Future perspectives on the treatment of cognitive deficits and negative symptoms in schizophrenia.

Drug discovery based on classic models for cognitive impairment and negative symptoms of schizophrenia have met with only modest success. Because cognitive impairment and negative symptoms may result from disruptions in neurodevelopment, more complex developmental models that integrate environmental and genetic risk factors are needed. In addition, it has become clear that biochemical pathways involved in schizophrenia form complex, interconnected networks. Points at which risk factors converge, such as brain-derived neurotrophic factor (BDNF) and protein kinase B (AKT), and from which processes involved in neuroplasticity diverge, are of particular interest for pharmacologic interventions. This paper reviews elements of neurodevelopmental models for cognitive deficits and negative symptoms of schizophrenia with the aim of identifying potential targets for interventions.