Mapping the neurodevelopmental predictors of psychopathology

Neuroimaging research has uncovered a multitude of neural abnormalities associated with psychopathology, but few prediction-based studies have been conducted during adolescence, and even fewer used neurobiological features that were extracted across multiple neuroimaging modalities. This gap in the literature is critical, as deriving accurate brain-based models of psychopathology is an essential step towards understanding key neural mechanisms and identifying high-risk individuals. As such, we trained adaptive tree-boosting algorithms on multimodal neuroimaging features from the Lifespan Human Connectome Developmental (HCP-D) sample that contained 956 participants between the ages of 8 to 22 years old. Our feature space consisted of 1037 anatomical, 1090 functional, and 192 diffusion MRI features, which were used to derive models that separately predicted internalizing symptoms, externalizing symptoms, and the general psychopathology factor. We found that multimodal models were the most accurate, but all brain-based models of psychopathology yielded out-of-sample predictions that were weakly correlated with actual symptoms (r² < 0.15). White matter microstructural properties, including orientation dispersion indices and intracellular volume fractions, were the most predictive of general psychopathology, followed by cortical thickness and functional connectivity. Spatially, the most predictive features of general psychopathology were primarily localized within the default mode and dorsal attention networks. These results were mostly consistent across all dimensions of psychopathology, except orientation dispersion indices and the default mode network were not as heavily weighted in the prediction of internalizing and externalizing symptoms. Taken with prior literature, it appears that neurobiological features are an important part of the equation for predicting psychopathology but relying exclusively on neural markers is clearly not sufficient, especially among adolescent samples with subclinical symptoms. Consequently, risk factor models of psychopathology may benefit from incorporating additional sources of information that have also been shown to explain individual differences, such as psychosocial factors, environmental stressors, and genetic vulnerabilities.