COGNITIVE DEFICITS AS INTERMEDIATE PHENOTYPE IN SCHIZOPHRENIA

Background: Cognitive deficits have been demonstrated both in patients with schizophrenia and in their unaffected first-degree relatives, suggesting that it might be considered as a familial vulnerability marker. Substantial impairment have been described for short term memory, attention, working memory, executive function. Therefore cognitive impairment has been suggested as a endophenotype We used the neuropsychological battery for estimate the principals schizophrenia cognitive disfunctions order to determine which components are impaired in both patients and their siblings, possibly reflecting shared genetic effects. Methods: We studied 184 subjects. 60 patients with schizophrenia: 36 males; mean ± SD; age = 33.6 ± 9.5 years; TIB (Intelligence Short Test, premorbid IQ) = 106.31 ± 9.56; parental socioeconomic status (Hollingshead Scale) = 30.1 ± 16.1; handedness (Edinburgh Scale) = 0.7 ± 0.4. 54 unaffected siblings: 30 males; mean + SD; age = 35.8 ± 9 years; TIB (Intelligence Short Test, premorbid IQ) = 107.7 ± 9.1; parental socioeconomic status (Hollingshead Scale) = 28.3 ± 16.2; handedness (Edinburgh Scale) = 0.7 ± 0.4. 70 normal controls: 31 males; mean + SD; age = 32.9 ± 7.2 years; TIB (Intelligence Short Test, premorbid IQ) = 113.7 ± 6; parental socioeconomic status (Hollingshead Scale) = 33.3 ± 13.4; handedness (Edinburgh Scale) = 0.7 ± 0.4. Subjects underwent a set of neuropsychological tests assessing WM (N-back), sustained attention (Continuous Performance Test, CPT), executive function (Wisconsin Card Sorting Test, WCST), cognitive flexibility (Trail Making Test A-B) and we calculated a Z score for all subjects. Results: There was no significant differences between diagnostic groups in any socio-demographic variables. Consistent with previous reports healthy siblings had an average performance at the composite score which was in between that of healthy controls and that of patients with schizophrenia. Moreover our results demonstrate a diagnosis effect on working memory performance and TMT score where siblings had an intermediate performance between that of schizophrenic patients and controls. Discussion: These results demonstrate a significant evidence of potential susceptibility of siblings to cognitive impairments suggesting an association with genetic predisposition to schizophrenia. Moreover this study suggests the opportunity of using WM and cognitive flexibility as a neurocognitive endophenotype for investigation in schizophrenia research