Excess of transmission of the G allele of the -1438A/G polymorphism of the 5-HT2A receptor gene in patients with schizophrenia responsive to antipsychotics.
BACKGROUND
The -1438A/G polymorphism of the 5-HT2A gene has been found to be associated with clinical response to clozapine and other second generation antipsychotics. Testing the impact of this marker on response to first generation antipsychotics (which have a lower affinity for the 5-HT2A receptor) provides the opportunity to help disentangling the two different roles that this polymorphism might have. A psychopharmacogenetic role should be detected only for antipsychotics with high affinity to the 5-HT2A receptor (therefore to second generation antipsychotics). An alternative role would imply tagging a subgroup of patients responsive to any antipsychotic, whatever their affinity, meaning that the association is more depending on non pharmacological charaterictics, such as clinical specificities.


METHODS
A family-based sample of 100 Algerian patients with schizophrenia (according to DSM-IV criteria) and their 200 biological parents was recruited, in order to avoid stratification biases. Patients were all treated, or have been treated, by conventional antipsychotics (mainly haloperidol) for at least four weeks, at appropriate dosage. May and Dencker scale was used to distinguish responders and non responders.


RESULTS
No allele of the -1438A/G polymorphism of the 5-HT2A gene was transmitted in excess (50 transmitted for 38 untransmitted) in the whole sample of patients with schizophrenia (p = .90). In contrast, a significant excess of transmission of the G allele was observed (p = .02) in the subgroup of patients with good treatment response (17 transmitted for 6 untransmitted).


CONCLUSIONS
Using a TDT approach, we showed that the G allele of the -1438A/G polymorphism of the gene coding for the 5-HT2A receptor was associated to schizophrenia with good response to conventional antipsychotics, although this conclusion is based on 88 informative patients only. Because previous data showed the same result with atypical antipsychotics, it can be concluded that the G allele tags a subgroup of schizophrenic patients with greater chance of improvement with antipsychotics of either type.
Etablissement Hospitalier Spécialisé Psychiatrique M. Boucebci. Cheraga, Alger, Algeria. ben.dalila@gmail.com
Dalila
D
Benmessaoud
Nora
N
Hamdani
Claudette
C
Boni
Nicolas
N
Ramoz
Michel
M
Hamon
Farid
F
Kacha
Philip
P
Gorwood
D000225:Adenine; D000328:Adult; D000462:Algeria; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005190:Family; D005260:Female; D005787:Gene Frequency; D006147:Guanine; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D016651:Lithium Carbonate / Q000627:therapeutic use; D008297:Male; D018579:Patient Selection; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D044402:Receptor, Serotonin, 5-HT2A; D016651:Lithium Carbonate; D006147:Guanine; D003024:Clozapine; D006220:Haloperidol; D000225:Adenine; D018967:Risperidone