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Symptoms of attention-deficit hyperactivity disorder, nonsyndromic orofacial cleft children, and dopamine polymorphisms: a pilot study.

ABSTRACT: Attention-deficit hyperactivity disorder (ADHD) is a common childhood neurobehavioral disorder characterized by inattention, poor impulse control, and motor restlessness. Risk factors include familial stressors, anxiety disorders, learning disabilities, abnormal brain development, heritability, and dopamine polymorphisms. Children with an orofacial clefting (OFC) history are at increased risk of familial stressors, anxiety disorders, learning disabilities, and abnormal brain development. Given this overlap, we present a conceptual model proposing that children with OFC may be more likely to exhibit ADHD symptoms than children without and explore this relationship using pilot data.This cross-sectional pilot study included 29 children with OFC or a first-degree relative with OFC recruited through a cleft research registry.The Disruptive Behavior Disorder Scale was used to collect data on children's ADHD symptoms. Saliva or whole blood samples were collected from children and parents for DNA analyses. ADHD-associated dopamine polymorphisms within the DRD4, DRD2, and DAT1 genes were genotyped. We tested for associations between presence of OFC and dopamine polymorphisms. Mixed-effects models tested whether children with OFC and dopamine polymorphisms had more ADHD symptoms.The DRD4 4-repeat allele was associated with increased inattentive ADHD symptoms (p = .03). Having the DRD2 Taq1A1 allele and OFC predicted fewer (p = .02) inattentive ADHD symptoms. Children with OFC were significantly less likely to have the DAT1 10-repeat allele (p = .04).Results indicate that further investigation among a larger sample of children with OFC is warranted, particularly for relationships with inattentive ADHD.

SUBMITTER: Hopkins EE

PROVIDER: S-EPMC4377310 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Symptoms of attention-deficit hyperactivity disorder, nonsyndromic orofacial cleft children, and dopamine polymorphisms: a pilot study.

Hopkins Emily E EE Wallace Meredith L ML Conley Yvette P YP Marazita Mary L ML

Biological research for nursing 20140929 3

<h4>Purpose</h4>Attention-deficit hyperactivity disorder (ADHD) is a common childhood neurobehavioral disorder characterized by inattention, poor impulse control, and motor restlessness. Risk factors include familial stressors, anxiety disorders, learning disabilities, abnormal brain development, heritability, and dopamine polymorphisms. Children with an orofacial clefting (OFC) history are at increased risk of familial stressors, anxiety disorders, learning disabilities, and abnormal brain deve ...[more]

PMID: 25271118

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Project description:BackgroundFor the diagnosis of attention-deficit/hyperactivity disorder (ADHD), the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) proposes that adherence to six symptoms in either group (inattention and hyperactivity/impulsivity) will lead to the diagnosis of one of three presentations of the disorder. Underlying this diagnostic algorithm is the assumption that the 18 symptoms have equal relevance for the diagnosis of ADHD, all are equally severe, and all have the same power to detect the presence of the disorder in all its degrees of severity, without considering the possibility of using marker symptoms. However, several studies have suggested that ADHD symptoms differ in both their power to discriminate the presence of the disorder and the degree of severity they represent. The aim of the present study was to replicate the results of previous research by evaluating the discriminative capacity and relative severity of ADHD symptoms, as well as to extend the investigation of this topic to Spanish-speaking Latin American samples.MethodsThe properties of ADHD symptoms rated by the parents of 474 Chilean children were analyzed. Symptom parameters were estimated using the graded response model.ResultsThe results suggest that symptoms of ADHD differ substantially in both the accuracy with which they reflect the presence of the disorder, and their relative severity. Symptoms "easily distracted by extraneous stimuli" and "have difficulty sustaining attention in tasks" (inattention) and "is on the go, acting as if driven by motor" (hyperactivity/impulsivity) were the most informative, and those with relatively lower severity thresholds.DiscussionThe fact that symptoms differ substantially in the probability of being observed conditionally to the trait level suggests the need to refine the diagnostic process by weighting the severity of the symptom, and even to assess the possibility of defining ADHD marker symptoms, as has been done in other disorders.

Project description:BACKGROUND:Previous studies have reported associations between attention-deficit/hyperactivity disorder symptoms and DNA methylation in children. We report the first epigenome-wide association study meta-analysis of adult attention-deficit/hyperactivity disorder symptoms, based on peripheral blood DNA methylation (Infinium HumanMethylation450K array) in three population-based adult cohorts. METHODS:An epigenome-wide association study was performed in the Netherlands Twin Register (N = 2258, mean age 37 years), Dunedin Multidisciplinary Health and Development Study (N = 800, age 38 years), and Environmental Risk Longitudinal Twin Study (N = 1631, age 18 years), and results were combined through meta-analysis (total sample size N = 4689). Region-based analyses accounting for the correlation between nearby methylation sites were also performed. RESULTS:One epigenome-wide significant differentially methylated position was detected in the Dunedin study, but meta-analysis did not detect differentially methylated positions that were robustly associated across cohorts. In region-based analyses, six significant differentially methylation regions (DMRs) were identified in the Netherlands Twin Register, 19 in the Dunedin study, and none in the Environmental Risk Longitudinal Twin Study. Of these DMRs, 92% were associated with methylation quantitative trait loci, and 68% showed moderate to large blood-brain correlations for DNA methylation levels. DMRs included six nonoverlapping DMRs (three in the Netherlands Twin Register, three in the Dunedin study) in the major histocompatibility complex, which were associated with expression of genes in the major histocompatibility complex, including C4A and C4B, previously implicated in schizophrenia. CONCLUSIONS:Our findings point at new candidate loci involved in immune and neuronal functions that await further replication. Our work also illustrates the need for further research to examine to what extent epigenetic associations with psychiatric traits depend on characteristics such as age, comorbidities, exposures, and genetic background.

Dataset Information

Symptoms of attention-deficit hyperactivity disorder, nonsyndromic orofacial cleft children, and dopamine polymorphisms: a pilot study.

Publications

Symptoms of attention-deficit hyperactivity disorder, nonsyndromic orofacial cleft children, and dopamine polymorphisms: a pilot study.

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