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 R50 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.European Journal of Endocrinology 155 S65-S69

Childhood Determinants of Adult Psychiatric Disorder

“…Using several linked population registers and therefore very large numbers, they have also confirmed clear associations between low birth lengths and later depression where short stature has persisted [65]. More interesting, perhaps, with such large numbers they were able to show a very large excess (OR 4.62; CIs 2.28 & 9.36) of schizophrenia in subjects whose fathers were over 50 years old at the time of conception, compared with those whose fathers were aged 21 to 24.…”

“…Where that short stature was maintained even in young adulthood and combined with low BMI, there was an increased risk, whereas short babies who became taller were not at increased risk [64, 65]. …”

Paternal age and psychiatric disorders: Findings from a Dutch population registry

“…In total, 17 cohort studies and 10 case-control studies investigated the association between increased paternal age and SCZ, ASD, MDD and/or BPD in the offspring (Brown et al, 2002; Byrne et al, 2003; Croen et al, 2007; Dalman and Allebeck, 2002; Durkin et al, 2008; Ekeus et al, 2006; Frans et al, 2008; Gillberg, 1982; Glasson et al, 2004; Grether et al, 2009; King et al, 2009; Lauritsen et al, 2005; Laursen et al, 2007; Lopez-Castroman et al, 2009; Malaspina et al, 2002; Malaspina et al, 2001; Menezes et al, 2010; Petersen et al, 2011; Rasmussen, 2006; Reichenberg et al, 2006; Sasanfar et al, 2010; Shelton et al, 2010; Sipos et al, 2004; Torrey et al, 2009; Tsuchiya et al, 2008; Tsuchiya et al, 2005; Zammit et al, 2003). Several studies with up to 13 297 patients (Miller et al , 2010) found that higher paternal age doubles or triples the risk for SCZ in the offspring of men above 40 years of age (Brown et al, 2002; Byrne et al, 2003; Dalman and Allebeck, 2002; Laursen et al, 2007; Malaspina et al, 2002; Malaspina et al, 2001; Rasmussen, 2006; Sipos et al, 2004; Torrey et al, 2009; Tsuchiya et al, 2005; Zammit et al, 2003).…”

“…Several studies with up to 13 297 patients (Miller et al , 2010) found that higher paternal age doubles or triples the risk for SCZ in the offspring of men above 40 years of age (Brown et al, 2002; Byrne et al, 2003; Dalman and Allebeck, 2002; Laursen et al, 2007; Malaspina et al, 2002; Malaspina et al, 2001; Rasmussen, 2006; Sipos et al, 2004; Torrey et al, 2009; Tsuchiya et al, 2005; Zammit et al, 2003). ASD was reported to be associated with both increased maternal and paternal age, with a recent emphasis for an increased paternal age (Croen et al, 2007; Durkin et al, 2008; Glasson et al, 2004; Grether et al, 2009; King et al, 2009; Lauritsen et al, 2005; Reichenberg et al, 2006; Sasanfar et al, 2010; Shelton et al, 2010; Tsuchiya et al, 2008).…”

Care of the Older Pregnant Patient Part II

“…Thus, a sperm produced by a 40-year-old man has gone through over 600 chromosome replications, thereby increasing the risk for spontaneous mutation. 37,38 Children born to older men also seem to have a slightly increased incidence of bipolar disorder 39,40 and are more likely to have lower intelligence 41 and poorer social 42 and neurocognitive 25 functioning. 32 Advanced paternal age thus places the offspring at increased risk for specific conditions associated with gene mutations caused by base substitutions.…”