Abstract Background We recently reported evidence that commonly comorbid early onset psychiatric disorders are predicted by a biopsychosocial model composed of adolescent externalizing (EXT) behaviors, early life adversity, and midbrain dopamine autoreceptor availability, as measured with positron emission tomography (PET). Aims 1.0 x 10-21). In every model, EXT and CTQ scores were individual predictors (p 0.001). At age 14, reward anticipation responses were significant predictors in the ventral striatum, caudate, putamen, and anterior cingulate. At age 19, significant predictors were in the ventral striatum. The relation between trauma and diagnoses was partially mediated by higher EXT (indirect path B = 0.0535, 95% CI = 0.0301-0.0835), and moderated by fMRI responses in the cingulate (p = 0.0038) and putamen (p = 0.014) at age 14. Low striatal reward anticipation responses were associated with higher anhedonia. In Study 2, the combination of high mesocorticolimbic responses to Alcohol vs. Juice cues, high EXT scores, and high CTQ scores predicted future alcohol use problems (p 0.05). fMRI responses were significant contributors to the model in the ventral striatum, associative striatum, anterior and posterior cingulate cortices, and ventromedial prefrontal cortex (p ≤ 0.05). Discussion & Conclusions These findings tentatively identify constituents of a hierarchical diathesis-stress model that has (i) transdiagnostic predictive value for commonly comorbid early onset disorders, and (ii) narrower predictive value for future alcohol problems. For the latter, high mesocorticolimbic responses to disease-specific cues might imbue the stimuli with aberrant salience leading to distinct symptoms and disorders – these perturbations might be best identified after controlling for early life adversity and behavioral trajectories.
Marco Leyton (Fri,) studied this question.