Regional differences in SERT occupancy after acute and prolonged SSRI intake investigated by brain PET

Baldinger, P.; Kranz, Georg S.; Haeusler, Daniela; Savli, Markus; Spies, Marie; Philippe, Cécile; Hahn, Andreas; Höflich, Anna; Wadsak, Wolfgang; Mitterhauser, Markus; Lanzenberger, Rupert; Kasper, Siegfried

doi:10.1016/j.neuroimage.2013.10.002

Cited by 54 publications

(58 citation statements)

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“…Assuming that NOS may remove the serotonin transporter, it may be acting similarly to selective serotonin reuptake inhibitors (SSRIs) which also inhibit the actions of the serotonin transporters [177][178][179][180]. Thus, by leptin-induced inhibition of NOS, serotonin metabolism and inactivation would be enhanced.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Leptin and the brain: Influences on brain development, cognitive functioning and psychiatric disorders

2015

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Section: Accepted Manuscriptmentioning

confidence: 99%

Leptin and the brain: Influences on brain development, cognitive functioning and psychiatric disorders

2015

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“…In theory, molecular imaging of 5-HTT in vivo might yield better-defined findings of the putative association between MDD and serotonergic transmission. 7, 8 …”

Section: Introductionmentioning

confidence: 99%

Meta-Analysis of Molecular Imaging of Serotonin Transporters in Major Depression

Gryglewski

Lanzenberger

Kranz

et al. 2014

J Cereb Blood Flow Metab

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130

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The success of serotonin-selective reuptake inhibitors has lent support to the monoamine theory of major depressive disorder (MDD). This issue has been addressed in a number of molecular imaging studies by positron emission tomography or single-photon emission computed tomography of serotonin reuptake sites (5-HTT) in the brain of patients with MDD, with strikingly disparate conclusions. Our meta-analysis of the 18 such studies, totaling 364 MDD patients free from significant comorbidities or medication and 372 control subjects, revealed reductions in midbrain 5-HTT (Hedges' g=−0.49; 95% CI: (−0.84, −0.14)) and amygdala (Hedges' g=−0.50; 95% CI: (−0.78, −0.22)), which no individual study possessed sufficient power to detect. Only small effect sizes were found in other regions with high binding (thalamus: g=−0.24, striatum: g=−0.32, and brainstem g=−0.22), and no difference in the frontal or cingulate cortex. Age emerged as an important moderator of 5-HTT availability in MDD, with more severe reductions in striatal 5-HTT evident with greater age of the study populations (P<0.01). There was a strong relationship between severity of depression and 5-HTT reductions in the amygdala (P=0.01). Thus, molecular imaging findings indeed reveal widespread reductions of ∼10% in 5-HTT availability in MDD, which may predict altered spatial–temporal dynamics of serotonergic neurotransmission.

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“…Following SSRI administration, the drugs are thought to increase extracellular serotonin concentrations by serotonin transporter (SERT) inhibition. Positron emission tomography (PET) studies using SERT-selective radioligands have demonstrated a reduction in striatal radioligand binding of about 64-72 % after a single escitalopram or citalopram dose (Baldinger et al 2014;Lanzenberger et al 2012;Lundberg et al 2007) and of 60-80 % in MDD patients during at least 3 weeks of escitalopram or citalopram treatment (Baldinger et al 2014;Herold et al 2006;Lanzenberger et al 2012;Lundberg et al 2012;Meyer et al 2004;Smith et al 2011). As the antidepressant action of SSRI treatment is delayed by several weeks, downstream effects, such as desensitization of presynaptic autoreceptors, e.g.…”

Section: Introductionmentioning

confidence: 99%

Serotonin transporter occupancy by escitalopram and citalopram in the non-human primate brain: a [11C]MADAM PET study

et al. 2015

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Escitalopram or citalopram doses nearly saturated SERT in previous monkey studies which examined serotonin sensitivity of receptor radioligands. PET-measured cross-species differential effects of SSRI on cortical serotonin concentration may thus be related to SSRI dose. Future monkey studies using SSRI doses inducing clinically relevant SERT occupancy may further illuminate the delayed onset of SSRI therapeutic effects.

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Regional differences in SERT occupancy after acute and prolonged SSRI intake investigated by brain PET

Cited by 54 publications

References 50 publications

Leptin and the brain: Influences on brain development, cognitive functioning and psychiatric disorders

Leptin and the brain: Influences on brain development, cognitive functioning and psychiatric disorders

Meta-Analysis of Molecular Imaging of Serotonin Transporters in Major Depression

Serotonin transporter occupancy by escitalopram and citalopram in the non-human primate brain: a [11C]MADAM PET study

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