Summary: A new study indicates that carriers of a specific mutation in the serotonin 2B receptor may have lower risk of obesity and increased insulin sensitivity, which could influence risk for type 2 diabetes.
Source: University of Helsinki.
Researchers at the University of Helsinki report that a point mutation in the serotonin 2B receptor gene (HTR2B Q20*)—previously linked to impulsive and aggressive behaviour—may also protect carriers from obesity and insulin resistance. The finding suggests this genetic variant affects both brain function and energy metabolism.
The study, published in the Journal of Psychiatric Research, examined metabolic measures in a group of 98 Finnish men aged 25–30 who had all been diagnosed with antisocial personality disorder (ASPD). Researchers measured body mass index (BMI), insulin sensitivity, beta cell activity, and glucose metabolism during a five-hour oral glucose tolerance test. They also assessed cerebrospinal fluid levels of the serotonin metabolite 5-hydroxyindoleacetic acid and serum testosterone.
Among these men, nine carried the heterozygous HTR2B Q20* loss-of-function mutation, while 89 did not. Compared with non-carriers, HTR2B Q20* carriers showed lower BMI and higher insulin sensitivity. Non-carriers displayed an insulin resistance–like profile characterized by higher insulin resistance, lower insulin sensitivity, and elevated indices of beta cell activity. In contrast, carriers of the HTR2B stop codon appeared protected from these pathophysiologies.
Importantly, the interaction between the HTR2B Q20* variant and testosterone levels influenced metabolic outcomes. Both the mutation and lower testosterone independently predicted lower BMI. However, in carriers with low testosterone, insulin sensitivity was further increased. This pattern suggests that reduced 5-HT2B receptor function at low or normal testosterone levels may contribute to protection against obesity-related metabolic dysfunction.
The authors note that these effects could have had evolutionary advantages. In a colder, resource-scarce post-Ice Age environment, a combination of higher testosterone and the protective metabolic effect of this mutation might have helped certain men survive on fewer calories while aggression related to higher testosterone could have aided competition for food. In modern societies with abundant nutrition, the mutation’s protective metabolic effect may be particularly relevant for people—especially women—who naturally have lower testosterone.
The researchers caution that the study population consisted solely of young Finnish men with antisocial personality disorder, which limits how broadly the findings can be generalized. Nonetheless, the results raise the possibility that men with antisocial traits in their thirties could represent a group at elevated risk for developing insulin resistance and type 2 diabetes later in life if they do not carry the HTR2B Q20* mutation.
Lead author Roope Tikkanen commented that it is striking for a single receptor mutation to influence both behavioural traits and metabolic regulation. The team plans to extend these findings by analysing larger, population-based datasets—such as FINRISKI—to evaluate the public health implications across Finnish, Swedish, and American cohorts.
Research context and implications
This study connects a genetic variant in the serotonin 2B receptor (5-HT2B) to measurable differences in energy metabolism, BMI, and insulin handling. By linking the HTR2B Q20* stop codon with improved insulin sensitivity and reduced beta cell workload in this cohort, the research opens new avenues for understanding how serotonergic signalling intersects with metabolic health. Any therapeutic or clinical relevance will require replication in broader and more diverse populations, including women and individuals without antisocial personality disorder.
Abstract (rephrased)
This investigation assessed insulin resistance, insulin sensitivity, beta cell function, and glucose metabolism in 98 Finnish males with antisocial personality disorder, stratified by the presence of a heterozygous HTR2B Q20* stop codon (n = 9) or its absence (n = 89). Measurements included a five-hour oral glucose tolerance test, BMI, cerebrospinal fluid 5-hydroxyindoleacetic acid, and serum testosterone. Subjects without the HTR2B Q20* allele exhibited an insulin resistance–like profile (high insulin resistance, low insulin sensitivity, and high beta cell activity). In contrast, carriers of the HTR2B Q20* allele showed lower BMI, reduced beta cell activity, enhanced glucose metabolism, and greater insulin sensitivity—particularly when testosterone levels were low. These findings indicate that reduced 5-HT2B receptor function may be protective against obesity-related metabolic disturbances, though results are specific to this cohort of Finnish males with ASPD and require broader validation.
Study: Roope Tikkanen et al., “The effects of a HTR2B stop codon and testosterone on energy metabolism and beta cell function among antisocial Finnish males,” Journal of Psychiatric Research. Published online June 25, 2016. DOI: 10.1016/j.jpsychires.2016.06.019