Turecki G, Briere R, Dewar K, Antonetti T, Lesage AD, Seguin M et al. Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide. Am J Psychiatry 156: 1456-1458
Postmortem studies have indicated that suicide victims have greater serotonin receptor 2A (5-HTR2A) binding in prefrontal brain regions. However, there remains some controversy regarding the biological specificity of these findings. The authors hypothesized that the variance observed in brain 5-HTR2A binding is genetically mediated, at least in part.
Postmortem data from 56 subjects who had committed suicide and 126 normal comparison subjects were studied; brain tissue was available from 11 subjects who committed suicide and 11 comparison subjects. Homogenate binding assays were carried out with [3H]ketanserin. Variation at the 5-HTR2A gene (HTR2A) was investigated by means of two polymorphisms: T102C and A-1438G.
5-HTR2A binding was greater in the prefrontal cortex of the subjects who committed suicide. In addition, the findings suggest that HTR2A variation significantly affects 5-HTR2A binding. However, no interaction between suicidal behavior and this locus was observed.
These results confirm previous reports of greater 5-HTR2A binding in subjects who committed suicide; they also provide preliminary evidence suggesting that the number of 5-HTR2A receptors is genetically mediated.
Available from: Pingyuan Gong
- "The expression of HTR2A is regulated by several functional polymorphisms (Polesskaya and Sokolov, 2002; Myers et al., 2007), among which T102C (rs6313) is the most studied single nucleotide polymorphism in the gene. Compared with the T allele, the C allele leads to lower receptor expressions (Polesskaya and Sokolov, 2002) and lower receptor binding potentials (Turecki et al., 1999), and therefore reduces excitation at post-synaptic neurons (Aghajanian and Marek, 1997). "
[Show abstract] [Hide abstract]
ABSTRACT: Previous studies have indicated that empathic traits, such as perspective taking, are associated with the levels of serotonin in the brain and with autism spectrum conditions. Inspired by the finding that the serotonin receptor 2A gene (HTR2A) modulates the availability of serotonin, this study investigated to what extent HTR2A modulates individuals' perspective taking ability and autistic-like traits. To examine the associations of the functional HTR2A polymorphism T102C (rs6313) with individuals' perspective taking abilities and autistic-like traits, we differentiated individuals according to this polymorphism and measured empathic and autistic-like traits with Interpersonal Reactivity Index (IRI) and Autism-Spectrum Quotient (AQ) scale in 523 Chinese people. The results indicated that this polymorphism was significantly associated with the scores on Perspective Taking and Personal Distress subscales of IRI, and Communication subscale of AQ. Individuals with a greater number of the C alleles were less likely to spontaneously adopt the point of view of others, more likely to be anxious when observing the pain endured by others, and more likely to have communication problems. Moreover, the genotype effect on communication problems was mediated by individuals' perspective taking ability. These findings provide evidence that the HTR2A T102C polymorphism is a predictor of individual differences in empathic and autistic-like traits and highlight the role of the gene in the connection between perspective taking and autistic-like traits.
Available from: Won Je Jeon
- "The serotonin 2A receptor (HTR2A) is particularly abundant in the mammalian cortex (Pazos et al., 1987), is important in controlling cortical functions (Nichols, 2009) and is responsive to changes in serotonergic activity (Rioux et al., 1999). Hence, reports of higher levels of cortical HTR2A levels in major depressive disorder (MDD) (Hrdina et al., 1993; Shelton et al., 2009) and suicide (Stanley and Mann, 1983; Mann et al., 1986; Arora and Meltzer, 1989; Arango et al., 1990; Hrdina et al., 1993; Turecki et al., 1999; Escriba et al., 2004) as well as lower levels of expression of that receptor in bipolar disorder (BD) (Lopez-Figueroa et al., 2004) support a role for the HTR2A in both mood disorders and suicide. However, such a hypothesis needs to be tempered by reports showing levels of HTR2A are not changed in either MDD (Crow et al., 1984; Cheetham et al., 1988; Arranz et al., 1994; Lowther et al., 1994; Stockmeier et al., 1997) or suicide (Owen et al., 1983; Crow et al., 1984; Cheetham et al., 1988; Arranz et al., 1994; Lowther et al., 1994; Stockmeier et al., 1997; Lopez-Figueroa et al., 2004; Rosel et al., 2004; Oquendo et al., 2006; Underwood et al., 2012). "
[Show abstract] [Hide abstract]
ABSTRACT: We have attempted to replicate studies showing higher levels of serotonin 2A receptors (HTR2A) in the cortex of people with mood disorders and to determine the effects of treating rats with antidepressant drugs on levels of that receptor. In situ [3H]ketanserin binding and autoradiography was used to measure levels of HTR2A in Brodmann's area (BA) 46 and 24 from people with major depressive disorders (MDD, n = 16), bipolar disorders (BD, n = 14) and healthy controls (n = 14) as well as the central nervous system (CNS) of rats (20 per treatment arm) treated for 10 or 28 d with fluoxetine (10 mg/kg/d) or imipramine (20 mg/kg/d). Compared with controls, HTR2A were lower in BA 24, but not BA 46, from people with MDD (p = 0.005); HTR2A were not changed in BD. Levels of HTR2A were lower in BA 24 (p = 0.007), but not BA 46, from people who had died by suicide. Finally, levels of HTR2A were lower in the CNS of rats treated with imipramine, but not fluoxetine, for 28 d, but not 10 d. From our current and previous data we conclude cortical HTR2A are lower in schizophrenia, MDD, people with mood disorders who died by suicide, rats treated with some antipsychotic or some antidepressant drugs. As levels of cortical HTR2A can be affected by the aetiologies of different disorders and mechanisms of action of different drugs, a better understanding of how such changes can occur needs to be elucidated.
Available from: John T Cacioppo
- "c o m / l o c a t e / p a i d functional polymorphisms in the HTR1A and HTR2A receptor genes are widely studied with respect to their association with affective responses. The C/C genotype of 102T>C (rs6313) in the HTR2A gene has been shown to be related to reduced post-synaptic serotonin receptor expression (Myers, Airey, Manier, Shelton, & Sanders- Bush, 2007; Turecki et al., 1999), increased levels of impulsivity (Bjork et al., 2002; Jakubczyk et al., 2012) and aggression (Hwu & Chen, 2000), and more frequent suicidal ideation (Du, Bakish, Lapierre , Ravindran, & Hrdina, 2000). In the HTR1A gene, the G allele of the functional SNP 1019C>G (rs6295) is associated with higher expression of pre-synaptic receptors, suicide (Lemonde et al., 2003), neuroticism (Strobel et al., 2003), susceptibility to depression (Parsey et al., 2006; Yu, Tsai, Liou, Hong, & Chen, 2006), responses to threatening stimuli (Mekli et al., 2011), and increased levels of impulsivity (Benko et al., 2010). "
[Show abstract] [Hide abstract]
ABSTRACT: Individual differences in the evaluation of affective stimuli, such as the positivity offset and negativity bias may have a biological basis. We tested whether two SNPs (HTR2A; 102T>C and HTR1A; 1019C>G) related to serotonin receptor function, a biological pathway associated with affective regulation, were differentially related to positivity offset and negativity bias for males and females. Participants were 109 cigarette smokers who rated a series of affective stimuli to assess reactions to positive and negative pictures. Gender × genotype interactions were found for both SNPs. Males with the 102T allele showed a greater positivity offset than males with the 102C allele. For females, in contrast, the 1019C allele was associated with a greater positivity offset than the 1019G allele, whereas the 102T allele was associated with a greater negativity bias than the 102C allele. Identifying how gender differences may moderate the effect of serotonin receptor genes on affective information processing may provide insight into their role in guiding behavior and regulating affect.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.