Higher 5-HT1A Receptor Binding Potential During a Major Depressive Episode Predicts Poor Treatment Response: Preliminary Data from a Naturalistic Study

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 31; no. 8; pp. 1745 - 1749
• Main Authors: Parsey, Ramin V, Olvet, Doreen M, Oquendo, Maria A, Huang, Yung-yu, Ogden, R Todd, Mann, J John
• Format: Journal Article
• Language: English
• Published: New York, NY Nature Publishing 01.08.2006; Nature Publishing Group
• Subjects: Adult; Adult and adolescent clinical studies; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Biological and medical sciences; Depression; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - genetics; Depressive Disorder, Major - metabolism; Female; Follow-Up Studies; Humans; Linear Models; Male; Medical sciences; Middle Aged; Mood disorders; Piperazines - metabolism; Predictive Value of Tests; Protein Binding - drug effects; Protein Binding - physiology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Pyridines - metabolism; Receptor, Serotonin, 5-HT1A - genetics; Receptor, Serotonin, 5-HT1A - metabolism; Treatment Outcome; Mood disorder; Study under natural conditions; SSRI; [11C]WAY-100635; 5-HT1A Serotonine receptor; Treatment; Depression; Predictive factor; positron emission tomography; PET; Selective serotonin reuptake inhibitor; Emission tomography
• DOI: 10.1038/sj.npp.1300992
• ISSN: 0893-133X

Serotonin 1A (5-HT1A) binding potential (BP) as assessed by positron emission tomography (PET) is higher in major depressive disorder (MDD) in association with the higher expressing GG genotype of the 5-HT1A C-1019G polymorphism. We hypothesize that higher 5-HT1A BP and the GG genotype predict remission failure on antidepressant treatment. We determined 5-HT1A BP by PET and 5-HT1A C-1019G genotype in 43 controls and 22 medication-free MDD subjects. MDD was treated naturalistically and remission was defined as >50% reduction and a score of <or=10 on the 24 item Hamilton Scale 1 year after initiation of treatment after scanning. Despite equivalent treatment, nonremitters have higher pretreatment cortical BP and the GG genotype is over-represented compared with remitters. Higher 5-HT1A BP, perhaps due to greater gene expression, may predict antidepressant medication nonremission. The findings should be tested in a controlled prospective treatment study.