5-HT 1A Receptor Binding in Temporal Lobe Epilepsy Patients With and Without Major Depression

Abstract

Major depressive disorder (MDD) is the most common comorbid psychiatric condition associated with temporal lobe epilepsy (TLE). Preclinical and clinical studies suggest that 5-HT(1A) receptors play a role in the pathophysiology of both TLE and MDD. There is preliminary evidence for an association between decreased 5-HT(1A) receptor binding in limbic brain areas and affective symptoms in TLE patients. The objective of this study was to compare 5-HT(1A) receptor binding between TLE patients with and without MDD. For the first time, 5-HT(1A) 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. 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 [(18)F]FCWAY, a fluorinated derivative of WAY100635, on a GE Medical Systems (Waukesha, Wisconsin) Advance scanner with continuous EEG monitoring. The 5-HT(1A) receptor binding was estimated by partial volume-corrected [(18)F]FCWAY V/f(1) values. In addition to decreased 5-HT(1A) receptor binding in the epileptic focus itself, comorbid MDD was associated with a significantly more pronounced reduction in 5-HT(1A) 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. Reductions in 5-HT(1A) receptor binding might help elucidate the neurobiological mechanisms underlying the TLE-MDD comorbidity.