The topology of adolescent mental health

The increased vulnerability to mental health problems in adolescence is frequently reported but poorly understood, hampered by a rigid diagnostic system which fails to capture intertwining symptoms and only loosely aligns with biological axes of variability. Here, we reconceptualised the mental health symptoms of young adolescents in the ABCD cohort (N=11862) as a latent topology of overlapping symptom dimensions, using an unsupervised machine learning algorithm to establish how transdiagnostic dimensions co-occur and overlap within individuals. Combining this with a novel classification approach, we delineated zones within this landscape, within which specific profiles of symptoms were robustly represented. These data-driven profiles were leveraged to establish associated resting-state functional connectivity and genetic characteristics. In doing so we recaptured the commonly reported p-factor axis as well as further symptom-subtype dimensions. Gene ontology analysis revealed that shared neurobiological and cellular mechanisms embedded in both the genome and transcriptome may confer risk for psychopathology.