Antidepressant treatment reduces serotonin-1A autoreceptor binding in major depressive disorder.

Background Chronic selective serotonin reuptake inhibitor (SSRI) administration to rodents desensitizes or downregulates raphe 5-hydroxytryptamine 1A (5-HT 1A ) autoreceptors. We previously found elevated 5-HT 1A binding in antidepressant-naive and not recently medicated major depressive disorder (MDD) and now report the effect of SSRI treatment on 5-HT 1A autoreceptors in depressed patients. Methods 5-HT 1A binding (BP F ) was quantified in medication-free subjects using positron emission tomography (PET) with [ 11 C]-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 [ 11 C]WAY-100635 PET scans with a metabolite-corrected arterial input function and depression severity was rated before and after the treatment course. Results 5-HT 1A autoreceptor BP F in the raphe was reduced 18% on SSRI treatment ( df = 1,18; F = 5.12; p = .036). However, the degree of reduction in 5-HT 1A autoreceptor BP F was unrelated to improvement in depression ( df = 1,16; F = 1.27; p = .276). Conclusions Downregulation of 5-HT 1A 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.