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-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.
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 [(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.
Results: 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.
Conclusions: Reductions in 5-HT(1A) receptor binding might help elucidate the neurobiological mechanisms underlying the TLE-MDD comorbidity.