Evidence of advanced parental age linked to sporadic schizophrenia

Νovel emergence of schizophrenia (SCZ) in its sporadic type has been linked, among many candidate epigenetic factors, with advanced paternal age (PA) and advanced maternal age (MA). The most common hypothesis to the paternal age effect is the increased "de novo mutations" during spermatogenesis, while the maternal age hypothesis, though controversial, is at most based on studies that support higher frequency of perinatal complications. Our sample consisted of 462 subjects with DSM-IV-TR SCZ spectrum disorders from the outpatient unit of Eginition Hospital in Athens, Greece, who were further screened for heritability and were divided in a group of sporadic cases (no reported family history for SCZ related disorders up to 2nd degree relatives) and a group of familial SCZ-spectrum disorder cases (positive reported history for SCZ spectrum). These two groups of patients were compared regarding either paternal or maternal age, while the familial type band was used as a control group. The aim of this retrospective file study was to examine whether advanced parental age may contribute in novel appearance of non-affective psychosis in offspring. Using logistic regression analysis, we found that the risk for the sporadic type, as compared to familial type, showed a significant increase for both advanced MA (OR=4.39, p=0.001) and PA (OR=1.92, p=0.012). After adjusting for confounding effects for the other parent's age and gender, the risk effect for the sporadic type of SCZ remained statistically significant for both advanced MA (OR=4.04, p=0.002) and advanced PA, but with a loss of statistical power (OR=1.72, p=0.049). Few studies have been conducted in Greece concerning the role of parental age in SCZ. Our study is consistent with current literature which indicates that both advanced MA and PA may contribute to an increased risk for emergence of sporadic type of SCZ. Furthermore, it is implied that this risk for the sporadic type as compared to the familial type could be higher for advanced MA than advanced PA. Patients with the sporadic type of SCZ, though clinically indistinguishable from the patients with the familial type of the disorder, may share other pathophysiological underlying mechanisms in which parental age, especially advanced MA, may be a candidate mediator. However, future studies could help clarify the role of both PA and MA in the pathophysiology of the disorder.