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Effects of Depression and Antidepressant Treatment

Peter A. Sargent, MRCPsych; Karen Husted Kjaer, MSc; Christopher J. Bench, MRCPsych; Eugenii A. Rabiner, FCPsych; Cristina Messa, MD; Jeff Meyer, MD; Roger N. Gunn, PhD; Paul M. Grasby, MRCPsych; Philip J. Cowen, FRCPsych

Arch Gen Psychiatry. 2000;57:174-180.

Background  Pharmacological and postmortem investigations suggest that patients with major depressive disorder have alterations in function or density of brain serotonin_1A (5-HT_1A) receptors. The aim of the present study was to use positron emission tomography with the selective 5-HT_1A receptor antagonist [¹¹C]WAY-100635 to measure 5-HT_1A receptor binding in depressed patients before and during treatment with selective serotonin reuptake inhibitors.

Methods  Positron emission tomographic scans with [¹¹C]WAY-100635 were performed on 25 patients with major depressive disorder. These included 15 unmedicated depressed patients. Ten of these unmedicated patients were scanned again during selective serotonin reuptake inhibitor treatment. A further 10 patients with major depressive disorder were scanned on one occasion only while taking selective serotonin reuptake inhibitors. Comparisons were made with [¹¹C]WAY-100635 positron emission tomographic scans in 18 healthy volunteer subjects. Region of interest analysis and statistical parametric mapping were performed on binding potential images generated using a reference tissue model.

Results  Binding potential values were reduced across many of the regions examined, including frontal, temporal, and limbic cortex in both unmedicated and medicated depressed patients compared with healthy volunteers. Binding potential values in medicated patients were similar to those in unmedicated patients.

Conclusions  Major depressive disorder is associated with a widespread reduction in 5-HT_1A receptor binding. This reduced 5-HT_1A receptor binding was not changed by selective serotonin reuptake inhibitor treatment.

From the Medical Research Council Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, London, England (Drs Sargent, Bench, Rabiner, Messa, Meyer, Gunn, and Grasby and Ms Husted Kjaer); Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, England (Drs Sargent and Cowen); Neurobiology Research Unit, University Hospital Rigshospitalet, Copenhagen, Denmark (Ms Husted Kjaer); Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, London (Drs Bench, Rabiner, and Grasby); University of Milan, Instituto Neuroscienze Bioimmagini–Consiglio Nazionale Ricerche, Institute H. S. Raffaele, Milan, Italy (Dr Messa); and Clarke Institute of Psychiatry, Department of Psychiatry, University of Toronto, Toronto, Ontario (Dr Meyer).

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