Paternal age, size at birth, and size in young adulthood – risk factors for schizophrenia

Abstract

It is appropriate to consider schizophrenia a neurodevelopmental disorder with its pathogenesis going back to gestation and early childhood. Schizophrenia is a rare disease and large cohorts are needed to study its etiology. The aim of this paper is to review the results of recent Swedish record-linkage studies with a focus on: (i) measures of fetal and childhood growth in relation to schizophrenia in adulthood and (ii) paternal age in relation to schizophrenia. A record-linkage was created between national registers, including the Medical Birth Register, the Military Service Conscription Register, and the Inpatient Hospital Discharge Register. More than 700 000 subjects born between 1973 and 1980 were followed in these registers from birth to 31 December 2001/2002. The results showed no evidence of an association between birth weight and schizophrenia. An association of birth length with schizophrenia was observed, with short babies showing the highest risk. Short stature and low BMI in young adulthood were associated with increased risk. Short babies who became tall, or developed high BMI as adults, were not at increased risk. In fully adjusted analyses, the risk of schizophrenia was 4.62 (95% confidence interval : 2.28; 9.36) times higher in subjects whose fathers were ≥50 years old and at time of conception than in subjects whose fathers were 21–24 years old. Growth and development in fetal life and childhood are influencing the risk of schizophrenia in adulthood, but the underlying causal pathways are still unknown. De novo mutations in the germ cells of older fathers may play a causal role in the etiology of some cases of schizophrenia.