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.
Hernandez
I
I
Department of Psychiatry, Mount Sinai School of Medicine, New York, USA.
Sokolov
B P
BP
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry*; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism
D014150:Antipsychotic Agents; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin