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. (Published Online November 9 2006) Key Words: adaptation; behavior genetics; Darwinian psychiatry; evolution; evolutionary genetics; evolutionary psychology; mental disorders; mutation-selection balance; psychiatric genetics; quantitative trait loci (QTL). (shrink)

Eating disorders are evolutionarily novel conditions that lead to some of the highest mortality rates of all psychiatric disorders. Several evolutionary hypotheses have been proposed for eating disorders, but only the intrasexual competition hypothesis is extensively supported by evidence. We present the mismatch hypothesis as a necessary extension to the current theoretical framework of eating disorders. This hypothesis explains the evolutionarily novel adaptive metaproblem that has arisen when mating motives and readily available food rewards conflict with one another. This situation (...) is exacerbated in contemporary environments characterized by sedentary lifestyles, caloric surplus and the ubiquity of social comparisons that take place via social media. Our psychoneuroimmunological model connects ultimate-level causation with proximate mechanisms by showing how the adaptive metaproblem between mating motives and food rewards leads to chronic stress and, further, to disordered eating. Chronic stress causes neuroinflammation, which increases susceptibility to OCD-like behaviors that typically co-occur with eating disorders. Chronic stress upregulates the serotonergic system and causes dysphoric mood in patients with restricting-type anorexia nervosa. Dieting, however, reduces serotonin levels and dysphoric mood, leading to a vicious serotonergic-homeostatic stress/starvation cycle whereby cortisol and neuroinflammation increase through stringent dieting. Between-individual and within-individual variation in eating disorders partially arises from (co)variation in gut microbiota and stress responsivity, which influence neuroinflammation and the serotonergic system. In binge-related eating disorders, even a short period of fasting drops serotonin levels, a state alleviated by binge eating. Eating disorder treatments should aim to reduce the chronic stress, neuroinflammation, stress responsivity and gut dysbiosis that fuel the disorders. We review the advances that have been made in recent years in understanding how to best treat eating disorders, outlining directions for future clinical research. Connecting ultimate causes with proximate mechanisms and treating biopsychosocial causes rather than manifest symptoms will enable more effective and sophisticated long-term interventions for the millions of people who suffer from eating disorders. (shrink)

This hypothesis is that anorexia nervosa is a biologically driven disorder, and mammalian hibernation may offer clues to its pathogenesis. Using this approach, this hypothesis offers suggestions for employing heart rate variability as an early diagnostic test for anorexia nervosa; employing the ketogenic diet for refeeding patients, attending to omega 3:6 ratio of polyunsaturated fatty acids in the refeeding diet; and exploring clinical trials of the endocannabinoid-like agent, palmitoylethanolamde for patients with anorexia nervosa. This hypothesis also explores the role of (...) lipids and autoimmune phenomena in anorexia nervosa, and suggest a lipodomics study to search for antibodies in the serum on patients with anorexia nervosa. (shrink)

Based on the case study of Jeanne, the objective of this article is to study patterns of anorexic people’s specific subjectivity. We seek to identify, in a first-person perspective, the core vulnerability features of anorexic existence, beyond the dimension of food alone. The identification of a psychopathological structure results in a better understanding of Jeanne’s clinical situation and helps formulate psychotherapeutic and prophylactic recommendations. We suggest that so-called “denial” is a psychological mechanism that should be reconsidered. Denial is not a (...) mechanism pertaining to anorexic subjects alone, but is also a process encountered both in the patient’s family and in the therapeutic environment. Anorexic denial is based on anosognosia and the refusal to see one’s own thinness, while other people’s denial consists in a widespread inability to perceive the altruism and intersubjective problematic on which the existence of an anorexic subject fundamentally depends. (shrink)