Brain Serotonin Transporter Binding Potential Measured With Carbon11–Labeled DASB Positron Emission Tomography

Meyer, Jeffrey H.; Houle, Sylvain; Sagrati, Sandra; Carella, Anna; Hussey, Doug; Ginovart, Nathalie; Goulding, Verdell S.; Kennedy, James L.; Wilson, Alan A.

doi:10.1001/archpsyc.61.12.1271

Cited by 249 publications

(184 citation statements)

References 75 publications

(132 reference statements)

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“…Our results confirm previous reports of similar SERT availability in the midbrain and diencephalon in MDD patients and healthy subjects [14][15][16][17][18]. Other studies have shown increased [19] or decreased [7][8][9][10][11][12][13] SERT availability in MDD patients compared with healthy subjects.…”

Section: Comparison With Previous Studiessupporting

confidence: 91%

“…Studies comparing depressed patients with healthy subjects have shown decreased [7][8][9][10][11][12][13], unchanged [14][15][16][17][18] or increased [19] SERT availability in MDD patients. A negative correlation between SERT availability and the severity of depression, measured in terms of Hamilton depression rating scale (HDRS) scores, has been reported in patients with primary MDD [9] or Wilson's disease [20].…”

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confidence: 99%

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Serotonin transporter binding with [123I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

Ruhé

Booij

Reitsma

et al. 2009

Eur J Nucl Med Mol Imaging

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Purpose The serotonin system is undoubtedly involved in the pathogenesis of major depressive disorder (MDD). More specifically the serotonin transporter (SERT) serves as a major target for antidepressant drugs. There are conflicting results about SERT availability in depressed patients versus healthy controls. We aimed to measure SERT availability and study the effects of age, gender and season of scanning in MDD patients in comparison to healthy controls. Methods We included 49 depressed outpatients (mean±SD 42.3±8.3 years) with a Hamilton depression rating scale score above 18, who were drug-naive or drug-free for ≥4 weeks, and 49 healthy controls matched for age (±2 years) and sex. Subjects were scanned with single photon emission computed tomography (SPECT) using [ 123 I]β-CIT. SERT availability was expressed as specific to nonspecific binding ratios (BP ND ) in the midbrain and diencephalon with cerebellar binding as a reference. Results In crude comparisons between patients and controls, we found no significant differences in midbrain or diencephalon SERT availability. In subgroup analyses, depressed males had numerically lower midbrain SERT availability than controls, whereas among women SERT availability was not different (significant diagnosis×gender interaction; p=0.048). In the diencephalon we found a comparable diagnosis×gender interaction (p=0.002) and an additional smoking×gender (p=0.036) interaction. In the midbrain the season of scanning showed a significant main effect (p=0.018) with higher SERT availability in winter. Conclusion Differences in SERT availability in the midbrain and diencephalon in MDD patients compared with healthy subjects are affected by gender. The season of scanning is a covariate in the midbrain. The diagnosis×gender and gender×smoking interactions in SERT availability should be considered in future studies of the pathogenesis of MDD.

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Section: Comparison With Previous Studiessupporting

confidence: 91%

mentioning

confidence: 99%

Serotonin transporter binding with [123I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

Ruhé

Booij

Reitsma

et al. 2009

Eur J Nucl Med Mol Imaging

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“…We found lower 5-HTT binding (BP P , proportional to the total number of available transporters) in midbrain and amygdala in vivo in major depressive disorder (MDD) using positron emission tomography (PET) with [ 11 C]McN5652 (Parsey et al, 2006b), in agreement with some (Lehto et al, 2006;Malison et al, 1998;Newberg et al, 2005), but not all (Ichimiya et al, 2002;Meyer et al, 2004a), previous reports.…”

Section: Objectives Of the Studysupporting

confidence: 87%

Serotonin transporter binding as a possible predictor of one-year remission in major depressive disorder

Miller

Oquendo

Ogden

et al. 2008

Journal of Psychiatric Research

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Objective-Lower serotonin transporter (5-HTT) binding (BP P = = f P B avail /K D ) is reported during a major depressive episode (MDE) compared to healthy controls. Higher 5-HTT binding in the diencephalon has previously been associated with acute response to antidepressant treatment. We assessed baseline 5-HTT binding as a predictor of one-year remission from a MDE, examining binding in brain regions implicated in the pathophysiology of major depressive disorder (MDD). Results-Significant differences in 5-HTT binding among the three groups (healthy controls, remitters, and non-remitters) were observed in a linear mixed-effects model. Post-hoc, non-remitters had lower 5-HTT binding than controls in midbrain, amygdala, and anterior cingulate. Remitters did not differ significantly from controls or non-remitters in 5-HTT binding. Remitters did not differ from non-remitters in clinical characteristics apart from greater family history of depression among non-remitters. A logistic regression model fit to determine the capacity of baseline 5-HTT binding to predict remission status at one year yielded a coefficient that was suggestive but not significant (p=0.057). Methods-5-HTTLimitations-The small sample size and heterogeneous treatments received reduced statistical power to detect differences in binding based on clinical outcome.Conclusions-Lower pretreatment 5-HTT binding may be predictive of non-remission from major depression following one year of naturalistic antidepressant treatment. Future studies using standardized treatment are warranted.

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“…Brain imaging techniques (positron emission tomography or single photon computed tomography, SPECT) allow for measurement of 5-HTT availability in the living human brain. While some studies suggest reductions in CNS 5-HTT availability in seasonal (Willeit et al, 2000) and nonseasonal depression (Malison et al, 1998;Parsey et al, 2006;Staley et al, 2006), recent studies failed to find altered 5-HTT binding (Meyer et al, 2004). An important limitation of current brain imaging techniques is that they are confined to quantification of 5-HTT binding sites but do not allow for functional assessments of transport processes.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Serotonin Transporter Function during Depression in Seasonal Affective Disorder

Willeit

Sitte

Thierry

et al. 2007

Neuropsychopharmacol

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Decreased synaptic serotonin during depressive episodes is a central element of the monoamine hypothesis of depression. The serotonin transporter (5-HTT, SERT) is a key molecule for the control of synaptic serotonin levels. Here we aimed to detect state-related alterations in the efficiency of 5-HTT-mediated inward and outward transport in platelets of drug-free depressed patients suffering from seasonal affective disorder (SAD). 5-HTT turnover rate, a measure for the number of inward transport events per minute, and tyramineinduced, 5-HTT-mediated outward transport were assessed at baseline, after 4 weeks of bright light therapy, and in summer using a case-control design in a consecutive sample of 73 drug-free depressed patients with SAD and 70 nonseasonal healthy controls. Patients were drug-naive or medication-free for at least 6 months prior to study inclusion, females patients were studied in the follicular phase of the menstrual cycle. All participants were genotyped for a 5-HTT-promoter polymorphism (5-HTTLPR) to assess the influence of this polymorphism on 5-HTT parameters. Efficiency of 5-HTT-mediated inward (p ¼ 0.014) and outward (p ¼ 0.003) transport was enhanced in depressed patients. Both measures normalized toward control levels after therapy and in natural summer remission. Changes in outward transport showed a clear correlation with treatment response (r ¼ 0.421, p ¼ 0.001). Changes in inward transport were mediated by changes in 5-HTT transport efficiency rather than affinity or density. 5-HTTLPR was not associated with any of the 5-HTT parameters. In sum, we conclude that the 5-HTT is in a hyperfunctional state during depression in SAD and normalizes after light therapy and in natural summer remission.

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Brain Serotonin Transporter Binding Potential Measured With Carbon11–Labeled DASB Positron Emission Tomography

Abstract: Serotonin transporters play an important role during depression. The magnitude of regional 5-HTT BP can provide a vulnerability to low levels of extracellular serotonin and symptoms of extremely negativistic dysfunctional attitudes.

Cited by 249 publications

References 75 publications

Serotonin transporter binding with [123I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

Serotonin transporter binding with [123I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

Serotonin transporter binding as a possible predictor of one-year remission in major depressive disorder

Enhanced Serotonin Transporter Function during Depression in Seasonal Affective Disorder

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