Neuroprotection in emerging psychotic disorders

Aim: The emerging phase of psychotic disorders is pleomorphic and fluctuates in presentation. Hence, from a clinical perspective, treatment modalities are often unclear. This paper investigates the rational and potential use of neuroprotective agents in emerging psychotic disorders. Methods: Medline databases were searched from 1966 to 2006 followed by the cross-checking of references using following keywords: neuroprotection, apoptosis, natural cell death, neurodevelopment, plasticity, neurogenesis, combined with brain and schizophrenia. Results: Agents such as atypical antipsychotics, antidepressants, omega-3 fatty acids, modulators of glutamateric neurotransmission (e.g. ampakines, glycine, memantine), erythropoietin, N-acetylcysteine, COX-2 inhibitors or antioxidants have neuroprotective (anti-apoptotic) properties and may therefore be able to protect brain maturational processes disturbed in emerging psychotic disorders. Clinical trials suggest that atypical antipsychotics, antidepressants, omega-3 fatty acids and lowdose lithium as sole treatments were able to improve symptoms and functioning, and delay or in some cases even prevent the onset of frank psychosis. Initially these substances have been chosen because they have been used either as sole or augmentation treatments in established psychotic disorders. However, chronicity and already effective treatments may overshadow their potential clinical use in emerging (prodromal) psychosis. Conclusion: Neuroprotection as a new treatment paradigm for at-risk mental states seems to be promising and pilot data are suggestive that more benign interventions may already be sufficient to delay or even prevent the onset of frank psychosis. A coordinated research effort will be necessary to address the question which agents should be used under which circumstances.