Serotonin 1A receptors, depression, and memory in temporal lobe epilepsy

Abstract

Purpose Memory deficits and depression are common in patients with temporal lobe epilepsy (TLE). Previous PET studies have shown reduced mesial temporal 5HT1A receptor binding in these patients. We examined the relationships among verbal memory performance, depression, and 5HT1A receptor binding binding measured with 18FCWAY positron emission tomography (PET) in a cross sectional study. Methods We studied 40 patients (24 male; mean age 34.5 ±10.7) with TLE. Seizure diagnosis and focus localization were based on ictal Video-Electoencephalographic recording. Patients had neuropsychological testing with Weschler Adult Intelligence Score III (WAIS III) and Weschler Memory Score III (WMS III) on stable AED regimens at least 24 hours since the last seizure. Beck Depression Inventory (BDI) scores were obtained. We performed interictal PET with [18F]FCWAY, a fluorinated derivative of WAY100635, a highly specific 5HT1A ligand, and structural magnetic resonance imaging (MRI) scans to estimate partial volume and plasma free fraction corrected [18F]FCWAY volume of distribution (V/f1). Key Findings Hippocampal V/f1 was significantly lower ipsilateral than contralateral to the epileptic focus (73.7 ± 27.3 versus 95.4 ± 28.4; p<.001). We found a significant relation between both left hippocampal FCWAY V/f1 (r= 0.41; p < 0.02) and left hippocampal volume (r=0.36; p < 0.03) and delayed auditory memory score. On multiple regression there was a significant effect of the interaction of left hippocampal FCWAY V/f1 and left hippocampal volume on delayed auditory memory, but not of either alone. High collinearity was present. In an analysis of variance including the side of the seizure focus, the effect of left hippocampal FCWAY V/f1 but not focus laterality retained significance. Mean BDI was 8.3 ±7.0. There was a significant inverse relation between BDI and FCWAY V/f1 ipsilateral to the patient’s epileptic focus (r= 0.38 p<0.02) There was no difference between patients with a right or left temporal focus. There was no relation between BDI and immediate or delayed auditory memory. Significance Our study suggests that reduced left hippocampal 5-HT1A receptor binding may play a role in memory impairment in patients with TLE.

Verbal memory and 5-HT1A receptors in healthy volunteers – A PET study with [carbonyl-11C]WAY-100635

“…The positive correlation between verbal memory and 5-HT1A receptor binding is consistent with a report on a positive correlation between hippocampal 5-HT1A receptor binding and memory in patients with temporal lobe epilepsy with another radioligand (Theodore et al, 2012), but in contrast to previous [carbonyl-11C]WAY-100635 PET studies in healthy subjects showing either no correlation (Borg et al, 2006;Borg et al, 2009) or a negative correlation between verbal memory and hippocampal 5-HT1A binding (Yasuno et al, 2003). Methodological issues may in part explain this discrepancy.…”

“…This negative finding was later replicated in a larger data set by the same authors (Borg et al, 2009). In a more recent study, a positive correlation was found between hippocampal 5-HT1A receptor binding and memory performance in patients with temporal lobe epilepsy with another radioligand (Theodore et al, 2012). We sought to further characterize the association between serotonin 5-HT1A receptor binding and verbal memory in healthy subjects using [carbonyl-11C]WAY-100635 PET.…”

Molecular Targets of Cannabidiol in Neurological Disorders

“…A very limited number of studies have reported changes in 5-HT receptor expression and function in people with epilepsy, although it remains unclear whether this is a consequence of the disease or a component of pathogenesis. Thus, while 5-HT involvement in pathogenesis remains uncertain, some 5-HT receptor subtypes may represent a valid therapeutic target in epilepsy through which CBD could be acting [145,146].…”

High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo

“…Moreover, a dysfunctional serotonergic system might be responsible for the occurrence of concomitant diseases such as temporal lobe epilepsy (tLE) and comorbid depression and cognitive impairments and depression (Kanner and Balabanov 2002;Garcia 2012;theodore et al 2012). Among the different 5-Ht receptor (R) subtypes, compelling pre-clinical and human studies have indicated an impairment of 5-Ht 1A signal in tLE and comorbid psychiatric disorders seen in these patients (theodore et al 2012).…”