Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [11C]WAY-100635.
Positron emission tomography (PET) studies with the selective 5-HT(1A) receptor ligand, [(11)C]WAY-100635, have indicated that the binding potential (BP) of brain 5-HT(1A) 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 [(11)C]WAY-100635 in conjunction with PET imaging to compare 5-HT(1A) 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-HT(1A) receptor BP in cortical areas in the recovered depressed subjects. In contrast, 5-HT(1A) BP in the raphe nuclei did not distinguish depressed subjects from controls. Our results suggest a persistent dysfunction in cortical 5-HT(1A) BP as measured by [(11)C]WAY-100635 in recovered depressed men. Lowered 5-HT(1A) receptor binding availability could represent a trait abnormality that confers vulnerability to recurrent major depression.
Bhagwagar
Z
Z
University Department of Psychiatry, Warneford Hospital, Oxford, UK.
Rabiner
E A
EA
Sargent
P A
PA
Grasby
P M
PM
Cowen
P J
PJ
D000928:Antidepressive Agents / Q000627:therapeutic use; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D010879:Piperazines / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000378:metabolism*; D019275:Radiopharmaceuticals; D011903:Raphe Nuclei / Q000000981:diagnostic imaging / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012016:Reference Values; D012702:Serotonin Antagonists / Q000378:metabolism*
D000928:Antidepressive Agents; D002247:Carbon Isotopes; D010879:Piperazines; D011725:Pyridines; D019275:Radiopharmaceuticals; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide