Paternal Age and Risk of Schizophrenia in Adult Offspring

Abstract

Objective-The study examined the relation between paternal age at the time of birth and risk of schizophrenia in the adult offspring.Method-Data from the birth cohort of the Prenatal Determinants of Schizophrenia study were used in this study. Virtually all members of this birth cohort had prospective information about paternal age at the time of the offspring's birth. Subjects with schizophrenia and other schizophrenia spectrum disorders (N=71) among members of this birth cohort were previously ascertained. In separate analyses, paternal age was modeled as a continuous variable and as a categorical variable, and its relation with the risk of adult schizophrenia and other schizophrenia spectrum disorders and with the risk of schizophrenia separately were examined.Results-There was a marginally significant, monotonic association between advancing paternal age and risk of adult schizophrenia and schizophrenia spectrum disorders. The association held after the analysis controlled for the effects of maternal age and other potential con-founders. Similar results were observed when only subjects with schizophrenia were included in the analysis.Conclusions-Advanced paternal age at the time of birth of the offspring may be a risk factor for adult schizophrenia.We sought to investigate whether older paternal age at the time of birth is associated with schizophrenia and other schizophrenia spectrum disorders among the offspring. Several lines of evidence support a relation between older paternal age and schizophrenia spectrum disorders. First, most previous studies that examined this relationship have demonstrated positive associations (1-5), although these studies have been criticized for methodologic limitations. Most recently, Malaspina et al. (1), in a large Israeli birth cohort, demonstrated a robust and "dose-related" effect of paternal age on risk of schizophrenia and related disorders, a finding that was unaltered after adjusting for maternal age.A second reason for examining paternal age in relation to schizophrenia is that older age of the father at the time of birth has been associated with several congenital disorders (6-10). The etiology of these associations is believed to involve new, autosomal dominant mutations in the male germ cell line. If a disruption of fetal development plays a role in the pathogenesis of schizophrenia, then new mutations secondary to advanced paternal age may operate to increase the risk of this disorder by adversely affecting brain development. In the present investigation, we used data from the birth cohort of the Prenatal Determinants of Schizophrenia study (11) to address the relation of paternal age to schizophrenia. We hypothesized that the risk of schizophrenia would increase with advancing paternal age.The Prenatal Determinants of Schizophrenia study had several design advantages that permitted us to address significant limitations of previous studies. First, most prior studies relied on exposure data from a variety of sources, some of questionable reliability. In co...

Maternal household crowding during pregnancy and the offspring's risk of schizophrenia

“…While offspring whose mothers resided in a household with 5 or more inhabitants had 47% higher risk to developed schizophrenia (compared to those who resided with 4 or less), this finding was explained primarily by the impact of the paternal age. These results are consistent with the growing literature demonstrating the significant impact of paternal age on the offspring's risk of schizophrenia (Tsuchiya et al, 2005;Sipos et al, 2004;El-Saadi et al, 2004;Zammit et al, 2003;Byrne et al, 2003;Dalman and Allebeck, 2002;Brown et al, 2002). The number of rooms in the mother's household during pregnancy and the household crowding per se did not have a significant impact on the offspring's risk to develop schizophrenia.…”

Influence of Paternal Age in Schizophrenia

“…Par exemple, il a été montré une augmentation du risque de 1,71 par tranche de 10 ans d"âge paternel dans les psychoses du spectre de la schizophrénie contre 1,89 dans la schizophrénie [2]. De la même manière, Sipsos et al, [34], montrent une augmentation du risque de 1,12 par tranche de 10 ans d"âge paternel pour les psychoses non schizophréniques, non thymiques contre 1,47 pour la schizophrénie.…”

“…Plusieurs études ont montré que l"âge maternel n"est pas associé à une augmentation du risque de schizophrénie [2,5,18,34,37,38,42]. Néanmoins, Byrne et al, [3] mettent en évidence une augmentation du risque de schizophrénie, lorsque la mère a plus de 40 ans, après ajustement sur l"âge paternel et l"existence d"antécédents psychiatriques familiaux, mais cette corrélation disparaît après ajustement sur les facteurs socio-économiques.…”

“…Par exemple, le risque de schizophrénie lié à l"âge paternel n"est pas modifié par le nombre de frères et soeurs [2,5,38].…”

“…Le statut marital [5] et économique [3,34], le niveau d"éducation parentale [2,3], les facteurs démographiques [3], les facteurs saisonniers [3,34], l"ethnie [2], les facteurs maternonéonataux (les antécédents de psychose maternelle [5], les complications obstétricales [5], le poids de naissance [34], le score d"APGAR [34]), le décès d"un parent avant 18 ans [34] ou avant la première hospitalisation [3], ne modifient pas significativement les résultats concernant l"influence de l"âge paternel sur le risque de schizophrénie.…”