ArticleGenes, brain, and behavior2010
TPH2 5'- and 3'-regulatory polymorphisms are differentially associated with HPA axis function and self-injurious behavior in rhesus monkeys.
Article in Genes, brain, and behavior, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- A Rhesus Monkey Model of Non-suicidal Self-Injury.Frontiers in behavioral neuroscience · 2021Review
- Proopiomelanocortin (POMC) sequencing and developmental delay: Preliminary evidence for a SNP in the 3' UTR region of the POMC gene-Possible relevance for biological risk and self-injurious behavior.Development and psychopathology · 2019Article
- Rhesus macaques (Applied animal behaviour science · 2017Article
- Early life environmental and pharmacological stressors result in persistent dysregulations of the serotonergic system.Frontiers in behavioral neuroscience · 2015Article
- Self-injurious behaviour in autistic children: a neuro-developmental theory of social and environmental isolation.Psychopharmacology · 2014Review
- Use of the cross-translational model to study self-injurious behavior in human and nonhuman primates.ILAR journal · 2014Article
- Tryptophan hydroxylase-2: an emerging therapeutic target for stress disorders.Biochemical pharmacology · 2013Article
- Stress, the HPA axis, and nonhuman primate well-being: A review.Applied animal behaviour science · 2013Article
- Genetic origins of social networks in rhesus macaques.Scientific reports · 2013Article
- Genetic load is associated with hypothalamic-pituitary-adrenal axis dysregulation in macaques.Genes, brain, and behavior · 2012Article
- Targeting brain serotonin synthesis: insights into neurodevelopmental disorders with long-term outcomes related to negative emotionality, aggression and antisocial behaviour.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2012Review
- Advances in tryptophan hydroxylase-2 gene expression regulation: new insights into serotonin-stress interaction and clinical implications.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2012Review
- Early Prevention of Severe Neurodevelopmental Behavior Disorders: An Integration.Journal of mental health research in intellectual disabilities · 2012Article
- An effort to use human-based exome capture methods to analyze chimpanzee and macaque exomes.PloS one · 2012Article
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
Tryptophan hydroxylase-2 (TPH2) synthesizes neuronal serotonin and is linked to numerous behavioral traits. We have previously characterized the functionality of polymorphisms (especially 2051A>C) in 3'-untranslated region (3'-UTR) of rhesus monkey TPH2 (rhTPH2). This study further assessed the functionality of additional polymorphisms (-1605T>C, -1491Tn, -1485(AT)n, -1454A>G, -1325In>Del and -363T>G) in rhTPH2 5'-flanking region (5'-FR), and evaluated the effects of rhTPH2 5' and 3' genotypes on central serotonin turnover, hypothalamic-pituitary-adrenal (HPA) axis function and self-injurious behavior (SIB) in 32 unrelated adult male monkeys of Indian origin. Haplotypes of the rhTPH2 5'-FR polymorphisms exert a significant, cell-dependent effect on reporter gene expression, primarily conferred by -1485(AT)n. The -1485(AT)n and 2051A>C polymorphisms interact to influence cerebrospinal fluid (CSF) 5-HIAA and plasma adrenocorticotropic hormone (ACTH) in the afternoon. While -1485(AT)n exerts significant main effects on the afternoon cortisol level and nocturnal HPA negative feedback, 2051A>C has significant main effects on the morning cortisol level and cortisol response to ACTH challenge, as well as marginally significant main effects on the daytime HPA negative feedback and self-biting rate. In addition, the genotype/allele frequency of the 5'-FR -1325Ins>Del differed significantly between the self-wounders and non-wounders, whereas 3'-UTR 2128S>L polymorphism differed significantly in genotype/allele frequency between the high- and low-frequency biters. This study shows the functionality of rhTPH2 5'-FR polymorphisms, and provides evidence for the differential association of rhTPH2 5'-FR and 3'-UTR polymorphisms with HPA axis function and SIB. Our findings shed light on the role of TPH2 gene variance in physiology and behavioral traits, and also contribute to the understanding of the pathophysiology and genetics of SIB.
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