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Serotonin 1A Receptor Binding of [(11)C]CUMI-101 in Bipolar Depression Quantified Using Positron Emission Tomography: Relationship to Psychopathology and Antidepressant Response

BACKGROUND: The pathophysiology of bipolar disorder (BD) remains largely unknown despite it causing significant disability and suicide risk. Serotonin signaling may play a role in the pathophysiology, but direct evidence for this is lacking. Treatment of the depressed phase of the disorder is limite...

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Autores principales: Lan, Martin J, Zanderigo, Francesca, Pantazatos, Spiro P, Sublette, M Elizabeth, Miller, Jeffrey, Ogden, R Todd, Mann, J John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352178/
https://www.ncbi.nlm.nih.gov/pubmed/34996114
http://dx.doi.org/10.1093/ijnp/pyac001
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author Lan, Martin J
Zanderigo, Francesca
Pantazatos, Spiro P
Sublette, M Elizabeth
Miller, Jeffrey
Ogden, R Todd
Mann, J John
author_facet Lan, Martin J
Zanderigo, Francesca
Pantazatos, Spiro P
Sublette, M Elizabeth
Miller, Jeffrey
Ogden, R Todd
Mann, J John
author_sort Lan, Martin J
collection PubMed
description BACKGROUND: The pathophysiology of bipolar disorder (BD) remains largely unknown despite it causing significant disability and suicide risk. Serotonin signaling may play a role in the pathophysiology, but direct evidence for this is lacking. Treatment of the depressed phase of the disorder is limited. Previous studies have indicated that positron emission tomography (PET) imaging of the serotonin 1A receptor (5HT1AR) may predict antidepressant response. METHODS: A total of 20 participants with BD in a current major depressive episode and 16 healthy volunteers had PET imaging with [(11)C]CUMI-101, employing a metabolite-corrected input function for quantification of binding potential to the 5HT1AR. Bipolar participants then received an open-labeled, 6-week clinical trial with a selective serotonin reuptake inhibitor (SSRI) in addition to their mood stabilizer. Clinical ratings were obtained at baseline and during SSRI treatment. RESULTS: Pretreatment binding potential (BP(F)) of [(11)C]CUMI-101 was associated with a number of pretreatment clinical variables within BD participants. Within the raphe nucleus, it was inversely associated with the baseline Montgomery Åsberg Rating Scale (P = .026), the Beck Depression Inventory score (P = .0023), and the Buss Durkee Hostility Index (P = .0058), a measure of lifetime aggression. A secondary analysis found [(11)C]CUMI-101 BP(F) was higher in bipolar participants compared with healthy volunteers (P = .00275). [(11)C]CUMI-101 BP(F) did not differ between SSRI responders and non-responders (P = .907) to treatment and did not predict antidepressant response (P = .580). Voxel-wise analyses confirmed the results obtained in regions of interest analyses. CONCLUSIONS: A disturbance of serotonin system function is associated with both the diagnosis of BD and its severity of depression. Pretreatment 5HT1AR binding did not predict SSRI antidepressant outcome. The study was listed on clinicaltrials.gov with identifier NCT02473250.
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spelling pubmed-93521782022-08-05 Serotonin 1A Receptor Binding of [(11)C]CUMI-101 in Bipolar Depression Quantified Using Positron Emission Tomography: Relationship to Psychopathology and Antidepressant Response Lan, Martin J Zanderigo, Francesca Pantazatos, Spiro P Sublette, M Elizabeth Miller, Jeffrey Ogden, R Todd Mann, J John Int J Neuropsychopharmacol Regular Research Articles BACKGROUND: The pathophysiology of bipolar disorder (BD) remains largely unknown despite it causing significant disability and suicide risk. Serotonin signaling may play a role in the pathophysiology, but direct evidence for this is lacking. Treatment of the depressed phase of the disorder is limited. Previous studies have indicated that positron emission tomography (PET) imaging of the serotonin 1A receptor (5HT1AR) may predict antidepressant response. METHODS: A total of 20 participants with BD in a current major depressive episode and 16 healthy volunteers had PET imaging with [(11)C]CUMI-101, employing a metabolite-corrected input function for quantification of binding potential to the 5HT1AR. Bipolar participants then received an open-labeled, 6-week clinical trial with a selective serotonin reuptake inhibitor (SSRI) in addition to their mood stabilizer. Clinical ratings were obtained at baseline and during SSRI treatment. RESULTS: Pretreatment binding potential (BP(F)) of [(11)C]CUMI-101 was associated with a number of pretreatment clinical variables within BD participants. Within the raphe nucleus, it was inversely associated with the baseline Montgomery Åsberg Rating Scale (P = .026), the Beck Depression Inventory score (P = .0023), and the Buss Durkee Hostility Index (P = .0058), a measure of lifetime aggression. A secondary analysis found [(11)C]CUMI-101 BP(F) was higher in bipolar participants compared with healthy volunteers (P = .00275). [(11)C]CUMI-101 BP(F) did not differ between SSRI responders and non-responders (P = .907) to treatment and did not predict antidepressant response (P = .580). Voxel-wise analyses confirmed the results obtained in regions of interest analyses. CONCLUSIONS: A disturbance of serotonin system function is associated with both the diagnosis of BD and its severity of depression. Pretreatment 5HT1AR binding did not predict SSRI antidepressant outcome. The study was listed on clinicaltrials.gov with identifier NCT02473250. Oxford University Press 2022-01-06 /pmc/articles/PMC9352178/ /pubmed/34996114 http://dx.doi.org/10.1093/ijnp/pyac001 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of CINP. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Regular Research Articles
Lan, Martin J
Zanderigo, Francesca
Pantazatos, Spiro P
Sublette, M Elizabeth
Miller, Jeffrey
Ogden, R Todd
Mann, J John
Serotonin 1A Receptor Binding of [(11)C]CUMI-101 in Bipolar Depression Quantified Using Positron Emission Tomography: Relationship to Psychopathology and Antidepressant Response
title Serotonin 1A Receptor Binding of [(11)C]CUMI-101 in Bipolar Depression Quantified Using Positron Emission Tomography: Relationship to Psychopathology and Antidepressant Response
title_full Serotonin 1A Receptor Binding of [(11)C]CUMI-101 in Bipolar Depression Quantified Using Positron Emission Tomography: Relationship to Psychopathology and Antidepressant Response
title_fullStr Serotonin 1A Receptor Binding of [(11)C]CUMI-101 in Bipolar Depression Quantified Using Positron Emission Tomography: Relationship to Psychopathology and Antidepressant Response
title_full_unstemmed Serotonin 1A Receptor Binding of [(11)C]CUMI-101 in Bipolar Depression Quantified Using Positron Emission Tomography: Relationship to Psychopathology and Antidepressant Response
title_short Serotonin 1A Receptor Binding of [(11)C]CUMI-101 in Bipolar Depression Quantified Using Positron Emission Tomography: Relationship to Psychopathology and Antidepressant Response
title_sort serotonin 1a receptor binding of [(11)c]cumi-101 in bipolar depression quantified using positron emission tomography: relationship to psychopathology and antidepressant response
topic Regular Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352178/
https://www.ncbi.nlm.nih.gov/pubmed/34996114
http://dx.doi.org/10.1093/ijnp/pyac001
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