A systematic review and meta‐analysis of the fertility of patients with schizophrenia and their unaffected relatives
Abstract
Bundy H, Stahl D, MacCabe JH. A systematic review and meta‐analysis of the fertility of patients with schizophrenia and their unaffected relatives. Objective: We aimed to systematically evaluate the empirical evidence for the commonly held view that the reduced reproductive output in patients with schizophrenia is compensated for by an increased fitness in unaffected relatives. Secondary aims were to quantify the magnitude of the fertility disadvantage and the apparent gender difference in fertility of patients with schizophrenia. Method: We carried out a systematic review and meta‐analysis of studies investigating the fertility of patients with schizophrenia, their siblings, their parents and the general population. Results: Patients with schizophrenia had reduced fertility compared with the general population, [Fertility Ratio (FR) = 0.39 (95% Confidence Interval (CI) = 0.35–0.44)]. Siblings of patients with schizophrenia had somewhat fewer offspring than the general population (FR = 0.96, 95% CI = 0.93–1.00). Parents of patients with schizophrenia had fertility similar to the general population (FR = 1.17, 95% CI = 0.94–1.46). Men had a greater impairment in fertility than women, both in patients (FR = 0.54, 95% CI = 0.50–0.57) and in their unaffected siblings (FR = 0.81, 95% CI = 0.71–0.92). Conclusion: Compensatory fitness advantage in siblings and parents cannot explain the maintenance of schizophrenia in the population. Alternative explanations include mutation‐selection balance and the role of quantitative traits.
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CNVs with large effects on risk are likely to be rapidly removed from the population by natural selection because of the low fecundity in people with schizophrenia and other neurodevelopmental phenotypes.
“As a consequence of the low fecundity in people with schizophrenia and other neurodevelopmental phenotypes to which these CNVs contribute, CNVs with large effects on risk are likely to be rapidly removed from the population by natural selection.”
From De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia (2012) · cites this paper as [20]
Schizophrenia is associated with reduced fecundity, ∼40% that of the general population.
“Schizophrenia is associated with reduced fecundity, ∼40% that of the general population,20 or even lower according to the largest population-based study.21”
From De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia (2012) · cites this paper as [20]
Schizophrenia has a lifetime risk of about 0.7% and heritability of 60-80% despite reduced reproductive fecundity.
“Schizophrenia is a psychiatric disorder with a lifetime risk of about 0.7%1 and a heritability of 60–80%2,3 despite greatly reduced reproductive fecundity4,5.”
From Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia (2016) · cites this paper as [4]
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- Authors
- Bundy, H., Stahl, D., & MacCabe, J. H.
- Affiliations
- King's College London (GB)
- Corresponding author
- MacCabe, J. H.
- Venue
- Acta Psychiatrica Scandinavica
- Publisher
- Wiley
- Published
- 2010-10-20
- Volume
- 123
- Issue
- 2
- Pages
- 98-106
- ISSN
- 0001-690X (ISSN-L)
- 1600-0447
- OpenAlex
- W1484857706
- Cited by
- 150
- References
- 35
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 6 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 46 · 2019: 10 · 2018: 7 · 2017: 5 · 2016: 8 · 2015: 9 · 2014: 8 · 2013: 4 · 2012: 17
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Psychiatrica Scandinavica (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Evolutionary Psychology and Human Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- schizophrenia, fertility, reproductive fitness, unaffected relatives, siblings, parents, gender differences in fertility, mutation-selection balance, quantitative traits
- MeSH terms
- Birth Rate, Family, Female, Fertility, Humans, Male, Parents, Schizophrenia, Sex Factors, Confidence Intervals, Chi-Square Distribution, Siblings
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