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

Tikkanen, Roope; Saukkonen, Tero; Fex, Malin LU ; Bennet, Hedvig LU ; Rautiainen, Marja Riitta; Paunio, Tiina; Koskinen, Mika; Panarsky, Rony; Bevilacqua, Laura and Sjöberg, Rickard L., et al. (2016) In Journal of Psychiatric Research 81. p.79-86
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... (More)

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.

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publication status
published
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keywords
5-HT2B receptor, ASPD, BMI, HTR2B, Insulin resistance, Testosterone
in
Journal of Psychiatric Research
volume
81
pages
8 pages
publisher
Elsevier
external identifiers
  • Scopus:84978062463
ISSN
0022-3956
DOI
10.1016/j.jpsychires.2016.06.019
language
English
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yes
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7857f1aa-126a-4bb6-ba12-b8382bfd4871
date added to LUP
2016-08-01 11:08:30
date last changed
2016-10-27 13:37:16
@misc{7857f1aa-126a-4bb6-ba12-b8382bfd4871,
  abstract     = {<p>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.</p>},
  author       = {Tikkanen, Roope and Saukkonen, Tero and Fex, Malin and Bennet, Hedvig and Rautiainen, Marja Riitta and Paunio, Tiina and Koskinen, Mika and Panarsky, Rony and Bevilacqua, Laura and Sjöberg, Rickard L. and Tiihonen, Jari and Virkkunen, Matti},
  issn         = {0022-3956},
  keyword      = {5-HT2B receptor,ASPD,BMI,HTR2B,Insulin resistance,Testosterone},
  language     = {eng},
  month        = {10},
  pages        = {79--86},
  publisher    = {ARRAY(0x938a9b8)},
  series       = {Journal of Psychiatric Research},
  title        = {The effects of a HTR2B stop codon and testosterone on energy metabolism and beta cell function among antisocial Finnish males},
  url          = {http://dx.doi.org/10.1016/j.jpsychires.2016.06.019},
  volume       = {81},
  year         = {2016},
}