title: Antidepressant treatment reduces serotonin-1A autoreceptor binding in major depressive disorder.
abstract: BACKGROUND
  Chronic selective serotonin reuptake inhibitor (SSRI) administration to rodents desensitizes or downregulates raphe 5-hydroxytryptamine 1A (5-HT1A) autoreceptors. We previously found elevated 5-HT1A binding in antidepressant-naive and not recently medicated major depressive disorder (MDD) and now report the effect of SSRI treatment on 5-HT1A autoreceptors in depressed patients.
  
  
  METHODS
  5-HT1A binding (BPF) was quantified in medication-free subjects using positron emission tomography (PET) with [11C]-WAY-100635 before and after treatment of MDD with an SSRI for 5 to 9 weeks (mean 47 ± 8 days). Nineteen subjects without recent history of antidepressant pharmacotherapy completed both [11C]WAY-100635 PET scans with a metabolite-corrected arterial input function and depression severity was rated before and after the treatment course.
  
  
  RESULTS
  5-HT1A autoreceptor BPF in the raphe was reduced 18% on SSRI treatment (df = 1,18; F = 5.12; p = .036). However, the degree of reduction in 5-HT1A autoreceptor BPF was unrelated to improvement in depression (df = 1,16; F = 1.27; p = .276).
  
  
  CONCLUSIONS
  Downregulation of 5-HT1A autoreceptor binding by SSRI treatment of major depression is consistent with animal studies. This may be a necessary but insufficient requirement for clinical response to SSRIs. A PET agonist ligand that binds selectively to the high-affinity conformation of this receptor can determine whether SSRIs also cause desensitization of the autoreceptor as reported by some rodent studies and whether that effect may be related to clinical response.
authors: Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, New York, New York, USA.
authors: Neil A
authors: NA
authors: Gray
authors: Matthew S
authors: MS
authors: Milak
authors: Christine
authors: C
authors: DeLorenzo
authors: R Todd
authors: RT
authors: Ogden
authors: Yung-Yu
authors: YY
authors: Huang
authors: J John
authors: JJ
authors: Mann
authors: Ramin V
authors: RV
authors: Parsey
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D017660:Autoreceptors / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D017660:Autoreceptors; D044282:Receptor, Serotonin, 5-HT1A; D017367:Selective Serotonin Reuptake Inhibitors
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