A paradigmatic shift in the approach to neuropsychiatric gene linkage may require an anthropogenetic perspective

A model for a new approach to neuropsychiatric gene linkage is proposed in the context of increased chromosomal breakage which has recently been reported in association with Tourette syndrome, schizophrenia, Rett syndrome and the psychopathology associated with mentally normal, female obligate fra-X carriers. Chromosomal fragility may be connected with the formation of unstable repeat sequences at multiple sites resulting in a continuum of effects, ranging from advantageous evolutionary changes, to more serious neurobehavioural disorders, with neurodegenerative states on the extreme end of the spectrum. The current major problem with phenotype-genotype correlations in complex neuropsychiatric disorders may, therefore, be due to the distance between a postulated breakage-enhancing effect of the primary gene(s), and the continuum of diverse phenotypes resulting from the secondary-gene involvement at a varying number of fragile sites. A unifying view of behavioural alteration, viewed in anthropogenetic context, rather than a DSM-based reductionist approach may be required for the elucidation of psyche-destabilizing genetic changes.