No abstract

Background Offspring to patients with schizophrenia exhibit poorer school performance compared to offspring of non-schizophrenic parents. We aimed to elucidate the mechanisms behind this association. Methods We linked longitudinal national population registers in Sweden and compared school performance among offspring to schizophrenic parents to offspring of non-schizophrenic parents (N=1,439,215 with final grades from compulsory school 1988–2006). To investigate the mechanisms, we studied offspring to 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 to schizophrenic fathers and to 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 to parents with schizophrenia had poorer overall school performance than unrelated offspring to non-schizophrenic parents (−0.31 SD). 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, and 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 to patients with schizophrenia could lead to earlier and better tailored interventions.

Male schizophrenia patients are known to have a heavier smoking pattern compared with the general population. However, the mechanism for this association is not known, though hypothesis that smoking could alleviate symptomatology of schizophrenia and reduce side effects of antipsychotics has been suggested. The aims of this study were to validate the heavier smoking pattern among male schizophrenia patients and to investigate the possible mechanisms for the association. To enhance the reliability of the study, we recruited two large independent samples with 604 and 535 male Chinese schizophrenia patients, and compared their smoking pattern with that of 535 healthy male controls recruited from general population. Validated multiple indicators and multiple causes structure equation model and regression models were used to investigate the association of smoking with factors of schizophrenia symptomatology and with the usage of antipsychotics and their extra-pyramidal side effects (EPS). Schizophrenia patients had significantly heavier smoking pattern compared with healthy controls in our sample (42.4% vs. 16.8%, p<0.001 for current smoking prevalence; 23.5% vs. 43.3%, p<0.001 for smoking cessation rate; 24.5% vs. 3.0%, p<0.001 for heavy smoker proportion). Their smoking status was also found to be consistently and significantly associated with reduced negative factor scores for schizophrenia symptomatology (β = −0.123, p = 0.051 for sample-A; β = −0.103, p = 0.035 for sample-B; β = −0.082, p = 0.017 for the combined sample). However, no significant association was found between smoking and antipsychotics usage or risk of EPS. These results support that smoking is associated with improved negative symptoms, which could account for the heavier smoking pattern among schizophrenia patients.