Reimagining the Biopsychosocial Model: Transdiagnostic Factors to Precision Psychiatry

Background We recently reported evidence that a biopsychosocial model predicts lifetime histories of commonly comorbid early-onset psychiatric disorders. This transdiagnostic model was produced when incorporating either positron emission tomography–measured midbrain dopamine autoreceptors or functional magnetic resonance imaging (fMRI)–measured mesocorticolimbic responses during a monetary incentive delay task. Here, we tested whether a variant of this model incorporating brain responses to alcohol cues specifically predicts future alcohol problems. Methods Forty-four youths were assessed longitudinally for externalizing (EXT) behaviors between ages 10 and 16 years, completed fMRI scans and the Childhood Trauma Questionnaire (CTQ) at age 18, and completed the Alcohol Use Disorders Identification Test (AUDIT) at age 25. Binomial logistic regressions were then run with each region of interest. Results As hypothesized, the combination of high mesocorticolimbic responses to alcohol cues, high adolescent EXT behaviors, and high CTQ scores predicted higher AUDIT scores 7 years later. Model performance was improved by adding sex as a fourth factor. Significant mesocorticolimbic contributors to the models included the ventral ( p = .028) and associative striatum ( p = .017), anterior ( p = .029) and posterior cingulate ( p = .005), and ventromedial prefrontal cortex ( p = .030). All models exhibited good-to-excellent classification performance, with area under the curve values ranging from 0.83 to 0.87, predictive accuracy from 80% to 84%, sensitivity from 74% to 79%, and specificity from 84% to 92%. Conclusions Together, this work delineates a novel hierarchical model with precision psychiatry factors superimposed on transdiagnostic liability. High mesocorticolimbic reactivity to specific stimuli might shape the expression of psychopathology.