BACKGROUND: Offspring of patients with schizophrenia exhibit poorer school performance compared with offspring of non-schizophrenic parents. We aimed to elucidate the mechanisms behind this association. METHOD: We linked longitudinal national population registers in Sweden and compared school performance among offspring of schizophrenic parents with offspring of non-schizophrenic parents (1 439 215 individuals with final grades from compulsory school 1988-2006). To investigate the mechanisms, we studied offspring of schizophrenic patients and controls within the same extended families. We investigated genetic effects by stratifying analyses of parent-child associations according to genetic relatedness (half-cousins, full cousins and half-siblings). Environmental effects were investigated by comparing school performance of offspring of schizophrenic fathers and of schizophrenic mothers, respectively, and by stratifying the analyses according to environmental relatedness while controlling genetic relatedness (paternal and maternal half-cousins, paternal and maternal half-siblings). RESULTS: Offspring of parents with schizophrenia had poorer overall school performance than unrelated offspring of non-schizophrenic parents (-0.31 s.d.). Variability in genetic relatedness greatly moderated the strength of the within-family association (β=-0.23 within exposure-discordant half-cousins, β=-0.13 within exposure-discordant full cousins, β=0.04 within exposure-discordant half-siblings), while no evidence was found that the environment affected offspring school performance. CONCLUSIONS: Genetic factors account for poorer school performance in children of parents with schizophrenia. This supports that cognitive deficits found in individuals with schizophrenia and their relatives might be genetically inherited. Early detection of prodromal signs and impaired functioning of offspring of patients with schizophrenia could lead to earlier and better tailored interventions.
BACKGROUND: Offspring of patients with schizophrenia exhibit poorer school performance compared with offspring of non-schizophrenic parents. We aimed to elucidate the mechanisms behind this association. METHOD: We linked longitudinal national population registers in Sweden and compared school performance among offspring of schizophrenic parents with offspring of non-schizophrenic parents (1 439 215 individuals with final grades from compulsory school 1988-2006). To investigate the mechanisms, we studied offspring of schizophrenicpatients and controls within the same extended families. We investigated genetic effects by stratifying analyses of parent-child associations according to genetic relatedness (half-cousins, full cousins and half-siblings). Environmental effects were investigated by comparing school performance of offspring of schizophrenic fathers and of schizophrenic mothers, respectively, and by stratifying the analyses according to environmental relatedness while controlling genetic relatedness (paternal and maternal half-cousins, paternal and maternal half-siblings). RESULTS: Offspring of parents with schizophrenia had poorer overall school performance than unrelated offspring of non-schizophrenic parents (-0.31 s.d.). Variability in genetic relatedness greatly moderated the strength of the within-family association (β=-0.23 within exposure-discordant half-cousins, β=-0.13 within exposure-discordant full cousins, β=0.04 within exposure-discordant half-siblings), while no evidence was found that the environment affected offspring school performance. CONCLUSIONS: Genetic factors account for poorer school performance in children of parents with schizophrenia. This supports that cognitive deficits found in individuals with schizophrenia and their relatives might be genetically inherited. Early detection of prodromal signs and impaired functioning of offspring of patients with schizophrenia could lead to earlier and better tailored interventions.
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