Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
17094843
TITLE
Resolving the paradox of common, harmful, heritable mental disorders: which evolutionary genetic models work best?
ABSTRACT
Given that natural selection is so powerful at optimizing complex adaptations, why does it seem unable to eliminate genes (susceptibility alleles) that predispose to common, harmful, heritable mental disorders, such as schizophrenia or bipolar disorder? We assess three leading explanations for this apparent paradox from evolutionary genetic theory: (1) ancestral neutrality (susceptibility alleles were not harmful among ancestors), (2) balancing selection (susceptibility alleles sometimes increased fitness), and (3) polygenic mutation-selection balance (mental disorders reflect the inevitable mutational load on the thousands of genes underlying human behavior). The first two explanations are commonly assumed in psychiatric genetics and Darwinian psychiatry, while mutation-selection has often been discounted. All three models can explain persistent genetic variance in some traits under some conditions, but the first two have serious problems in explaining human mental disorders. Ancestral neutrality fails to explain low mental disorder frequencies and requires implausibly small selection coefficients against mental disorders given the data on the reproductive costs and impairment of mental disorders. Balancing selection (including spatio-temporal variation in selection, heterozygote advantage, antagonistic pleiotropy, and frequency-dependent selection) tends to favor environmentally contingent adaptations (which would show no heritability) or high-frequency alleles (which psychiatric genetics would have already found). Only polygenic mutation-selection balance seems consistent with the data on mental disorder prevalence rates, fitness costs, the likely rarity of susceptibility alleles, and the increased risks of mental disorders with brain trauma, inbreeding, and paternal age. This evolutionary genetic framework for mental disorders has wide-ranging implications for psychology, psychiatry, behavior genetics, molecular genetics, and evolutionary approaches to studying human behavior.
DATE PUBLISHED
2006 Aug
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2006/11/11 09:00
medline 2007/01/24 09:00
entrez 2006/11/11 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Keller MC Keller Matthew C MC Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23219. matthew.c.keller@gmail.com
Miller G Miller Geoffrey G
INVESTIGATORS
JOURNAL
VOLUME: 29
ISSUE: 4
TITLE: The Behavioral and brain sciences
ISOABBREVIATION: Behav Brain Sci
YEAR: 2006
MONTH: Aug
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0140-525X
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Behav Brain Sci
COUNTRY: England
ISSNLINKING: 0140-525X
NLMUNIQUEID: 7808666
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
T32 MH-20030 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adaptation, Physiological genetics
Adaptation, Psychological genetics
Evolution, Molecular genetics
Genetic Predisposition to Disease genetics
Humans genetics
Mental Disorders genetics
Models, Genetic genetics
Quantitative Trait Loci genetics
Selection, Genetic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's