FATHERS AGE RAISED VERY SIGNIFICANTLY IN SCHIZOPHENIA

We have two theories in the paternal age research one is men who wait to father until later in life for the first time and the other road is the last born child. In both cases the rate of schizophrenia is higher; in both cases the man is older. If he has six normal children and the last one (a daughter is schizophrenic) or he never had any children and he is in not 20, not 30, not 40, but 45+++++ and his son/daughter is schizophrenic. It seems that daughters have a higher chance of paternal age autism or schizophrenia at younger paternal ages. Researchers have found the reason for this and it is due to vital genes on the father's X chromosome that mutate and is passed only to daughters.

Seminal findings
We initially examined the relationship between paternal age and the risk for schizophrenia because it is well established that paternal age is the major source of de novo mutations in the human population, and most schizophrenia cases have no family history of psychosis. In 2001, we demonstrated a monotonic increase in the risk of schizophrenia as paternal age advanced in the rich database of the Jerusalem Perinatal Cohort. Compared with the offspring of fathers aged 20-24 years, in well-controlled analyses, each decade of paternal age multiplied the risk for schizophrenia by 1.4 (95 percent confidence interval: 1.2-1.7), so that the relative risk (RR) for offspring of fathers aged 45+ was 3.0 (1.6-5.5), with 1/46 of these offspring developing schizophrenia. There were no comparable maternal age effects (Malaspina et al., 2001).






If we had only considered the risk in the cases with paternal age >30 years, our risk would be equivalent to that reported by Sipos et al. (2004) in the Swedish study (15.5 percent). When paternal ages >25 years are considered, the calculated risk is much higher. Although the increment in risk for fathers age 26 through 30 years is small (~14 percent), this group is very large, which accounts for the magnitude of their contribution to the overall risk. The actual percentage of cases with paternal germ line-derived schizophrenia in a given population will depend on the demographics of paternal childbearing age, among other factors. With an upswing in paternal age, these cases would be expected to become more prevalent.









1979The British Journal of Psychiatry 134: 169-177 (1979)
© 1979 The Royal College of Psychiatrists

Raised parental age in psychiatric patients: evidence for the constitutional hypothesis
EH Hare and PA Moran

In two series of psychiatric patients (numbering about 6,000 and 2,000 respectively), the mean age of the mothers at the time of the patients' birth was found to be very significantly above expectation from the general population, and this was so for each of the major diagnostic groups. In the second series, the age of the fathers was also found to be very significantly above that expected from a sample survey of the general population, and this was so for each diagnostic group. Fathers' age was raised more than mothers', and was highest for schizophrenia. The raised parental age could not be explained in terms of the patient's year of birth or his father's social class. The raised mothers' age could largely be accounted for by regression on the raised fathers' age. The present findings, and those of previous studies, seem best explained on the hypothesis of a constitutional parental trait leading to delayed marriage
-------------------------------------------------------------------------------------
However, we think that approximately one third or one quarter of all schizophrenia cases may be attributable to paternal age. Paternal age is the major source of de novo genetic diseases in the human population, which was first described by Penrose8 in the 1950s. He hypothesized that this was due to copy errors that arose in the male germ line over the many cycles of sperm cell replications. These mutations accumulate as paternal age advances. After the Penrose report, medical researchers identified scores of sporadic diseases in the offspring of older fathers, suggesting that these could occur from gene mutations. Particular attention was paid to conditions in last-born children. In the 1960s, an excess of schizophrenia in last-born children was also reported.


-------------------------------------------------------------------------------------
-------------------------------------------------------------------------------------
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.










Malaspina D, Harlap S, Fennig S, Heiman D, Nahon D, Feldman D, Susser ES: Advancing paternal age and the risk of schizophrenia. Arch Gen Psychiatry 2001; 58:361-367[Abstract/Free Full Text]
Hare EH, Moran PA: Raised paternal age in psychiatric patients: evidence for the constitutional hypothesis. Br J Psychiatry 1979; 134:169-177[Abstract]
Gregory I: An analysis of family data on 1000 patients admitted to a Canadian mental hospital. Acta Genet Stat Med 1959; 9:54-96[Medline]
Johanson E: A study of schizophrenia in the male. Acta Psychiatr Scand Suppl 1958; 125
Kinnell HG: Parental age in schizophrenia (letter). Br J Psychiatry 1983; 142:204[Medline]