Association between DBH 19 bp insertion/deletion polymorphism and cognition in first-episode schizophrenic patients

Li, Hui; Zhang, Xuan; Yu, Yan-Hao; Han, Mei; Huang, Xu‐Feng; Chen, Da Chun; Wang, Zhi Ren; Du, Wei; Kou, Chang Gui; Yu, Qiong; Kosten, Thomas R.; Zhang, Xiang Yang

doi:10.1016/j.schres.2013.04.035

Cited by 18 publications

(12 citation statements)

References 57 publications

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“…DBH is an enzyme in the dopamine degradation pathway and earlier studies demonstrated its role in prefrontal dopamine inactivation and cognitive performance [53,54]. A functional polymorphism in DBH has been associated with cognitive performance in both healthy and clinical populations [7,8]. The dopamine transporter (DAT1) actively clears dopamine from the synaptic cleft and genetic polymorphisms have been associated with individual differences in cognitive abilities [14,55,56].…”

Section: Discussionmentioning

confidence: 99%

“…Pharmacological manipulation of dopaminergic tone and receptors impacts cognitive capacities [5]. Genetic variation in dopaminergic genes is associated with cognitive performance in both healthy and clinical populations [6][7][8]. According to twin studies, cognitive ability is influenced by individual genetics with heritability estimates ranging from 40 −80%, with genetic influence increasing with age [9].…”

Section: Introductionmentioning

confidence: 99%

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Dopaminergic gene methylation is associated with cognitive performance in a childhood monozygotic twin study

et al. 2019

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Individual differences in cognitive function are due to a combination of heritable and non-heritable factors. A large body of evidence from clinical, cognitive, and pharmacological neuroscience implicates dopaminergic gene variants as modulators of cognitive functions. Neuroepigenetic studies demonstrate environmental factors also influence complex phenotypes by affecting gene expression regulation. To evaluate the mechanism of environmental influence on cognitive abilities, we examined if epigenetic regulation of dopaminergic genes plays a role in cognition. Using a DNA methylation profiling microarray, we used a monozygotic (MZ) twin difference design to evaluate if co-twin differences in methylation of CpG sites near six dopaminergic genes predicted differences in response inhibition and memory performance. Studying MZ twins allows us to assess if environmentally driven differences in methylation affect differences in phenotype while controlling for the influence of genotype and shared family environment. Response inhibition was assessed with the flanker task and short-term and working memory were assessed with digit span recall. We found MZ co-twin differences in DRD4 gene methylation predicted differences in short-term memory. MZ differences in COMT, DBH, DAT1, DRD1, and DRD2 gene methylation predicted differences in response inhibition. Taken together, findings suggest methylation status of dopaminergic genes may influence cognitive functions in a dissociable manner. Our results highlight the importance of the epigenome and environment, over and above the influence of genotype, in supporting complex cognitive functions. ARTICLE HISTORYORCID Candace R. Lewis http://orcid.org/0000-0001-5253-9989 Reagan S. Breitenstein http://orcid.org/0000-0001-9998-166X

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dopaminergic gene methylation is associated with cognitive performance in a childhood monozygotic twin study

et al. 2019

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“…Extensive work from the Zhang group examined whether the upstream 19‐insertion/deletion variant in DβH (rs72393728/rs141116007) could influence cognitive function such as immediate memory performance in schizophrenia (Hui et al ; Hui et al ). This polymorphism was shown to be directly linked with first‐episode schizophrenic patients compared to healthy controls (Hui et al ; Hui et al ). Similar work by Sun et al () found no association with the 19‐insertion/deletion in the risk of development of SCZ, but did observe a significant interaction between the 19bp insertion (rs72393728) and the interleukin‐10 upstream variant rs1800872 on the development of negative symptoms based on the Positive and Negative Syndrome Scale.…”

Section: Neuropsychiatric Issues and Dβhmentioning

confidence: 99%

Dopamine beta‐hydroxylase and its genetic variants in human health and disease

Gonzalez-Lopez

Vrana

2019

Journal of Neurochemistry

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Dopamine beta-hydroxylase (DbH) is an essential neurotransmitter-synthesizing enzyme that catalyzes the formation of norepinephrine (NE) from dopamine and has been extensively studied since its discovery in the 1950s. NE serves as a neurotransmitter in both the central and peripheral nervous systems and is the precursor to epinephrine synthesis in the brain and adrenal medulla. Alterations in noradrenergic signaling have been linked to both central nervous system and peripheral pathologies. DbH protein, which is found in circulation, can, therefore, be evaluated as a marker of norepinephrine function in a plethora of different disorders and diseases. In many of these diseases, DbH protein availability and activity are believed to contribute to disease presentation or select symptomology and are believed to be under strong genetic control. Alteration in the DbH protein by genetic polymorphisms may result in DbH becoming ratelimiting and directly contributing to lower NE and epinephrine levels and disease. With the completion of the human genome project and the advent of next-generation sequencing, new insights have been gained into the existence of naturally occurring DbH sequencing variants (genetic polymorphisms) in disease. Also, biophysical tools coupled with genetic sequences are illuminating structure-function relationships within the enzyme. In this review, we discuss the role of genetic variants in DbH and its role in health and disease.

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“…In particular, it has been shown that polymorphism of dopamine beta hydroxylase, an enzyme that catalyzes the conversion of dopamine to noradrenaline, has an association with a risk of the development of schizophrenia only in the group with a first episode but not in patients with a longer duration of the disease [84]. The "pathological" variant of the enzyme is almost two times less active; therefore, it is possible to expect that the contents of noradrenaline and adrenaline will be decreased in its carriers.…”

Section: The Adrenergic Systemmentioning

confidence: 99%

The neuromediator mechanisms of the cognitive deficit in schizophrenia

2015

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In this review, we summarized the modern concepts on the association between a cognitive deficit in schizophrenia and alterations of the functional activities of different neuromediator systems. We analyzed the modern experimental data on the roles of the monoaminergic, aminoacidergic, and cholinergic systems of the brain in the mechanisms of attention and executive functions, as well as in the disturbances of these cognitive processes that occur in patients with schizophrenia. Special attention is paid to the mechanisms of neurotransmission in the prefrontal cortex and striatum. We show that with a high probability the cognitive deficit in schizophrenia is determined by the individual profile of disturbances of neuromediator processes. Identification of the individual mechanisms of a cognitive deficit at the level of neurotransmission may be used for the formation of a complex and selective strategy that is directed at the maintenance and recovery of functions, including both pharmacotherapy and non drug methods of treatment.

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Association between DBH 19 bp insertion/deletion polymorphism and cognition in first-episode schizophrenic patients

Cited by 18 publications

References 57 publications

Dopaminergic gene methylation is associated with cognitive performance in a childhood monozygotic twin study

Dopaminergic gene methylation is associated with cognitive performance in a childhood monozygotic twin study

Dopamine beta‐hydroxylase and its genetic variants in human health and disease

The neuromediator mechanisms of the cognitive deficit in schizophrenia

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