The role of neuroprotection in schizophrenia

There have been several recent advances in the ability to identify people at high risk of developing psychosis. This development has spawned efforts at preventing progression to psychosis in individuals with prodromal symptoms of schizophrenia with different approaches including cognitive-behavioral therapy, family psychoeducation, and low-dose antipsychotic medication (e.g., risperidone [Risperdal], olanzapine).³⁰ Although data emerging from some of these trials have been promising, a recent review concluded that there was insufficient evidence to draw any definitive conclusions about the effectiveness of any of these therapeutic approaches at present due to small sample sizes.³⁰ Larger, well-designed studies are now required to replicate these preliminary observations. Ultimately, greater success in preventing the onset of psychosis in patients may depend upon developing a better understanding of the underlying pathophysiology of schizophrenia. Several lines of evidence suggest that anatomic pathology is present at the first episode of schizophrenia. While schizophrenia is widely believed to be a neurodevelopmental disorder, it also seems to encompass limited neurodegenerative features in the early phase of illness. Some data suggest that progression of these anatomic deficits in both the prodromal phase and during the first episode of illness may predict longitudinal course. Strategies aimed at reducing gray matter loss in the early phase of illness potentially hold promise for improving functional outcomes. The observation that gray matter loss may be ameliorated with some second-generation antipsychotics suggests that these drugs may offer some degree of neuroprotection. It is possible that the improved clinical outcomes associated with clozapine and olanzapine treatment may in part be mediated by the neuroprotective properties of these agents.