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.

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Resolving the paradox of common, harmful, heritable mental disorders: which evolutionary genetic models work best?

The hypothesis is presented that the etiology of schizophrenia is neurodevelopmental: schizophrenia is a disorder occurring in extremely late maturers, whereas manic-depressive psychosis affects early maturers. This hypothesis is related to recent neurobiological findings and also to the following epidemiological and demographic topics covered by the author in her review of social class, marriage, and fertility in schizophrenia: Kretschmer's observations of body type differences between patients with schizophrenia and manic-depressive psychosis; trends in the incidence of schizophrenia and manic-depressive psychosis in industrialized versus developing economies; changing epidemiology of the subtypes of schizophrenia and of manic-depressive psychosis; sex differences in manic-depressive psychosis and schizophrenia; fertility and childlessness in schizophrenia; selection for marriage in schizophrenia; marriage patterns, inbreeding, and schizophrenia; social class, social mobility, and occupation in schizophrenia; social mobility and social selection; excess of schizophrenia in the lowest strata of society; social class, course, and outcome; and social stress and schizophrenia.

/pdf/social-class-marriage-and-fertility-in-schizophrenia-4fadetney1.pdf

Social Class, Marriage, and Fertility in Schizophrenia

OBJECTIVE: This study determined the general fertility rate and age-specific fertility rates for women with psychotic disorders. METHOD: This historical matched-cohort study of patient records from a primary care database (the General Practice Research Database) was carried out for women of childbearing age (15–44 years) with psychotic disorders. RESULTS: The women with psychotic disorders (N=7,936) had a lower overall general fertility rate than the normal comparison subjects (N=23,023), although fertility was only significantly lower in the women aged 25 and above. This lower fertility rate was less marked in women with affective psychoses. There was no evidence that treatment with neuroleptics influenced the fertility rate in women with nonaffective psychoses. CONCLUSIONS: This study found markedly lower fertility rates in women with psychotic disorders than in matched normal comparison subjects, particularly in women with nonaffective disorders. Knowledge of fertility rates in women with psychotic dis...

The general fertility rate in women with psychotic disorders.

Fertility and pregnancy in women with psychotic disorders.

Although women with serious mental illness have normal fertility rates, the literature points to multiple risk factors and a paucity of emotional and economic support during the initial phases of parenthood. Since most research has focused on child outcomes, the extent and nature of parenting problems experienced by these mothers are not adequately understood. An emphasis on the context of parenting and the meaning of pregnancy and childbearing to these mothers is called for and implications for research and clinical practice are discussed.

MOTHERHOOD FOR WOMEN WITH SERIOUS MENTAL ILLNESS: Pregnancy, Childbirth, and the Postpartum Period

The fertility rates of 223 female schizophrenic outpatients and 479 female nonschizophrenic outpatients were compared to a probability sample of 300 women residing in the same geographic area, metropolitan Atlanta, and from the same social strata as the patients. Age- and race-adjusted comparisons showed that the mean number of children per woman and levels of unwanted and unplanned fertility did not differ in the different diagnostic groups. Furthermore, the rates were not lower for the psychiatric patients than for the general population. In order to reduce an important source of psychiatric morbidity, those in the mental health professions need to pay more attention to the family planning desires of their patients.

Winthrop A. Burr

Papers

Fertility in psychiatric outpatients.

Fertility in PsychiatricOutpatients