Fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse vs their unaffected siblings.
Level 3 - non-randomized controlled study
Nationwide population-based registry cohort study
PubMed 23147713 · doi:10.1001/jamapsychiatry.2013.268
What was done
Using Swedish nationwide registers (Multi-Generation Register and Hospital Discharge Register), researchers evaluated 2.3 million individuals born between 1950 and 1970. They calculated fertility ratios (FR)—the average number of children relative to the general population, adjusted for age, sex, family size, and diagnosis—for individuals diagnosed with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse, as well as for their unaffected siblings.
What was found
Except for women with depression, individuals with psychiatric disorders had significantly fewer children (FR 0.23–0.93; P < 10^-10), with greater reductions observed in men. Sisters of patients with schizophrenia and bipolar disorder had slightly higher fecundity (FR 1.02–1.03; P < .01), but this did not offset the deficit of affected individuals. Brothers of patients with schizophrenia and autism had reduced fecundity (FR 0.94–0.97; P < .001). Siblings of patients with depression and substance abuse had increased fecundity (FR 1.01–1.05; P < 10^-10), which fully compensated for the reduced fitness of affected individuals in depression.
Why it matters
This study clarifies how genetic liability to psychiatric conditions persists despite reduced reproduction. Strong negative selection acts against schizophrenia, autism, and anorexia nervosa (suggesting maintenance via de novo mutations or complex mechanisms), whereas depression and substance abuse susceptibility may persist partly through balancing selection favoring unaffected relatives.
Limits
Cases were ascertained via hospital discharge records, capturing more severe or inpatient presentations while potentially missing milder outpatient cases. The measure of fecundity reflects both biological fertility and social/behavioral childbearing patterns without distinguishing between them. Findings are derived from a single country's birth cohort (Sweden, 1950–1970) and may not generalize across different cultural or social environments.
Cited by
- supports Autism spectrum disorder (ASD) traits and associated genetic variants are associated with significantly lower fertility.