Later paternal age and sex differences in schizophrenia symptoms

Objective: Advanced paternal age is consistently associated with an increased risk for schizophrenia, accounting for up to a quarter of cases in some populations. If paternal age-related schizophrenia (PARS) involves a distinct etiopathology, then PARS cases may show specific characteristics, vis-à-vis other schizophrenia cases. This study examined if PARS exhibits the symptom profile and sex differences that are consistently observed for schizophrenia in general, wherein males have an earlier onset age and more severe negative symptoms than females. Method: Symptoms were assessed at baseline (admission) and during medication-free and treatment phases for 153 inpatients on a schizophrenia research unit, 38 of whom fulfilled operationally defined criteria for PARS (sporadic cases with paternal age ≥ 35). Results: Males and females with PARS had the same age at onset and a similar preponderance of negative symptoms, whereas the other (non-PARS) cases showed the typical earlier onset age and more severe negative symptoms in males. When medications were withdrawn, PARS cases showed significantly worse symptoms than non-PARS cases (higher total PANSS scores and positive, activation, and autistic preoccupation scores). However these symptoms globally improved with antipsychotic treatment, such that the differences between the PARS and other schizophrenia cases receded. Conclusion: The lack of sex differences in the age at onset and the greater severity of medication-free symptoms bolster the hypothesis that PARS has a distinct etiopathology. It also suggests that female sex does not exert a protective effect on the course of PARS, as it may in other forms of schizophrenia.