Tissue-binding factor in schizophrenic sera: a clinical and genetic study

The hypothesis that pathologic immune mechanisms, characterized by production of brain autoantibodies, operate in schizophrenia, was the basis for this study. Binding of serum globulin substance by human brain septal region obtained at autopsy was measured by radioimmunofixation assay in 27 schizophrenic probands, 28 first-degree relatives, 12 patients with primary affective disorder (depression), and 117 normal controls. Schizophrenic individuals tended to have higher levels of brain-serum affinity than controls. Age and sex did not appear to affect results. Within families, elevation of serum-binding activity showed intra sib-pair resemblance, distinguished healthy relatives from probands and ill relatives and relatives of probands with positive sera from relatives of probands with negative serum activity. Serum activity distinguished well relatives from normal controls and was independent of clinical state. This suggests that brain-serum affinity may be compatible with characteristics of a genetic marker of vulnerability to schizophrenia. Within sib-pairs, concordance rates for elevated serum activity and for subtype diagnosis, mode, and age of illness onset were positively related. This finding supports clinico-genetic disposition in a subgroup of schizophrenic persons. To determine distribution patterns of antigenic components, selected schizophrenic and normal sera were tested against human liver and mouse brain, thymus, and liver. Wide tissue cross-reactivity was observed in schizophrenic, but not in normal sera, a finding consistent with overlap of serological reactions affecting specific tissues in autoimmune processes. The assay employed in the present study and investigation of inheritance of brain-serum affinity have not previously been reported.