2022_6_20_CIMBI36 MDE 5HT-Rel_MANUS_V11_FINAL to co-authors_withfigures and supplements.pdf (778.28 kB)
Brain serotonin release is reduced in patients with depression: a [11C]Cimbi-36 Positron Emission Tomography study with a d-amphetamine challenge
journal contribution
posted on 2023-06-10, 07:06 authored by David Erritzoe, Beata R Godlewska, Gaia Rizzo, Graham E Searle, Claudio Agnorelli, Yvonne Lewis, Abhishekh H Ashok, Alessandro ColasantiAlessandro Colasanti, Iro Boura, Chloe Farrell, Hollie Parfitt, Oliver Howes, Jan Passchier, Roger N Gunn, othersBackground: The serotonin hypothesis of depression proposes that diminished serotonergic (5-HT) neurotransmission is causal in the pathophysiology of the disorder. Although the hypothesis is over 50 years old, there is no firm in vivo evidence for diminished 5-HT neurotransmission. We recently demonstrated that the 5-HT2A receptor agonist positron emission tomography (PET) radioligand [11C]Cimbi-36 is sensitive to increases in extracellular 5-HT induced by an acute d-amphetamine challenge. Here we applied [11C]Cimbi-36 PET to compare brain 5-HT release capacity in patients experiencing a major depressive episode (MDE) to that of healthy control subjects (HCs) without depression. Methods: Seventeen antidepressant-free patients with MDE (3 female/14 male, mean age 44 ± 13 years, Hamilton Depression Rating Scale score 21 ± 4 [range 16–30]) and 20 HCs (3 female/17 male, mean age 32 ± 9 years) underwent 90-minute dynamic [11C]Cimbi-36 PET before and 3 hours after a 0.5-mg/kg oral dose of d-amphetamine. Frontal cortex (main region of interest) 5-HT2A receptor nondisplaceable binding was calculated from kinetic analysis using the multilinear analysis-1 approach with the cerebellum as the reference region. Results: Following d-amphetamine administration, frontal nondisplaceable binding potential (BPND) was significantly reduced in the HC group (1.04 ± 0.31 vs. 0.87 ± 0.24, p < .001) but not in the MDE group (0.97 ± 0.25 vs. 0.92 ± 0.22, not significant). ?BPND of the MDE group was significantly lower than that of the HC group (HC: 15% ± 14% vs. MDE: 6.5% ± 20%, p = .041). Conclusions: This first direct assessment of 5-HT release capacity in people with depression provides clear evidence for dysfunctional serotonergic neurotransmission in depression by demonstrating reduced 5-HT release capacity in patients experiencing an MDE.
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Publication status
- Published
File Version
- Accepted version
Journal
Biological PsychiatryISSN
0006-3223Publisher
ElsevierExternal DOI
Page range
S0006Event location
United StatesDepartment affiliated with
- BSMS Neuroscience Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2023-05-19First Compliant Deposit (FCD) Date
2023-05-19Usage metrics
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