Parental age difference and schizophrenia

H. Bourne

Via P. De Cristofaro 40, 00136 Roma, Italy

To offer hypotheses based simply on clinical experience is pathetically out of date. Perhaps it may be allowed, for a moment, in deference to my advancing years.

Fifty years ago, with some other purpose in mind, I surveyed some 370 cases of schizophrenia in young men. It struck me that, with mild but undue frequency, there was a tendency for their parents’ ages to be unusual in one of two ways – either by there being a > 10-year age difference in the couple, or by the mother being older than the father. In decades of practice since, my impression has remained that this association with schizophrenia occurs a little too often to be accidental. Of course, to prove that would have required time, money, thousands of cases, and the inclination to undertake a major statistical enterprise, and none of those was in my reach.

It is therefore gratifying now to find that, at long last, my hypothesis has been solidly supported, albeit inadvertently, by Zammit et al (2003). They demonstrate, in a 26-year follow-up of some 50 000 teenagers, that advancing paternal age is a risk factor for schizophrenia, while maternal age is not – the latter being a significant negative finding to which, however, they pay no further attention. Since this means that, compared with the normal population, people with schizophrenia tend to have fathers who are older but mothers who are not, it follows necessarily that the age difference between the parents also tends to be greater than in the general population.

This does away with Zammit et al’s hypothesis that advancing paternal age is pathogenic for schizophrenia by virtue of increasing germ cell mutations. There is no need to invoke genetic mutation with age, given the linkage they have uncovered, in passing, between parental age difference and schizophrenia. A more economical hypothesis is that to be born to a statistically off-centre parental couple is a risk factor for schizophrenia – or, in more ordinary language, there is some psychological risk in being the child of an odd couple.

Are there other social oddities waiting to be identified statistically in schizophrenogenic couples?

REFERENCES

Zammit, S., Allebeck, P., Dalman, C., et al (2003) Paternal age and risk for schizophrenia. British Journal of Psychiatry, 183, 405 -408.[Abstract/Free Full Text]


 

Authors’ reply

S. Zammit

Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK

P. Allebeck

Department of Social Medicine, Gothenburg University, Sweden

C. Dalman

Psychiatric Epidemiology, Stockholm Centre of Public Health, Sweden

I. Lundberg and T. Hemmingson

Department of Public Health Sciences, Karolinska Institute, Stockholm, Sweden

M. J. Owen

Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK

G. Lewis

Division of Psychiatry, University of Bristol, Bristol, UK

Dr Bourne suggests that as advancing paternal, but not maternal age is associated with schizophrenia, then people with schizophrenia tend to have fathers who are older than the normal population, but mothers who are not. This is incorrect. In our study, as others have previously shown, advancing maternal age is associated with schizophrenia, but this association can be explained by paternal age, a consequence of the fact that there is strong correlation between parental ages.

Dr Bourne makes an interesting point, however, based on his observations in clinical practice that large differences in parental ages may result in some sort of psychological risk factor for schizophrenia in the offspring. In fact, the absolute difference between parental ages in our study is associated with schizophrenia in the crude analysis, but this association is eliminated after adjusting for the effects of paternal age (Table 1). As paternal age increases, the difference between maternal and paternal ages must also increase given the biological age threshold for motherhood. However, in younger fathers with older mothers, even large differences in parental ages is not associated with increasing risk of schizophrenia. In contrast, the association between advancing paternal age and risk of developing schizophrenia is not altered by adjusting for parental differences. The hypothesis of increasing germ cell mutations remains the most likely explanation for this association between advancing paternal age and risk of schizophrenia.


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Table 1 Crude and adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for developing schizophrenia according to maternal—paternal age difference
 





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