Targeting information-processing deficit in schizophrenia: a novel approach to psychotherapeutic drug discovery.
Current observations indicate that dysfunction of neuronal circuitry dynamics contributes to the abnormal information processing in the brain in schizophrenia. It is presumed that disrupted auditory gating, abnormal P300-evoked potentials and deficits in mismatch negativity in schizophrenic patients indicate impaired processing of information. Recently, abnormalities in neuronal synchrony and oscillatory activity have been postulated as the mechanisms that underlie the distorted perception and cognitive dysfunction associated with schizophrenia. These novel observations might reveal the pathophysiology of the disorder, and indicate potential targets for antipsychotic drug therapy. Neuronal circuitry dynamics, such as network oscillations and sensory-gating processes, are conserved phylogenetically, which provides excellent opportunities for designing translational biomarkers. Whether preclinical, experimental compounds that impact on network oscillations and sensory processing (such as agonists and modulators of alpha7 nicotinic acetylcholine receptors) elicit the same neurophysiological events in schizophrenic patients and, subsequently, improve perception and cognitive functions will be determined when these drug candidates are available clinically.
Hajós
Mihály
M
Neuroscience Department, CNS Discovery, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. mihaly.hajos@pfizer.com
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000503:physiopathology; D002540:Cerebral Cortex / Q000503:physiopathology; D004195:Disease Models, Animal; D015195:Drug Design; D004569:Electroencephalography / Q000187:drug effects; D004594:Electrophysiology; D006801:Humans; D008606:Mental Processes / Q000187:drug effects*; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents