Genetic analysis of plasma amine oxidase activity in schizophrenia

Plasma amine oxidase (PAO) activity has been implicated in the biology of schizophrenia. PAO activity is, in part, under genetic control, but its mode of inheritance has not been determined. To assess the genetic pattern of PAO activity and its relation to the transmission of schizophrenia, we studied 73 chronic schizophrenic probands and 217 first-degree relatives (siblings and parents). Single-major-locus hypotheses were tested by pedigree analysis methods for quantitative traits. The distribution of PAO activity indicated significant admixture. When the transmission probability model was used, the familial pattern of PAO activity was consistent with mendelian transmission; the environmental hypothesis was rejected. PAO activity was lower in schizophrenic patients than in unaffected relatives, but the mean reduction in enzyme activity was small (10.7%) and the two groups of subjects overlapped greatly in their PAO values. The difference between ill and well relatives was not statistically significant. However, schizophrenia spectrum disorders segregated with low PAO activity in families of low-activity probands, and a greater proportion of ill than well subjects clustered in the low PAO activity mode. The results are interpreted as follows: (1) The transmission of PAO activity may be determined in part by a single major autosomal gene. (2) Low PAO activity does not qualify as a major risk factor in the schizophrenic population at large; however, a relationship may exist between low PAO activity and the transmission of schizophrenia in families of patients with extremely low enzyme activity.