title: The 'big bang' theory of the origin of psychosis and the faculty of language.
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.
  
  
  OBJECTIVE
  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 'big 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.
  
  
  CONCLUSIONS
  Language and psychosis have a common origin in the genetic event (the 'big bang') that defined the species.
authors.affiliation: SANE POWIC, University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX, United Kingdom. tim.crow@psych.ox.ac.uk
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Crow
mesh_terms: D000818:Animals; D005075:Biological Evolution; D041321:Chromosomes, Human, X / Q000235:genetics; D041322:Chromosomes, Human, Y / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007804:Language Development; D008957:Models, Genetic; D015995:Prevalence; D012559:Schizophrenia / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D012737:Sex Factors; D012931:Social Environment