1. ¹Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA
2. ²Department of Neuroscience, New York State Psychiatric Institute, New York, NY, USA
3. ³Department of Biostatistics, Columbia University School of Public Health, New York, NY, USA
4. ⁴Department of Radiology, Columbia University College of Physicians and Surgeons, New York, NY, USA

Correspondence: Dr R Parsey, Department of Psychiatry and Radiology, New York State Psychiatric Institute, 1051 Riverside Drive, Box #42, New York, NY 10032, USA. Tel: +212 543 6101; Fax: +212 543 6017, E-mail: rparsey@neuron.cpmc.columbia.edu

Received 12 May 2005; Revised 3 October 2005; Accepted 24 October 2005; Published online 4 January 2006.

Abstract

Serotonin 1A (5-HT_1A) 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-HT_1A C-1019G polymorphism. We hypothesize that higher 5-HT_1A BP and the GG genotype predict remission failure on antidepressant treatment. We determined 5-HT_1A BP by PET and 5-HT_1A 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 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-HT_1A BP, perhaps due to greater gene expression, may predict antidepressant medication nonremission. The findings should be tested in a controlled prospective treatment study.