The effects of a HTR2B stop codon and testosterone on energy metabolism and beta cell function among antisocial Finnish males

• Published in: Journal of psychiatric research 2016-10, Vol.81, p.79-86
• Main Authors: Tikkanen, Roope, Saukkonen, Tero, Fex, Malin, Bennet, Hedvig, Rautiainen, Marja-Riitta, Paunio, Tiina, Koskinen, Mika, Panarsky, Rony, Bevilacqua, Laura, Sjöberg, Rickard L, Tiihonen, Jari, Virkkunen, Matti
• Format: Article
• Language: English
• Subjects: 5-HT2B receptor; Adult; Antisocial Personality Disorder - genetics; Antisocial Personality Disorder - metabolism; Antisocial Personality Disorder - pathology; Area Under Curve; ASPD; Blood Glucose - genetics; BMI; Body Mass Index; Clinical Medicine; Codon, Terminator - genetics; Cohort Studies; Energy Metabolism - genetics; Finland; Glucose Tolerance Test; HTR2B; Humans; Indoles - cerebrospinal fluid; Insulin - blood; Insulin resistance; Insulin-Secreting Cells - physiology; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Psychiatric Status Rating Scales; Psychiatry; Psykiatri; Receptor, Serotonin, 5-HT2B - genetics; Testosterone; Testosterone - blood; Young Adult
• ISSN: 0022-3956; 1879-1379; 1879-1379
• DOI: 10.1016/j.jpsychires.2016.06.019

Abstract Herein, we examined insulin resistance (IR), insulin sensitivity (IS), beta cell activity, and glucose metabolism in subjects with antisocial personality disorder (ASPD), and (ii) whether the serotonin 2B (5-HT2B) receptor and testosterone have a role in energy metabolism. A cohort of subjects belonging to a founder population that included 98 ASPD males, aged 25–30, was divided into groups based on the presence of a heterozygous 5-HT2B receptor loss-of-function gene mutation ( HTR2B Q20*; n = 9) or not (n = 89). Serum glucose and insulin levels were measured in a 5 h oral glucose tolerance test (75 g) and indices describing IR, IS, and beta cell activity were calculated. Body mass index (BMI) was also determined. Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were measured in cerebrospinal fluid, and testosterone levels from serum. An IR-like state comprising high IR, low IS, and high beta cell activity indices was observed among ASPD subjects without the HTR2B Q20* allele. By contrast, being an ASPD HTR2B Q20* carrier appeared to be preventive of these pathophysiologies. The HTR2B Q20* allele and testosterone predicted lower BMI independently, but an interaction between HTR2B Q20* and testosterone lead to increased insulin sensitivity among HTR2B Q20* carriers with low testosterone levels. The HTR2B Q20* allele also predicted reduced beta cell activity and enhanced glucose metabolism. Reduced 5-HT2B receptor function at low or normal testosterone levels may be protective of obesity. Results were observed among Finnish males having an antisocial personality disorder, which limits the generality.