Increasing Paternal Age Associated With Decreased Learning Capacity in 1989, Maurice Auroux

Hum Reprod. 1989 Oct;4(7):794-7. Links
Paternal age and mental functions of progeny in man.Auroux MR, Mayaux MJ, Guihard-Moscato ML, Fromantin M, Barthe J, Schwartz D.
Biologie de la Reproduction et du Developpement, CHU Bicetre, Le Kremlin-Bicetre, France.

Hum Reprod. 1989 Oct;4(7):794-7. Links
Paternal age and mental functions of progeny in man.Auroux MR, Mayaux MJ, Guihard-Moscato ML, Fromantin M, Barthe J, Schwartz D.
Biologie de la Reproduction et du Développement, CHU Bicêtre, Le Kremlin-Bicêtre, France.

The effects of maternal age on the quality of offspring are well known. Those due to the father's age are less obvious, apart from the role of increasing paternal age in the onset of many dominant autosomal disorders. But an experimental model has demonstrated that, in rats, increasing paternal age, without any other anomalies, might produce a decreased learning capacity in progeny. The object of the epidemiological investigation presented here was to verify whether this effect might also occur in man. The study involved the distribution of scores obtained in psychometric tests by 18-year-old male subjects, according to their father's age at the time of their birth. This distribution indicated not only that increasing paternal age is accompanied by effects similar to those observed in animals, but also that very young paternal age was also related to these effects. Thus, the curve of such scores produced an inverted U-shape, with maximum scores obtained when the father was about thirty years of age. Maternal age did not appear to play a part in this event. These results pose the problem of identifying genetic and/or psychosocial factors which might have an impact on the quality of the conceptus.

PMID: 2606957 [PubMed - indexed for MEDLINE]


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"Next, we examined if parental age was related to intelligence in healthy adolescents. We reasoned that if de novo genetic changes can cause schizophrenia, there might be effects of later paternal age on cognitive function, since cognitive problems are intertwined with core aspects of schizophrenia. For this study, we cross-linked data from the Jerusalem birth cohort with the neuropsychological data from the Israeli draft board (Malaspina et al., 2005a). We found that maternal and paternal age had independent effects on IQ scores, each accounting for ~2 percent of the total variance. Older paternal age was exclusively associated with a decrement in nonverbal (performance) intelligence IQ, without effects on verbal ability, suggestive of a specific effect on cognitive processing. In controlled analyses, maternal age showed an inverted U-shaped association with both verbal and performance IQ, suggestive of a generalized effect."

The effects of maternal age on the quality of offspring are well known. Those due to the father's age are less obvious, apart from the role of increasing paternal age in the onset of many dominant autosomal disorders. But an experimental model has demonstrated that, in rats, increasing paternal age, without any other anomalies, might produce a decreased learning capacity in progeny. The object of the epidemiological investigation presented here was to verify whether this effect might also occur in man. The study involved the distribution of scores obtained in psychometric tests by 18-year-old male subjects, according to their father's age at the time of their birth. This distribution indicated not only that increasing paternal age is accompanied by effects similar to those observed in animals, but also that very young paternal age was also related to these effects. Thus, the curve of such scores produced an inverted U-shape, with maximum scores obtained when the father was about thirty years of age. Maternal age did not appear to play a part in this event. These results pose the problem of identifying genetic and/or psychosocial factors which might have an impact on the quality of the conceptus.

Finally, we examined if paternal age was related to the risk for autism in our cohort. We found very strong effects of advancing paternal age on the risk for autism and related pervasive developmental disorders (Reichenberg et al., in press). Compared to the offspring of fathers aged 30 years or younger, the risk was tripled for offspring of fathers in their forties and was increased fivefold when paternal age was >50 years. Together, these studies provide strong and convergent support for the hypothesis that later paternal age can influence neural functioning. The translational animal model offers the opportunity to identify candidate genes and epigenetic mechanisms that may explain the association of cognitive functioning with advancing paternal age.

A variant of schizophrenia
A persistent question is whether the association of paternal age and schizophrenia could be explained by psychiatric problems in the parents that could both hinder their childbearing and be inherited by their offspring. If this were so, then cases with affected parents would have older paternal ages. This has not been demonstrated. To the contrary, we found that paternal age was 4.7 years older for sporadic than familial cases from our research unit at New York State Psychiatric Institute (Malaspina et al., 2002). In addition, epidemiological studies show that advancing paternal age is unrelated to the risk for familial schizophrenia (Byrne et al., 2003; Sipos et al., 2004). For example, Sipos found that each subsequent decade of paternal age increased the RR for sporadic schizophrenia by 1.60 (1.32 to 1.92), with no significant effect for familial cases (RR = 0.91, 0.44 to 1.89). The effect of late paternal age in sporadic cases was impressive. The offspring of the oldest fathers had a 5.85-fold risk for sporadic schizophrenia (Sipos et al., 2004); relative risks over 5.0 are very likely to reflect a true causal relationship (Breslow and Day, 1980).