Frokjaer, V. G. | Search bioRxiv

bioRxiv2023

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

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.

neuroscience↗

bioRxiv2019

Chronic paroxetine blunts stress response and normalizes adverse behavioral effects seen acutely in nulliparous rats

Selective serotonin reuptake inhibitors (SSRI) are widely used antidepressants and their effect is partly mediated by restoring stress axis dynamics, which may depend on sex and hormonal states. In the present study, we investigate the effect of daily injections of the SSRI paroxetine (5 mg/kg s.c.) on swim stress-induced corticosterone (CORT) response, depressive-like behavior (forced swim test) and anxiety-like behavior (open field test) in nulliparous Sprague Dawley rats. Data were acquired after either 1-3 (acute PXT) or 11-13 (chronic PXT) injections. We found that chronic, but not acute, paroxetine blunted the swim stress-induced CORT response. We observed an increase in depressive-like and anxiety-like behavior following acute PXT, and a normalization after chronic PXT treatment. Intriguingly, our findings of rapid recovery from adverse SSRI effects differ from corresponding studies performed by our group in postpartum rats. Thus, the study emphasizes that mechanisms of action and efficacy of SSRIs differ according to reproductive states, which if translated to humans may inform treatment strategies, beyond SSRIs alone, for hormone transition related depressive states.

neuroscience↗