Cannabinoid receptor 1 (CNR1) gene: impact on antidepressant treatment response and emotion processing in major depression.
The endocannabinoid system has been implicated in the pathogenesis of depression and anxiety, the mediation of antidepressant drug effects in animal models and the neurobiology of emotion processing in healthy volunteers. Therefore, the impact of cannabinoid receptor 1 gene (CNR1) variants rs1049353 and rs12720071 on antidepressant treatment response was evaluated in 256 Caucasian patients with Major Depression. A subsample of 33 depressed patients was additionally scanned by fMRI under visual presentation of emotional faces. The CNR1 rs1049353 G allele conferred an increased risk of antidepressant treatment resistance, particularly in female patients with high comorbid anxiety. CNR1 rs1049353 G allele carriers also demonstrated weaker bilateral amygdala, putamen and pallidum activity as well as left lateralized caudate and thalamus activity in response to masked happy faces. This analysis provides preliminary support for a role of CNR1 gene variation in depression and anxiety, potentially mediated by subcortical hypo-responsiveness to social reward stimuli.
Domschke
Katharina
K
Department of Psychiatry, University of Muenster, Germany.
Dannlowski
Udo
U
Ohrmann
Patricia
P
Lawford
Bruce
B
Bauer
Jochen
J
Kugel
Harald
H
Heindel
Walter
W
Young
Ross
R
Morris
Phillip
P
Arolt
Volker
V
Deckert
Jürgen
J
Suslow
Thomas
T
Baune
Bernhard T
BT
D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D004644:Emotions / Q000187:drug effects*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010597:Pharmacogenetics; D011569:Psychiatric Status Rating Scales; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D012189:Retrospective Studies; D012737:Sex Factors
D000928:Antidepressive Agents; D043884:Receptor, Cannabinoid, CB1; D010100:Oxygen