Is desire for social relationships mediated by the serotonergic system in the prefrontal cortex? An [¹⁸F]setoperone PET study

Abstract

Social behavior and desire for social relationships have been independently linked to the serotonergic system, the prefrontal cortex, especially the orbitofrontal cortex (OFC), and the anterior cingulate cortex (ACC). The goal of this study was to explore the role of serotonin 5HT_2A receptors in these brain regions in forming and maintaining close interpersonal relationships. Twenty-four healthy subjects completed the Temperament and Character Inventory (TCI) prior to undergoing [¹⁸F]setoperone brain positron emission tomography (PET) to measure serotonin 5HT_2A receptor availability within the OFC (BA 11 and 47) and ACC (BA 32). We explored the relationship between desire for social relationships, as measured by the TCI reward dependence (RD) scale, and 5HT_2A receptor non-displaceable binding potential (BP_nd) in these regions. Scores of RD were negatively correlated with 5HT_2A BP_nd in the ACC (BA 32, r = –.528, p = .012) and OFC (BA 11, r = –.489, p = .021; BA 47, r = –.501, p = .017). These correlations were corroborated by a voxel-wise analysis. These results suggest that the serotonergic system may have a regulatory effect on the OFC and ACC for establishing and maintaining social relationships.

Keywords:

• Social behavior
• Serotonin
• Serotonin 5HT_2A receptor
• Orbitofrontal cortex
• Anterior cingulate cortex
• Positron emission tomography

The authors thank Penny Baroum, Alan A. Wilson, Armando Garcia, Winston Stableford, Min Wong, Alvina Ng, Terry Bell, Ted Harris-Brandts, and Peter Bloomfield for their expert technical assistance. Funding of the PET camera system HRRT was supported by the Canada Foundation for Innovation, the Ontario Innovation Trust, and the Ontario Research and Development Challenge Fund.

PG, MM, NV, and SH report no biomedical financial interests or potential conflicts of interest. DM has received grants, consultant fees, or other financial support from the Canadian Psychiatric Research Foundation, the Schizophrenia Society of Canada, the Stanley Medical Research Institute, and Bristol-Myers Squibb, and has received speaker's honoraria from AstraZeneca within the past 5 years. SK has received grant support from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, EMD-Darmstadt, GlaxoSmithKlein, Janssen, Neuromolecular Inc., and Pfizer, and has served as a consultant, scientific advisor, or speaker for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKlein, Janssen, Otsuka, Organon, Pfizer, Sanofi-Synthelabo, Servier, and Solvay Wyeth within the past 5 years. BGP serves on the advisory board of Lundbeck Canada and is a faculty member of the Lundbeck International Neuroscience Institute. AG-G has received professional services compensation from Abbott Laboratories and Janssen-Cilag.