Association analysis of the 5-HT5A gene in depression, psychosis and antipsychotic response.
The serotonergic system is targeted by both antidepressants and atypical antipsychotic drugs such as clozapine. Genetic variation in the 5-HT5A gene might be involved in susceptibility to depression, the major psychoses or in influencing clinical response to treatment. To examine this hypothesis we genotyped two polymorphisms (-19G/C; 12A/T) in the human 5-HT5A receptor gene in a sample of 269 unrelated schizophrenic patients treated with clozapine, 112 bipolar patients, 75 unipolar patients and 187 controls. After five-fold correction for multiple testing, allelic association was found with the -19G/C polymorphism and bipolar affective disorder, (p = 0.025; OR 0.56), unipolar depression (p = 0.004; OR 0.52) and schizophrenia (p = 0.036; OR 0.67) indicating a potential protective effect of the G19 allele. For the 12A/T polymorphism allelic association was observed with unipolar depression only (p = 0.004). We conclude that allelic variation in the human 5-HT5A receptor gene may be involved in susceptibility to schizophrenia and affective disorders but not in determining response to clozapine.
Birkett
J T
JT
Division of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London, UK.
Arranz
M J
MJ
Munro
J
J
Osbourn
S
S
Kerwin
R W
RW
Collier
D A
DA
D000483:Alleles; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000235:genetics; D003024:Clozapine / Q000627:therapeutic use; D003863:Depression / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000235:genetics*; D011985:Receptors, Serotonin / Q000235:genetics*; D012016:Reference Values; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics
D014150:Antipsychotic Agents; D011985:Receptors, Serotonin; C078730:serotonin 5 receptor; D003024:Clozapine