The authors recommend undertaking multivariate studies of monoamine oxidase, dopamine beta-hydroxylase, and other traits associated with schizophrenia in single, large pedigrees ascertained through schizophrenic probands.
Data were subjected to a logistic analysis in which the dependent variable was the presence of schizophrenia spectrum disorders in relatives, and the independent variables were the presence or absence of HLA A1 and CRAG A1 antigens, the sex of the proband, the sex of the relative, the severity of illness in the proband, and the type of relationship.
To evaluate whether the susceptibility gene on 5q11-13 is a common cause of schizophrenia in other populations, we examined five affected North American pedigrees using probes to the D5S39, D5S76 and dihydrofolate reductase loci.
Genetic variants of red-cell acid phosphatase (ACP1), esterase D (ESD), transferrin (TF) and the group-specific component (GC) were investigated in schizophrenic patients with and without a family history of both schizophrenia and other psychiatric disorders.
Although ASA levels did not differ significantly between the groups, schizophrenics without a family history of schizophrenia had significantly lower ASA levels than those with.
Using a metabolic pathway approach, it can be shown that the best current candidate gene locus for a subtype of schizophrenia located on chromosome 5q11-13 (HGML10 # SCZD1 and OMIM #181510) is in the serotonergic pathway, i.e. a receptor for 5-hydroxytryptamine (subtype 1A; HGML10 #HTR1A) which also maps in the same chromosomal region.5.
We conclude that the genetic predisposition to schizophrenia in these pedigrees is not due to aberrations in the DRD2 locus or the porphobilinogen deaminase locus.
Recent reports of cytogenetic abnormalities linked to psychiatric illness and the localisations of the genes for the dopamine (D2) receptor and tyrosinase on the long arm of chromosome 11 have suggested that susceptibility loci for schizophrenia and manic depression might be situated in this region.
No structural changes were found, suggesting that alteration in the structure of the dopamine D2 receptor is not commonly involved in the etiology of schizophrenia.