Information processing impairment: a clinical & neurodevelopmental perspective

Information processing impairments are a cardinal feature of patients with schizophrenia spectrum disorders. In human studies, these spectrum disorders are associated with abnormalities of gating functions, as measured by cerebral event related potential (ERP) P50 suppression and the prepulse inhibition (PPI) of the startle response. In a newly gathered cohort of 100 schizophrenia patients, failures of startle prepulse inhibitory function correlate differentially with positive and negative symptoms of schizophrenia. Impaired gating is also dramatically correlated with thought disorder, as measured by the Ego Impairment Index. Gender is a critical variable in this pattern of results. Thus, there is an orderly rational database that identifies PPI failures in schizophrenia patients and other subjects who fall within the schizophrenia spectrum. In related animal studies, there is a growing corpus of work relevant to neurodevelopmental risk factors that lead to impaired gating and are associated with specific CNS abnormalities. The early induction of ibotenic acid lesions of the ventral hippocampus in rat pups leads to post-adolescent failures in PPI. These lesioned rat pups have relatively normal levels of PPI until later in life (i.e., post-adolescence) when their PPI is reduced and supersensitive to disruption by dopamine agonists. These data indirectly support theories of second trimester viral insults to the developing hippocampus in pre-schizophrenic humans where there is a hypothesized delayed emergence of cognitive and behavioral deficits that are identifiable in the post-adolescent epoch of life. Experiments using the non-lesion, non-pharmacological manipulation of social isolation rearing (SIR) illustrate that SIR can lead to impaired PPI in adult rats. The SIR intervention is also associated with significant changes in brain organization and function. Thus, human and animal studies of gating functions allow us to draw important inferences about symptom correlates, neurobiological vulnerability and neurodevelopmental factors in the schizophrenia spectrum of disorders.