Effect of a Triallelic Functional Polymorphism of the Serotonin-Transporter-Linked Promoter Region on Expression of Serotonin Transporter in the Human Brain

• Published in: The American journal of psychiatry Vol. 163; no. 1; pp. 48 - 51
• Main Authors: Parsey, Ramin V., Hastings, Ramin S., Oquendo, Maria A., Hu, Xianzhang, Goldman, David, Huang, Yung-yu, Simpson, Norman, Arcement, Julie, Huang, Yiyun, Ogden, R. Todd, Van Heertum, Ronald L., Arango, Victoria, Mann, J. John
• Format: Journal Article
• Language: English
• Published: Washington, DC American Psychiatric Publishing 01.01.2006; American Psychiatric Association
• Subjects: Adult; Adult and adolescent clinical studies; Age Factors; Alleles; Binding sites; Biological and medical sciences; Brain; Brain - diagnostic imaging; Brain - metabolism; Carbon Radioisotopes; Depression; Depressive Disorder, Major - diagnostic imaging; Depressive Disorder, Major - genetics; Depressive Disorder, Major - metabolism; Effects; Female; Gene Expression; Gene Frequency; Genotype; Humans; Isoquinolines; Male; Medical sciences; Mental depression; Mood disorders; Neurotransmitters; Phenotype; Physical examinations; Polymorphism; Polymorphism, Genetic; Positron-Emission Tomography; Promoter Regions, Genetic - genetics; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Serotonin Plasma Membrane Transport Proteins - genetics; Serotonin Plasma Membrane Transport Proteins - metabolism; Mood disorder; Human; Serotonin; Central nervous system; Depression; Metabolism; Gene expression; Genetic determinism; Encephalon; Biological fixation; Serotonin transporter; Neurotransmitter; Genetics; Biological effect; Positron emission tomography; Comparative study; Polymorphism
• ISSN: 0002-953X; 1535-7228
• DOI: 10.1176/appi.ajp.163.1.48

OBJECTIVE: The authors examined effects of a triallelic functional polymorphism of the human serotonin-transporter-linked promoter region (5-HTTLPR) on in vivo expression of serotonin transporter in the brain in healthy volunteers and subjects with major depressive disorder. METHOD: Twenty-five medication-free subjects with DSM-IV major depressive disorder during a major depressive episode and 42 healthy volunteers were clinically evaluated and genotyped. Serotonin transporter binding potential (f1Bmax Kd) was determined by using positron emission tomography with the radiotracer [11C]McN 5652 and metabolite-corrected arterial input functions. RESULTS: There was no difference in serotonin transporter binding potential by genotype in healthy volunteers or in subjects with major depressive disorder. Allelic frequencies did not differ between subjects with major depressive disorder and healthy volunteers. CONCLUSIONS: Associations of the 5-HTTLPR polymorphism to clinical phenotypes appear to be due to developmental effects of 5-HTTLPR on expression and not due to its direct effect on serotonin transporter binding in adulthood.