There is considerable scope for developing a more explicit role for ethnography within the research program proposed in the article. Ethnographic studies of cultural micro-evolution would complement experimental approaches by providing insights into the “natural” settings in which cultural behaviours occur. Ethnography can also contribute to the study of cultural macro-evolution by shedding light on the conditions that generate and maintain cultural lineages.

Mesoudi et al.'s new synthesis for cultural evolution closely parallels the evolutionary synthesis of Neo-Darwinism. It too draws inspiration from population genetics, recruits other fields, and, unfortunately, also ignores development. Enculturation involves many serially acquired skills and dependencies that allow us to build a rich cumulative culture. The newer synthesis, evolutionary developmental biology, provides a key tool, generative entrenchment, to analyze them.

We are encouraged that the majority of commentators endorse our evolutionary framework for studying culture, and several suggest extensions. Here we clarify our position, dwelling on misunderstandings and requests for exposition. We reiterate that using evolutionary biology as a model for unifying the social sciences within a single synthetic framework can stimulate a more progressive and rigorous science of culture.

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.

The target article skillfully evaluates data on mental disorders in relation to predictions from evolutionary genetic theories of neutral evolution, balancing selection, and polygenic mutation-selection balance, resulting in a negative outlook for the likelihood of success finding genes for mental disorders. Nevertheless, new conceptualizations, methods, and continued interactions across disciplines provide hope.

In this commentary, we critique the appropriate behavioural features for evolutionary genetic analysis, the role of the environment, and the viability of a general evolutionary genetic model for all common mental disorders. In light of these issues, we suggest that the authors may have prematurely discounted the role of some of the mechanisms they review, particularly balancing selection.

Genetically and neurodevelopmentally, there may be a thousand schizophrenias, yet there would be no schizophrenia at all without active contribution from all of us; none – outside the primitive processes that regulate our relationship with one another. In order to understand the nature of schizophrenia as it unfolds relatively uniformly in the social context, we need to depart from an evolutionarily more feasible understanding of society.

Keller & Miller (K&M) propose that many psychiatric disorders are best explained in terms of a genetic watershed model. This view challenges traditional evolutionary accounts of psychiatric disorders, many of which have tried to argue in support of a presumed balanced polymorphism, implying some hidden adaptive advantage of the alleles predisposing people to psychiatric disorders. Does this mean that evolutionary ideas are no longer viable to explain psychiatric disorders? The answer is no. However, K&M's critical evaluation supports the view that psychiatric disorders are not categorically distinct from normalcy, and that evolutionary psychopathology should be grounded in rigorous empirical testing.

The mutation-selection hypothesis may extend to understanding normal personality variation. Traits such as emotional stability, agreeableness, and conscientiousness figure strongly in mate selection and show evidence of non-additive genetic variance. They are linked with reproductively relevant outcomes, including longevity, resource acquisition, and mating success. Evolved difference-detection adaptations may function to spurn individuals whose high mutation load signals a burdensome relationship load.

The target article excludes ancestral neutrality as a cause for the inheritance of schizophrenia, with an argument relating to selection against a single allele in the Finnish population. However, drift would predominate over selection within subisolates of the Finnish population. Comparisons of subisolates with heterogeneous populations may provide clues to the endophenotypic structure of complex polygenetic heritable mental disorders.

Diverse evidence from genomics, epidemiology, neurophysiology, psychology, and evolutionary biology converges on simple general mechanisms, based on negative secondary effects of strong selection, for how mental disorders such as psychosis have evolved and how they are sustained.

We describe delusional disorder–jealous type (“morbid jealousy”) with the adaptationist perspective used by Darwinian psychiatrists and evolutionary psychologists to explain the relatively common existence and continued prevalence of mental disorders. We then apply the “harmful dysfunction” analysis to morbid jealousy, including a discussion of this disorder as (1) an end on a continuum of normal jealousy or (2) a discrete entity.

We address two points. First, one must explain how different, rare mutations ultimately lead to common psychopathological conditions. The developmental instability model offers one solution. Second, Keller & Miller (K&M) perhaps miss the major processes other than variation fueled by rare deleterious mutations that account for interesting genetic variation in psychopathology, particularly when single alleles have non-negligible effects: Red Queen processes.

We assert that one of the examples used by Keller & Miller (K&M), namely, autism, is indeed common, and heritable, but we question whether it is harmful. We provide a brief review of cognitive science literature in which autistics perform superiorly to non-autistics in perceptual, reasoning, and comprehension tasks; however, these superiorities are often occluded and are instead described as dysfunctions.

Keller & Miller (K&M) briefly mention and promptly dismiss the idea that genes for harmful mental disorders may confer certain advantages to affected individuals. However, the authors fail to consider that the same genes (in low doses or reduced penetrance) may be adaptive for relatives, and that this may in part explain why they are retained in the gene pool.

Keller & Miller's (K&M's) conclusion appears to be correct; namely, that common, harmful, heritable mental disorders are largely maintained at present frequencies by mutation-selection balance at many different loci. However, their “paradox” is questionable.

Schizophrenia has attracted more than its fair share of evolutionary-based theories. The theories involving balancing selection are based on the assumption that the incidence of schizophrenia is invariant across time and place. Modern epidemiology allows us to reject this dogmatic belief. Once variations in the genetic and epidemiological landscape of schizophrenia are acknowledged, more productive research models can be generated.

Keller & Miller (K&M) make a persuasive case for the role of mutation-selection balance in the persistence of such disorders as schizophrenia. However, there is evidence relating illness liability to creativity, which seems to imply balancing selection. I argue for a hybrid position, where schizotypal personality traits can have fitness advantages or disadvantages, with mutational load and neurodevelopmental conditions determining which outcome is observed.

The only commonality between the various psychiatric disorders is that they reflect contemporary problematic behaviors. Some psychiatric disorders have a substantial genetic component, whereas others are essentially shaped by prevailing environmental factors. Because psychiatric ailments are so heterogeneous, any universal explanation of mental illness is not likely to have any clinical or theoretical utility.

Grouping severe mental disorders into a global category is likely to lead to a “theory of everything” which forcefully explains everything and nothing. Speculation even at the phenotypic level of the single disorder cannot be fruitful, unless specific and testable models are proposed. Inclusive fitness must be incorporated in such models.