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Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry
Author(s) -
Böök J. A.,
Wetterberg L.,
Modrzewska K.
Publication year - 1978
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.1978.tb02105.x
Subject(s) - schizophrenia (object oriented programming) , pedigree chart , genotype , genetics , genetic epidemiology , biology , population , psychosis , methylenetetrahydrofolate reductase , genetic linkage , disease , allele , medicine , psychiatry , gene , environmental health
Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program. Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine‐β‐hydroxylase, and (3) with the genetic marker Gc 2 (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved. As a model for continued research, schizophrenia is explained as based on a double dominant‐recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO‐ and DBH‐reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.