Findings published in the Archives of General Psychiatry show that patients with schizophrenia, autism, and anorexia nervosa have significantly fewer children compared with the general population, suggesting these conditions are under strong selection to be removed from the population.
Conversely, bipolar disorder (BD) was not under strong negative selection, with depression and substance abuse possibly maintained by genes that are beneficial under some circumstances but detrimental in others, say Robert Power (King's College London, UK) and co-authors.
"Gene-environment or gene-gene interactions have a large role in these disorders, for which some supporting evidence exists in depression," they note.
They add: "Our results suggest that strong selection exists against schizophrenia, autism, and anorexia nervosa and that these variants may be maintained by new mutations or an as-yet unknown mechanism."
For the study, the team measured the reproductive fitness of patients with schizophrenia, autism, BD, depression, anorexia nervosa, and substance disorder and their unaffected siblings compared with the general population.
Findings from a total of 2.3 million individuals born during 1950‑1970 in Sweden revealed that, except for women with depression, patients had significantly fewer children than the general population, with greater reductions seen among men (fertility ratio [FR]=0.23‑0.93) than women (FR=0.47‑0.92).
The researchers observed a similar gender difference in fecundity among siblings of affected individuals, with patients' sisters having an increased fecundity, at an FR range of 1.02‑1.03. This increase was too small on its own to counterbalance the reduced fitness of affected patients, say the authors. In comparison, brothers of patients with schizophrenia and autism showed a reduced fecundity, at an FR range of 0.94‑0.97.
Power and team also found that the degree of fecundity reduction in affected individuals and the associated increase among siblings differed by disorder, suggesting that "different types of psychiatric disorders are under different selection pressures."
According to the authors, the finding that men had greater affected fecundity suggests that psychiatric morbidity impairs interest or ability to find suitable mating partners, inhibits biologic fertility to a greater extent, or that male fertility is more susceptible to adverse effects of psychiatric treatment than female fertility.
The team notes that given the considerable overlap and shared genetic risk variants in psychiatric disorders, adjusting for comorbidities in the present study had little effect on the findings. However, the heterogeneity found within psychiatric disorders cautions against the generalization of genetic etiology.
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