NO DIFFERENCE IN THE EXPRESSION OF THE D4 GENE IN POSTMORTEM FRONTAL-CORTEX FROM CONTROLS AND SCHIZOPHRENICS

The primary biochemical theory of schizophrenia has centered on the ro le of dopaminergic dysfunction in the illness. The D2 receptor has bee n primarily indicated however, some atypical neuroleptics may not act at D2. The D4 receptor has a high affinity for the atypical antipsycho tic clozapine and is therefore a potential target for drug design. The role of D4 in the aetiology of schizophrenia has, however, been the s ubject of controversy. Using radioligand binding assays some researche rs have detected an elevation of D4-like receptors in schizophrenic st riatum whilst conversely other workers claim that D4 receptors are und etectable in this region. Analysis of receptor levels is difficult due to the lack of a ligand selective for D4. We have therefore examined D4 at the level of gene expression. D4 mRNA levels have been examined in post-mortem frontal cortex from nine controls and eight schizophren ics using a reverse transcription-polymerase chain reaction (RT-PCR) m ethod. No significant difference in D4 mRNA levels was found between t he two groups. This result does not support a major role for variabili ty of D4 gene expression in the aetiology of schizophrenia.