Short duration of marriage at conception as an independent risk factor for schizophrenia

Short duration of marriage (DoM) is a risk factor for preeclampsia that is also related to the risk for schizophrenia. This analysis examined the risk for schizophrenia associated with DoM and its independence from parental psychiatric disorders, parental ages and fathers' age at marriage.

Method: Relative Risks (RR) for schizophrenia were estimated using continuous and stratified Cox proportional hazards models in the 90,079 offspring from the prospective population-based Jerusalem birth cohort study (1964-1976). Schizophrenia diagnos in offspring and parental diagnoses of schizophrenia or other psychiatric conditions were identified by cross-linkage to Israel's psychiatric case registry. DoM and paternal age at marriage were abstracted from birth certificates.

Results: In the full model, RR for schizophrenia decreased for each 5 years DoM: 0.83 (0.75-0.95), p_trend = 0.0015. Stratified analyses showed the greatest RR risk for DoM <2 years: 1.53 (1.11-1.66) with lesser risk for 2-4 years DoM: 1.38 (1.05-1.81) compared to more DOM of 10+ years. DoM effects were independent from parental psychiatric diagnoses (RRs = 2-6, p~0.00001), paternal age (1.34: p = 0.0001 /5 years- including fathers of 25-34 years). The apparent risk related to later fathers' age at marriage (1.27: p < 0.0001) was eliminated in after accounting for DoM and later paternal age.

Conclusions: Offspring born to couples married for less than 3 years, across all paternal ages, harbored a small increased risk for schizophrenia, which was independent of parental psychiatric disorders and paternal age. Fathers who married late had particularly short DoM, which, along with paternal age, completely explained the risks related to later paternal age at marriage. Further studies are needed to replicate these results and examine if pathogenic pathways include prenatal immune activation.