The alpha 2A-adrenergic receptor gene polymorphism modifies antidepressant responses to milnacipran.
OBJECTIVE
The alpha 2A-adrenergic receptor (ADRA2A) plays a central role in the regulation of systemic sympathetic activity. Recently, the functional defect of ADRA2A has been implicated as a cause of depression, attention deficit hyperactivity disorder, and Tourette syndrome. In this study, the effect of genetic variants of the ADRA2A gene on the response to selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) was examined in depressed patients.


METHODS
Ninety-three Japanese depressed patients were recruited in the present study, assigned randomly to paroxetine or milnacipran, and assessed by the Hamilton Rating Scale for Depression (HAM-D) scoring every 2 weeks before and after drug administration. The ADRA2A C-1297G polymorphism was considered in the association analysis with the efficacy of antidepressants.


RESULTS
There were significant differences in the HAM-D percent score change over time (P = 0.019) among C/C, C/G, and G/G of the ADRA2A C-1297G polymorphism in the total subjects. The C allele carriers of the ADRA2A C-1297G polymorphism showed a significantly better improvement than G/G subjects at weeks 2, 4, and over time (P = 0.037) in the milnacipran group.


CONCLUSIONS
Our findings suggest that ADRA2A plays an important role in depression therapy. The level of ADRA2A expression could be associated with the efficacy of SSRIs/SNRIs, especially milnacipran, although the functional change brought about by C-1297G polymorphism has not yet been fully identified in vivo and in vitro.


CONCLUSIONS
The ADRA2A polymorphism could be a reasonable candidate to predict the response to milnacipran. Our results are still preliminary, and a large sample size will be required to confirm our findings. However, to the best of our knowledge, this study is the first to suggest a possible association of ADRA2A variants with the SNRI response.
Wakeno
Masataka
M
Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan. wakenoma@takii.kmu.ac.jp
Kato
Masaki
M
Okugawa
Gaku
G
Fukuda
Tsuyoshi
T
Hosoi
Yuka
Y
Takekita
Yoshiteru
Y
Yamashita
Megumi
M
Nonen
Shinpei
S
Azuma
Junichi
J
Kinoshita
Toshihiko
T
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D044466:Asian People; D003521:Cyclopropanes / Q000494:pharmacology* / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D000078764:Milnacipran; D017374:Paroxetine / Q000494:pharmacology / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D013997:Time Factors
C547768:ADRA2A protein, human; D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D003521:Cyclopropanes; D018341:Receptors, Adrenergic, alpha-2; D017374:Paroxetine; D000078764:Milnacipran