Fertility of first-degree relatives of patients with schizophrenia: a three generation perspective

We explored the fertility in three generations; fertility of parents, siblings and offspring to patients with schizophrenia, to test the hypothesis that the decreased reproductive rate in the patients is compensated by an increased rate in their first-degree relatives. A population-based national database was created by linking the Swedish Multi-Generation and Hospital Discharge Registers. To maximize follow-up time for schizophrenia and reproductive history, three birth cohorts were selected: parental generation, born 1918-1927 (n=274464); affected generation, born 1932-1941 (n=108502) and offspring to affected generation, born 1951-1960 (n=103105). Ratios of estimated mean number of offspring were measured (fertility ratios), comparing the study subjects to the general population. The fertility among males with schizophrenia was decreased by over 70% (fertility ratio(patients/population)=0.29, 95% CI 0.25-0.35), whereas female patients had less than half as many offspring as the general female population (fertility ratio(patients/population)=0.48, 95% CI 0.42-0.55). When accounting for selection bias of larger families, no statistically significant difference was found among parents of patients with and without a diagnosis of schizophrenia. Further, the fertility among siblings of schizophrenic patients did not differ from the general population. A reduction in fertility was found among offspring to patients with schizophrenia, male offspring had 12% fewer offspring (fertility ratio(offspring/population)=0.88, 95%CI 0.77-1.01), while female offspring had 6% fewer offspring (fertility ratio(offspring/population)=0.94, 95% CI 0.84-1.05). In conclusion, we found reduced fertility in patients with schizophrenia and among their offspring that was not compensated by higher parental or sibling fertility.