The ʻbig bangʼ theory of the origin of psychosis and the faculty of language

https://doi.org/10.1016/j.schres.2008.03.010Get rights and content

Abstract

Objective

To achieve a unified concept of the aetiology of psychosis.

Background

The nuclear symptoms of “schizophrenia” occur with approximately the same age- and sex-specific incidence in all human populations. No substantive environmental precipitant has been identified, and yet these “illnesses” are associated with deviations in brain structure that are uniform across populations, are established late in development and relate to the capacity for language. No genes have been identified by linkage or association strategies.

Argument

It is postulated that the variation

  • 1.

    relates precisely to the genetic mechanism that distinguishes the species Homo sapiens from its precursor.

  • 2.

    constitutes a class of epigenetic diversity intrinsic to the genetic control of the species characteristic (the “specific mate recognition system” according to the theory of HEH Paterson).

  • 3.

    reflects the role of the cerebral torque in the neuro-developmental re-organization that enabled the faculty of language.

A genetic mechanism involving both the X and the Y chromosomes is suggested by 1) evidence for anomalies of asymmetry of brain structure and function in the sex chromosome aneuploidies, 2) a same sex concordance effect for handedness, 3) sex differences in lateralization, and verbal and spatial ability, and their inter-relationships.

These three facts direct attention to the Xq21.3/Yp11.2 homology block that was established by an X to Y duplication 6 million years ago, ie at the time of origin of the hominid lineage. Within this block a gene pair (Protocadherin11X and Y) expressed as two cell surface adhesion molecules at axo-dendritic synapses has been subject to change (16 amino-acid substitutions in the Y, and critically 5 in the X sequence) in the hominid lineage. The X to Y duplication and its subsequent modification (4 deletions and a paracentric inversion) on the Y may have played a central role in hominid speciation with the most recent change (at around 160,000 years) representing the transition to language and modern Homo sapiens (the ʻbig bang'). The expression of genes within the homologous region is influenced by the extent to which the X and Y chromosomes pair in male meiosis (referred to as MSUC “meiotic suppression of unpaired chromosomes"). This mechanism generates epigenetic diversity relating to the species capacity for language; it is proposed as the basis of the genetic predisposition to psychosis.

Conclusion

Language and psychosis have a common origin in the genetic event (the ʻbig bang') that defined the species.

Section snippets

The search for the causes of “schizophrenia”

The notion, although not the name, of schizophrenia as a disease entity, is attributable to the conceptual move that E. Kraepelin made in 1899. By linking together (Kraepelin, 1919) as dementia praecox concepts of illness that previously were unrelated and separating them from the manic-depressive insanities he created a category that has dominated psychiatric nosology and thinking. The notion of a disease entity was cemented in E. Bleuler's claim (1950) that a fundamental abnormality (a

Ground rules and principles

I will argue three principles are needed to reach a solution. Firstly that the condition is universal in human populations; secondly that it is intrinsic ie that there are no environmental causes; and thirdly that there are no categories, ie that schizophrenia is not a disease entity distinct from other conditions, but that states described as schizophrenic merge imperceptibly into affective psychotic and non-psychotic conditions. These can be called the principles of universality,

The context of epidemiology: universal incidence

As comprehensive an estimate of the incidence of schizophrenia as we have comes from the WHO Ten Country Study (Jablensky et al., 1992). In each of ten centres distributed across populations as different as those of Japan, India, Northern Europe and Hawaii, the authors defined a catchment area and identified each of those facilities to which individuals experiencing psychotic symptoms for the first time might present (Fig. 1).

Whereas with a “broad” definition (that included diagnoses allocated

The failure of the Kraepelinian binary system and Kretschmer's alternative

Different definitions (that may or may not depend upon the presence of first rank symptoms) define different populations of patients (Endicott et al., 1982), in general on the basis of the extent to which they include or exclude illnesses with differing degrees of affective change. This fact calls in question Kraepelin's delineation of schizophrenia by separation from the affective psychoses, a doubt that he was probably the first to express —

No experienced psychiatrist will deny that there is

The quest for an environmental precipitant

Uniformity of incidence across populations is by itself evidence for an intrinsic ie genetic causation (Crow, 1993b). There have nonetheless been arguments that environmental agents that are common and of wide geographical distribution, for example viral infection and pregnancy and birth complications, are relevant.

Polygenes or multiple false positives?

In recent years research in genetics has been motivated by the conviction that genes for major psychiatric disorder (of unspecified function) will emerge without prior hypothesis from systematic linkage studies. That hope is now cast into doubt. A number of systematic searches (genome scans) for genetic linkage employing polymorphic markers spaced across the genome in multiply affected families have now been conducted. The number of positive claims has been large (DeLisi, 2004) and in

Which neurodevelopmental gene(s)?

A singular feature of psychosis is age of onset. Onsets are uncommon before the age of 15, but incidence then rises rapidly to a peak at around 25 years for males and 28 years for females. Onsets thus occur throughout the reproductive – that is normally the fittest – phase of life. This distribution in itself poses problems for an environmental aetiology. What type of agent might be expected to have a discrete impact at this age? The problem is further complicated by the recognition that onsets

The central paradox: persistence in the face of a fecundity disadvantage

If the principle of universality is accepted it has profound implications particularly for the genetic basis (eg Crow, 1993a, Crow, 1993b, Crow, 1995b, Crow, 1997d). First one must conclude that either the genetic variation itself or the mechanism by which it is generated must be old. It must precede the diaspora of modern Homo sapiens, that is it must go back to the origin of the species (Fig. 3). I argue (Crow, 1997d, Crow, 1997e, Crow, 2000c and below) that it is the key to this origin.

The meaning of the nuclear symptoms: anomalies of the transition from thought to speech

Language disturbances in psychosis are well documented (see eg Chaika, 1990, Sims, 1995), but a sceptical view is that they are neither universal nor more marked than deviations in other aspects of psychological function eg intellect or perception.

To the objection that language abnormalities are not always a feature I propose the answer that they are not only present but integral to the core syndrome – that the nuclear symptoms themselves are abnormalities of language – specifically that these

An X–Y homologous gene can account for sex differences

No agreed genetic locus for asymmetry has been identified. It is widely assumed as in the case of psychosis, that such a locus will be autosomal. However the fact that there are sex differences in psychosis (eg with respect to age of onset, pre-morbid precursors and outcome) and in relation to handedness (females are generally reported as somewhat more right-handed than males) raised the question of sex-linkage (Crow, 1987, Crow, 1988b). Neither handedness nor psychosis follows a classical

Five universals of variation in human populations

The above arguments suggest that certain apparently unrelated characteristics of human populations have a common origin and together bear upon the nature of the genetic variation that defines the species:

  • 1)

    the incidence of psychosis as documented in the WHO study (Jablensky et al., 1992).

  • 2)

    the complexity of language structure as encapsulated in Chomsky's (1988) concept of a “Universal Grammar”, (see Newmeyer, 2003 for a discussion of the uniformitarian hypothesis of the constancy of structure of

The identity of the speciation event: X–Y transposition and the paracentric inversion

What functional change can account for the biological success of Homo sapiens? This species multiplied in numbers, covered the surface of the globe and changed the environment in a way that no other primate species had done (Fig. 3). The obvious correlate is language (Bickerton, 1990, Bickerton, 1995). Language has characteristics (grammatical structure, the use of null elements, embedding of clauses) that are absent in other primate communication systems. Evidence of language in the

Sexual selection, mate recognition and the identity of species

Sexual dimorphisms differ between closely related species. On the basis of studies of the rapid speciation observed in Drosophila in Hawaii Kaneshiro (1980) suggested that mutational change in a sexually dimorphic characteristic is followed by a phase of sexual selection to establish species separations through accentuated dimorphisms. Others agree that the mechanisms of speciation and sexual selection are somehow related (Carson, 1997, Dominey, 1984, Linn and Roelofs, 1995, White et al., 1995).

Conclusion: the origins of psychosis and language are linked through the genetics of the speciation event

The components of the argument are that;

  • 1)

    Universality of the core syndrome and persistence of the biological disadvantage are consistent with the thesis that schizophrenia is “the price that Homo sapiens pays for language” (Crow, 1997d).

  • 2)

    The core features (the nuclear symptoms) can be considered as disorders of language, (Crow, 1997d, Crow, 1998b, Crow, 2004a) the axis of indexicality (the deictic distinction between the “I” of the speaker and the “you” of the hearer) lies at the heart of a

Role of Funding Source

During a part of the time this paper was written the author was external scientific staff member supported by the UK Medical Research Council. He is honorary director of the SANE Prince of Wales International Centre for Research on Schizophrenia and Depression.

Conflict of interest

The author is aware of no conflict-of-interest other than arising in relation to contrary views of the aetiology of psychosis.

Contributors

Dr Crow is the sole author of this paper.

Acknowledgments

The author acknowledges the intellectual stimulus he has received from other workers in the field and particularly from conferences on the topic such as The Search for the Causes of Schizophrenia, the Dahlem conference on The Biological Basis of Schizophrenia, and the Mental Health and Benzon Foundations conferences and the encouragement of the editors of Schizophrenia Research.

References (249)

  • CullenT.J. et al.

    A post-mortem study of the mediodorsal nucleus of the thalamus in schizophrenia

    Schiz. Res.

    (2003)
  • DannJ.C. et al.

    Search for linkage to X and Y chromosomes in families with schizophrenia and schizoaffective disorder

    Schiz. Res.

    (1996)
  • AffaraN. et al.

    Report of the second international workshop on Y chromosome mapping 1995

    Cytogenet. Cell. Genet.

    (1996)
  • AnnettM.

    Left, Right, Hand and Brain: The Right Shift Theory

    (1985)
  • AnnettM.

    The right shift theory of a genetic balanced polymorphism for cerebral dominance and cognitive processing

    Curr. Psychol. Cogn.

    (1995)
  • BadnerJ. et al.

    Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia

    Mol. Psychiatry

    (2002)
  • BakerH.F. et al.

    A re-investigation of the behavioural effects of intracerebral injection in marmosets of cytopathic cerebrospinal fluid from patients with schizophrenia or neurological disease

    Psychol. Med.

    (1989)
  • BarrettR.J.

    Kurt Schneider in Borneo: do first rank symptoms of schizophrenia apply to the Iban?

  • BebbingtonP. et al.

    Schizophrenia, The Major Issues

    (1988)
  • BeemanM. et al.

    Right Hemisphere Language Comprehension

    (1998)
  • BickertonD.

    Language and Species

    (1990)
  • BickertonD.

    Language and Human Behavior

    (1995)
  • BilderR.M. et al.

    Absence of regional hemispheric volume asymmetries in first episode schizophrenia

    Am. J. Psychiatry

    (1994)
  • BlancoP. et al.

    Conservation of PCDHX in mammals; expression of human X/Y genes predominantly in the brain

    Mam. Gen.

    (2000)
  • BleulerE.

    Dementia Praecox or the Group of Schizophrenias (translated by J Zinkin)

    (1950)
  • BogertsB.

    Recent advances in the neuropathology of schizophrenia

    Schiz. Bull.

    (1993)
  • BogertsB. et al.

    Basal ganglia and limbic system pathology in schizophrenia: a morphometric study of brain volume and shrinkage

    Arch. Gen. Psychiatry

    (1985)
  • BrownR. et al.

    Postmortem evidence of structural brain changes in schizophrenia. Differences in brain weight, temporal horn area, and parahippocampal gyrus compared with affective disorder

    Arch. Gen. Psychiatry

    (1986)
  • BrutonC.J. et al.

    Schizophrenia and the brain: a prospective clinico-neuropathological study

    Psychol. Med.

    (1990)
  • BuehlerK.

    Sprachtheorie. Translated (1990) by D W Goodwin as Theory of Language: The Representational Function of Language

    (1934)
  • BurgoyneP.S.

    Mammalian X and Y crossover

    Nature

    (1986)
  • BurgoyneP.S. et al.

    Does X–Y pairing during male meiosis protect the paired region of the X chromosome from subsequent X-inactivation?

    Hum. Genet.

    (1985)
  • BussD.M.

    Human mate selection

    Am. Sci.

    (1985)
  • ButlerL.E. et al.

    Contagion in schizophrenia: a critique of Crow and Done (1986)

    Schiz. Bull.

    (1993)
  • CannonM. et al.

    Obstetric complications and schizophrenia; historical and meta-analytic review

    Am. J. Psychiatry

    (2002)
  • CarsonH.L.

    Sexual selection: a driver of genetic change in Hawaiian Drosophila

    J. Hered.

    (1997)
  • ChaikaE.

    Understanding Psychotic Speech: Beyond Freud and Chomsky

    (1990)
  • ChanceS.A. et al.

    Amygdala volume in schizophrenia: post-mortem study and review of magnetic resonance imaging findings

    Br. J. Psychiatry

    (2002)
  • ChenH.M. et al.

    Homologous loci DXYS156X and DXYS156Y contain a polymorphic pentanucleotide repeat (TAAAA) and map to human X chromosome and Y chromosome

    Hum. Mutation

    (1994)
  • ChomskyN.

    Language and the Problems of Knowledge: The Managua Lectures

    (1988)
  • ChristiansenM.H. et al.

    Language Evolution

    (2003)
  • CloustonT.S.

    The Nature of Development (The Morrison Lectures, 1890)

    (1890)
  • CodeC.

    Language, Aphasia and the Right Hemisphere

    (1987)
  • CookN.D.

    The Brain Code: Mechanisms for Information Transfer and the Role of the Corpus Callosum

    (1986)
  • CookN.D.

    Bihemispheric language: how the two hemispheres collaborate in the processing of language

  • CorballisM.C.

    The genetics and evolution of handedness

    Psychol. Rev.

    (1997)
  • CorballisM.C. et al.

    Location of the handedness gene on the X and Y chromosomes

    Am. J. Med. Genet. (Neuropsychiatric Genet.)

    (1996)
  • CoyneJ.A. et al.

    Two rules of speciation

  • Crichton-BrowneJ.

    On the weight of the brain and its component parts in the insane

    Brain

    (1879)
  • CrowT.J.

    A re-evaluation of the viral hypothesis: is psychosis the result of retroviral integration at a site close to the cerebral dominance gene?

    Br. J. Psychiatry

    (1984)
  • Cited by (179)

    • Laterality

      2021, Encyclopedia of Behavioral Neuroscience: Second Edition
    View all citing articles on Scopus
    View full text