DESCRIPTION (provided by applicant): It has long been known that cannabis use can cause an acute psychotic episode in some individuals and recent epidemiologic studies suggest that frequent cannabis use in adolescents may lead to an acute psychosis that by itself develops into chronic schizophrenia. However, the majority of individuals who use cannabis do not develop a psychosis or schizophrenia. Thus, some additional mechanism must underlie the development of schizophrenia in those that are affected. If cannabis use can interact with an underlying genetic basis for the illness, changes in brain structure characteristic of patients with schizophrenia will be seen in those cannabis users who later develop schizophrenia. The brain changes may represent the genetic vulnerability for schizophrenia and be predictive of who develops the illness. Thus, Aim #1 (primary aim) of this proposal is to determine whether brain structural deviances in temporal and frontal lobes and their white matter connections will predict which cannabis users develop schizophrenia. To accomplish this we will evaluate consecutive admissions with a first psychotic episode subsequent to cannabis use admitted to two large NYC psychiatric emergency rooms. These patients will be compared with adolescent cannabis users who never had a psychotic episode, and age, sex, and social class matched non-cannabis using controls. The presence of brain structural anomalies, particularly those characteristic of patients with chronic schizophrenia psychoses will be determined by MRI scans. All cannabis using subjects will have a diagnostic follow-up evaluation one and two years subsequent to the first psychotic episode to determine who developed a diagnosis of schizophrenia or whether the initially non-psychotic individuals remained symptom-free. Aim #2 of this proposal is to examine whether brain abnormalities among cannabis users with a first schizophrenic-like psychosis are associated with increased genetic risk for schizophrenia. This will be achieved by obtaining family information from reliable family informants. This study will ultimately have implications for early treatment strategies in adolescent cannabis users who are at high genetic-risk for psychosis and suggest early biological warning signs through MRI evaluations of individuals who have an acute psychosis following cannabis use.