The 5-HT _1A receptor and 5-HT transporter in temporal lobe epilepsy

Abstract

Objective: To study 5-HT transport and 5-HT 1A receptors in temporal lobe epilepsy (TLE) and depression. Conclusions: Our study showed increased [ Methods11 C]DASB asymmetry in insula and fusiform gyrus, and relatively reduced transporter activity, in subjects with both TLE and depression, as compared to subjects with TLE alone, implying reduced reuptake and thus increased synaptic 5-HT availability. This finding may represent a compensatory mechanism for 5-HT 1A receptor loss. Altered serotonergic mechanisms have an important role in TLE and concomitant depression. Serotonin (5-HT) exerts antiseizure effects in experimental models mediated by 5-HT 1A receptors, by hyperpolarizing hippocampal CA3 membranes.1 Some antiepileptic drugs (AEDs) may exert antiseizure effects by blocking 5-HT reuptake. 2PET studies showed reduced 5-HT 1A receptor binding ipsilateral to temporal lobe epilepsy (TLE) foci.3-5 Not due to hippocampal atrophy, reductions are more pronounced in seizure onset than secondary spread regions. 5,6 Epidemiologic and clinical data support relationships between epilepsy and depression, one of the most common epilepsy comorbidities.7 A history of depression increases risk for later epilepsy development.8 Otherwise healthy patients with major depressive disorders (MDD) may have limbic 5-HT 1A receptor binding reductions.9-11 5-HT 1A receptor PET studies in patients with both TLE and depression showed additional binding alterations compared to TLE alone.

Frontolimbic brain networks predict depressive symptoms in temporal lobe epilepsy

“…However, recent evidence indicates that aberrant FC in depression is related to the serotonin transporter genotype, in that individuals who carry the short allele of the serotonin transporter-linked polymorphic region show either increased or decreased functional coupling of the limbic and PFC regions (Hariri and Holmes, 2006). Given reported serotonin receptor abnormalities in TLE (Martinez et al, 2013), it is possible that serotonin-related genetic variations account for altered functional coupling in patients with TLE who have higher levels of self-reported depression symptoms. Exploring the mechanisms underlying the altered FC may be essential not only for understanding co-morbid depression but also for predicting post-surgical emotional functioning, since surgical resection alters frontolimbic FC and may further disrupt serotonergic transmission.…”

Biomarkers of Epileptogenesis: Psychiatric Comorbidities (?)

“…In the insular cortex there was a correlation between 5-HT-transporter and 5-HT 1A asymmetry for patients with TLE, but not for healthy controls, suggesting greater loss of 5-HT 1A receptors to compensate for reduced transport, such that higher synaptic 5-HT levels can be expected to be maintained at the sites that have fewer 5-HT 1A receptors [19].…”

A positron emission tomography study of the serotonergic system in relation to anxiety in depression

“…Specifically, two studies reported negative correlations between anxiety symptom severity and the 5-HTT binding in the thalamus (Reimold et al, 2008) (Reimold et al, 2011), and one reported such correlations in the midbrain and amygdala regions as well (Reimold et al, 2008). In studies examining panic disorder, one found a positive correlation between panic disorder symptoms and binding in all areas except the hippocampus (Maron et al, 2011) and, in the other, the relationship was only seen in the anterior cingulate cortex and midbrain (Martinez et al, 2013). In both studies, this relationship was observed only in male patients and not controls or females.…”

“…Although the previous regression analysis (of 5-HT 1A and anxiety) used sex as a covariate, previous studies have found no sex differences in [ 11 C]DASB binding (Martinez et al, 2013). Therefore, it was not included in regression models for [ 11 C]DASB in the current study.…”