Influence of 5-HT3 receptor subunit genes HTR3A, HTR3B, HTR3C, HTR3D and HTR3E on treatment response to antipsychotics in schizophrenia.
OBJECTIVE
Among serotonin (5-HT) receptors, the 5-HT3 receptor is the only ligand-gated ion channel. 5-HT3 antagonists such as ondansetron and tropisetron may improve auditory gating and neurocognitive deficits in schizophrenic patients. Moreover, many antipsychotic drugs are antagonists at 5-HT3 receptors. However, the role of 5-HT3 receptor variants on response to antipsychotic drugs in schizophrenic patients is still unclear.


METHODS
In a prospective, randomized, double-blind study, we have assessed six functional and coding variants of the subunit genes HTR3A, HTR3B as well as the novel HTR3C, HTR3D, and HTR3E subunits in the response to haloperidol or risperidone. Seventy patients were treated for 4 weeks and positive symptoms, negative symptoms, and general psychopathology were measured by the Positive and Negative Syndrome Scale (PANSS).


RESULTS
HTR3E had an effect on the speed of response to antipsychotics. GG-allele carriers responded more quickly to treatment on the PANSS negative symptom subscale (P = 0.03) and on the total PANSS score (P = 0.04) irrespective of medication. In a second independent study of 144 schizophrenia patients treated with atypical antipsychotics, this effect could not be confirmed.


CONCLUSIONS
Our findings argue against a major effect of HTR3 variants in response to antipsychotics. Solely, the HTR3E and also the HTR3A variant could exert a weak effect on the speed of response to antipsychotics.
Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
Anna
A
Schuhmacher
Rainald
R
Mössner
Boris B
BB
Quednow
Kai-Uwe
KU
Kühn
Michael
M
Wagner
Gabriela
G
Cvetanovska
Dan
D
Rujescu
Peter
P
Zill
Hans-Jürgen
HJ
Möller
Marcella
M
Rietschel
Petra
P
Franke
Wolfgang
W
Wölwer
Wolfgang
W
Gaebel
Wolfgang
W
Maier
D000328:Adult; D000596:Amino Acids / Q000235:genetics; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003710:Demography; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics*; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome
D000596:Amino Acids; D014150:Antipsychotic Agents; D021122:Protein Subunits; D044406:Receptors, Serotonin, 5-HT3