Online research in philosophy

Schizophrenia is a worldwide, prevalent disorder with a multifactorial but highly genetic aetiology. A constant prevalence rate in the face of reduced fecundity has caused some to argue that an evolutionary advantage exists in unaffected relatives. Here, I critique this adaptationist approach, and review – and find wanting – Crow's “speciation” hypothesis. In keeping with available biological and psychological evidence, I propose an alternative theory of the origins of this disorder. Schizophrenia is a disorder of the social brain, and it exists as a costly trade-off in the evolution of complex social cognition. Paleoanthropological and comparative primate research suggests that hominids evolved complex cortical interconnectivity (in particular, frontotemporal and frontoparietal circuits) to regulate social cognition and the intellectual demands of group living. I suggest that the ontogenetic mechanism underlying this cerebral adaptation was sequential hypermorphosis and that it rendered the hominid brain vulnerable to genetic and environmental insults. I argue that changes in genes regulating the timing of neurodevelopment occurred prior to the migration of Homo sapiens out of Africa 100,000–150,000 years ago, giving rise to the schizotypal spectrum. While some individuals within this spectrum may have exhibited unusual creativity and iconoclasm, this phenotype was not necessarily adaptive in reproductive terms. However, because the disorder shared a common genetic basis with the evolving circuitry of the social brain, it persisted. Thus schizophrenia emerged as a costly trade-off in the evolution of complex social cognition. Key Words: cortical connectivity; evolution; heterochrony; metarepresentation; primates; psychiatry; schizophrenia; social brain; social cognition.

This commentary challenges the argument that the diathesis for hallucinations is equivalent to that for schizophrenia. Evidence against this comes from data on the prevalence of hallucinations in schizophrenia, their nonspecificity, and their relationships with moderating variables. We also highlight, however, the manner in which the Behrendt & Young (B&Y) hypothesis extends recent neuroscientific theories of schizophrenia, and its potential treatment applications.

This commentary compares clinical aspects of ketamine with the amphetamine model of schizophrenia. Hallucinations and loss of insight, associated with amphetamine, seem more schizophrenia-like. Flat affect encountered with ketamine is closer to the clinical presentation in schizophrenia. We argue that flat affect is not a sign of schizophrenia, but rather, a risk factor for chronic schizophrenia.

Machine generated contents note: -- Clinical Theory -- 1. Psychiatry on schizophrenia: clinical pictures of a sublime object -- 2. Schizophrenia: the sublime text of psychoanalysis -- Cultural Theory -- 3. Antipsychiatry: schizophrenic experience and the sublime -- 4. Anti-Oedipus and the politics of the schizophrenic sublime -- 5. Schizophrenia, modernity, postmodernity -- 6. Postmodern schizophrenia -- 7. Glamorama, postmodernity and the schizophrenic sublime -- Conclusion.

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).

Evolutionary theories of schizophrenia must account for the maintenance of putative alleles in past and present populations despite reduced fitness among the affected. Such models must also account for extant intersex and population-level variability in the expression of schizophrenia. We argue that genetic balanced-polymorphism hypotheses remain the most robust in terms of modeling and testing these processes in populations.

While schizophrenia may be genetically determined up to a point, neither it nor its nearest relatives offer any sort of reproductive advantage to its sufferers. Instead, from an evolutionary point of view, schizophrenia is benign – it neither promotes nor inhibits survival to reproduction. Because it is benign, its rate of occurrence should remain fairly constant over time.

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. (Published Online November 9 2006).

If alleles that predispose to schizophrenia have reduced Darwinian fitness, their persistence in modern times is puzzling. Burns identifies the evolutionary genetics of schizophrenia as a central issue, but his treatment of it is not clear. Recent advances in evolutionary genetics can help explain the persistence of alleles that predispose to debilitating disorders such as schizophrenia, and can buttress Burns' core argument.

An evolutionary theory of schizophrenia needs to address all symptoms associated with the condition. Burns' framework could be extended in a way embracing behavioural signs such as catatonia. Burns' theory is, however, not specific to schizophrenia. Since no one single symptom exists that is pathognomonic for “schizophrenia,” an evolutionary proposal of psychiatric disorders raises the question whether our anachronistic psychiatric nosology warrants revision.