Altered serotonin 1A binding in major depression: a [carbonyl-C-11]WAY100635 positron emission tomography study.
BACKGROUND
Serotonin 1A receptors (5-HT(1A)) are implicated in the pathophysiology of major depressive disorder (MDD) and in the action of selective serotonin reuptake inhibitors (SSRI). SSRI desensitize 5-HT(1A) and down-regulate 5-HT transporters (5-HTT) with the latter persisting for weeks after discontinuation of SSRI. MDD subjects are more likely to be homozygous for the functional 5-HT(1A) G(-1019) allele of the promoter polymorphism and are postulated to have higher 5-HT(1A) than healthy volunteers (controls). We measure 5-HT(1A) in MDD, assess the effects of antidepressant exposure (AE), and examine the role of the C(-1019)G polymorphism.


METHODS
Genotyped and determined 5-HT(1A) binding potential (BP) by positron emission tomography (PET) using [carbonyl-C-11]-WAY-100635 in 28 medication-free MDD subjects during a current major depressive episode and 43 controls.


RESULTS
No difference in BP between controls and MDD subjects (p = .235). There was a difference in BP comparing the controls, antidepressant naive (AN) MDD subjects, and subjects with AE across all regions (p = .013). Post hoc testing reveals higher BP in AN compared to controls (p = .008) and to AE (p = .007). The GG genotype is overrepresented in MDD subjects (p = .059), and BP appears higher with the G allele.


CONCLUSIONS
AN have higher 5-HT(1A) than controls and AE suggesting a model of depression characterized by an over expression of autoinhibitory somatodendritic 5-HT(1A) receptors, perhaps due to the higher expressing G allele, that may result in reduced terminal field 5-HT release. AE appears to have long-term effects on 5-HT(1A).
Parsey
Ramin V
RV
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York, USA. rparsey@neuron.cpmc.columbia.edu
Oquendo
Maria A
MA
Ogden
R Todd
RT
Olvet
Doreen M
DM
Simpson
Norman
N
Huang
Yung-Yu
YY
Van Heertum
Ronald L
RL
Arango
Victoria
V
Mann
J John
JJ
D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D002250:Carbon Radioisotopes / Q000378:metabolism; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D010879:Piperazines / Q000378:metabolism; D011110:Polymorphism, Genetic; D049268:Positron-Emission Tomography; D011401:Promoter Regions, Genetic / Q000235:genetics; D011725:Pyridines / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D012016:Reference Values; D012702:Serotonin Antagonists / Q000378:metabolism
D000928:Antidepressive Agents; D002250:Carbon Radioisotopes; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide