders across diagnostic categories. However, whether these two transdiagnostic dimensions are linked to common or distinct brain networks that convey resilience or risk for the development of psychiatric disorders remains unclear.

Methods: The current study is a longitudinal investigation with 11,875 youths from the Adolescent Brain Cognitive Development (ABCD) Study at ages 9 to 10 years at the onset of the study. A machine learning approach based on canonical correlation analysis was used to identify latent dimensional associations of the resting-state functional connectome with multidomain behavioral assessments including cognitive functions and psychopathological measures. For the latent resting-state functional connectivity factor showing a robust behavioral association, its ability to predict psychiatric disorders was assessed using 2-year follow-up data, and its genetic association was evaluated using twin data from the same cohort.

Results: A latent functional connectome pattern was identified that showed a strong and generalizable association with the multidomain behavioral assessments (5-fold cross-validation: ρ = 0.68-0.73 for the training set [n = 5096]; ρ = 0.56-0.58 for the test set [n = 1476]). This functional connectome pattern was highly heritable (h = 74.42%, 95% CI: 56.76%-85.42%), exhibited a dose-response relationship with the cumulative number of psychiatric disorders assessed concurrently and at 2 years post-magnetic resonance imaging scan, and predicted the transition of diagnosis across disorders over the 2-year follow-up period.

Conclusions: These findings provide preliminary evidence for a transdiagnostic connectome-based measure that underlies individual differences in the development of psychiatric disorders during early adolescence.