Brain Serotonin 1A Receptor Binding as a Predictor of Treatment Outcome in Major Depressive Disorder

• Published in: Biological psychiatry (1969) Vol. 74; no. 10; pp. 760 - 767
• Main Authors: Miller, Jeffrey M., Hesselgrave, Natalie, Ogden, R. Todd, Zanderigo, Francesca, Oquendo, Maria A., Mann, J. John, Parsey, Ramin V.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.11.2013; Elsevier
• Subjects: Adult; Adult and adolescent clinical studies; Antidepressant; Antidepressive Agents, Second-Generation - administration & dosage; Antidepressive Agents, Second-Generation - therapeutic use; Biological and medical sciences; Citalopram - administration & dosage; Citalopram - therapeutic use; Depression; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - metabolism; Female; Humans; Male; Medical sciences; Miscellaneous; Mood disorders; Neuropharmacology; PET imaging; Pharmacology. Drug treatments; Positron-Emission Tomography; prediction; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Raphe Nuclei - metabolism; Receptor, Serotonin, 5-HT1A - metabolism; serotonin 1A receptor; Treatment Outcome; Antidepressant; prediction; depression; PET imaging; serotonin 1A receptor; treatment outcome; Radionuclide study; Mood disorder; Psychotropic; Treatment efficiency; Central nervous system; Prediction; Depression; Encephalon; 5-HT1A Serotonine receptor; Antidepressant agent; Predictive factor; Positron emission tomography
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2013.03.021

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 [11C]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. Twenty-four MDD subjects in a current major depressive episode and 51 previously studied healthy control subjects underwent positron emission tomography scanning with [11C]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. 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. 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.