TPH2 gene polymorphisms and bipolar disorder: A meta‐analysis

Gao, Jin; Jia, Mingrui; Qiao, Dan; Qiu, Hui-Min; Sokolove, Jeremy; Zhang, Jingxuan; Pan, Zhencun

doi:10.1002/ajmg.b.32381

Cited by 14 publications

(7 citation statements)

References 32 publications

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“…Supporting this proposal, a recent meta-analysis confirmed two gene SNPs related to the production of tryptophan hydroxylase-2, a rate-limiting enzyme for 5HT in the brain, are consistently associated with the development of bipolar disorder. 196 However, existing PET and SPECT imaging evidence has not yet substantiated the permissive hypothesis. It appears that there is a variability in SERT availability across mood states in BD.…”

Section: Pet and Spect Literature: Bdmentioning

confidence: 99%

Neurobiology of Chronic Stress-Related Psychiatric Disorders: Evidence from Molecular Imaging Studies

et al. 2017

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Chronic stress accounts for billions of dollars of economic loss annually in the United States alone, and is recognized as a major source of disability and mortality worldwide. Robust evidence suggests that chronic stress plays a significant role in the onset of severe and impairing psychiatric conditions, including major depressive disorder, bipolar disorder, and posttraumatic stress disorder. Application of molecular imaging techniques such as positron emission tomography and single photon emission computed tomography in recent years has begun to provide insight into the molecular mechanisms by which chronic stress confers risk for these disorders. The present paper provides a comprehensive review and synthesis of all positron emission tomography and single photon emission computed tomography imaging publications focused on the examination of molecular targets in individuals with major depressive disorder, posttraumatic stress disorder, or bipolar disorder to date. Critical discussion of discrepant findings and broad strengths and weaknesses of the current body of literature is provided. Recommended future directions for the field of molecular imaging to further elucidate the neurobiological substrates of chronic stress-related disorders are also discussed. This article is part of the inaugural issue for the journal focused on various aspects of chronic stress.

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Section: Pet and Spect Literature: Bdmentioning

confidence: 99%

Neurobiology of Chronic Stress-Related Psychiatric Disorders: Evidence from Molecular Imaging Studies

et al. 2017

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“…Other investigations revealed several polymorphisms associated with genes such as TPH1 (Tryptophan Hydroxylase 1), BDNF (Brain Derived Neurotrophic Factor), DAO (D-Amino Acid Oxidase), DRD4 (Dopamine Receptor D4) etc. have been also reported [79]. To further understand the genetics associated with the disease, large cohort based GWAS studies involving 40,000 individuals have been conducted [80].…”

Section: Gwas In Bipolar Disordermentioning

confidence: 99%

Neurology in the Light of Genomics: Application of NGS and GWAS in Understanding Complex Neurological Disorders

Banerjee¹,

Arora²

2018

Neuropsychiatry

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Understanding structure and function of human brain remains the most intriguing region of advanced research. Neurological disorders also constitute a major proportion of ongoing brain associated research as several disorders are still not known in a comprehensive manner from a molecular, causative and functional perspective. Earlier linkage studies were considered the most reliable means to answer certain neurogenetics related questions in relevance to heredity and disease inheritance. Technical limitations and ethical issues always hindered the path of deriving more useful insight and understanding neurological diseases such as Schizophrenia, Epilepsy, Parkinson's disease, Alzheimer's disease, Bipolar Disorder, ADHD, ALS and other neurological issues. Improvement in the interdisciplinary approaches including genomics based analyses such as NGS, GWAS, GCTA enabled us to explore and understand the causes and factors responsible for onset of neurological conditions and effect of such neurological conditions on human well-being. This review summarizes the recent and ongoing research carried out globally to unravel the mysteries of various neurological disorders employing latest genomics based technologies. The technological background and disease specific implementations are described in detail.

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“…It is plausible, however, that SNPs in genes of the 5-HT pathway might be involved in aggressive behavior in SMI. Indeed, the link between 5-HT genes and SMI has been deeply investigated through candidate genes , and nonhypothesis driven approaches . Specifically, SNPs within genes coding for tryptophan hydroxylase-1 (TPH1), , tryptophan hydroxylase-2 (TPH2), monoamine oxidase A (MAOA), 5-HT transporter (5-HTT), 5-HT 1A , 5-HT 2A , and 5-HT 3B receptor have been identified as risk variants for the development of MDD, BD, and SCZ.…”

Section: Serotonin Levels Severe Mental Illness and Aggressionmentioning

confidence: 99%

“…Indeed, the link between 5-HT genes and SMI has been deeply investigated through candidate genes , and nonhypothesis driven approaches . Specifically, SNPs within genes coding for tryptophan hydroxylase-1 (TPH1), , tryptophan hydroxylase-2 (TPH2), monoamine oxidase A (MAOA), 5-HT transporter (5-HTT), 5-HT 1A , 5-HT 2A , and 5-HT 3B receptor have been identified as risk variants for the development of MDD, BD, and SCZ. However, the risk conferred by these variants remains of small magnitude as shown, e.g., by the effect size of TPH1 rs1800532 SNP (OR = 1.24) and TPH2 rs11178998 and rs7954758 SNPs (OR = 1.33 and 1.36, respectively) in BD. , …”

Section: Serotonin Levels Severe Mental Illness and Aggressionmentioning

confidence: 99%

Serotonin Dysfunction, Aggressive Behavior, and Mental Illness: Exploring the Link Using a Dimensional Approach

Manchia

Carpiniello

Valtorta

et al. 2017

ACS Chem. Neurosci.

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Aggressive individuals have higher rates of mental illness compared to non-aggressive individuals. Multiple factors, including psychosocial, genetic, and neurobiological determinants modulate the liability to both aggressive behavior and mental illness. Concerning the latter factors, multiple lines of evidence have shown a dysfunction in the serotonin (5-HT) system occurring in aggressive and in mentally ill individuals. In particular, reduced 5-HT activity has been associated with depression as well as with aggressive behavior, especially with impulsive aggression. Consistently, psychopharmacological interventions aimed at boosting the 5-HT system (e.g., with selective serotonin reuptake inhibitors) have demonstrated therapeutic efficacy in a high percentage of patients with either or both pathological conditions. Current knowledge does not yet allow to clearly disentangle whether 5-HT dysfunction, most often a 5-HT deficiency, is the cause or the consequence of the aggressive/violent behavior, of the underlying mental disease/s, or the expression of the comorbidity. Future studies are thus needed to clarify the association between changes in 5-HT levels, altered activity of 5-HT receptors and their intracellular signaling cascades, and modifications of 5-HT genes, and in particular the neurobiological link between the altered 5-HT machinery and aggressive behavior in the context or in the absence of mental illness. In this Review, we employ a dimensional approach to discuss the trivariate relationship among the 5-HT system, aggressive behavior, and mental illness, focusing our attention on 5-HT levels, 5-HT receptors, metabolic enzymes, and their genes. Emphasis is given to controversial findings, still unanswered questions, and future perspectives.

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TPH2 gene polymorphisms and bipolar disorder: A meta‐analysis

Abstract: rs4760820 and rs11178998 were identified to have strong genetic association with BD in present study though confirmation will require larger sample sizes and in additional populations.

Cited by 14 publications

References 32 publications

Neurobiology of Chronic Stress-Related Psychiatric Disorders: Evidence from Molecular Imaging Studies

Neurobiology of Chronic Stress-Related Psychiatric Disorders: Evidence from Molecular Imaging Studies

Neurology in the Light of Genomics: Application of NGS and GWAS in Understanding Complex Neurological Disorders

Serotonin Dysfunction, Aggressive Behavior, and Mental Illness: Exploring the Link Using a Dimensional Approach

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