There is much interest, derived from current neurochemical, genetic, and therapeutic research, in the role of brain neurotrophins in schizophrenia. Neurotrophins play key roles in neuronal development and differentiation (i.e., promoting dendritogenesis and synaptogenesis), and in orchestrating the neuronal response to stress/noxious stimuli. Additionally, neurotrophins are modulators across monominergic (dopamine and serotonin), gabaergic and cholinergic systems. These roles focus on important areas of the etiopathophysiology of schizophrenia. Clinical studies show reductions in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NFG) in schizophrenic patients as compared to normal control subjects, as well as differences in patients receiving first-generation antipsychotics (FGAs) or second-generation antipsychotics (SGAs). We now report on BDNF levels in subjects with first-episode psychosis in comparison with normal healthy controls. Compared to normal controls (N=14; 290.5+/-38.81 pg/ml), first-episode psychotic patients showed significant reduction (N=15; 135+/-21.77 pg/ml; P=0.001; f=12.873) in plasma BDNF. Additionally, plasma BDNF levels showed a significant negative correlation (N=13' r=0.584, P=0.0362) only with positive symptom scores at base line and no significant correlations were found with any of the cognitive performance test battery or motor function test scores. Low BDNF levels at the onset of psychosis suggest that it may contribute to the pathogenesis of schizophrenia and/or perhaps could be a helpful neurobiological marker for possible early treatment intervention.