title: The effects of a HTR2B stop codon and testosterone on energy metabolism and beta cell function among antisocial Finnish males.
abstract: Herein, we examined insulin resistance (IR), insulin sensitivity (IS), beta cell activity, and glucose metabolism in subjects with antisocial personality disorder (ASPD), and 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.
authors.affiliation: Department of Psychiatry, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland; Research and Development, Rinnekoti Foundation, Espoo, Finland. Electronic address: roope.tikkanen@gmail.com.
authors.forename: Roope
authors.initials: R
authors.lastname: Tikkanen
authors.affiliation: Children's Hospital, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland; Novo Nordisk Farma Oy, Espoo, Finland.
authors.forename: Tero
authors.initials: T
authors.lastname: Saukkonen
authors.affiliation: Department of Clinical Science, Lund University Diabetes Center, Scania University Hospital, Malmö, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Fex
authors.affiliation: Department of Clinical Science, Lund University Diabetes Center, Scania University Hospital, Malmö, Sweden.
authors.forename: Hedvig
authors.initials: H
authors.lastname: Bennet
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Rautiainen
authors.affiliation: Department of Psychiatry, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland; National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Paunio
authors.affiliation: Oy Aava Development Ltd., Helsinki, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Koskinen
authors.affiliation: Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: Rony
authors.initials: R
authors.lastname: Panarsky
authors.affiliation: Department of Psychiatry, New York University School of Medicine, New York, NY, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Bevilacqua
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
authors.forename: Rickard L
authors.initials: RL
authors.lastname: Sjöberg
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Tiihonen
authors.affiliation: Department of Psychiatry, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Virkkunen
mesh_terms: D000328:Adult; D000987:Antisocial Personality Disorder / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019540:Area Under Curve; D001786:Blood Glucose / Q000235:genetics; D015992:Body Mass Index; D018388:Codon, Terminator / Q000235:genetics*; D015331:Cohort Studies; D004734:Energy Metabolism / Q000235:genetics*; D005387:Finland; D005951:Glucose Tolerance Test; D006801:Humans; D007211:Indoles / Q000134:cerebrospinal fluid; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D011569:Psychiatric Status Rating Scales; D044403:Receptor, Serotonin, 5-HT2B / Q000235:genetics*; D013739:Testosterone / Q000097:blood*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D018388:Codon, Terminator; D007211:Indoles; D007328:Insulin; D044403:Receptor, Serotonin, 5-HT2B; D013739:Testosterone; C024139:indole-3-lactic acid
keywords: 5-HT2B receptor; ASPD; BMI; HTR2B; Insulin resistance; Testosterone