Genetic antecedents of dopamine dysfunction in schizophrenia

Background: Relatives of schizophrenic probands frequently manifest attenua ted features of this illness including the negative symptoms and the milder positive psychotic symptoms. These two symptom dimensions are hypothesized to be associated with decreased and increased brain dopamine (DA) function s, respectively, raising the possibility that DA abnormalities may be prese nt in the relatives of schizophrenic probands. Methods: Plasma homovanillic acid (HVA), the major DA metabolite and an ind icator of brain DA activity, was measured in nonpsychotic, physically healt hy first-degree relatives (n = 55) of schizophrenic probands and in normal subjects (n = 20) without a family history of schizophrenia. Results: Plasma HVA inversely correlated with negative symptoms and positiv ely correlated with attenuated positive symptoms. Also, relatives had decre ased plasma HVA compared to normal subjects, consistent with the fact that these relatives are characterized by negative symptoms, These findings were not related to major peripheral factors that could affect plasma HVA sugge sting that the findings may reflect changes in brain DA activity. Conclusions: Negative symptoms indicating a genetic diathesis to schizophre nia in relatives may have a biologic basis in reduced DA activity and the D A dysfunction of schizophrenia may have genetic antecedents, Tn is opens an important new avenue for further study of DA in this illness. (C) 1999 Soc iety of Biological Psychiatry.