A peripheral marker for schizophrenia: Increased levels of D-3 dopamine receptor mRNA in blood lymphocytes

Dopamine is a major neurotransmitter in the central nervous system, and its receptors are associated with a number of neuropathological disorders such as Parkinson's disease and schizophrenia. Although the precise pathophysio logy of schizophrenia remains unknown, the dopaminergic hypothesis of the i llness assumes that the illness results from excessive activity at dopamine synapses in the brain. Because, at present, the diagnosis of schizophrenia relies on descriptive behavioral and symptomatic information, a peripheral measurable marker may enable a simpler, more rapid, and more accurate diag nosis and monitoring. In recent years, human peripheral blood lymphocytes h ave been found to express several dopamine receptors (D-3, D-4, and D-5) by using molecular biology techniques and binding assays. It has been suggest ed that these dopamine receptors found on lymphocytes may reflect receptors found in the brain. Here we demonstrate a correlation between the D-3 dopa mine receptor on lymphocytes and schizophrenia and show a significant eleva tion of at least 2-fold in the mRNA level of the D-3, but not of the D4, do pamine receptor in schizophrenic: patients. This increase is not affected b y different antipsychotic. drug treatments (typical or atypical). Moreover, nonmedicated patients exhibit the same pattern, indicating that this chang e is not a result of medical treatment. We propose the D-3 receptor mRNA on blood lymphocytes as a marker for identification and followup of schizophr enia.