Gene-environment interaction in schizophrenia: season-of-birth effect reveals etiologically different subgroups

Compared to the general population, one consistent finding in schizophrenia research is a significant surplus of schizophrenic births in the winter/spring months. There is little evidence that this is attributed to statistical artefacts. The "harmful effects' hypothesis offers the most plausible explanation for this phenomenon. Exogenous harmful effects, predominant during the cold season, may affect the developing immature fetal brain and thus constitute some of the factors predisposing to schizophrenic breakdown in adulthood. Neuropathological and epidemiological studies point to the second trimenon of gestation as the crucial period of fetal brain maturation. Recently, some studies found that the surplus in schizophrenic winter/spring births is mainly due to sporadic forms. In contrast, patients with high genetic risk of the disease even tended to have a birth deficit during this period. This suggests that schizophrenia is not a disease entity but consists of etiologically distinct subgroups on which the influence of genes and/or environment has to be weighted differently. On the one hand, in sporadic forms of the disease exogenous noxious agents may be of major etiological importance. On the other hand, in fetuses at high genetic risk neurodevelopment may already be disturbed due to a genetic defect and additional environmentally noxious agents can cause abortions, stillbirths and sudden infant deaths.