The interactions among organophosphate pesticide exposure, oxidative stress, and genetic polymorphisms of dopamine receptor D4 increase the risk of attention deficit/hyperactivity disorder in children

Chang, Ching Chih; Yu, Ching-Jung; Du, Jung‐Chieh; Chiou, Hsien-Chih; Chen, Hsin‐Chang; Yang, Winnie; Chung, Ming Yi; Chen, Ying-Sheue; Hwang, Betau; Mao, I‐Fang; Chen, Mei-Lien

doi:10.1016/j.envres.2017.10.011

Cited by 41 publications

(17 citation statements)

References 64 publications

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“…Research are still going on to understand the connection however, by physiological point of view inhibition response is very poor[ 71 72 ] and considered as the key point for ADHD and inhibits the working procedure and operate the other process in between include amygdale, raphe nucleus, septohippocampal system, hypothalamus, locus ceruleus, and neurocircuitry incorporating the frontal cortex. [ 72 73 74 ] Faulty, BIS process unsuccessful to cooperate with normal, adaptive activation responses and normal stress action which comes out as a fearful reinforcement. [ 73 ]…”

Section: Resultsmentioning

confidence: 99%

Network and pathway enrichment analysis of Attention Deficit/Hyperactivity Disorder candidate genes

Singh

2020

Indian J Psychiatry

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Background: Attention deficit/hyperactivity disorder (ADHD) is a well-known multigenic neurodevelopment disorder. It is a psychiatric disease which mainly affects the children and adolescence. Globally, 3%–5% of children are suffering from this mental disorder. Aims and Objectives: This disease is characterized by hyperactivity, impulsiveness and inattentiveness. Suffering individuals are also observed with sleep related problems. Though, its polygenic, to study the complexity of these genes, we used a purely network approach. Firstly, we collected all the candidate genes involved in ADHD through a literature survey. Materials and Methods: We investigated these genes using STRING 10 and Cytoscape v 3.3.0 for protein protein interaction network. Accordingly, we attempted to identify the hub genes based on definite parameters like betweenness centrality, clustering coefficient and node degree using Network analyzer. Likewise, the key transcriptional regulators were acknowledged by means of MatInspector program. Finally, the enrichment analysis was executed using ClueGO. Results: As a result, dopamine receptor D2, brain derived neurotrophic factor, HTRF1A , and dopamine receptor D4 were recognized as hub genes among the reported ADHD genes. While, 17 transcription factors (TFs) were conveyed as the key TFs for these hub genes. Conclusion: Functional enrichment analysis revealed regulation of dopamine and behavioral fear response pathways. These pathways have been assumed to play a central role in the ADHD within the selected candidate genes.

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Section: Resultsmentioning

confidence: 99%

Network and pathway enrichment analysis of Attention Deficit/Hyperactivity Disorder candidate genes

Singh

2020

Indian J Psychiatry

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“…For other SNPs: rs7395429, rs3758653, rs11246228, rs752306 [49][50][51] ; rs4646984 52 ; rs916457 53 ; rs936465 54 , nometa-analyses can be performed, because very few studies were available (minimum three studies), considering that Yu and colleagues 49,50 and Chang and colleagues 51 studied the same population.…”

Section: Newcastle-ottawa Scalementioning

confidence: 99%

DRD4 48 bp multiallelic variants as age-population-specific biomarkers in attention-deficit/hyperactivity disorder

et al. 2020

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The identification of biomarkers to support the diagnosis and prediction of treatment response for attention-deficit/ hyperactivity disorder (ADHD) is still a challenge. Our previous works highlighted the DRD4 (dopamine receptor D4) as the best potential genetic marker for childhood diagnosis and methylphenidate (MPH) response. Here, we aimed to provide additional evidence on biomarkers for ADHD diagnosis and treatment response, by using more specific approaches such as meta-analytic and bioinformatics tools. Via meta-analytic approaches including over 3000 cases and 16,000 controls, we demonstrated that, among the different variants studied in DRD4 gene, the 48-base pair, Variable Tandem Repeat Polymorphism, VNTR in exon 3 showed an age/population-specificity and an allelic heterogeneity. In particular, the 7R/"long" allele was identified as an ADHD risk factor in European-Caucasian populations (d = 1.31, 95%CI: 1.17-1.47, Z = 4.70/d = 1.36, 95%CI: 1.20-1.55, Z = 4.78, respectively), also, from the results of last meta-analysis, linked to the poor MPH efficacy. The 4R/"short" allele was a protective factor in European-Caucasian and South American populations (d = 0.83, 95%CI: 0.75-0.92, Z = 3.58), and was also associated to positive MPH response. These results refer to children with ADHD. No evidence of such associations was detected for adults with persistent ADHD (data from the last meta-analysis). Moreover, we found evidence that the 4R allele leads to higher receptor expression and increased sensitivity to dopamine, as compared with the 7R allele (d = 1.20, 95%CI: 0.71-1.69, Z = 4.81), and this is consistent with the ADHD protection/susceptibility effects of the respective alleles. Using bioinformatics tools, based on the latest genome-wide association (GWAS) meta-analysis of the Psychiatry Genomic Consortium (PGC), we demonstrated that the 48 bp VNTR is not in Linkage Disequilibrium with the DRD4 SNPs (Single Nucleotide Polymorphisms), which were not found to be associated with ADHD. Moreover, a DRD4 expression downregulation was found in ADHD specific brain regions (Putamen, Z score = −3.02, P = 0.00252). Overall, our results suggest that DRD4 48 bp VNTR variants should be considered as biomarkers to support the diagnosis of ADHD and to predict MPH response, although the accuracy of such a biomarker remains to be further elucidated.

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“…Обнаружен значительно более высокий уровень метаболитов органофосфатных пестицидов и биомаркеров окислительного стресса в крови у детей с СДВГ по сравнению со здоровым контролем. При этом у детей с аллелем GA/AA (rs7523060) в гене DRD4 (D4-рецептор дофамина) вероятность возникновения СДВГ ниже по сравнению с генотипом GG DRD4 [34]. Выявлена ассоциация развития СДВГ у детей, матери которых курили [35], употребляли ацетаминофен [36] и антидепрессанты во время беременности [37].…”

Section: роль внешнесредовых факторовunclassified

Genetics and epigenetics of attention deficit hyperactivity disorder

Мустафин¹,

Enikeeva²,

Malykh³

et al. 2018

Z. nevrol. psikhiatr. im. S.S. Korsakova

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Синдром дефицита внимания и гиперактивности (СДВГ)-сложное поведенческое расстройство [1] с высокой степенью наследуемости [2]. Оно характеризуется невнимательностью, гиперактивностью и импульсивностью [1]. Согласно DSM-5 cимптомы СДВГ возникают в возрасте до 12 лет, вызывая значительные нарушения социальных, академических и профессиональных функций на протяжении всей жизни [3]. Распространенность СДВГ

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The interactions among organophosphate pesticide exposure, oxidative stress, and genetic polymorphisms of dopamine receptor D4 increase the risk of attention deficit/hyperactivity disorder in children

Cited by 41 publications

References 64 publications

Network and pathway enrichment analysis of Attention Deficit/Hyperactivity Disorder candidate genes

Network and pathway enrichment analysis of Attention Deficit/Hyperactivity Disorder candidate genes

DRD4 48 bp multiallelic variants as age-population-specific biomarkers in attention-deficit/hyperactivity disorder

Genetics and epigenetics of attention deficit hyperactivity disorder

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