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Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [11C]WAY-100635

Abstract

Positron emission tomography (PET) studies with the selective 5-HT1A receptor ligand, [11C]WAY-100635, have indicated that the binding potential (BP) of brain 5-HT1A receptors is lowered in unmedicated subjects with acute major depression. However, it is unclear if these changes persist after recovery from depression. To resolve this issue, we used [11C]WAY-100635 in conjunction with PET imaging to compare 5-HT1A BP in 18 healthy controls and 14 male subjects with recurrent major depression who were clinically recovered and free of antidepressant medication. BP values, derived from a reference tissue model, were analysed by region of interest and statistical parametric mapping. Both analyses showed a widespread and substantial (17%) decrease in 5-HT1A receptor BP in cortical areas in the recovered depressed subjects. In contrast, 5-HT1A BP in the raphe nuclei did not distinguish depressed subjects from controls. Our results suggest a persistent dysfunction in cortical 5-HT1A BP as measured by [11C]WAY-100635 in recovered depressed men. Lowered 5-HT1A receptor binding availability could represent a trait abnormality that confers vulnerability to recurrent major depression.

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Acknowledgements

We thank all the volunteers without whom this study would not be possible. Thanks are also due to Andrew Blythe, Joanne Holmes, David Turton, Ray Khan, Safiye Osman, Jasbir Grewal, Vijaykumar Vaja, Keith Poole, Leonard Schnorr, Abdellah Haida, Ann Peers and others at the MRC Cyclotron Unit, London, for expert technical assistance. The study was supported by an MRC Co-operative Group grant. ZB was a MRC Clinical Training Fellow.

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Correspondence to P J Cowen.

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Bhagwagar, Z., Rabiner, E., Sargent, P. et al. Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [11C]WAY-100635. Mol Psychiatry 9, 386–392 (2004). https://doi.org/10.1038/sj.mp.4001401

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