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A systematic review and meta-analysis examining the interrelationships between chemical and non-chemical stressors and inherent characteristics in children with ADHD.

ABSTRACT: Children may be more vulnerable to the combined interactions of chemical and non-chemical stressors from their built, natural, and social environments when compared to adults. Attention deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed childhood neurodevelopmental disorder and is considered a major public health issue, as 75% of childhood cases persist into adulthood. ADHD is characterized by developmentally inappropriate levels of hyperactivity, impulsivity, and inattention, with the neurotransmitter serotonin regulating these symptoms. Monoamine oxidase A (MAOA) aids in serotonin uptake and is often implicated in behavioral and emotional disorders, including ADHD. When children are exposed to cigarette smoke, bisphenol A (BPA), or organophosphate pesticides, MAOA activity is inhibited. Non-chemical stressors, such as traumatic childhood experiences, and lifestyle factors, complicate the relationship between genotype and exposures to chemical stressors. But the co-occurrence among outcomes between exposures to chemical stressors, non-chemical stressors, and the low activity MAOA genotype suggest that mental illness in children may be influenced by multiple interacting factors. In this systematic review, we examine the existing literature that combines exposures to chemical and non-chemical stressors (specifically childhood trauma), MAOA characteristics, and ADHD diagnosis to investigate the interrelationships present. We observe that chemical (lead [Pb], phthalates/plasticizers, persistent organic pollutants, and cigarette smoke) exposure is significantly related to ADHD in children. We also observed that existing literature examining the interaction between MAOA, exposures to chemical stressors, and traumatic experiences and their effect on ADHD outcomes is sparse. We recommend that future studies investigating childhood ADHD include chemical and non-chemical stressors and inherent characteristics to gain a holistic understanding of childhood mental health outcomes.

SUBMITTER: Nilsen FM

PROVIDER: S-EPMC6937727 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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A systematic review and meta-analysis examining the interrelationships between chemical and non-chemical stressors and inherent characteristics in children with ADHD.

Nilsen Frances M FM Tulve Nicolle S NS

Environmental research 20191101

Children may be more vulnerable to the combined interactions of chemical and non-chemical stressors from their built, natural, and social environments when compared to adults. Attention deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed childhood neurodevelopmental disorder and is considered a major public health issue, as 75% of childhood cases persist into adulthood. ADHD is characterized by developmentally inappropriate levels of hyperactivity, impulsivity, and inattention, ...[more]

PMID: 31706600

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Project description:INTRODUCTION:Attention-deficit hyperactivity disorder (ADHD) has been related to increased rates of unintentional injuries. However, the magnitude of the effect and to which extent variables such as sex, age or comorbidity can influence this relationship is unknown. Additionally, and importantly, it is unclear if, and to which degree, ADHD medications can decrease the number of unintentional injuries. Due to the amount of economic and social resources invested in the treatment of injuries, filling these gaps in the literature is highly relevant from a public health standpoint. Here, we present a protocol for a systematic review and meta-analysis to estimate the relationship between ADHD and unintentional injuries and assess the impact of pharmacological treatment for ADHD METHODS AND ANALYSIS: We will combine results from 114 bibliographic databases for studies relating ADHD and risk of injuries. Bibliographic searches and data extraction will be carried out independently by two researchers. The studies' risk of bias will be assessed using the Newcastle-Ottawa Scale. Articles reporting ORs or HRs of suffering an injury in ADHD compared with controls (or enough data to calculate them) will be combined using Robust Variance Estimation, a method that permits to include multiple non-independent outcomes in the analysis. All analyses will be carried out in Stata. Age, sex and comorbid conduct disorders will be considered as potential causes of variance and their effect analysed through meta-regression and subgroup analysis. Sensitivity analyses will exclude articles with longer follow-ups, non-stringent definitions of ADHD or controls and statistically uncontrolled/controlled outcomes. Studies implementing a self-controlled case series methodology to investigate if ADHD drugs reduce the risk of injuries will be combined with a generalised linear mixed model using the Poisson distribution and a log link function. REGISTRATION DETAILS:PROSPERO-Prospective Register of Systematic Reviews (CRD42017064967).

Project description:Childhood behavioral outcomes have been linked to low quality intrauterine environments caused by prenatal exposures to both chemical and non-chemical stressors. The effect(s) from the many stressors a child can be prenatally exposed to may be influenced by complex interactive relationships that are just beginning to be understood. Chemical stressors influence behavioral outcomes by affecting the monoamine oxidase A (MAOA) enzyme, which is involved in serotonin metabolism and the neuroendocrine response to stress. Non-chemical stressors, particularly those associated with violence, have been shown to influence and exacerbate the externalizing behavioral outcomes associated with low MAOA activity and slowed serotonin metabolism. The adverse developmental effects associated with high stress and maternal drug use during pregnancy are well documented. However, research examining the combined effects of other non-chemical and chemical stressors on development and childhood outcomes as a result of gestational exposures is scarce but is an expanding field. In this systematic review, we examined the extant literature to explore the interrelationships between exposures to chemical and non-chemical stressors (specifically stressful/traumatic experiences), MAOA characteristics, and childhood externalizing behaviors. We observed that exposures to chemical stressors (recreational drugs and environmental chemicals) are significantly related to externalizing behavioral outcomes in children. We also observed that existing literature examining the interactions between MAOA characteristics, exposures to chemical stressors, and traumatic experiences and their effects on behavioral outcomes is sparse. We propose that maternal stress and cortisol fluctuations during pregnancy may be an avenue to link these concepts. We recommend that future studies investigating childhood behaviors include chemical and non-chemical stressors as well as children's inherent genetic characteristics to gain a holistic understanding of the relationship between prenatal exposures and childhood behavioral outcomes.

Project description:Abstract Background: Attention-deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder, and methylphenidate (MPH) is considered one of the first-line medicine for ADHD. Unfortunately, this medication is only effective for some children with ADHD. This meta-analysis was conducted to evaluate whether noradrenergic gene polymorphisms impact the efficacy of MPH in children with ADHD. Methods: Candidate gene studies published in English until March 1, 2020, were identified through literature searches on PubMed, Web of Science, and Embase. Data were pooled from individual clinical trials considering MPH pharmacogenomics. According to the heterogeneity, the odds ratio and mean differences were calculated by applying fixed-effects or random-effects models. Results: This meta-analysis includes 15 studies and 1382 patients. Four polymorphisms of the NET gene (rs5569, rs28386840, rs2242446, rs3785143) and 2 polymorphisms of the α2A-adrenergic receptor gene (ADRA2A) gene (MspI and DraI) were selected for the analysis. In the pooled data from all studies, T allele carriers of the rs28386840 polymorphism were significantly more likely to respond to MPH (P < .001, ORTcarriers = 2.051, 95% confidence interval [CI]:1.316, 3.197) and showed a relationship with significantly greater hyperactive-impulsive symptoms improvement (P < .001, mean difference:1.70, 95% CI:0.24, 3.16). None of the ADRA2A polymorphisms correlated significantly with MPH response as a whole. However, G allele carriers of the MspI polymorphism showed a relationship with significantly inattention symptoms improvement (P < .001, mean difference:0.31, 95% CI: 0.15, 0.47). Conclusion: Our meta-analysis results indicate that the noradrenergic gene polymorphisms may impact MPH response. The NET rs28386840 is linked to improved MPH response in ADHD children. And the ADRA2A MspI is associated with inattention symptom improvements. Further investigations with larger samples will be needed to confirm these results. Registration: PROSPERO (no. CRD42021265830).

Dataset Information

A systematic review and meta-analysis examining the interrelationships between chemical and non-chemical stressors and inherent characteristics in children with ADHD.

Publications

A systematic review and meta-analysis examining the interrelationships between chemical and non-chemical stressors and inherent characteristics in children with ADHD.

Similar Datasets

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