Schizophrenia has been associated with heightened stress responsivity in adolescence that precedes onset of psychosis. We now report that multiple stressors during adolescence in normal rats leads to deficits in adults analogous to that seen in schizophrenia patients. Moreover, impairment of stress control by lesion of the prelimbic prefontal cortex in adolescence caused previously subthreshold levels of stress to induce these deficit states when tested as adults. Thus, predisposition to stress hyper-responsivity, or exposure to substantial stressors, during adolescence can trigger a cascade of events that result in a schizophrenia-like profile in adults. This data can provide crucial information with respect to identifying markers for schizophrenia vulnerability early in life and, by mitigating the impact of stressors, prevent the transition to psychosis.