SSRI response in depression may be influenced by SNPs in HTR1B and HTR1A.
OBJECTIVE
Desensitization of serotonin 1A (HTR1A) and 1B (HTR1B) autoreceptors has been proposed to be involved in the delayed onset of response to selective serotonin reuptake inhibitors (SSRIs). Variations in gene expression in these genes may thus affect SSRI response.


METHODS
Here, we test this hypothesis in two samples from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D), and show evidence for involvement of several genetic variants alone and in interaction. Initially, three functional single nucleotide polymorphisms (SNPs) in the HTR1B gene and in the HTR1A gene were analyzed in 153 depressed patients treated with citalopram. The 16-item Quick Inventory of Depressive Symptomatology Clinician scores were evaluated over time with respect to genetic variation.


RESULTS
Individuals homozygous for the -1019 G allele (rs6295) in HTR1A showed the higher baseline 16-item Quick Inventory of Depressive Symptomatology Clinician scores (P=0.033), and by 12 weeks had a significantly lower response rate (P=0.005). HTR1B haplotypes were estimated according to the previously reported in-vitro expression levels. Individuals who were homozygous for the high-expression haplotype showed significantly slower response to citalopram (P=0.034). We then analyzed more SNPs in the extended overall STAR*D sample. Although we could not directly test the same functional SNPs, we found that homozygotes for the G allele at rs1364043 in HTR1A (P=0.045) and the C allele of rs6298 in HTR1B showed better response to citalopram over time (P=0.022). Test for interaction between rs6298 in HTR1B and rs1364043 in HTR1A was significant (overall P=0.032).


CONCLUSIONS
Our data suggest that an enhanced capacity of HTR1B or HTR1A transcriptional activity may impair desensitization of the autoreceptors during SSRI treatment.
Villafuerte
Sandra M
SM
Molecular & Behavioral Neuroscience Institute, Department of Psychiatry, University of Michigan, Ann Arbor, Michigan 48109-2200, USA. svillafu@umich.edu
Vallabhaneni
Kamala
K
Sliwerska
Elzbieta
E
McMahon
Francis J
FJ
Young
Elizabeth A
EA
Burmeister
Margit
M
D003863:Depression / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics*; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
D044282:Receptor, Serotonin, 5-HT1A; D044302:Receptor, Serotonin, 5-HT1B; D017367:Selective Serotonin Reuptake Inhibitors