The gap between parents’ knowledge and causal beliefs about etiology of autism: A key variable to understand parents’ anxiety

Autism Spectrum Disorders (ASD) are associated with higher levels of anxiety for parents [1]. Provide medical information about autism etiology is the first step to help parents to understand the child disorder and to cope with it. The medical current community accepts that autism is a neurodevelopmental disorder in which genes play a role but that environmental factors likely contribute as well [2]. This conception can meet parent's beliefs constructed on their cultural values and personal experiences. In line with causal attribution theory [3], it is important to consider to parental beliefs because it can impact the treatment choices and the child developmental trajectory [4]. The Main purpose is to evaluate the consistency between parental knowledge and beliefs about ASD etiology. The second purpose is to explore the impact of consistency on parents’ anxiety. We interviewed through open-ended questions 89 parents of ASD children aged between 3 to 10 years about their knowledge and their beliefs about ASD etiology. A content analysis was performed using the Nvivo10 software. Anxiety is evaluated with the subscale of the Hospital Anxiety and Depression Scale (HADS). In agreement with previous work four categories of causes have been identified: biological (BIO), psychological (PSY), multifactorial etiology (BIO + PSY), others (OT). A percentage of 55.1% of parents is consistent between their knowledge and beliefs about ASD etiology while 43.8% are inconsistent. Parent anxiety is significantly higher (T (71.91) = 2.34; P < 0.05) when knowledge and beliefs are inconsistent than when they are consistent. This study demonstrates the deleterious impact of inconsistency between knowledge and beliefs about ASD etiology, on parental anxiety. In order to provide relevant support for parents, information delivered after diagnosis must consider pre-existing parental beliefs. A systematic assessment of parental beliefs would adjust the information provided after the diagnosis.

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Can a Digital Awareness Campaign Change Knowledge and Beliefs Regarding Cochlear Implants? A Study in Older Adults in 5 European Countries

INQUIRY The Journal of Health Care Organization Provision and Financing ◽

10.1177/0046958020910566 ◽

2020 ◽

Vol 57 ◽

pp. 004695802091056

Author(s):

Patrick S. C. D’Haese ◽

Vincent Van Rompaey ◽

Marc De Bodt ◽

Paul Van de Heyning

Keyword(s):

Older Adults ◽

Hearing Loss ◽

Cochlear Implants ◽

Medical Information ◽

The Internet ◽

Awareness Campaign ◽

Health Crisis ◽

Knowledge And Beliefs ◽

The United Kingdom ◽

The Impact

There are 466 million people living with a disabling hearing loss and the challenges of managing this public health crisis cannot be underestimated. Yet, adult utilization of cochlear implants is poor with less than 10% of suitable candidates receiving one. The aim of this study was to investigate the awareness levels regarding cochlear implants in older adults after a digital campaign to raise awareness of cochlear implantation in this population. To address the lack of awareness of the cochlear implants in the general population, adverts were placed in online medical magazines and mainstream newspapers. Data were collected in 400 subjects via an online market research questionnaire, in Germany, Austria, Sweden, and the United Kingdom, and compared with baseline data collected in a previous study. Median click rates were in line with expectations for the medical industry and approximately 22 000 individuals clicked through to the cochlear implant Web site. However, there were few significant differences between the 2 sets of data. The Internet was consulted as much as the doctor for medical information in Germany, Austria, and Sweden. The study reinforces the importance of the Internet in accessing information about health, including hearing loss. The click through rates shows that there is interest in learning about cochlear implants. Further work is needed to assess the impact of this type of campaign on individuals who have already been identified as hearing impaired.

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Understanding the impact of SNPs associated with autism spectrum disorder on biological pathways in the human fetal and adult cortex

Scientific Reports ◽

10.1038/s41598-021-95447-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

E. Golovina ◽

T. Fadason ◽

T. J. Lints ◽

C. Walker ◽

M. H. Vickers ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Protein Interactions ◽

Ribosome Biogenesis ◽

Neurodevelopmental Disorder ◽

Autism Spectrum ◽

Biological Pathways ◽

Spectrum Disorder ◽

Biological Information ◽

Immune Pathways ◽

The Impact

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by significant and complex genetic etiology. GWAS studies have identified genetic variants associated with ASD, but the functional impacts of these variants remain unknown. Here, we integrated four distinct levels of biological information (GWAS, eQTL, spatial genome organization and protein–protein interactions) to identify potential regulatory impacts of ASD-associated SNPs (p < 5 × 10–8) on biological pathways within fetal and adult cortical tissues. We found 80 and 58 SNPs that mark regulatory regions (i.e. expression quantitative trait loci or eQTLs) in the fetal and adult cortex, respectively. These eQTLs were also linked to other psychiatric disorders (e.g. schizophrenia, ADHD, bipolar disorder). Functional annotation of ASD-associated eQTLs revealed that they are involved in diverse regulatory processes. In particular, we found significant enrichment of eQTLs within regions repressed by Polycomb proteins in the fetal cortex compared to the adult cortex. Furthermore, we constructed fetal and adult cortex-specific protein–protein interaction networks and identified that ASD-associated regulatory SNPs impact on immune pathways, fatty acid metabolism, ribosome biogenesis, aminoacyl-tRNA biosynthesis and spliceosome in the fetal cortex. By contrast, in the adult cortex they largely affect immune pathways. Overall, our findings highlight potential regulatory mechanisms and pathways important for the etiology of ASD in early brain development and adulthood. This approach, in combination with clinical studies on ASD, will contribute to individualized mechanistic understanding of ASD development.

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Autism spectrum disorder: understanding the impact of SNPs on biological pathways in the fetal and adult cortex

10.1101/2021.03.03.433667 ◽

2021 ◽

Author(s):

E. Golovina ◽

T. Fadason ◽

T.J. Lints ◽

C. Walker ◽

M.H. Vickers ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Protein Interactions ◽

Ribosome Biogenesis ◽

Neurodevelopmental Disorder ◽

Autism Spectrum ◽

Biological Pathways ◽

Spectrum Disorder ◽

Biological Information ◽

Immune Pathways ◽

The Impact

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by significant and complex genetic etiology. GWAS studies have identified genetic variants associated with ASD, but the functional impacts of these variants remain unknown. Here, we integrated four distinct levels of biological information (GWAS, eQTL, spatial genome organization and protein-protein interactions) to identify potential regulatory impacts of ASD-associated SNPs (p < 5×10-8) on biological pathways within fetal and adult cortical tissues. We found 80 and 58 SNPs that mark regulatory regions (i.e. expression quantitative trait loci or eQTLs) in the fetal and adult cortex, respectively. These eQTLs were also linked to other psychiatric disorders (e.g. schizophrenia, ADHD, bipolar disorder). Functional annotation of ASD-associated eQTLs revealed that they are involved in diverse regulatory processes. In particular, we found significant enrichment of eQTLs within regions repressed by Polycomb proteins in the fetal cortex compared to the adult cortex. Furthermore, we constructed fetal and adult cortex-specific protein-protein interaction networks and identified that ASD-associated regulatory SNPs impact on immune pathways, fatty acid metabolism, ribosome biogenesis, aminoacyl-tRNA biosynthesis and spliceosome in the fetal cortex. By contrast in the adult cortex, they largely affect immune pathways. Overall, our findings highlight potential regulatory mechanisms and pathways important for the etiology of ASD in early brain development and adulthood. This approach, in combination with clinical studies on ASD, will contribute to individualized mechanistic understanding of ASD development.

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Autism Spectrum Disorder: Understanding the Impact of SNPs on Biological Pathways in the Fetal and Adult Cortex

10.21203/rs.3.rs-417234/v1 ◽

2021 ◽

Author(s):

Evgeniia Golovina ◽

Tayaza Fadason ◽

Thierry Jean Lints ◽

Caroline Walker ◽

Mark Hedley Vickers ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Protein Interactions ◽

Ribosome Biogenesis ◽

Neurodevelopmental Disorder ◽

Autism Spectrum ◽

Biological Pathways ◽

Spectrum Disorder ◽

Biological Information ◽

Immune Pathways ◽

The Impact

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by significant and complex genetic etiology. GWAS studies have identified genetic variants associated with ASD, but the functional impacts of these variants remain unknown. Here, we integrated four distinct levels of biological information (GWAS, eQTL, spatial genome organization and protein-protein interactions) to identify potential regulatory impacts of ASD-associated SNPs (p < 5×10-8) on biological pathways within fetal and adult cortical tissues. We found 80 and 58 SNPs that mark regulatory regions (i.e. expression quantitative trait loci or eQTLs) in the fetal and adult cortex, respectively. These eQTLs were also linked to other psychiatric disorders (e.g. schizophrenia, ADHD, bipolar disorder). Functional annotation of ASD-associated eQTLs revealed that they are involved in diverse regulatory processes. In particular, we found significant enrichment of eQTLs within regions repressed by Polycomb proteins in the fetal cortex compared to the adult cortex. Furthermore, we constructed fetal and adult cortex-specific protein-protein interaction networks and identified that ASD-associated regulatory SNPs impact on immune pathways, fatty acid metabolism, ribosome biogenesis, aminoacyl-tRNA biosynthesis and spliceosome in the fetal cortex. By contrast in the adult cortex, they largely affect immune pathways. Overall, our findings highlight potential regulatory mechanisms and pathways important for the etiology of ASD in early brain development and adulthood. This approach, in combination with clinical studies on ASD, will contribute to individualized mechanistic understanding of ASD development.

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Mothers’ and Fathers’ Perspectives on the Causes of Their Child’s Disorder

Journal of Pediatric Psychology ◽

10.1093/jpepsy/jsaa056 ◽

2020 ◽

Vol 45 (7) ◽

pp. 803-811

Author(s):

Anna Felnhofer ◽

Theresa Bussek ◽

Andreas Goreis ◽

Johanna X Kafka ◽

Dorothea König ◽

...

Keyword(s):

Neurodevelopmental Disorders ◽

Help Seeking ◽

Neurodevelopmental Disorder ◽

Illness Perception ◽

Parental Beliefs ◽

Autism Spectrum ◽

Future Research ◽

Psychosomatic Disorders ◽

Psychosomatic Disorder ◽

Mothers And Fathers

Abstract Background Parental beliefs about the cause of their child’s illness are thought to affect parents’ help-seeking behaviors, treatment decisions, and the child’s health outcomes. Yet, research on parental beliefs about disease causation is still scarce. While a small number of studies assesses parental cause attributions for singular disorders (e.g., neurodevelopmental disorders), no study has compared disorders with differing physical versus mental conditions or with mixed comorbidities in children and adolescents or their caregivers. Furthermore, most pediatric research suffers from a lack of data on fathers. Objective Hence, the objective of the current study was to test for possible differences in mothers’ and fathers’ perceptions about the etiology of their child’s illness. Methods Forty-two parent couples (overall N = 84) whose child had been diagnosed either with Attention Deficit Hyperactivity-Disorder (ADHD) or Autism Spectrum Disorder (ASD) (category “neurodevelopmental disorder”) or with a primary physical illness and a comorbid mental disorder, e.g. depression (category “psychosomatic disorder”) were asked to rate possible causes of their child’s illness using a modified version of the revised Illness Perception Questionnaire (IPQ) Cause scale. Results A two-way ANOVA showed that psychosomatic disorders were significantly more strongly attributed to be caused by medical and environmental stressors than neurodevelopmental disorders. A significant parent × illness category interaction revealed that this effect was more pronounced in fathers. Conclusions By providing first insights into parental beliefs about the etiology of their children’s neurodevelopmental versus psychosomatic disorders, this study paves ground for future research and tailored counseling of affected families.

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Integration and segregation in Autism Spectrum Disorders modulated by age, disease, and interaction: A graph theoretic study of intrinsic functional connectivity

10.1101/278846 ◽

2018 ◽

Author(s):

Vatika Harlalka ◽

Shruti Naik ◽

Raju S. Bapi ◽

P.K. Vinod ◽

Dipanjan Roy

Keyword(s):

Data Exchange ◽

Diffusion Tensor ◽

Neurodevelopmental Disorder ◽

Autism Spectrum ◽

Developmental Trajectory ◽

Clustering Coefficient ◽

Functional Networks ◽

Graph Theoretic ◽

Network Measures ◽

Effect Of Age

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 50 children between the ages of 6 and 17 years. Brain connectivity and graph theoretic methods have been particularly very useful in shedding light on the differences between high functioning autistic children compared to typically developing (TD) ones. However, very recent developments in network measures raise a cautionary note by highlighting gross under- and over-connectivity in ASD may be an oversimplified hypothesis. Thus the primary aim of our study is to investigate these notions in functional connectomics of ASD versus TD by subjecting the data to reproducibility experiments using two independent datasets.Further, we tested the hypothesis of alteration in network segregation and integration in the ASD subjects. We have analyzed the resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) data from the University of California Los Angeles (UCLA) multimodal connectivity database (n=42 ASD, n=37 TD) and rs-fMRI data from the Autism Brain Imaging Data Exchange (ABIDE) (n=187 ASD, n=176 TD) dataset. We assessed the differences in connection strength between TD and ASD subjects. We also performed graph theoretical analysis to analyze the effect of disease on various network measures. Further, using the larger ABIDE dataset, we performed two-factor ANOVA test, to study the effect of age, disease and their interaction by classifying the TD and ASD participants into two cohorts: children (9-12 years, n=73 TD and n=87 ASD) and adolescents (13-16 years, n=103 TD and n=100 ASD). In ASD, we show the existence of atypical connectivity within and between functional networks as compared to TD. We also found in ASD both hypo-and hyper-connectivity within functional networks such as the default mode network (DMN). Further, graph theoretic analysis showed that there is significant effect of age and disease on modularity, clustering coefficient, and local efficiency. We also identified specific areas within the DMN, sensorimotor, visual and attention networks that are affected by age, disease and their interaction. Overall, our findings suggest that maturation, disease and their interaction are critical for unraveling the biological basis and developmental trajectory in ASD and other neuropsychiatric disorders.

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Shared microbial community changes in female rats and humans with Rett syndrome

10.21203/rs.2.19018/v1 ◽

2019 ◽

Author(s):

Allison Gallucci ◽

Kelsey Patterson ◽

Abigael Weit ◽

William Van Der Pol ◽

Laura Dubois ◽

...

Keyword(s):

Microbial Community ◽

Rett Syndrome ◽

Zinc Finger ◽

Rat Model ◽

Gut Microbiome ◽

Neurodevelopmental Disorder ◽

Autism Spectrum ◽

Zinc Finger Nuclease ◽

Female Rats ◽

The Impact

Abstract Background Rett syndrome (RTT) is an X-linked neurodevelopmental disorder predominantly caused by alterations of the methyl-CpG-binding protein 2 (MECP2) gene. The gut microbiome has been implicated in neurodevelopmental disorders such as Autism Spectrum Disorder (ASD) as a regulator of disease severity. Although the gut microbiome has been previously characterized in humans with RTT, the impact of MECP2 mutation on the composition of the gut microbiome in animal models where the host and diet can be experimentally controlled remains to be elucidated.Methods We evaluated the microbial community through 16S sequencing of fecal samples collected across postnatal development as behavioral symptoms appear and progress in a novel zinc-finger nuclease rat model of RTT. Additionally, we profiled fecal levels of fatty acids in MecP2 deficient rats. Lastly, we compared our results to predicted functional shifts in the microbiota of females with RTT compared to their mothers to further examine the translational potential of the current RTT rat model.Results We have identified microbial taxa that are differentially abundant across key timepoints in a zinc-finger nuclease rat model of RTT compared to WT. Furthermore, we have characterized functional categories of gut microbes that are similarly affected in females with RTT and female RTT rats, including similar alterations in pathways related to short chain fatty acid (SCFA) activity. Lastly, we have demonstrated that SCFA levels are decreased in the feces of RTT rats compared to WT.Limitations The current study is potentially limited by age related differences in the microbiome of RTT participants and controls as well as medication effects on the microbiome. Additionally, the current study did not assess male MeCP2-deficient rats, and it may be relevant in future studies to address potentially disparate microbial changes in male and female rats and humans with RTT.Conclusions The results of our studies establish distinct microbial community shifts that occur in RTT across developmental time points independently of diet or environmental factors. We identify p105 as a key translational timepoint at which microbial shifts most closely mirror reported microbiota communities in RTT patients. Overall, these results represent an important step in translational RTT research.

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Translating genetic and preclinical findings into autism therapies

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2017.19.4/cmanzini ◽

2017 ◽

Vol 19 (4) ◽

pp. 335-343

Keyword(s):

Neurodevelopmental Disorder ◽

Genetic Research ◽

Autism Spectrum ◽

In Vitro Models ◽

Valuable Insight ◽

Current State ◽

Copy Number Changes ◽

The Impact

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and repetitive/restrictive interests. ASD is associated with multiple comorbidities, including intellectual disability, anxiety, and epilepsy. Evidence that ASD is highly heritable has spurred major efforts to unravel its genetics, revealing possible contributions from hundreds of genes through rare and common variation and through copy-number changes. In this perspective, we provide an overview of the current state of ASD genetics and of how genetic research has spurred the development of in vivo and in vitro models using animals and patient cells to evaluate the impact of genetic mutations on cellular function leading to disease. Efforts to translate these findings into successful therapies have yet to bear fruit. We discuss how the valuable insight into the disorder provided by these new models can be used to better understand ASD and develop future clinical trials.

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A Perturbação do Espetro do Autismo na Primeira Infância: O Modelo do Centro de Estudos do Bebé e da Criança de Avaliação Diagnóstica e Intervenção Terapêutica

Acta Médica Portuguesa ◽

10.20344/amp.13397 ◽

2021 ◽

Vol 34 (13) ◽

Author(s):

Cristina Martins Halpern ◽

Pedro Caldeira da Silva ◽

Diana Costa ◽

Maria João Nascimento ◽

Joana Mesquita Reis ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Language Disorder ◽

Autism Spectrum ◽

Developmental Trajectory ◽

Early Infancy ◽

Spectrum Disorder ◽

Initial Assessment ◽

Diagnostic Challenge ◽

Axis I ◽

The Impact

Introduction: The Centro de Estudos do Bebé e da Criança in Hospital Dona Estefânia has organized a multidisciplinary model for children under three with suspected autism spectrum disorder, thus implementing the recent guidelines established by the Directorate General for Health. The aim of this study is to describe this model and case series.Material and Methods: A retrospective descriptive study of observed children with suspected ASD. They were observed according to the model of the Centro de Estudos do Bebé e da Criança and DC:0-5TM classification, between January 2018 and September 2019.Results: The study included 178 children. The average age at the initial assessment was 27 months. From the total sample, 116 children concluded the diagnostic sessions (axis I): Autism Spectrum Disorder/Early Atypical (36%), Developmental Language Disorder (18%), Other (19%). Factors of axes II, III, IV and V of DC:0-5TM were determinant for clinical diagnosis in 26%.Discussion: Of 116 children, 36% were diagnosed with Autism Spectrum Disorder. This highlights the diagnostic challenge posed by neurodevelopmental disorders in early infancy. The sample shows that the characteristics of the relationship with the caregiver (axis II), presence of physical conditions (axis III), psycho-social stressors (axis IV) and developmental trajectory (axis V) have a significant clinical impact. In the future, the initial assessment should take place well before the age of 27 months because of the impact on prognosis.Conclusion: This model is a pioneering approach in Portugal. It promotes a common approach of Child and Adolescent Psychiatry and Neuropediatrics/Developmental Pediatrics in early infancy. Moreover, it increases the diagnostic acuity of Autism Spectrum Disorders and early therapeutic intervention.

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Autism Spectrum Disorder Risk Factor Met Regulates the Organization of Inhibitory Synapses

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.659856 ◽

2021 ◽

Vol 14 ◽

Author(s):

Pauline Jeckel ◽

Martin Kriebel ◽

Hansjürgen Volkmer

Keyword(s):

Autism Spectrum Disorder ◽

Neurodevelopmental Disorder ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Scaffolding Protein ◽

Inhibitory Synapses ◽

Gabaergic Synapses ◽

The Impact

A common hypothesis explains autism spectrum disorder (ASD) as a neurodevelopmental disorder linked to excitatory/inhibitory (E/I) imbalance in neuronal network connectivity. Mutation of genes including Met and downstream signaling components, e.g., PTEN, Tsc2 and, Rheb are involved in the control of synapse formation and stabilization and were all considered as risk genes for ASD. While the impact of Met on glutamatergic synapses was widely appreciated, its contribution to the stability of inhibitory, GABAergic synapses is poorly understood. The stabilization of GABAergic synapses depends on clustering of the postsynaptic scaffolding protein gephyrin. Here, we show in vivo and in vitro that Met is necessary and sufficient for the stabilization of GABAergic synapses via induction of gephyrin clustering. Likewise, we provide evidence for Met-dependent gephyrin clustering via activation of mTOR. Our results support the notion that deficient GABAergic signaling represents a pathomechanism for ASD.

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