Mutation and psychosis: a suggested explanation of seasonality of birth.

The persistence of psychosis at a high and relatively constant prevalence in the various populations of the world is rendered difficult to explain by the absence of identified environmental precipitants and by reduced fertility of affected individuals. The problem is not confined to schizophrenia but applies also to affective disorder. The 'virogene' concept attempts to explain this paradox as follows. (1) Psychosis in general is, as suggested by Böök (1953) and Lewis (1958) for schizophrenia, associated with a high rate of mutation. (2) The new mutations occur at a specific site (a 'hot-spot') in the genome and consist of rearrangements (e.g. transpositions or new insertions occurring as a result of unequal recombination) in a sequence which has a degree of potential autonomy, i.e. an integrated pathogen or 'virogene'. (3) The mutations occur specifically in the courses of gametogenesis in the male. By its location in the scrotal sac and its extended time course, gametogenesis in the male is susceptible to insertional mutagenesis as a function of variations in environmental temperature. Such temperature-dependent mutations are reflected in the seasonality of birth seen in both schizophrenic and affective illnesses. The increased likelihood of such mutations occurring with time is held to account for the association of psychosis with increased paternal age. (4) Such new events are held responsible not only for 'sporadic' cases in individuals without a family history of psychosis, but also for increases in severity of illness between generations. Psychosis is viewed as a continuum extending from unipolar through bipolar affective disorder and schizoaffective illness to schizophrenia with increasing degrees of defect.(ABSTRACT TRUNCATED AT 250 WORDS)