Association of Mu-Opioid Receptor Variants and Response to Citalopram Treatment in Major Depressive Disorder

• Published in: The American journal of psychiatry Vol. 167; no. 5; pp. 565 - 573
• Main Authors: Garriock, Holly A., Tanowitz, Michael, Kraft, Jeffrey B., Dang, Vu C., Peters, Eric J., Jenkins, Greg D., Reinalda, Megan S., McGrath, Patrick J., von Zastrow, Mark, Slager, Susan L., Hamilton, Steven P.
• Format: Journal Article
• Language: English
• Published: Arlington, VA American Psychiatric Association 01.05.2010
• Subjects: Adult and adolescent clinical studies; Antidepressants; Antidepressive Agents, Second-Generation - therapeutic use; Biological and medical sciences; Citalopram - therapeutic use; Deoxyribonucleic acid; Depression; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - genetics; DNA; European Continental Ancestry Group - genetics; Genetic Association Studies; Genetic testing; Genotype; Genotype & phenotype; Haplotypes - genetics; Hispanic Americans - genetics; Humans; Medical sciences; Mood disorders; Neuropharmacology; Pharmacology. Drug treatments; Phenotype; Polymorphism, Single Nucleotide - genetics; Psychiatric Status Rating Scales; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Receptors, Opioid, mu - genetics; Treatment Outcome; Mood disorder; Treatment; Serotonin; Psychotropic; μ Opioid receptor; Neurotransmitter; Antidepressant agent; Depression; Reuptake inhibitor; Selective serotonin reuptake inhibitor; Citalopram
• ISSN: 0002-953X; 1535-7228
• DOI: 10.1176/appi.ajp.2009.08081167

ObjectiveBecause previous preclinical and clinical studies have implicated the endogenous opioid system in major depression and in the neurochemical action of antidepressants, the authors examined how DNA variation in the μ-opioid receptor gene may influence population variation in response to citalopram treatment. MethodA total of 1,953 individuals from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study were treated with citalopram and genotyped for 53 single nucleotide polymorphisms (SNPs) in a 100-kb region of the OPRM1 gene. The sample consisted of Non-Hispanic Caucasians, Hispanic Caucasians, and African Americans. Population stratification was corrected using 119 ancestry informative markers and principal components analysis. Markers were tested for association with phenotypes for general and specific citalopram response as well as remission. ResultsAssociation between one SNP and specific citalopram response was observed. After Bonferroni correction, the strongest finding was the association between the rs540825 SNP and specific response. The rs540825 polymorphism is a nonsynonymous SNP in the final exon of the μ-opioid receptor-1X isoform of the OPRM1 gene, resulting in a histidine to glutamine change in the intracellular domain of the receptor. When Hispanic and Non-Hispanic Caucasians were analyzed separately, similar results in the population-corrected analyses were detected. ConclusionsThese results suggest that rates of response to antidepressants and consequent remission from major depressive disorder are influenced by variation in the μ-opioid receptor gene as a result of either an effect on placebo response or true pharmacologic response.