Reduced brain serotonin transporter availability in major depression as measured by [123I]-2β-carbomethoxy-3β-(4-iodophenyl)tropane and single photon emission computed tomography

Malison, Robert T.; Price, Lawrence H.; Berman, R.; Dyck, Christopher H. van; Pelton, Gregory H.; Carpenter, Linda L.; Sanacora, Gerard; Owens, Michael J.; Nemeroff, Charles B.; Rajeevan, N.; Baldwin, R.M.; Seibyl, John; Innis, Robert B.; Charney, Dennis S.

doi:10.1016/s0006-3223(98)00272-8

Cited by 440 publications

(263 citation statements)

References 41 publications

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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: 88%

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: 88%

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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“…It is unclear whether 5-HTT B max data acquired in platelets can be expected to reflect the situation in the CNS (Malison et al, 1998;Rausch et al, 2005). Several additional regulatory processes, such as degradation or pruning of new synapses and de novo synthesis of 5-HTTs may contribute to the regulation of 5-HTT quantity in the CNS.…”

Section: -Htt Function In Sadmentioning

confidence: 99%

“…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: 97%

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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“…In humans, in vivo [ 123 I]b-CIT SPECT imaging of the SERT has been used, among others, to study SERT availability in depression and alcoholism and to study the neurotoxic effects of ecstasy (Malison et al, 1998;Heinz et al, 1998;Reneman et al, 2001a, b (Pirker et al, 1995(Pirker et al, , 2000 or to study the effects of [ 123 I]b-CIT binding to SERTs and DATs in vivo in humans after blocking of SERTs with a SSRI (Pirker et al, 1995;Tauscher et al, 1999;Kugaya et al, 2003). One study validated the use of in vivo [ 123 I]b-CIT SPECT in detecting MDMA-induced serotonergic neurotoxicity in SERT-rich brain areas in a monkey (Reneman et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…Some of these studies were performed in depressed patients, whereas depression may be an important confounder. For example, lower [ 123 I]b-CIT binding ratios were reported in SERT-rich areas in depressed patients treated with SSRIs compared to healthy volunteers (Pirker et al, 1995;Tauscher et al, 1999), whereas also in untreated depressive patients decreased SERT binding has been described (Malison et al, 1998). Only Kugaya and co-workers (2003) studied the in vivo alterations of [ 123 I]b-CIT binding during SSRI treatment in both depressive patients and in healthy volunteers.…”

Section: Introductionmentioning

confidence: 99%

Validation of [123I]β-CIT SPECT to Assess Serotonin Transporters In Vivo in Humans: a Double-Blind, Placebo-Controlled, Crossover Study with the Selective Serotonin Reuptake Inhibitor Citalopram

Win

Habraken

Reneman

et al. 2005

Neuropsychopharmacol

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Reduced brain serotonin transporter availability in major depression as measured by [123I]-2β-carbomethoxy-3β-(4-iodophenyl)tropane and single photon emission computed tomography

Cited by 440 publications

References 41 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

Validation of [123I]β-CIT SPECT to Assess Serotonin Transporters In Vivo in Humans: a Double-Blind, Placebo-Controlled, Crossover Study with the Selective Serotonin Reuptake Inhibitor Citalopram

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