title: Brain serotonin 1A receptor binding as a predictor of treatment outcome in major depressive disorder.
abstract: BACKGROUND
  We previously reported higher serotonin 1A receptor (5-HT1A) binding in subjects with major depressive disorder (MDD) during a major depressive episode using positron emission tomography imaging with [(11)C]WAY-100635. 5-HT1A receptor binding is also associated with treatment outcome after nonstandardized antidepressant treatment. We examined whether pretreatment 5-HT1A binding is associated with treatment outcome following standardized escitalopram treatment in MDD. We also compared 5-HT1A binding between all MDD subjects in this cohort and a sample of healthy control subjects.
  
  
  METHODS
  Twenty-four MDD subjects in a current major depressive episode and 51 previously studied healthy control subjects underwent positron emission tomography scanning with [(11)C]WAY-100635, acquiring a metabolite-corrected arterial input function and free-fraction measurement to estimate 5-HT1A binding potential (BPF = Bmax/KD, where Bmax = available receptors and KD = dissociation constant). Major depressive disorder subjects then received 8 weeks of treatment with escitalopram; remission was defined as a posttreatment 24-item Hamilton Depression Rating Scale <10 and ≥ 50% reduction in Hamilton Depression Rating Scale.
  
  
  RESULTS
  Remitters to escitalopram had 33% higher baseline 5-HT1A binding in the raphe nuclei than nonremitters (p = .047). Across 12 cortical and subcortical regions, 5-HT1A binding did not differ between remitters and nonremitters (p = .86). Serotonin 1A receptor binding was higher in MDD than control subjects across all regions (p = .0003). Remitters did not differ from nonremitters in several relevant clinical measures.
  
  
  CONCLUSIONS
  Elevated 5-HT1A binding in raphe nuclei is associated with subsequent remission with the selective serotonin reuptake inhibitor escitalopram; this is consistent with data from a separate cohort receiving naturalistic antidepressant treatment. We confirmed our previous findings of higher 5-HT1A binding in current MDD compared with control subjects.
authors.affiliation: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York; Department of Psychiatry, Columbia University, New York. Electronic address: jm2233@columbia.edu.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Miller
authors.forename: Natalie
authors.initials: N
authors.lastname: Hesselgrave
authors.forename: R Todd
authors.initials: RT
authors.lastname: Ogden
authors.forename: Francesca
authors.initials: F
authors.lastname: Zanderigo
authors.forename: Maria A
authors.initials: MA
authors.lastname: Oquendo
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000627:therapeutic use*; D015283:Citalopram / Q000008:administration & dosage / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D011903:Raphe Nuclei / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D044282:Receptor, Serotonin, 5-HT1A
keywords: Antidepressant; PET imaging; depression; prediction; serotonin 1A receptor; treatment outcome