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Objective: To assess the 2-year impact of teacher-delivered, brief, personality-targeted interventions on internalizing and externalizing symptoms in an adolescent U.K. sample. Method: This cluster-randomized trial was run in 19 London schools (N = 1,024 adolescents). Trained school-based professionals delivered two 90-minute, CBT-based group interventions targeting 1 of 4 personality-risk profiles: anxiety sensitivity, hopelessness, impulsivity, or sensation seeking. Self-report depression, anxiety, and conduct disorder symptoms were assessed at 6-month intervals. Results: Interventions were associated with significantly reduced depressive, anxiety, and conduct symptoms (p < .05) over 2 years in the full sample, reduced odds of severe depressive symptoms (odds ratio [OR] = 0.74, CI = 0.58-0.96), and conduct problems (OR = 0.79, CI = 0.65-0.96), and a nonsignificant reduction in severe anxiety symptoms (OR = 0.79, CI = 0.59-1.05). Evaluating a priori personality-specific hypotheses revealed strong evidence for impulsivity-specific effects on severe conduct problems, modest evidence of anxiety sensitivity-specific effects on severe anxiety, and no evidence for hopelessness-specific effects on severe depressive symptoms. Conclusions: Brief, personality-targeted interventions delivered by educational professionals can have a clinically significant impact on mental health outcomes in high-risk youth over 2 years, as well as personality-specific intervention effects in youth most at risk for a particular problem, particularly for youth with high levels of impulsivity. Clinical trial registration information--Adventure: The Efficacy of Personality-Targeted Interventions for Substance Misuse and Other Risky Behaviors as Delivered by Educational Professionals; http://clinicaltrials.gov; NCT00776685. [ABSTRACT FROM AUTHOR]