The interleukin 1 beta (IL1B) gene is associated with failure to achieve remission and impaired emotion processing in major depression.
BACKGROUND
Accumulating evidence suggests the involvement of inflammatory processes and cytokines in particular in the pathophysiology of major depression (MDD) and resistance to antidepressant treatment. Furthermore, amygdala and anterior cingulate cortex (ACC) responsiveness to emotional stimuli has been suggested as a predictor of treatment response. This study investigated the association between genetic variants of the interleukin 1 beta (IL1B) gene and amygdala and ACC responsiveness to emotional stimuli and response to antidepressant treatment.


METHODS
In this analysis, 256 Caucasian patients with MDD (145 women, 111 men) were genotyped for variants rs16944, rs1143643, and rs1143634 in the IL1B gene (2q14). Response to antidepressant treatment over 6 weeks was defined as remission (< or = 7 on the Hamilton Rating Scale for Depression-21-question) and response (>50% decrease on Hamilton Rating Scale for Depression-21-question). Brain activity under visual presentation of emotional faces was assessed in a subsample of 32 depressed patients by means of functional magnetic resonance imaging at 3 T.


RESULTS
Pharmacogenetic analyses show significant associations of the GG genotypes of single nucleotide polymorphisms (SNPs) rs16944 (odds ratio = 1.74; 95% confidence interval 1.2-4.3) and rs1143643 (odds ratio = 3.1; 95% confidence interval 1.3-7.8) (compared with the AA genotype) with nonremission after 6 weeks. The imaging analyses show that the number of G-alleles in both SNPs (rs16944 and rs1143643) was associated with reduced responsiveness of the amygdala and ACC to emotional stimulation.


CONCLUSIONS
The present study suggests a negative effect of the IL1B gene on pharmacological response and amygdala and ACC function involving the same genotypes of two SNPs (rs16944, rs116343), which taken together increase the risk of nonremission over 6 weeks of antidepressant treatment in MDD.
Baune
Bernhard T
BT
Department of Psychiatry and Psychiatric Neuroscience, James Cook University, Queensland, Australia. bernhard.baune@jcu.edu.au
Dannlowski
Udo
U
Domschke
Katharina
K
Janssen
Debbie G A
DG
Jordan
Margaret A
MA
Ohrmann
Patricia
P
Bauer
Jochen
J
Biros
Erik
E
Arolt
Volker
V
Kugel
Harald
H
Baxter
Alan G
AG
Suslow
Thomas
T
D000328:Adult; D000368:Aged; D000679:Amygdala / Q000098:blood supply / Q000502:physiology; D000928:Antidepressive Agents / Q000627:therapeutic use; D016001:Confidence Intervals; D046690:Deep Brain Stimulation / Q000379:methods; D003865:Major Depressive Disorder / Q000150:complications*; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006179:Gyrus Cinguli / Q000098:blood supply / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D053583:Interleukin-1beta / Q000235:genetics*; D016015:Logistic Models; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010597:Pharmacogenetics; D010775:Photic Stimulation / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013315:Stress, Psychological / Q000209:etiology* / Q000235:genetics* / Q000473:pathology / Q000628:therapy
D000928:Antidepressive Agents; D053583:Interleukin-1beta; D010100:Oxygen