A study of the serotonin transporter in the prefrontal cortex in late‐life depression and Alzheimer's disease with and without depression

Abstract

Previous studies investigating the serotonin transporter (SERT) in depression have been inconsistent and included a large proportion of subjects who had committed suicide. In Alzheimer's disease studies have generally reported a reduction in SERT density but have not compared Alzheimer's disease subjects with and without comorbid major depression. We conducted a post mortem study of SERT density in the prefrontal cortex in normal elderly, a group of elderly depressed subjects and in Alzheimer's disease subjects with and without major depression. A post mortem study comparing SERT density in the prefrontal cortex in elderly controls (n = 10), subjects with major depression (n = 8) and subjects with Alzheimer's disease with (n = 9) and without (n = 5) comorbid major depression. We used autoradiography to measure the density of [3H]CN-IMI binding (non-specific binding determined with citalopram) to the SERT in the prefrontal cortex. We found a marked reduction in specific SERT binding in the prefrontal cortex in Alzheimer's disease subjects compared with both control (P = 0.002) and depressed subjects (P = 0.004) but no difference in SERT binding between depressed and control subjects or between Alzheimer's disease subjects with and without depression. Our study confirms previous reports of a reduction in SERT binding in Alzheimer's disease but indicates this reduction is not greater in Alzheimer's disease subjects who also have had major depression. In a group of subjects more typical of late-life depression we did not identify any alterations in SERT density.

Association Study and Meta-Analysis of Polymorphisms, Methylation Profiles, and Peripheral mRNA Expression of the Serotonin Transporter Gene in Patients with Alzheimer's Disease

“…This is the first study showing an elevated SLC6A4 mRNA expression level in leukocytes from AD patients. Although the result of our study was not consistent with previous studies performed by Thomas et al [31] or Chen et al [32] who examined postmortem AD brains, we should consider differences in genotype and allele frequencies, psychological symptoms, and tissues. Therefore, our results must be confirmed in other races including Caucasians.…”

“…Although previous studies consistently demonstrated that SLC6A4 mRNA levels in leukocytes are significantly higher in patients with MDD compared to healthy controls [29,30], the mRNA expression level in leukocytes from AD patients has not been examined yet. Thomas et al [31] reported that expression of serotonin transporters in the prefrontal cortex is lower in postmortem AD brains from patients both with and without depression than in brains of healthy subjects. Chen et al [32] examined protein and mRNA levels of the serotonin transporter in postmortem prefrontal cortex and showed that levels are reduced significantly in AD compared with controls.…”

Motor cortex excitability in vascular depression

“…Serotonin is well documented to play a significant role in the pathophysiology of nonvascular major depression and other psychiatric disorders. Conversely, neuropathological studies in late-life depression did not find evidence of a loss of serotoninergic neurons in the dorsal raphe nucleus (Hendricksen et al, 2004) or reduction in serotonin transporter density at the level of the prefrontal cortex (Thomas et al, 2006). However, membrane excitability of pyramidal neurons is not or is poorly modulated by serotonin (Gerdelat-Mas et al, 2005).…”

Les symptômes dépressifs de la maladie d’Alzheimer : trouble affectif

“…Cependant, d'autres résultats viennent contredire ou tempérer ces hypothèses. Par exemple, concernant l'hypothèse sérotoninergique, une étude a montré que la dMA n'était pas corrélée à la perte neuronale dans le noyau du raphé dorsal [52] et une autre, plus récente, que la dMA n'était pas associée à une perte plus importante du transporteur de la sérotonine par rapport à la perte constatée chez des sujets présentant une MA sans dépression [53].…”