Brain serotonin 1A receptor binding as a predictor of treatment outcome in major depressive disorder

Biol Psychiatry. 2013 Nov 15;74(10):760-7. doi: 10.1016/j.biopsych.2013.03.021. Epub 2013 May 9.


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.

Trial registration: NCT00456014.

Keywords: Antidepressant; PET imaging; depression; prediction; serotonin 1A receptor; treatment outcome.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents, Second-Generation / administration & dosage
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Citalopram / administration & dosage
  • Citalopram / therapeutic use*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / metabolism
  • Female
  • Humans
  • Male
  • Positron-Emission Tomography
  • Raphe Nuclei / metabolism*
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Treatment Outcome


  • Antidepressive Agents, Second-Generation
  • Citalopram
  • Receptor, Serotonin, 5-HT1A

Associated data