Relapse in schizophrenia has devastating impacts of worsening symptoms, functional decline, emergence of injurious behaviors, and repeated hospitalizations. Its public health significance is indisputable, with now compelling need to understand the neurobiology and treatment of relapse. Antipsychotic medications reduce the frequency and severity of relapses, with postulated mechanisms including sustained cortical integrity, neurogenesis, and arrest of apoptosis. Recent preclinical - clinical studies now point to the importance of brain neurotrophins, ubiquitous agents, which play key roles in neuronal integrity/survival, in promoting synaptic plasticity, and serve as neurotransmitter modulators across monoaminergic (dopamine - serotonin), gabaergic, and cholinergic systems ... all areas of fundamental interest in schizophrenia research. Short-term translational studies point to changes in neurotrophins upon in schizophrenia and, more extensively studied, in relapse during mood disorders. Accordingly, the long term course and clinical import of alterations in neurotrophins in schizophrenia is now timely for systematic and extended study. The recently funded NIMH multicenter relapse prevention trial PROACTIVE now also provides a timely platform for complementary translational research in this supplemental application to evaluate the neurobiological significance of neurotrophins on relapse. Blood will be collected to determine plasma levels (previously shown to reflect brain concentration) of the neurotrophins - Brain Derived Neurotrophic Factor and Nerve Growth Factor - at baseline and at frequent intervals (including time of relapse) in over three hundred patients, with comprehensive evaluations over two and a half years of symptoms, functionality, relapse, and medication tolerability. This study has significance and innovation and it could advance understanding of the translational neurobiology of relapse in schizophrenia. [unreadable] [unreadable] [unreadable]