{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The serotonin receptor 1B (HTR1B) gene encodes a G protein–coupled receptor that exerts diverse actions through its role as both a presynaptic autoreceptor and a postsynaptic heteroreceptor. Its activation modulates serotonin release and downstream signaling across multiple tissues. In the brain, genetic studies have implicated HTR1B in neuropsychiatric conditions: associations with attention‐deficit/hyperactivity disorder—in particular, with the inattentive subtype—and with substance abuse and depressive phenotypes have been observed, with evidence of parent‐of‐origin effects in transmission of specific alleles."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition, altered expression of HTR1B mRNA has been reported in conditions such as bipolar disorder and schizophrenia"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", and functional studies have shown that regulation of receptor trafficking by interacting proteins (for example, p11) is critical for mediating antidepressant effects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Outside the central nervous system, activation of the HTR1B receptor plays a role in peripheral physiology; for instance, gut‐derived serotonin binds to HTR1B on osteoblasts and, via downstream effectors such as CREB, inhibits their proliferation leading to reduced bone formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, promoter polymorphisms (including the G861C and A–161T variants) have been shown to modulate HTR1B transcription, with these regulatory changes being associated with alcohol dependence and possibly other behavioral phenotypes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, experimental models with spatially and temporally regulated HTR1B expression have revealed dissociable functions: early postnatal receptor expression in the forebrain is linked to the development of neural circuits underlying adult aggression, whereas receptor expression during adulthood modulates impulsivity—at least in part via regulation of dopamine release in the nucleus accumbens."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Taken together, these findings indicate that HTR1B plays a multifaceted role in regulating serotonergic signaling that impacts behavioral regulation, mood, and peripheral processes such as bone homeostasis. Genetic variability and promoter regulation of HTR1B underscore its contribution to the susceptibility and pathophysiology of several neuropsychiatric disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ian R Gizer, Courtney Ficks, Irwin D Waldman "}, {"type": "b", "children": [{"type": "t", "text": "Candidate gene studies of ADHD: a meta-analytic review."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-009-0694-x"}], "href": "https://doi.org/10.1007/s00439-009-0694-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19506906"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19506906"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "J F Quist, C L Barr, R Schachar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.mp.4001244"}], "href": "https://doi.org/10.1038/sj.mp.4001244"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12556913"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12556913"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jordan W Smoller, Joseph Biederman, Lori Arbeitman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between the 5HT1B receptor gene (HTR1B) and the inattentive subtype of ADHD."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Psychiatry (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopsych.2005.07.017"}], "href": "https://doi.org/10.1016/j.biopsych.2005.07.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16197923"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16197923"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Antonio L López-Figueroa, Camille S Norton, Manuel O López-Figueroa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serotonin 5-HT1A, 5-HT1B, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Psychiatry (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopsych.2003.09.017"}], "href": "https://doi.org/10.1016/j.biopsych.2003.09.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14744462"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14744462"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jennifer L Warner-Schmidt, Marc Flajolet, Abigail Maller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of p11 in cellular and behavioral effects of 5-HT4 receptor stimulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.5343-08.2009"}], "href": "https://doi.org/10.1523/JNEUROSCI.5343-08.2009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19211900"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19211900"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Vijay K Yadav, Je-Hwang Ryu, Nina Suda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2008.09.059"}], "href": "https://doi.org/10.1016/j.cell.2008.09.059"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19041748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19041748"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yung-yu Huang, Maria A Oquendo, Jill M Harkavy Friedman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Substance abuse disorder and major depression are associated with the human 5-HT1B receptor gene (HTR1B) G861C polymorphism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropsychopharmacology (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.npp.1300000"}], "href": "https://doi.org/10.1038/sj.npp.1300000"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12496953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12496953"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hsiao Fang Sunny Sun, Yuh Terng Chang, Cathy Shen-Jang Fann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association study of novel human serotonin 5-HT(1B) polymorphisms with alcohol dependence in Taiwanese Han."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Psychiatry (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-3223(01)01366-x"}], "href": "https://doi.org/10.1016/s0006-3223(01"}, {"type": "t", "text": "01366-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12022963"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12022963"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "J Duan, A R Sanders, J E Vander Molen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms in the 5'-untranslated region of the human serotonin receptor 1B (HTR1B) gene affect gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.mp.4001403"}], "href": "https://doi.org/10.1038/sj.mp.4001403"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14593427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14593427"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Katherine M Nautiyal, Kenji F Tanaka, Mary M Barr, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct Circuits Underlie the Effects of 5-HT1B Receptors on Aggression and Impulsivity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2015.03.041"}], "href": "https://doi.org/10.1016/j.neuron.2015.03.041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25892302"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25892302"}]}]}]}