Higher 5-HT1A receptor binding potential during a major depressive episode predicts poor treatment response: preliminary data from a naturalistic study.
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.
Parsey
Ramin V
RV
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA. rparsey@neuron.cpmc.columbia.edu
Olvet
Doreen M
DM
Oquendo
Maria A
MA
Huang
Yung-yu
YY
Ogden
R Todd
RT
Mann
J John
JJ
D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000378:metabolism; D011237:Predictive Value of Tests; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome
D000928:Antidepressive Agents; D010879:Piperazines; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide