5-HT(1A) receptor dysfunction in female patients with schizophrenia.
BACKGROUND
Serotonin (5-HT)(1A) receptors are of interest in the pathophysiology of schizophrenia (SCH) and the mechanism of action of atypical antipsychotic drugs. To test the hypothesis that 5-HT(1A) receptor responsivity is significantly different in patients with SCH compared to normal control subjects, the neuroendocrine study was performed using ipsapirone (IPS), a 5-HT(1A) partial agonist, as a probe.


METHODS
Ipsapirone 0.5 mg/kg, p.o. or placebo were administered, in random order, to patients with SCH (n = 43; 32 male) and normal controls (n = 33; 21 male). Blood samples for plasma cortisol and body temperature were obtained from 30 min before to 180 min after administration of IPS or placebo.


RESULTS
Female normal control subjects had markedly greater increases in plasma cortisol following IPS than did male control subjects. The placebo response-corrected plasma cortisol response to IPS was significantly blunted in female SCH compared to female normal control subjects (p =.0001). The IPS-stimulated plasma cortisol response in male SCH did not differ from that of male normal control subjects or female SCH. There were no significant differences in the IPS-induced hypothermia in men and women or between patients with SCH and normal control subjects. Behavioral responses to IPS, including nausea, dizziness, irritability, and feeling less well, did not differ between groups.


CONCLUSIONS
These results suggest that the post-synaptic 5-HT(1A) receptor mediated endocrine response is diminished in female SCH compared to female normal control subjects, possibly secondary to an abnormality in intracellular signal transduction mechanism.
Lee
M A
MA
Department of Psychiatry, School of Medicine, Vanderbilt University, Nashville, Tennessee 37212, USA.
Meltzer
H Y
HY
D000328:Adult; D001833:Body Temperature Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D011569:Psychiatric Status Rating Scales; D011743:Pyrimidines; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012559:Schizophrenia / Q000175:diagnosis / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D017366:Serotonin Receptor Agonists; D012737:Sex Factors
D011743:Pyrimidines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; C043077:ipsapirone; D006854:Hydrocortisone