Spatial working memory as an endophenotype for schizophrenia

Background: Spatial working memory impairments are among the neurocognitive deficits that may mark genetic predisposition toward schizophrenia. We previously reported that impairment on the spatial span subtask of the Wechsler Adult Intelligence Scale-Revised increased in a dose-dependent manner with increasing genetic predisposition toward schizophrenia in a sample of discordant twins; however, it remains to be determined whether these deficits reflect difficulties with encoding, maintenance, manipulation, time-tagging of visual spatial information, storage capacity, or complex motor response. Methods: We developed a spatial delayed response task in which memory set size was parametrically varied, holding constant manipulation and decision processes. We then reassessed 80 of the previously studied twins (17 probands with 8 monozygotic co-twins and 13 dizygotic co-twins, and 42 healthy twins). Results: The spatial delayed response task was sensitive to genetic loading for schizophrenia but did not provide evidence for capacity limitations in probands or their co-twins. Conclusions: The findings suggest that deficits in the encoding or storage aspects of short-term spatial mnemonic processing may be an effective endophenotypic marker for schizophrenia. (C) 2003 Society of Biological Psychiatry.