A systematic review and meta-analysis of the fertility of patients with schizophrenia and their unaffected relatives

Objective: We aimed to systematically evaluate the empirical evidence for the commonly held view that the reduced reproductive output in patients with schizophrenia is compensated for by an increased fitness in unaffected relatives. Secondary aims were to quantify the magnitude of the fertility disadvantage and the apparent gender difference in fertility of patients with schizophrenia. Method: We carried out a systematic review and meta-analysis of studies investigating the fertility of patients with schizophrenia, their siblings, their parents and the general population. Results: Patients with schizophrenia had reduced fertility compared with the general population, [Fertility Ratio (FR) = 0.39 (95% Confidence Interval (CI) = 0.35-0.44)]. Siblings of patients with schizophrenia had somewhat fewer offspring than the general population (FR = 0.96, 95% CI = 0.93-1.00). Parents of patients with schizophrenia had fertility similar to the general population (FR = 1.17, 95% CI = 0.94-1.46). Men had a greater impairment in fertility than women, both in patients (FR = 0.54, 95% CI = 0.50-0.57) and in their unaffected siblings (FR = 0.81, 95% CI = 0.71-0.92). Conclusion: Compensatory fitness advantage in siblings and parents cannot explain the maintenance of schizophrenia in the population. Alternative explanations include mutation-selection balance and the role of quantitative traits.