Low brain serotonin transporter binding in major depressive disorder

Myrna Brind Center of Integrative Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Psychiatry Research (Impact Factor: 2.47). 06/2012; 202(2):161-7. DOI: 10.1016/j.pscychresns.2011.12.015
Source: PubMed


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. [(123)I]-ADAM SPECT scans were acquired from 20 drug free, depressed subjects and 20 drug-free depressed subjects and 10 drug-free healthy volunteers. The primary outcome measure was the DVR value for [(123)I]-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 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.

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Available from: Nancy Wintering, Oct 13, 2015
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    • "Newberg et al. [26] used SPET to demonstrate alterations in SERT binding in patients with major depression; in this study, SERT binding was decreased in the midbrain region of patients with major depressive disorder and the degree of decrease correlated significantly with the severity of depressive symptoms [26]. These findings were generally corroborated by a later study by the same group using a larger sample size [27]. However, to our knowledge, no studies of SERT binding have been conducted in patients with epilepsy. "
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    ABSTRACT: Purpose of the study was to investigate alterations in midbrain serotonin transporter (SERT) binding in patients with epilepsy and symptoms of depression compared to patients with epilepsy with no symptoms of depression. We studied 12 patients with epilepsy (7 patients had focal and 5 had generalized epilepsy syndromes). The presence of self-reported symptoms of depression was assessed using Beck Depression Inventory (BDI) and the Emotional State Questionnaire (EST-Q). The binding potential of the SERT was assessed by performing brain single photon emission tomography (SPET) using the SERT radioligand 2-((2-((dimethylamino)methyl)phenyl)thio)-5-(123)iodophenylamine (123I-ADAM). Seven patients had BDI and EST-Q subscale scores greater than 11 points, which was interpreted as the presence of symptoms of depression. We found that 123I-ADAM binding was not significantly different between patients with epilepsy with and without symptoms of depression. In addition, 123I-ADAM binding did not show a significant correlation to either BDI or EST-Q depression subscale scores and did not differ between patients with focal vs. generalized epilepsy. The results of our study failed to demonstrate alterations of SERT binding properties in patients with epilepsy with or without symptoms of depression.
    BMC Neurology 12/2013; 13(1):204. DOI:10.1186/1471-2377-13-204 · 2.04 Impact Factor
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    • "This is primarily based on human studies of 5-HTT binding using positron emission tomography (PET). These studies showed both increases and decreases in 5-HTT binding, as well as negative findings (Newberg et al., 2012; Savitz and Drevets, 2012). These results may be due in part to methodological differences, disease heterogeneity, prior drug exposure , gender and age of the participants (Malison et al., 1998; Newberg et al., 2005; Reimold et al., 2008). "
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    ABSTRACT: The serotonin transporter (5-HTT) regulates the extracellular concentration of serotonin, influencing neurotransmission. Evidence suggests that 5-HTT is altered during depression, but the precise changes in 5-HTT expression in the pathogenesis and treatment of depression are not clear. We investigated the protein expression of hippocampal 5-HTT in CD-1 mice exposed to unpredictable chronic mild stress for 10 continuous weeks. Following 6 weeks of the stress procedure, the mice were separated into anhedonic and non-anhedonic groups, which were then treated with fluoxetine (FLX, 10mg/kg/day, i.p.) for 4 weeks. Behavioral state and therapeutic efficacy of the drug treatment were assessed using sucrose preference, physical state of the coat and body weight. Our results show that changes in hippocampal 5-HTT protein expression correlated with stress-induced behavioral states. Decreases in 5-HTT expression were associated with the stress-induced anhedonic state, whereas increases were associated with the stress-induced non-anhedonic state. Following FLX treatment, the changes in 5-HTT expression were reversed in a subpopulation of anhedonic mice, i.e. the treatment-responsive anhedonic mice. The treatment did not alter the changes in the treatment-resistant anhedonic mice or in the non-anhedonic mice. The data indicate that down-regulation of hippocampal 5-HTT protein expression is a signature change associated with anhedonia, a key endophenotype of clinical depression. Differential changes in 5-HTT expression may contribute to variations in the susceptibility to anhedonia.
    Brain research 04/2013; 1513. DOI:10.1016/j.brainres.2013.03.042 · 2.84 Impact Factor
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    ABSTRACT: Several studies have reported low brain serotonin transporter (SERT) binding in individuals with major depression. We hypothesized that the SERT standardized uptake ratio (SUR) values using [(123) I]-ADAM single photon emission computed tomography would increase in depressed subjects who responded to cognitive behavior therapy (CBT) compared to CBT nonresponders. [(123) I]-ADAM scans were acquired before and after 12 weeks of CBT from 20 depressed subjects and on two occasions 12 weeks apart from 10 nondepressed, healthy volunteers. The primary outcome measure was change over time in SUR values in the midbrain, medial temporal lobe, and basal ganglia regions. Depressed subjects demonstrated low pretreatment mean SUR values that significantly increased over time in the midbrain (P = .011), right medial temporal lobe (P = .008), and left medial temporal lobe (P = .000) regions. Treatment responders showed a significant increase over time in SUR values in left medial temporal lobe (P = .029) and right medial temporal lobe (P = .007) regions. Partial and nonresponder subjects also showed a significant increase over time in SUR values in the left medial temporal region (P = .040) (vs. healthy volunteers), but to a lesser degree. The findings suggest that low pretreatment SERT binding may increase over time in some depressed individuals who experience symptom improvement.
    Journal of neuroimaging: official journal of the American Society of Neuroimaging 06/2013; 23(4). DOI:10.1111/jon.12035 · 1.73 Impact Factor
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