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Brain serotonin release is reduced in patients with depression: a [¹¹C]Cimbi-36 Positron Emission Tomography study with a d-amphetamine challenge.

A new article from SARIC researcher Dr Alessandro Colasanti:

Erritzoe, David, Godlewska, Beata R, Rizzo, Gaia, Searle, Graham E, Agnorelli, Claudio, Lewis, Yvonne, Ashok, Abhishekh H, Colasanti, Alessandro, Boura, Iro, Farrell, Chloe, Parfitt, Hollie, Howes, Oliver, Passchier, Jan, Gunn, Roger N, others, , Unset, Unset, Unset and Unset (2022) Brain serotonin release is reduced in patients with depression: a [¹¹C]Cimbi-36 Positron Emission Tomography study with a d-amphetamine challenge. Biological Psychiatry. S0006. ISSN 0006-3223

Abstract:

Background: 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). ΔBPND 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.

https://sro.sussex.ac.uk/id/eprint/112431/

https://www.biologicalpsychiatryjournal.com/article/S0006-3223(22)01704-8/fulltext

Further information: https://sro.sussex.ac.uk/id/eprint/112431/

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