Knowledge of the neurobiology of early onset psychosis is limited. We used proton magnetic resonance spectroscopy to investigate the possible existence of dorsolateral prefrontal brain biochemical abnormalities in adolescents with psychosis and to determine possible differential effects related to specific psychotic diagnoses. We measured the ratios of N-acetyl-aspartate (NAA), choline (Cho), and creatine (Cr) to water in two groups of adolescents with a first episode of psychosis (schizophrenia n=8; non-schizophrenia n=15) and in 32 healthy controls matched for age, gender, and years of education. Proton magnetic resonance spectroscopy at 1.5 T was used to study two 6.75-cc voxels placed in the left and right dorsolateral prefrontal region. The schizophrenia patients presented statistically significant reductions in NAA/water levels in the left dorsolateral prefrontal voxel as compared with non-schizophrenia patients and healthy controls. No significant differences were detected between groups for NAA/water in the right dorsolateral prefrontal voxel or for Cho/water and Cr/water levels in any hemisphere. A reduction of the NAA/water level in the left dorsolateral prefrontal region may be selectively present at the onset of psychosis during adolescence in patients who later progress to schizophrenia, but not in those who later progress to other psychotic disorders.