Spatial working memory as a cognitive endophenotype of schizophrenia: assessing risk for pathophysiological dysfunction

Research suggests that first-degree relatives and individu-als with schizophrenia spectrum personality disorders (SSPD) may represent nonpenetrant carriers of the genetic diathesis for schizophrenia. This study examined visuospa-tial working memory (SWM) as a cognitive endophenotype of schizophrenia by expanding the concept of risk for path-ophysiological dysfunction beyond overt psychosis. Risk was thus defined by familial status and the presence or absence of SSPD. SWM was assessed in the following groups, in order of decreasing likelihood of genetic vulner-ability: 23 patients with schizophrenia, 17 SSPD relatives of patients with schizophrenia, 23 non-SSPD relatives of patients with schizophrenia, 14 SSPD community members with no family history of psychosis, and 36 non-SSPD com-munity members. SWM performance during a computer task was quantified by A-Prime. Relative risk ratios for SWM deficits were compared among the groups. Com-pared with community non-SSPD volunteers, relative risk (RR) of SWM deficits was significantly elevated in patients with schizophrenia (RR = 3.76, p =.002) and SSPD family members (RR = 2.97, p =.027), but not in the family non-SSPD (RR = 1.88, p =.241) or community SSPD (RR = 1.03, p =.971) groups. The pattern of SWM performance deficits reflected the proposed model of latent genetic liability, upholding SWM as a viable cognitive endophenotype. The results underscore the importance of including both familial liability and the schizophrenia spectrum when considering risk for schizophrenia and schizophrenia-related traits. This is particularly relevant for research efforts to identify pathophysiological compo-nents of the disease. Key words: relative risk/genetics/schizotyp