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

Emma S Høgsted, Vincent Beliveau, Brice Ozenne, Martin K Madsen, Claus Svarer, Vibeke H Dam, Annette Johansen, Patrick Fisher, Gitte M Knudsen, Vibe G Frokjaer, Anjali Sankar

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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.

OriginalsprogEngelsk
TidsskriftThe British journal of psychiatry : the journal of mental science
Antal sider7
ISSN0960-5371
DOI
StatusE-pub ahead of print - 2024

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