Brain serotonin transporter availability predicts treatment response to selective serotonin reuptake inhibitors

Kugaya, Akira; Sanacora, Gerard; Staley, Julie K.; Malison, Robert T.; Bozkurt, Ali; Khan, Shaukat; Anand, Amit; Dyck, Christopher H. van; Baldwin, Ronald M.; Seibyl, John; Charney, Dennis S.; Innis, Robert B.

doi:10.1016/j.biopsych.2004.07.001

Cited by 69 publications

(49 citation statements)

References 40 publications

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“…This may reflect a lack of difference between the two groups, or may be attributed to the relatively small sample size and heterogeneous treatments administered in this study. The direction of our findings is consistent with a previous report of higher 5-HTT binding predicting a better acute antidepressant response (Kugaya et al, 2004). We extend these previous results by finding differences between non-remitters and controls in previously unexamined brain structures, amygdala and anterior cingulate.…”

Section: Discussionsupporting

confidence: 92%

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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: Discussionsupporting

confidence: 92%

“…A SPECT study of depressed patients using [ 123 I]β-CIT found that higher 5-HTT binding in the diencephalon predicts better acute antidepressant response to selective serotonin reuptake inhibitors (SSRIs) (Kugaya et al, 2004). They also observed a similar trend between brainstem 5-HTT and treatment response.…”

Section: Objectives Of the Studymentioning

confidence: 94%

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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“…Single-photon emission computed tomography and positron emission tomography (PET) studies reported that higher pre-treatment availability and greater SSRI occupancy of the SERT might predict better treatment response (Kugaya et al 2004;Yeh et al 2015). The most confirmed pharmacogenetic finding was an association of the S allele with worse antidepressant efficacy than the LL genotype in Caucasian patients treated with SSRIs (Porcelli et al 2012).…”

Section: Genetic Polymorphismsmentioning

confidence: 99%

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Fabbri

Hosák

Mößner

et al. 2016

The World Journal of Biological Psychiatry

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Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under-or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in anti-depressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4 and HTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (including BDNF, cortisol and soluble TNF-a receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions.

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“…For example, these symptoms resolve after chronic treatment with serotonin reuptake inhibitors (SSRIs), which enhance serotonin transmission by blocking the serotonin transporter (5-HTT). 5-HTT is the molecule responsible for clearing serotonin released in the synapse (Blakely et al, 1994) and alterations in its expression have been linked to mood disorders (Arango et al, 2001;Kugaya et al, 2004). The fact that both OT and serotonin can modulate stress and affiliative responses naturally raises the question of how serotonin might influence the OT system, and the specific brain regions in which this occurs.…”

Section: Introductionmentioning

confidence: 99%

The Interface of Oxytocin-Labeled Cells and Serotonin Transporter-Containing Fibers in the Primate Hypothalamus: A Substrate for SSRIs Therapeutic Effects?

Emiliano

Cruz

Pannoni

et al. 2006

Neuropsychopharmacol

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Oxytocin (OT) is a neuropeptide synthesized in the paraventricular (PVN) and supraoptic nuclei (SON) in the hypothalamus. Although OT is more commonly known for its role in the milk-ejection reflex, in recent years research has indicated that OT participates in the expression of social behavior, memory processing, modulation of fear, and stress responses. The demonstration that OT influences affiliative behaviors, such as parental care and reproduction, and decreases anxiety has lead to speculations that it may have a role in mood disorders. Evidence from pharmacologic studies, pointing out the modulation of the OT system by serotonin, has argued in favor of OT as a mediator of serotonin reuptake inhibitors (SSRIs) antidepressant properties. In the present study, we investigated the distribution and overlap of OT-labeled cells and serotonin transporter (5-HTT) immunoreactive (IR) fibers in the Macaque hypothalamus, utilizing immunocytochemical and double-immunofluorescent techniques. Consistent with previous reports, the distribution of OT-labeled cells in the hypothalamus is confined to the PVN and SON. In these nuclei, we demonstrate that the distribution of 5-HTT-labeled fibers follows the distribution of OT-labeled cells. Overlap of OT-labeled neurons and 5-HTT-IR fibers occurs in the parvicellular, magnocellular, dorsal, and posterior subdivisions of the PVN. In the SON, 5-HTT-labeled fibers and OTlabeled cells overlap in the ventromedial subdivision and in the 'capsular' part of the dorsolateral SON. These findings provide neuroanatomic support for the idea that SSRIs' therapeutic effects on social affiliation and anxiety may be mediated in part through components of the OT system. Neuropsychopharmacology (2007) 32, 977-988.

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Brain serotonin transporter availability predicts treatment response to selective serotonin reuptake inhibitors

Cited by 69 publications

References 40 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

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

The Interface of Oxytocin-Labeled Cells and Serotonin Transporter-Containing Fibers in the Primate Hypothalamus: A Substrate for SSRIs Therapeutic Effects?

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