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Brain Advance Access originally published online on September 2, 2008
Brain 2008 131(10):2765-2782; doi:10.1093/brain/awn194
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© The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Comorbidity between temporal lobe epilepsy and depression: a [18F]MPPF PET study

A. Lothe1,2, A. Didelot3,4, A. Hammers5, N. Costes2,6, M. Saoud7, F. Gilliam8 and P. Ryvlin1,2,3

1CTRS-IDEE, Hospices Civils de Lyon, 2INSERM U821, University Claude Bernard Lyon 1 and Neuroscience Federative Institute of Lyon, Lyon, 3Department of Functional Neurology and Epileptology, Hospices Civils de Lyon, 4INSERM U879, University Claude Bernard Lyon 1 and Neuroscience Federative Institute of Lyon, Lyon, France, 5Department of Clinical Neuroscience, Division of Neuroscience and Mental Health, Imperial College, London, UK, 6CERMEP-imagerie du vivant, 7EA4166 and CH le Vinatier, University Claude Bernard Lyon 1 and Neuroscience Federative Institute of Lyon, Lyon, France and 8Department of Neurology, Columbia University, New York, NY, USA

Correspondence to: P. Ryvlin, Unité 301, Hôpital Neurologique, 59 bd Pinel, 69003, Lyon, France E-mail: ryvlin{at}cermep.fr

Brain and brainstem changes of serotoninergic 5-hydroxytryptophan (5-HT)1A receptor density have been reported in patients with major depressive disorder as well as in patients with temporal lobe epilepsy (TLE), using PET and the selective antagonist radiotracers [11C]WAY-100635 or [18F]FC-WAY. We used a distinct 5-HT1A antagonist, [18F]MPPF, whose binding potential depends on both receptor density and extracellular serotonin concentration, in 24 patients with drug-resistant TLE and MRI evidence of hippocampal sclerosis but without prior antidepressant exposure. Their Beck Depression Inventory (BDI-2) score ranged from 0 to 34, with nine patients having a score >11. We used a simplified reference tissue model, statistical parametric mapping and anatomical regions of interest (ROIs) to correlate parametric images of [18F]MPPF BP with the total BDI score and its four subclasses. The total BDI score, as well as symptoms of psychomotor anhedonia and negative cognition, correlated positively with [18F]MPPF BP in the raphe nuclei and in the insula contralateral to seizure onset, whereas somatic symptoms correlated positively with [18F]MPPF binding potential in the hippocampal/parahippocampal region ipsilateral to seizure onset, the left mid-cingulate gyrus and the inferior dorsolateral frontal cortex, bilaterally. We confirm an association of depressive symptoms in TLE patients with changes of the central serotoninergic pathways, in particular within the raphe nuclei, insula, cingulate gyrus and epileptogenic hippocampus. These changes are likely to reflect lower extracellular serotonin concentration in more depressed patients, with an upregulation of receptors a less likely alternative.

Key Words: depressive symptoms; TLE; [18F]MPPF

Abbreviations: 5-HT, 5-hydroxytryptophan; BDI, Beck Depression Inventory; BP, binding potential; MDD, major depressive disorder; TLE, temporal lobe epilepsy

Received September 11, 2007. Revised July 26, 2008. Accepted July 31, 2008.


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