Low brain serotonin transporter binding in major depressive disorder

Abstract

We examined midbrain, medial temporal lobe, and basal ganglia serotonin transporter (SERT) distribution volume ratio (DVR) values in subjects with major depressive disorder versus healthy volunteers using a selective SERT radioligand and single photon emission computed tomography (SPECT). We hypothesized that the DVR value for SERT binding would be lower in depressed versus non-depressed subjects. [123I]-ADAM SPECT scans were acquired from 20 drug free, depressed subjects and 10 drug free, healthy volunteers. The primary outcome measure was the DVR value for [123I]-ADAM uptake in the midbrain, medial temporal lobe, and basal ganglia regions. Depressed subjects demonstrated significantly lower DVR values in the midbrain, right and left medial temporal lobe, and right and left basal ganglia. There was s significant probability that lower DVR values could distinguish between depressed and non-depressed subjects in the midbrain, medial temporal lobe, and the right and left basal ganglia. These findings confirm prior observations of lower SERT binding in depression, and suggest that low SERT binding may represent a putative biomarker of depression. Future studies are needed to confirm these observations.

Subregion‐specific decreases in hippocampal serotonin transporter protein expression and function associated with endophenotypes of depression

“…In agreement with our findings, several studies have reported decreases in 5‐HTT density (Leake et al, ; Arango et al, ), 5‐HTT binding (Joensuu et al, ), and 5‐HTT immunoreactive axons (Austin et al, ) in various brain regions in depressed patients. PET studies also suggest that depression is linked to reduced 5‐HTT binding in various brain regions, which was reversed as patients recovered (Ichimiya et al, ; Parsey et al, ; Bhagwagar et al, ; Selvaraj et al, ; Newberg et al, ). Although, the connection between lower 5‐HTT function and depression is not universally observed (Staley et al, ; Savitz and Drevets, ), they raise the question of why patients with depression respond to SSRIs, which could lead to further decrease in 5‐HTT.…”

“…Recent studies show that a functional polymorphism in the human 5-HTT gene promoter (the 5-HTT gene-linked polymorphic region, 5-HTTLPR) is linked to an increased risk of developing major depression, linked to poor memory function, and linked to reduced hippocampal tissue volume (Caspi et al, 2003;O'Hara et al, 2007;Daniele et al, 2011). Moreover, neuroimaging studies show that hippocampal 5-HTT binding is altered in patients with depression (Newberg et al, 2012 ;Savitz and Drevets, 2012).…”

N‐Acetyl Cysteine Is Associated With Dopaminergic Improvement in Parkinson's Disease

“…As a secondary outcome, we found a significantly increased SERT binding in the midbrain after NAC supplementation. Because several studies have shown a relationship between reduced SERT binding and depression, it is possible there could be a mood benefit in patients with PD receiving NAC. The present study excluded patients with substantial depressive symptoms; however, future studies could be more inclusive of a broader range of symptoms, including depression.…”

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

“…In some studies, patients with MDD exhibit lower 5-HTT binding in the amygdala (Murrough et al, 2011), midbrain (Malison et al, 1998; Parsey et al, 2006a) medial temporal lobe, and basal ganglia (Newberg et al, 2012) compared with healthy volunteers. However, using the ligand [ 11 C]-3-amino-4-(3-dimethylamino-methylphenylsulfanyl)-benzonitrile ([ 11 C]DASB), we previously found no differences in 5-HTT binding between MDD and healthy controls (Miller et al, 2013).…”