Craddock & Owen vs Kraepelin: 85 years late, mesmerised by "polygenes".

The case for replacing the binary Kraepelinian system with a continuum concept originated with Kraepelin [Kraepelin, E. (1920) Die Erscheinungsformen des Irreseins (translated by H Marshall as: Patterns of mental disorder. In: Themes and Variations in European Psychiatry. Eds S.R. Hirsch & M. Shepherd. Wright, Bristol, pp7-30, l974). Zeitschrift Gesamte Neurologie Psychiatrie, vol. 62, 1-29.], and is based upon studies of familial aggregation and phenomenology. Craddock and Owen's [Craddock, N.J., Owen, M.J. (2007) Rethinking psychosis: the disadvantages of a dichotomous classification now outweigh the advantages. World Psychiatry 6: 20-27.] claim for the "beginning of the end for the Kraepelinian dichotomy" on the basis of linkage and association is undermined by un-replicability of findings across studies (Crow, T.J. (2007) How and why genetic linkage has not solved the problem of psychosis: review and hypothesis. American Journal of Psychiatry, 164, 13-21). Absence of evidence of linkage is consistent with the concept that the variation is epigenetic in form rather than DNA sequence-based. But what are the dimensions that underly the continuum? The BBC Internet survey (Peters, M., Reimers, S., Manning, J.T. (2006) Hand preference for writing and associations with selected demographic and behavioral variables in 255,100 subjects: the BBC internet study. Brain and Cognition 62, 177-189), reinforces the concept that lateralisation is a major and sex-dependent dimension of human variation in verbal and spatial ability: twin studies indicate that inter-individual variation in dominance for language is epigenetic and the paternal age effect can be similarly explained. Thus an epigenetic imprint, arising in relation to the sapiens specific torque and persisting over one or two generations is a better fit to the genetics of the psychotic continuum than Craddock and Owen's elusive "polygenic" variations.