The association between brain serotonin 2A receptor binding and neuroticism in healthy individuals: A Cimbi database independent replication study

Hogsted, E. S.; Beliveau, V.; Ozenne, B.; Madsen, M. K.; Svarer, C.; Dam, V. N. H.; Johansen, A.; Fisher, P. M.; Knudsen, G. M.; Frokjaer, V. G.; Sankar, A.

doi:10.1101/2023.08.24.554575

bioRxiv · 10.1101/2023.08.24.554575

The association between brain serotonin 2A receptor binding and neuroticism in healthy individuals: A Cimbi database independent replication study

Hogsted, E. S.·Beliveau, V.·Ozenne, B.·Madsen, M. K.·Svarer, C.·Dam, V. N. H.·Johansen, A.·Fisher, P. M.·Knudsen, G. M.·Frokjaer, V. G.·Sankar, A.

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Abstract

BackgroundUsing the [18F]altanserin tracer to image serotonin 2A receptors (5-HT2AR), we previously showed that there exists a positive association between cortical 5-HT2AR binding and the inward facets of neuroticism, namely depression, anxiety, self-consciousness, and vulnerability. Fairly recently, the [11C]Cimbi-36 tracer was also shown to be a suitable radioligand for imaging 5-HT2A receptors in the human brain. In the present study, we examined whether our previously reported finding of the association between 5-HT2AR binding and the inward facets of neuroticism can be replicated in an independent sample of healthy individuals scanned using the newer [11C]Cimbi-36 tracer. Furthermore, to determine whether this association of 5-HT2AR binding with neuroticism merely reflects its known relation to stress-coping related indices such as cortisol dynamics. The present study also investigated the potential role of cortisol awakening response on the association between 5-HT2AR binding and the inward facets of neuroticism. MethodsSixty-nine healthy volunteers underwent a [11C]CIMBI-36 scan for the assessment of 5-HT2AR binding, completed the standardized NEO-PI-R personality questionnaire, and provided salivary samples for the determination of cortisol awakening response. A linear latent variable model (LVM) was used to examine the association between 5-HT2AR binding and the inward facets of neuroticism with adjustment for age, sex, cortisol awakening response, and MR scanner. A second latent variable model examined the potential moderating effect of cortisol awakening response on the association between 5-HT2AR binding and the inward facets of neuroticism. ResultsWe replicated a positive association between 5-HT2AR binding and the inward facets of neuroticism (r=0.37, p=0.015). We saw no moderating effect of the cortisol awakening response on this association (p=0.98). ConclusionsIn an independent cohort of healthy individuals imaged with the [11C]CIMBI-36 tracer, we confirm the link between serotonin 2A receptor binding and the inward-directed facets of neuroticism that is independent of cortisol dynamics.

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Hogsted, E. S., Beliveau, V., Ozenne, B., Madsen, M. K., Svarer, C., Dam, V. N. H., Johansen, A., Fisher, P. M., Knudsen, G. M., Frokjaer, V. G., Sankar, A.. 2023-08-26. The association between brain serotonin 2A receptor binding and neuroticism in healthy individuals: A Cimbi database independent replication study. https://doi.org/10.1101/2023.08.24.554575

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