Dataset Information

Glutamatergic and GABAergic gene sets in attention-deficit/hyperactivity disorder: association to overlapping traits in ADHD and autism.

ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) often co-occur. Both are highly heritable; however, it has been difficult to discover genetic risk variants. Glutamate and GABA are main excitatory and inhibitory neurotransmitters in the brain; their balance is essential for proper brain development and functioning. In this study we investigated the role of glutamate and GABA genetics in ADHD severity, autism symptom severity and inhibitory performance, based on gene set analysis, an approach to investigate multiple genetic variants simultaneously. Common variants within glutamatergic and GABAergic genes were investigated using the MAGMA software in an ADHD case-only sample (n=931), in which we assessed ASD symptoms and response inhibition on a Stop task. Gene set analysis for ADHD symptom severity, divided into inattention and hyperactivity/impulsivity symptoms, autism symptom severity and inhibition were performed using principal component regression analyses. Subsequently, gene-wide association analyses were performed. The glutamate gene set showed an association with severity of hyperactivity/impulsivity (P=0.009), which was robust to correcting for genome-wide association levels. The GABA gene set showed nominally significant association with inhibition (P=0.04), but this did not survive correction for multiple comparisons. None of single gene or single variant associations was significant on their own. By analyzing multiple genetic variants within candidate gene sets together, we were able to find genetic associations supporting the involvement of excitatory and inhibitory neurotransmitter systems in ADHD and ASD symptom severity in ADHD.

SUBMITTER: Naaijen J

PROVIDER: S-EPMC5545734 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Glutamatergic and GABAergic gene sets in attention-deficit/hyperactivity disorder: association to overlapping traits in ADHD and autism.

Naaijen J J Bralten J J Poelmans G G Glennon J C JC Franke B B Buitelaar J K JK

Translational psychiatry 20170110 1

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) often co-occur. Both are highly heritable; however, it has been difficult to discover genetic risk variants. Glutamate and GABA are main excitatory and inhibitory neurotransmitters in the brain; their balance is essential for proper brain development and functioning. In this study we investigated the role of glutamate and GABA genetics in ADHD severity, autism symptom severity and inhibitory performance, based on ...[more]

PMID: 28072412

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Project description:Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD) are two of the most represented neurodevelopmental conditions in childhood. The diagnostic shift introduced by the DSM-5, allowing a combined diagnosis of ADHD and ASD, poses different clinical challenges related to diagnostic overshadowing, accuracy of clinical judgment and potential delay in an ASD diagnosis in children presenting with ADHD. Here we tried to disentangle the clinical phenotype and specificity of the two co-occurring conditions in relation to autism traits and empathy, by comparing children with ASD with and without comorbid ADHD with children presenting ADHD only and children with typical development. The child versions of the Autism Quotient (C-AQ) and Empathy Quotient (C-EQ) were administered to a total sample of 198 male children between 6 and 14 years old with age appropriate language skills and normal intelligence. Univariate analysis demonstrated no significant differences in the C-AQ total and subscale scores as well as the C-EQ between children with ASD and children with ASD + ADHD, while children with ADHD alone presented an intermediate phenotype between ASD and TD. Furthermore, a receiver operating characteristic (ROC) analysis was applied to discriminate among the different phenotypes. We found that the C-AQ and C-EQ were accurate at distinguishing with satisfactory reliability between: (a) ASD vs. non- ASD (N-ASD) groups comprising both ADHD and TD children (Area Under the Curve AUC 88% for C-AQ and 81% for C-EQ); (b) ASD and TD (AUC 92% for C-AQ and 95% for C-EQ); (c) ASD and ADHD (AUC 80% for C-AQ and 68% for C-EQ). Our data confirm the reliability of the C-AQ and C-EQ as behavioral markers to differentiate ASD (regardless of comorbid ADHD) from an ADHD condition and TD. Interestingly, in our sample an ADHD condition does not increase the severity of the clinical phenotype in terms of autism traits distribution and empathy, suggesting that the psychological measures detected by the two quantitative instruments are independent of ADHD traits. This evidence will contribute to the translational efforts in developing better tailored treatments and preventive strategies.

Project description:While psychiatric comorbidities of attention-deficit/hyperactivity disorder (ADHD) have been extensively explored, less attention has been paid to somatic conditions possibly associated with this disorder. However, mounting evidence in the last decade pointed to a possible significant association between ADHD and certain somatic conditions, including obesity. This papers provides an update of a previous systematic review on the relationship between obesity and ADHD (Cortese and Vincenzi, Curr Top Behav Neurosci 9:199-218, 2012), focusing on pertinent peer-reviewed empirical papers published since 2012. We conducted a systematic search in PubMed, Ovid, and Web of Knowledge databases (search dates: from January 1st, 2012, to July 16th, 2016). We retained a total of 41 studies, providing information on the prevalence of obesity in individuals with ADHD, focusing on the rates of ADHD in individuals with obesity, or reporting data useful to gain insight into possible mechanisms underlying the putative association between ADHD and obesity. Overall, over the past 4 years, an increasing number of studies have assessed the prevalence of obesity in individuals with ADHD or the rates of ADHD in patients with obesity. Although findings are mixed across individual studies, meta-analytic evidence shows a significant association between ADHD and obesity, regardless of possible confounding factors such as psychiatric comorbidities. An increasing number of studies have also addressed possible mechanisms underlying the link between ADHD and obesity, highlighting the role, among others, of abnormal eating patterns, sedentary lifestyle, and possible common genetic alterations. Importantly, recent longitudinal studies support a causal role of ADHD in contributing to weight gain. The next generation of studies in the field should explore if and to which extent the treatment of comorbid ADHD in individuals with obesity may lead to long-term weight loss, ultimately improving their overall well-being and quality of life.

Dataset Information

Glutamatergic and GABAergic gene sets in attention-deficit/hyperactivity disorder: association to overlapping traits in ADHD and autism.

Publications

Glutamatergic and GABAergic gene sets in attention-deficit/hyperactivity disorder: association to overlapping traits in ADHD and autism.

Similar Datasets

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