ABSTRACT Background Using the [ 18 F]altanserin tracer to image serotonin 2A receptors (5-HT 2A R), we previously showed that there exists a positive association between cortical 5-HT 2A R binding and the inward facets of neuroticism, namely depression, anxiety, self-consciousness, and vulnerability. Fairly recently, the [ 11 C]Cimbi-36 tracer was also shown to be a suitable radioligand for imaging 5-HT 2A receptors in the human brain. In the present study, we examined whether our previously reported finding of the association between 5-HT 2A R 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-HT 2A R 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-HT 2A R binding and the inward facets of neuroticism. Methods Sixty-nine healthy volunteers underwent a [ 11 C]CIMBI-36 scan for the assessment of 5-HT 2A R 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-HT 2A R 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-HT 2A R binding and the inward facets of neuroticism. Results We replicated a positive association between 5-HT 2A R 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). Conclusions In an independent cohort of healthy individuals imaged with the [ 11 C]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.

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