5-HT1A Receptor Binding in Temporal Lobe Epilepsy Patients With and Without Major Depression

Received 6 December 2006; received in revised form 8 February 2007; accepted 10 February 2007. published online 25 June 2007.

Background

Major depressive disorder (MDD) is the most common comorbid psychiatric condition associated with temporal lobe epilepsy (TLE). Preclinical and clinical studies suggest that 5-HT1A receptors play a role in the pathophysiology of both TLE and MDD. There is preliminary evidence for an association between decreased 5-HT1A receptor binding in limbic brain areas and affective symptoms in TLE patients. The objective of this study was to compare 5-HT1A receptor binding between TLE patients with and without MDD. For the first time, 5-HT1A receptor binding was measured in a sample large enough to permit sensitive comparisons between TLE patients with and without comorbid MDD diagnosed by clinical and structured psychiatric interviews.

Methods

Thirty-seven epilepsy patients with temporal lobe foci confirmed by ictal video-electroencephalogram (EEG) monitoring were recruited from the Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke. We performed interictal positron emission tomography scanning, with [18F]FCWAY, a fluorinated derivative of WAY100635, on a GE Medical Systems (Waukesha, Wisconsin) Advance scanner with continuous EEG monitoring. The 5-HT1A receptor binding was estimated by partial volume-corrected [18F]FCWAY V/f1 values.

Results

In addition to decreased 5-HT1A receptor binding in the epileptic focus itself, comorbid MDD was associated with a significantly more pronounced reduction in 5-HT1A receptor binding in TLE patients, extending into non-lesional limbic brain areas outside the epileptic focus. Focus side and the presence of mesial temporal sclerosis were not associated with the presence of comorbid depression.

Conclusions

Reductions in 5-HT1A receptor binding might help elucidate the neurobiological mechanisms underlying the TLE–MDD comorbidity.

Key Words: [18F]FCWAY-PET, 5-HT1A receptor binding, major depressive disorder, psychiatric comorbidity, serotonin, temporal lobe epilepsy

a Department of Psychiatry, University Hospital, Zürich, Switzerland

b The Clinical Epilepsy Section, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland

c Mood and Anxiety Disorders Program, Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland.

Address reprint requests to Gregor Hasler, M.D., Department of Psychiatry, University Hospital, Culmannstrasse 8, 8091 Zürich, Switzerland

The authors do not have conflicts of interest, neither financial nor otherwise, and they do not have any conflicts to disclose.

PII: S0006-3223(07)00155-2

doi:10.1016/j.biopsych.2007.02.015

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