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 M. Fisher, Gitte M. Knudsen, Vibe G. Frøkjær, Anjali Sankar
The British Journal of Psychiatry December 5, 2024 DOI: 10.1192/bjp.2024.143 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 80 |
| Population | Healthy volunteers |
| Topics | Depression Serotonin |
| Keywords | Personality research Neuroimaging Serotonin 2a receptor Cortisol Latent variable modelling Neuroticism Positron-emission tomography Mental health Brain chemistry |
| Citations | 4 |
| Key findings | Serotonin 2A receptor binding is positively associated with inward facets of neuroticism, and this association is not moderated by cortisol awakening response. |
Abstract
Background: Using [ 18 F]altanserin, a serotonin 2A receptor (5-HT 2A R) antagonist Positron Emission Tomography (PET) tracer, a positive association between cortical 5-HT 2A R binding and the inward-directed facets of neuroticism has been demonstrated in healthy individuals. Psilocybin, a 5-HT 2A R agonist, shows promise for the treatment of depression, reducing neuroticism and mood symptoms potentially via hypothalamic-pituitary-adrenal (HPA) modulation. 5-HT 2A R and neuroticism are both modulated by HPA axis function.
Aims: In this study, we examined whether the association between 5-HT 2A R binding and the inward facets of neuroticism can be replicated in an independent healthy cohort using the new 5-HT 2A R agonist tracer [ 11 C]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-HT 2A R and reduce neuroticism.
Method: Eighty healthy volunteers underwent [ 11 C]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-HT 2A R 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-HT 2A R 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-HT 2A R and causes changes in personality could be particularly beneficial if implemented as a targeted approach based on neuroticism profiles.
Comparable studies
Other observational and cohort studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Healthy volunteers | 2019 | Observational cohort | n = 8 |
| Memory impairment in abstinent MDMA ("Ecstasy") users Abstinent MDMA users | 1998 | Observational cohort | |
| Dynamic coupling of whole-brain neuronal and neurotransmitter systems Healthy humans | 2020 | Observational study | |
| The Serotonin System and Spiritual Experiences Normal male subjects, ages 20-45 years | 2003 | Observational cohort | n = 15 |
| Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD. Healthy human participants | 2018 | Observational study with computational modeling |
Citations in the library
Cites 5
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- Effects of psilocybin therapy on personality structure Acta Psychiatrica Scandinavica June 19, 2018
- Serotonin 2A receptors are a stress response system: implications for post-traumatic stress disorder. Behavioural Pharmacology April 1, 2019
- Psilocybin induces acute and persisting alterations in immune status in healthy volunteers: An experimental, placebo-controlled study Brain, Behavior, and Immunity September 7, 2023
- 5-HT2A Receptors Stimulate ACTH, Corticosterone, Oxytocin, Renin, and Prolactin Release and Activate Hypothalamic CRF and Oxytocin-Expressing Cells Journal of Neuroscience May 15, 2001