Generalized and Specific Neurocognitive Deficits in Prodromal Schizophrenia

Background Neurocognitive deficits are considered to be central to the pathophysiology of schizophrenia, and the neurodevelopmental model suggests that such deficits precede full-blown psychosis. The present study examined performance on a broad neuropsychological battery of young subjects considered to be at clinical high risk for schizophrenia, who were subsequently followed to determine clinical outcome. Methods Subjects were 38 clinical high-risk patients (58% male patients; mean age = 16.5) and 39 sex- and age-matched healthy control subjects. At baseline, all high-risk patients had attenuated (subpsychotic) schizophrenialike positive symptoms. Clinical follow-up data of at least 6 months duration was available on 33 patients, of whom 12 developed nonaffective psychotic disorders. Results At baseline, clinical high-risk patients had significantly impaired global cognitive performance relative to control subjects and to estimates of their own prior intellectual functioning. Measures of verbal memory and executive functioning/working memory showed significantly greater impairments; visuospatial functioning was relatively spared. Prodromal patients who later developed psychosis had significantly lower verbal memory scores at baseline compared with patients who remained nonpsychotic. Conclusions Verbal memory deficits may be an important risk marker for the development of schizophrenia-spectrum psychotic disorders, possibly indicating the presence of a prefrontal-hippocampal neurodevelopmental abnormality. Generalized neurocognitive impairment may be a nonspecific vulnerability marker.