Dataset Information

Neuregulin1 types mRNA level changes in autism spectrum disorder, and is associated with deficit in executive functions.

ABSTRACT:

Background

Autism spectrum disorder (ASD) is a pediatric heterogeneous psychiatric and neurodevelopmental disorder with social and communication deficits, language impairment and ritualistic or repetitive behaviors. ASD has significant genetic bases but candidate genes and molecular mechanisms of disorder are not clarified. Neuregulin1 (NRG1) gene, located in 8p12 is involved in development of central nervous system and was indicated as candidate gene in schizophrenia.

Methods

mRNA level of types I, II and III of NRG1 gene were studied in peripheral blood of 1540 ASD patients (IQ?>?70) and 1490 control children by quantitative Real Time PCR. Also three domains of executive functions (working memory, response inhibition and vigilance) were examined in all subjects.

Findings

All three types were significantly down regulated in ASD patients. Significant deficiencies in executive functions (EF) were found in ASD patients. EF deficiencies mostly were associated with down expression of mRNA level of types I and III. Also correlations were found between NRG1 expression with gender and severity of ASD symptoms.

Interpretations

Findings primarily have been suggested involvement of NRG1 in etiology of ASD. Also correlation of NRG1 mRNA level with EF deficiencies could shed lights on EF mechanisms and may suggest targeted treatments to improve particular executive functions. FUND: Young researchers and elites club funded the project due to the annual grant of special talents of Club that gave to Arvin Haghighatfard.

SUBMITTER: Abbasy S

PROVIDER: S-EPMC6284419 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Neuregulin1 types mRNA level changes in autism spectrum disorder, and is associated with deficit in executive functions.

Abbasy Samane S Shahraki Fazlollah F Haghighatfard Arvin A Qazvini Masoume Ghasemzadeh MG Rafiei Sahel Towfigh ST Noshadirad Elnaz E Farhadi Mahdi M Rezvani Asl Horie H Shiryazdi Atena Alsadat AA Ghamari Rana R Tabrizi Zeinab Z Mehrfard Rashed R Esmaili Kakroudi Fereshteh F Azarnoosh Mahsima M Younesi Faeghe F Parsamehr Narges N Garaei Nooriyeh N Abyari Soroush S Salehi Maede M Gholami Maryam M Zolfaghari Pardis P Bagheri Seyede Mahsa SM Pourmehrabi Melika M Rastegarimogaddam Elham E Nobakht Elnaz E Nobakht Elmira E Partovi Rayan R

EBioMedicine 20181108

<h4>Background</h4>Autism spectrum disorder (ASD) is a pediatric heterogeneous psychiatric and neurodevelopmental disorder with social and communication deficits, language impairment and ritualistic or repetitive behaviors. ASD has significant genetic bases but candidate genes and molecular mechanisms of disorder are not clarified. Neuregulin1 (NRG1) gene, located in 8p12 is involved in development of central nervous system and was indicated as candidate gene in schizophrenia.<h4>Methods</h4>mRN ...[more]

PMID: 30415889

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Project description:Background It is well known that children with autism spectrum disorder (ASD) had executive functions deficit. However, it is still unclear whether the poor dietary quality is related to the impairment of executive functions. The current study aimed to explore the association between dietary quality and executive functions in children with ASD. Methods A total of 106 children with ASD (7.7 ± 1.3 years) and 207 typically developing (TD) children (7.8 ± 1.3 years) were enrolled from Guangzhou, China. The Chinese version of Behavior Rating Scale of Executive function (BRIEF), the working memory subscales of the Chinese version of Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV), and the Stroop Color-Word Test (SCWT) were used to measure the participant's executive functions. The food frequency questionnaire (FFQ) was used to collect the dietary intake information, and the Chinese Diet Balance Index (DBI_16) was used to evaluate the dietary quality. Generalized linear models were used to estimate the association between dietary quality and executive functions. Results In children with ASD, Low Bound Score (LBS) was positively correlated with the working memory subscale score of BRIEF (β = 0.23, 95% CI: 0.02–0.44, P < 0.05), while High Bound Score (HBS) and LBS were positively correlated with the organizable subscale score of BRIEF (β = 0.44, 95% CI: 0.11–0.77, P < 0.01; β = 0.19, 95% CI: 0.01–0.37, P < 0.05). Compared to TD children, children with ASD had a higher proportion of moderate and high levels of insufficient dietary intake (moderate level, 37.7% vs. 23.2%, high level, 4.7% vs. 1.4%) and moderate level of unbalanced dietary intake (36.8% vs.21.3%), higher scores on all subscales of BRIEF (P < 0.01), and lower score on the working memory (81.3 ± 32.3 vs. 104.6 ± 12.5, P < 0.01), while there was no difference on the SCWT. Conclusion Poor dietary quality was associated with the impairment of working memory and organizational capacity in children with ASD. This study emphasized the importance of dietary quality in executive functions among children with ASD, and attention should be paid to improving their dietary quality.

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:Background Empathy dysfunction is one of the hallmarks of psychopathy, but it is also sometimes thought to characterise autism spectrum disorders (ASD). Individuals with either condition can appear uncaring towards others. This study set out to compare and contrast directly boys with psychopathic tendencies and boys with ASD on tasks assessing aspects of affective empathy and cognitive perspective taking. The main aim of the study was to assess whether a distinct profile of empathy deficits would emerge for boys with psychopathic tendencies and ASD, and whether empathy deficits would be associated with conduct problems in general, rather than psychopathic tendencies or ASD specifically.Methods Four groups of boys aged between 9 and 16 years (N = 96) were compared: 1) psychopathic tendencies, 2) ASD, 3) conduct problems and 4) comparison. Tasks were included to probe attribution of emotions to self, empathy for victims of aggression and cognitive perspective-taking ability.Results Boys with psychopathic tendencies had a profile consistent with dysfunctional affective empathy. They reported experiencing less fear and less empathy for victims of aggression than comparison boys. Their cognitive perspective-taking abilities were not statistically significantly different from those of comparison boys. In contrast, boys with ASD had difficulties with tasks requiring cognitive perspective taking, but reported emotional experiences and victim empathy that were in line with comparison boys. Boys with conduct problems did not differ from comparison boys, suggesting that the affective empathy deficit seen in boys with psychopathic tendencies was specific to that group, rather than common to all boys with conduct problems.Conclusions Although both groups can appear uncaring, our findings suggest that the affective/information processing correlates of psychopathic tendencies and ASD are quite different. Psychopathic tendencies are associated with difficulties in resonating with other people's distress, whereas ASD is characterised by difficulties in knowing what other people think.

Project description:BackgroundImpairment of executive function (EF), the goal-directed regulation of thoughts, actions, and emotions, drives negative outcomes and is common across neurodevelopmental disorders including attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). A primary challenge to its amelioration is heterogeneity in symptom expression within and across disorders. Parsing this heterogeneity is necessary to attain diagnostic precision, a goal of the NIMH Research Domain Criteria Initiative. We aimed to identify transdiagnostic subtypes of EF that span the normal to impaired spectrum and establish their predictive and neurobiological validity.MethodsCommunity detection was applied to clinical parent-report measures in 8-14-year-old children with and without ADHD and ASD from two independent cohorts (discovery N = 320; replication N = 692) to identify subgroups with distinct behavioral profiles. Support vector machine (SVM) classification was used to predict subgroup membership of unseen cases. Preliminary neurobiological validation was obtained with existing functional magnetic resonance imaging (fMRI) data on a subsample (N = 84) by testing hypotheses about sensitivity of EF subgroups versus DSM categories.ResultsWe observed three transdiagnostic EF subtypes characterized by behavioral profiles that were defined by relative weakness in: (a) flexibility and emotion regulation; (b) inhibition; and (c) working memory, organization, and planning. The same tripartite structure was also present in the typically developing children. SVM trained on the discovery sample and tested on the replication sample classified subgroup membership with 77.0% accuracy. Split-half SVM classification on the combined sample (N = 1,012) yielded 88.9% accuracy (this SVM is available for public use). As hypothesized, frontal-parietal engagement was better distinguished by EF subtype than DSM diagnosis and the subgroup characterized with inflexibility failed to modulate right IPL activation in response to increased executive demands.ConclusionsThe observed transdiagnostic subtypes refine current diagnostic nosology and augment clinical decision-making for personalizing treatment of executive dysfunction in children.

Dataset Information

Neuregulin1 types mRNA level changes in autism spectrum disorder, and is associated with deficit in executive functions.

Background

Methods

Findings

Interpretations

Publications

Neuregulin1 types mRNA level changes in autism spectrum disorder, and is associated with deficit in executive functions.

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