Abnormalities in 5-HT2A receptor mRNA expression in frontal cortex of chronic elderly schizophrenics with varying histories of neuroleptic treatment

Alterations in the 5-HT2A receptor gene expression in the prefrontal cortex have been suggested to play a role in the pathophysiology and pharmacotherapy of schizophrenia. This study measured mRNA encoding 5-HT2A receptor in the left superior frontal gyrus from chronic elderly schizophrenics (n = 21) with varying neuroleptic-free intervals before death (72 hr to more than 5 years), and normal drug-free elderly controls (n = 14). Levels of 5-HT2A mRNA in schizophrenics correlated significantly and inversely with neuroleptic-free interval before death (r = -0.77; P < 0.0001). In schizophrenics who had been receiving neuroleptic until time of death, levels of 5-HT2A mRNA were similar to controls or greater. In schizophrenics who had been free of neuroleptic for more than six months levels of 5-HT2A mRNA were significantly lower than in controls. These results confirm previous findings of decreased expression of the 5-HT2A receptor gene in the frontal cortex of some schizophrenics and suggest that regulation of this gene may be involved in the therapeutic actions of typical neuroleptics.