Lower Serotonin Transporter Binding Potential in the Human Brain During Major Depressive Episodes

Parsey, Ramin V.; Hastings, Ramin; Oquendo, María A.; Huang, Yung‐yu; Simpson, Norman R.; Arcement, Julie; Huang, Yiyun; Ogden, R. Todd; Heertum, Ronald L. Van; Arango, Victoria; Mann, J. John

doi:10.1176/appi.ajp.163.1.52

Cited by 276 publications

(196 citation statements)

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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%

“…This is a follow-up to a previous study of 5-HTT binding in depression, which contains details regarding methods (Parsey et al, 2006b). Nineteen subjects in a SCID-diagnosed DSM-IV MDE (APA, 1994) and 41 healthy volunteers completed a 24-item Hamilton Depression Rating Scale (HAMD-24) and PET scans while medication-free (Table 1).…”

Section: Subjectsmentioning

confidence: 99%

“…PET and magnetic resonance imaging (MRI) data acquisition, analysis, and measurement of metabolite corrected arterial input functions were performed as previously described (Parsey et al, 2006a;Parsey et al, 2006b;Parsey et al, 2000). After a ten-minute transmission scan, [ 11 C]McN5652 was injected intravenously and emission data acquired for 130 minutes.…”

Section: Image Analysis and Modelingmentioning

confidence: 99%

“…Regions of interest (ROIs) were traced on MRIs obtained for each individual subject using brain atlases (Duvernoy, 1991;Talairach & Tournoux, 1988) and published reports (Kates, Abrams, Kaufmann, Breiter, & Reiss, 1997;Killiany, Moss, Nicholson, Jolesz, & Sandor, 1997). Six ROIs previously associated with serotonergic abnormalities in depression were included in this study: the anterior cingulate, amygdala, putamen, hippocampus, midbrain, and thalamus (Parsey et al, 2006b). Derivation of [ 11 C]McN5652 regional distribution volumes (V T ) was performed using likelihood estimation in graphical approach (LEGA) (Ogden, 2003;Ogden, Parsey, & Mann, 2002;Parsey, Ogden, & Mann, 2003).…”

Section: Image Analysis and Modelingmentioning

confidence: 99%

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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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Section: Objectives Of the Studysupporting

confidence: 87%

Section: Subjectsmentioning

confidence: 99%

Section: Image Analysis and Modelingmentioning

confidence: 99%

Section: Image Analysis and Modelingmentioning

confidence: 99%

See 2 more Smart Citations

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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“…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: 98%

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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Differential Effects of 5-HTTLPR Genotypes on the Behavioral and Neural Responses to Tryptophan Depletion in Patients With Major Depression and Controls

Neumeister¹,

Hu²,

Luckenbaugh³

et al. 2006

Arch Gen Psychiatry

143

125

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Lower Serotonin Transporter Binding Potential in the Human Brain During Major Depressive Episodes

Abstract: Subjects in a major depressive episode have lower serotonin transporter binding potential in the amygdala and midbrain, compared to healthy subjects.

Cited by 276 publications

References 42 publications

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

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

Differential Effects of 5-HTTLPR Genotypes on the Behavioral and Neural Responses to Tryptophan Depletion in Patients With Major Depression and Controls

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