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Consistent evidence that brain serotonin 2A receptor binding is positively associated with personality-based risk markers of depression

Published online by Cambridge University Press:  05 December 2024

Emma S. Høgsted ,
Vincent Beliveau ,
Brice Ozenne ,
Martin K. Madsen ,
Claus Svarer ,
Vibeke H. Dam ,
Annette Johansen ,
Patrick Fisher ,
Gitte M. Knudsen  and
Vibe G. Frokjaer
...Show all authors
Emma S. Høgsted
Affiliation:
Neurobiology Research Unit, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
Vincent Beliveau
Affiliation:
Neurobiology Research Unit, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark Department of Neurology, Medical University of Innsbruck, Austria
Brice Ozenne
Affiliation:
Neurobiology Research Unit, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark Department of Public Health, Section of Biostatistics, University of Copenhagen, Denmark
Martin K. Madsen
Affiliation:
Neurobiology Research Unit, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
Claus Svarer
Affiliation:
Neurobiology Research Unit, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
Vibeke H. Dam
Affiliation:
Neurobiology Research Unit, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
Annette Johansen
Affiliation:
Neurobiology Research Unit, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
Patrick Fisher
Affiliation:
Neurobiology Research Unit, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark Department of Drug Design and Pharmacology, University of Copenhagen, Denmark
Gitte M. Knudsen
Affiliation:
Neurobiology Research Unit, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark Department of Clinical Medicine, University of Copenhagen, Denmark
Vibe G. Frokjaer
Affiliation:
Neurobiology Research Unit, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark Department of Clinical Medicine, University of Copenhagen, Denmark Mental Health Center Copenhagen, Copenhagen University Hospital – Mental Health Services CPH, Copenhagen, Denmark
Anjali Sankar*
Affiliation:
Neurobiology Research Unit, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
*
Correspondence: Anjali Sankar. Email: anjali.sankar@nru.dk
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Abstract

Background

Using [18F]altanserin, a serotonin 2A receptor (5-HT2AR) antagonist Positron Emission Tomography (PET) tracer, a positive association between cortical 5-HT2AR binding and the inward-directed facets of neuroticism has been demonstrated in healthy individuals. Psilocybin, a 5-HT2AR agonist, shows promise for the treatment of depression, reducing neuroticism and mood symptoms potentially via hypothalamic-pituitary-adrenal (HPA) modulation. 5-HT2AR and neuroticism are both modulated by HPA axis function.

Aims

In this study, we examined whether the association between 5-HT2AR binding and the inward facets of neuroticism can be replicated in an independent healthy cohort using the new 5-HT2AR agonist tracer [11C]Cimbi-36, and if their association is moderated by cortisol awakening response (CAR), an index of HPA axis function. If so, this could advance mechanistic insights into interventions that target the 5-HT2AR and reduce neuroticism.

Method

Eighty healthy volunteers underwent [11C]Cimbi-36 PET scans and completed the NEO personality inventory (NEO-PI-R) for the assessment of neuroticism. Salivary samples were available for determination of CAR in 70 of the participants. Using linear latent variable models, we evaluated the association between 5-HT2AR binding and inward facets of neuroticism, namely depression, anxiety, self-consciousness and vulnerability to stress, and whether CAR moderated this association.

Results

The study confirms the positive association between 5-HT2AR binding and the inward facets of neuroticism (β = 0.01, 95% CI = [0.0005: 0.02], P = 0.04), and this association is independent of CAR (P = 0.33).

Conclusions

The findings prompt consideration of whether novel interventions such as psilocybin that actively targets 5-HT2AR and causes changes in personality could be particularly beneficial if implemented as a targeted approach based on neuroticism profiles.

Keywords

Serotonin 2A receptorneuroticismcortisolpositron-emission tomographylatent variable modelling
Type
Original Article
Information
The British Journal of Psychiatry , Volume 226 , Issue 3 , March 2025 , pp. 137 - 143
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Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of Royal College of Psychiatrists

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Footnotes

*

Joint last authors.

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