|
1
|
Hou Y, Yu L, Liu D, Wilson-Lemoine E, Wu X, Moreira JP, Mujica BF, Mukhopadhyay ES, Novotney AN, Payne JM. Systematic Review and Meta-Analysis: Attention-Deficit/Hyperactivity Disorder Symptoms in Children With Neurofibromatosis Type 1. J Am Acad Child Adolesc Psychiatry 2025; 64:447-462. [PMID: 39709008 DOI: 10.1016/j.jaac.2024.09.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 08/30/2024] [Accepted: 12/12/2024] [Indexed: 12/23/2024]
Abstract
OBJECTIVE This meta-analysis aimed to robustly estimate differences in attention-deficit/hyperactivity disorder (ADHD) symptoms between children and adolescents with and without neurofibromatosis type 1 (NF1). METHOD Systematic literature searches were conducted in Scopus, PsycINFO, Web of Science, PubMed, and ProQuest in September 2022, with a supplemental search conducted in Google Scholar in February 2023. The searches identified 2,153 unique articles. Screening identified 114 academic journal articles that assessed parent/caregiver- or teacher-reported ADHD symptoms for children/adolescents with NF1. Two researchers independently screened articles and extracted data. The primary outcome was group differences in ADHD symptoms between children/adolescents with and without NF1 (Hedges g). Data were analyzed using robust variance estimation and random-effects models. RESULTS The meta-analysis included 70 studies (138 effect sizes), involving 3,653 children/adolescents with NF1 (46% female; mean age = 9.69 years, SD = 2.60 years) and 4,895 children/adolescents without NF1 (48% female; mean age = 10.03 years, SD = 3.10 years). According to parent/caregiver reports, children/adolescents with NF1 exhibited more severe inattentive symptoms (g = 1.20; 95% CI = 1.06-1.35), hyperactive/impulsive symptoms (g = 0.85; 95% CI = 0. 68-1.03), and combined ADHD symptoms (g = 1.02; 95% CI = 0.87-1.17) than unaffected controls. Inattentive ADHD symptoms were more elevated than hyperactivity/impulsivity for children/adolescents with NF1. Larger effect sizes for inattention and hyperactivity/impulsivity were associated with older age, lower intelligence quotient (IQ), and parent/caregiver vs teacher reports. CONCLUSION NF1 is a monogenic condition that has strong associations with elevated ADHD symptoms. Findings highlight the importance of early intervention and targeted support for ADHD-related problems in children with NF1. PLAIN LANGUAGE SUMMARY Increasing evidence has suggested a higher risk for attention-deficit/hyperactivity disorder (ADHD) in individuals with neurofibromatosis type 1 (NF1). In this study of ADHD symptom severity in youth with NF1, the authors analyzed data from 70 articles. The authors found much more severe ADHD symptoms in children and adolescents with NF1 compared to youth without NF1. Inattentive symptoms were more pronounced in children with NIF who were older or had a lower IQ. STUDY PREREGISTRATION INFORMATION Compare the ADHD problems between NF1 and control groups; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=462063.
Collapse
Affiliation(s)
- Yang Hou
- Florida State University, Tallahassee, Florida, USA.
| | - Liyan Yu
- Florida State University, Tallahassee, Florida, USA
| | - Dan Liu
- Florida State University, Tallahassee, Florida, USA
| | | | - Xian Wu
- University of Kentucky, Lexington, Kentucky, USA
| | | | | | | | | | - Jonathan M Payne
- Murdoch Children's Research Institute, Australia and The University of Melbourne, Australia
| |
Collapse
|
|
2
|
Kowal K, Skrzypek M. Altered body as a source of interactional problems in the family of individuals with neurofibromatosis type 1 - A polish study. PLoS One 2024; 19:e0310501. [PMID: 39536012 PMCID: PMC11559997 DOI: 10.1371/journal.pone.0310501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 09/02/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, whose clinical picture is dominated by visible body changes as well as numerous somatic and behavioural abnormalities. AIM The aim of the study was to explore the ways in which the individual experiences NF1 in everyday life, with particular emphasis on the impact of the altered body on family interactions, in addition to the personal and social identity of individuals with NF1. METHODS A qualitative study was performed using individual in-depth interviews with 93 individuals with NF1 (median age: 36.69; range: 18 to 64; 26% males). RESULTS Body changes caused by NF1 determine the specificity of social interactions in the families of the sick. The strength and direction of the impact of body changes on social interactions depends on their type (visibility, invisibility), as well as the meanings given to them. The visibility of disease lesions triggers an attitude of excessive control and stigmatization in the family, especially on the part of the mothers of individuals with NF1, and prompts a tendency to define the individual through the prism of the disease and its bodily manifestations. In turn, the lack of visibility of disease symptoms gives rise to, especially on the part of the fathers of the sick, opposing attitudes of disease denial, normalization of its symptoms and a tendency to question the disease identity of individuals with NF1. The great intensity of interactional problems concerns especially those families in which NF1 was transmitted through inheritance, and family members blame each other for the disease. This leads to repression and denial of the disease, excluding it from the scope of issues discussed in the family, which is an attempt to avoid the attribution of blame for the disease. CONCLUSIONS The body changes resulting from NF1 have social consequences that are of critical importance in the lives of the sick. The impact of NF1 on family interactions depends on the ways in which the disease is understood by the sick individual and his or her family members. The obtained patient-driven data constitute a convenient starting point for designing personalized interventions supporting individuals with NF1 and their families.
Collapse
Affiliation(s)
- Katarzyna Kowal
- Chair of Health Science and Physiotherapy, Wladyslaw Bieganski Collegium Medicum in Jan Dlugosz University in Czestochowa, Czestochowa, Poland
| | - Michał Skrzypek
- DOCENTMED Individual Specialist Medical Practice in Lublin, Lublin, Poland
| |
Collapse
|
|
3
|
Pardej SK, Casnar CL, Yund BD, Klein-Tasman BP. An evaluation of computerized attention and executive function measures for use with school age children with neurofibromatosis type 1. Child Neuropsychol 2024; 30:938-953. [PMID: 38214530 DOI: 10.1080/09297049.2024.2302634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 12/21/2023] [Indexed: 01/13/2024]
Abstract
The present study investigated the performance of children with neurofibromatosis type 1 on computerized assessments of attention and executive function. Relations to ADHD symptomatology were also examined. Participants included 37 children (20 male) with NF1 (9-13 years; Mage = 11.02). Participants completed the NIH Toolbox Dimensional Change Card Sort, List Sort Working Memory (LSWM), and Flanker tasks, as well as Cogstate Identification and One Back tests. ADHD symptomatology was assessed using the K-SADS. Average performance was significantly different from the normative mean on every measure, except LSWM. The NIH Toolbox Flanker and Cogstate Identification tasks detected the highest proportion of participants with at least mild difficulty, and the Cogstate Identification task detected the highest proportion of participants with severe difficulty. Analyses revealed significant relations with ADHD symptomatology for two NIH toolbox tasks. The various computerized measures of attention and executive function offer different information when working with school age children with NF1. The NIH Flanker may offer the most room for change and offers face validity, which may be beneficial for clinical trials research. However, the LSWM shows most support for relations with behavioral indicators of attention and executive challenges.
Collapse
Affiliation(s)
- Sara K Pardej
- Department of Psychology, University of Wisconsin - Milwaukee, Milwaukee, WI, USA
| | | | - Brianna D Yund
- Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
| | | |
Collapse
|
|
4
|
Hocking DR, Sun X, Haebich K, Darke H, North KN, Vivanti G, Payne JM. Delineating Visual Habituation Profiles in Preschoolers with Neurofibromatosis Type 1 and Autism Spectrum Disorder: A Cross-Syndrome Study. J Autism Dev Disord 2024; 54:1998-2011. [PMID: 36877426 DOI: 10.1007/s10803-023-05913-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/21/2023] [Indexed: 03/07/2023]
Abstract
Atypical habituation to repetitive information has been commonly reported in Autism Spectrum Disorder (ASD) but it is not yet clear whether similar abnormalities are present in Neurofibromatosis Type 1 (NF1). We employed a cross-syndrome design using a novel eye tracking paradigm to measure habituation in preschoolers with NF1, children with idiopathic ASD and typically developing (TD) children. Eye movements were recorded to examine fixation duration to simultaneously presented repeating and novel stimuli. Children with NF1 showed a bias for longer look durations to repeating stimuli at the expense of novel stimuli, and slower habituation in NF1 was associated with elevated ASD traits. These findings could indicate aberrant modulation of bottom-up attentional networks that interact with the emergence of ASD phenotypes.
Collapse
Affiliation(s)
- Darren R Hocking
- School of Psychology and Public Health, La Trobe University, Melbourne, Australia.
| | - Xiaoyun Sun
- School of Psychology and Public Health, La Trobe University, Melbourne, Australia
| | - Kristina Haebich
- Murdoch Children's Research Institute, Parkville, Australia
- Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia
| | - Hayley Darke
- Murdoch Children's Research Institute, Parkville, Australia
| | - Kathryn N North
- Murdoch Children's Research Institute, Parkville, Australia
- Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia
| | - Giacomo Vivanti
- A.J. Drexel Autism Institute, Drexel University, 3020 Market Street, Suite 560, 19104-3734, Philadelphia, PA, USA
| | - Jonathan M Payne
- Murdoch Children's Research Institute, Parkville, Australia
- Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia
| |
Collapse
|
|
5
|
Debbaut E, Steyaert J, El Bakkali M. Autism spectrum disorder profiles in RASopathies: A systematic review. Mol Genet Genomic Med 2024; 12:e2428. [PMID: 38581124 PMCID: PMC10997847 DOI: 10.1002/mgg3.2428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 03/10/2024] [Accepted: 03/19/2024] [Indexed: 04/08/2024] Open
Abstract
BACKGROUND RASopathies are associated with an increased risk of autism spectrum disorder (ASD). For neurofibromatosis type 1 (NF1) there is ample evidence for this increased risk, while for other RASopathies this association has been studied less. No specific ASD profile has been delineated so far for RASopathies or a specific RASopathy individually. METHODS We conducted a systematic review to investigate whether a specific RASopathy is associated with a specific ASD profile, or if RASopathies altogether have a distinct ASD profile compared to idiopathic ASD (iASD). We searched PubMed, Web of Science, and Open Grey for data about ASD features in RASopathies and potential modifiers. RESULTS We included 41 articles on ASD features in NF1, Noonan syndrome (NS), Costello syndrome (CS), and cardio-facio-cutaneous syndrome (CFC). Individuals with NF1, NS, CS, and CFC on average have higher ASD symptomatology than healthy controls and unaffected siblings, though less than people with iASD. There is insufficient evidence for a distinct ASD phenotype in RASopathies compared to iASD or when RASopathies are compared with each other. We identified several potentially modifying factors of ASD symptoms in RASopathies. CONCLUSIONS Our systematic review found no convincing evidence for a specific ASD profile in RASopathies compared to iASD, or in a specific RASopathy compared to other RASopathies. However, we identified important limitations in the research literature which may also account for this result. These limitations are discussed and recommendations for future research are formulated.
Collapse
Affiliation(s)
- Edward Debbaut
- Center for Developmental Psychiatry, Department of NeurosciencesKU LeuvenLeuvenBelgium
- Leuven Autism Research (LAuRes)KU LeuvenLeuvenBelgium
| | - Jean Steyaert
- Center for Developmental Psychiatry, Department of NeurosciencesKU LeuvenLeuvenBelgium
- Leuven Autism Research (LAuRes)KU LeuvenLeuvenBelgium
| | | |
Collapse
|
|
6
|
Fournier H, Calcagni N, Morice-Picard F, Quintard B. Psychosocial implications of rare genetic skin diseases affecting appearance on daily life experiences, emotional state, self-perception and quality of life in adults: a systematic review. Orphanet J Rare Dis 2023; 18:39. [PMID: 36823650 PMCID: PMC9951542 DOI: 10.1186/s13023-023-02629-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 02/06/2023] [Indexed: 02/25/2023] Open
Abstract
BACKGROUND Since the beginning of human genetic research, there are very few publications sharing insights of the negative impact of rare genetic skin diseases (RGSD) on patients' experiences. This systematic review assessed the psychosocial implications of these conditions in terms of daily life experiences, emotional state, self-perception, and Quality of Life (QoL). METHODOLOGY A systematic review was carried out on albinism, neurofibromatosis type 1 (NF1), birthmarks and inherited ichthyosis. The PubMed, Scopus, PsycArticle, PsychInfo, Psychology and Behavioral Sciences Collection, and SOCindex databases were queried. Inclusion criteria were adult patients with one of these RGSDs. Simple descriptive statistics and qualitative content analysis were conducted to summarize the main results reported by the authors. RESULTS Of the 9987 articles retrieved, 48 articles were included: albinism (16), NF1 (16), inherited ichthyosis (10), birthmarks (6). The majority of the studies on albinism were conducted in Africa. Twenty-seven studies quantitatively assessed diverse psychological parameters: 13 showed a significant impact of the disease on QoL, five on emotional state, two on self-representation and two others on psychiatric comorbidities. Disease severity and visibility were good predictors of QoL (except for albinism). Body image and appearance concerns were also associated with QoL and emotional state. The 19 qualitative studies highlighted recurring themes across each of these diseases: discrimination and stigma during childhood and adolescence, discomfort in social interactions, guilt of transmission, the importance of social support from family and friends, altered daily life functioning, altered romantic and sex life, limited academic and professional aspirations, lack of interest and support from the medical field, and the unpredictability of the evolution of the disease. The only two mixed-method studies in this review were unable to contribute to any inferential analyses but could corroborate some of the qualitative findings. CONCLUSION These results showed that RGSDs have a significant impact on different aspects of patients' lives. This review has demonstrated that there is a real need for support systems for patients with these diseases. Such systems should be developed to provide them with necessary information and to guide them through an appropriate care pathway.
Collapse
Affiliation(s)
- Hugo Fournier
- Laboratoire de Psychologie (LabPsy) EA4139, Univ. Bordeaux, 3 ter Place de la Victoire, Bâtiment A - 1er étage, 33000 Bordeaux, France
| | | | | | - Bruno Quintard
- Laboratoire de Psychologie (LabPsy) EA4139, Univ. Bordeaux, 3 ter Place de la Victoire, Bâtiment A - 1er étage, 33000 Bordeaux, France
| |
Collapse
|
|
7
|
Chiavarino F, Pruccoli J, Cecconi I, Vancini N, Cordelli DM, Parmeggiani A. Eating disorders in young patients with neurofibromatosis type 1. J Paediatr Child Health 2023; 59:723-728. [PMID: 36789625 DOI: 10.1111/jpc.16377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 01/17/2023] [Accepted: 02/01/2023] [Indexed: 02/16/2023]
Abstract
AIM We describe the association of neurofibromatosis type 1 (NF1) and feeding and eating disorders (FED) in five patients admitted to our third level centre for both FED and NF1. METHODS Case series of five adolescent females with NF1 treated for FED. RESULTS We collected data from five patients with NF1 aged between 14 and 22 years, all females. The onset of eating disorder symptoms occurred between 13 and 19 years of age and was characterised by food intake restriction, associated with physical hyperactivity in three out of five cases. One patient also reported self-injurious acts and episodic binges. Patients received diagnoses of anorexia nervosa (AN, n = 2), atypical AN (n = 1), bulimia nervosa (n = 1), unspecified feeding and eating disorder (n = 1). CONCLUSION The current literature reports a single case of an adult with NF1 and comorbid AN, focusing on the dermatological features of NF1. Our article describes a case series of five patients in developmental age affected by NF1 and FED. Clinical and psychological features of NF1 may play a role in the pathogenesis of FED when these two conditions co-occur. The dermatological alterations of NF1 may contribute to body image distortion that characterises AN. Further research is required to systematically screen populations of patients with NF1 for the presence of FED.
Collapse
Affiliation(s)
- Francesca Chiavarino
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Centro Regionale per i Disturbi della Nutrizione e dell'Alimentazione in Età Evolutiva, Centro HUB Regionale Neurofibromatosi, U.O.C. Neuropsichiatria dell'Età Pediatrica, Bologna, Italy.,Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy
| | - Jacopo Pruccoli
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Centro Regionale per i Disturbi della Nutrizione e dell'Alimentazione in Età Evolutiva, Centro HUB Regionale Neurofibromatosi, U.O.C. Neuropsichiatria dell'Età Pediatrica, Bologna, Italy.,Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy
| | - Ilaria Cecconi
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Centro Regionale per i Disturbi della Nutrizione e dell'Alimentazione in Età Evolutiva, Centro HUB Regionale Neurofibromatosi, U.O.C. Neuropsichiatria dell'Età Pediatrica, Bologna, Italy
| | - Nicolò Vancini
- Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy
| | - Duccio M Cordelli
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Centro Regionale per i Disturbi della Nutrizione e dell'Alimentazione in Età Evolutiva, Centro HUB Regionale Neurofibromatosi, U.O.C. Neuropsichiatria dell'Età Pediatrica, Bologna, Italy.,Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy
| | - Antonia Parmeggiani
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Centro Regionale per i Disturbi della Nutrizione e dell'Alimentazione in Età Evolutiva, Centro HUB Regionale Neurofibromatosi, U.O.C. Neuropsichiatria dell'Età Pediatrica, Bologna, Italy.,Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy
| |
Collapse
|
|
8
|
Demographic and Disease-Related Predictors of Socioemotional Development in Children with Neurofibromatosis Type 1 and Plexiform Neurofibromas: An Exploratory Study. Cancers (Basel) 2022; 14:cancers14235956. [PMID: 36497438 PMCID: PMC9737030 DOI: 10.3390/cancers14235956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 11/24/2022] [Accepted: 11/29/2022] [Indexed: 12/05/2022] Open
Abstract
Individuals with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PNs) have a higher risk for socioemotional problems. The current study aims to identify the socioemotional developmental pattern and its predictors across childhood and adolescence in individuals with NF1 and PNs. Participants included 88 children with NF1 and PNs (aged 6-18 years old, M = 12.05, SD = 3.62, 57% male) in a natural history study. Neuropsychological assessments were administered three times over six years. There are large variabilities in socioemotional development in the study participants. Developmental patterns varied across socioemotional domains, respondent type (parent-report [PR] vs. child-report [CR]), demographic factors, and NF1 disease-related factors. For instance, lower parental education was associated with a greater decline in internalizing problems (PR) but a greater increase in school disconnectedness (CR) over time. Non-White (vs. White) children were more likely to experience increased adaptive skills (PR) but decreased personal adjustment (CR). Children with more visible tumors experienced a greater decrease in school disconnectedness (CR). Children with more NF1 complications experienced a greater decrease in externalizing problems (PR). These findings indicate the necessity of using multi-informants and investigating subdomains of socioemotional functions. They also highlight the importance of developing individualized approaches to patient care and interventions.
Collapse
|
|
9
|
Houpt AC, Schwartz SE, Coover RA. Assessing Psychiatric Comorbidity and Pharmacologic Treatment Patterns Among Patients With Neurofibromatosis Type 1. Cureus 2021; 13:e20244. [PMID: 35004058 PMCID: PMC8735883 DOI: 10.7759/cureus.20244] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/03/2021] [Indexed: 11/17/2022] Open
Abstract
Background and objective Neurofibromatosis 1 (NF1) is a genetic disorder that is accompanied by psychiatric comorbidities such as depression, anxiety, and attention-deficit hyperactivity disorder (ADHD) in more than half of the patients. However, there are limited data describing optimal treatment strategies for these conditions. This study aimed to address that gap in understanding and explore the neurobiological basis of psychiatric comorbidities in NF1. Materials and methods A retrospective cohort study was conducted among NF1 patients with a comorbid diagnosis of depression, anxiety, and/or ADHD. These disease states were chosen based on their relatively high reported prevalence in NF1 and shared pathophysiological mechanisms via monoaminergic dysfunction. Information regarding demographics, psychotherapeutic medication use, and clinical outcomes was gathered from electronic medical records. Relationships between patient- and medication-related factors and outcome measures were assessed using statistical analysis. Results The study population (n = 82) consisted of NF1 patients with a comorbid diagnosis of depression (76.8%), anxiety (53.7%), and/or ADHD (23.2%). The use of second-generation antipsychotic agent augmentation therapy or hydroxyzine monotherapy was associated with significantly more behavioral health (BH)-related emergency department (ED) visits, admissions, and inpatient days in the study population. Conversely, the use of bupropion augmentation therapy, buspirone augmentation therapy, and stimulants was associated with improved clinical outcomes, though these results were not statistically significant. Conclusions Based on our findings in this real-world study setting, patients with NF1 and psychiatric comorbidities appear to experience significant benefits from medications that enhance dopaminergic neurotransmission (e.g., bupropion, stimulants) when compared to drugs that oppose it (e.g., second-generation antipsychotics).
Collapse
|
|
10
|
Nadeem MS, Hosawi S, Alshehri S, Ghoneim MM, Imam SS, Murtaza BN, Kazmi I. Symptomatic, Genetic, and Mechanistic Overlaps between Autism and Alzheimer's Disease. Biomolecules 2021; 11:1635. [PMID: 34827633 PMCID: PMC8615882 DOI: 10.3390/biom11111635] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 10/26/2021] [Accepted: 11/01/2021] [Indexed: 02/02/2023] Open
Abstract
Autism spectrum disorder (ASD) and Alzheimer's disease (AD) are neurodevelopmental and neurodegenerative disorders affecting two opposite ends of life span, i.e., childhood and old age. Both disorders pose a cumulative threat to human health, with the rate of incidences increasing considerably worldwide. In the context of recent developments, we aimed to review correlated symptoms and genetics, and overlapping aspects in the mechanisms of the pathogenesis of ASD and AD. Dementia, insomnia, and weak neuromuscular interaction, as well as communicative and cognitive impairments, are shared symptoms. A number of genes and proteins linked with both disorders have been tabulated, including MECP2, ADNP, SCN2A, NLGN, SHANK, PTEN, RELN, and FMR1. Theories about the role of neuron development, processing, connectivity, and levels of neurotransmitters in both disorders have been discussed. Based on the recent literature, the roles of FMRP (Fragile X mental retardation protein), hnRNPC (heterogeneous ribonucleoprotein-C), IRP (Iron regulatory proteins), miRNAs (MicroRNAs), and α-, β0, and γ-secretases in the posttranscriptional regulation of cellular synthesis and processing of APP (amyloid-β precursor protein) have been elaborated to describe the parallel and overlapping routes and mechanisms of ASD and AD pathogenesis. However, the interactive role of genetic and environmental factors, oxidative and metal ion stress, mutations in the associated genes, and alterations in the related cellular pathways in the development of ASD and AD needs further investigation.
Collapse
Affiliation(s)
- Muhammad Shahid Nadeem
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (M.S.N.); (S.H.)
| | - Salman Hosawi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (M.S.N.); (S.H.)
| | - Sultan Alshehri
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; (S.A.); (S.S.I.)
| | - Mohammed M. Ghoneim
- Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Saudi Arabia;
| | - Syed Sarim Imam
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; (S.A.); (S.S.I.)
| | - Bibi Nazia Murtaza
- Department of Zoology, Abbottabad University of Science and Technology (AUST), Abbottabad 22310, Pakistan;
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (M.S.N.); (S.H.)
| |
Collapse
|
|
11
|
Glad DM, Casnar CL, Yund BD, Lee K, Klein-Tasman BP. Parent-Reported Social Skills in Children with Neurofibromatosis Type 1: Longitudinal Patterns and Relations with Attention and Cognitive Functioning. J Dev Behav Pediatr 2021; 42:656-665. [PMID: 34618723 PMCID: PMC8944791 DOI: 10.1097/dbp.0000000000000939] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 01/27/2021] [Indexed: 11/25/2022]
Abstract
OBJECTIVE Social skills difficulties are commonly reported by parents and teachers of school age (SA) children with neurofibromatosis type 1 (NF1). Investigations of social skills of young children with NF1 are scarce. This study aimed to characterize the emergence of social skills challenges beginning in early childhood, examine social skills longitudinally into SA, and explore interrelations with attention-deficit hyperactivity disorder (ADHD) symptomatology and cognitive functioning among children with NF1 cross-sectionally and longitudinally. METHOD Three samples of children with NF1 and their parents participated: (1) early childhood (n = 50; ages 3-6; mean [M] = 3.96, SD = 1.05), (2) SA (n = 40; ages 9-13; [M] = 10.90, SD = 1.59), and (3) both early childhood and SA (n = 25). Parent-reported social skills (Social Skills Rating System and Social Skills Improvement System), ADHD symptomatology (Conners Parent Rating Scales - Revised and Conners - Third Edition), and parent-reported cognitive abilities (Differential Ability Scales - Second Edition) were evaluated. RESULTS Parental ratings of social skills were relatively stable throughout childhood. Ratings of social skills at the end of early childhood significantly predicted school-age social skills. Parental ratings of ADHD symptomatology showed significant negative relations with social skills. Early childhood inattentive symptoms predicted school-age social skills ratings. Cognitive functioning was not significantly related to social skills. CONCLUSION Parent-reported social skills difficulties are evident during early childhood. This work adds to the literature by describing the frequency and stability of social skills challenges in early childhood and in the school-age period in NF1. Research about interventions to support social skills when difficulties are present is needed.
Collapse
Affiliation(s)
- Danielle M. Glad
- Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI
| | - Christina L. Casnar
- Department of Neurology, Division of Neuropsychology, Medical College of Wisconsin, Wauwatosa, WI
| | - Brianna D. Yund
- Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN
| | - Kristin Lee
- Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI
| | | |
Collapse
|
|
12
|
Al-Beltagi M. Autism medical comorbidities. World J Clin Pediatr 2021; 10:15-28. [PMID: 33972922 PMCID: PMC8085719 DOI: 10.5409/wjcp.v10.i3.15] [Citation(s) in RCA: 117] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 02/12/2021] [Accepted: 03/17/2021] [Indexed: 02/06/2023] Open
Abstract
Medical comorbidities are more common in children with autism spectrum disorders (ASD) than in the general population. Some genetic disorders are more common in children with ASD such as Fragile X syndrome, Down syndrome, Duchenne muscular dystrophy, neurofibromatosis type I, and tuberous sclerosis complex. Children with autism are also more prone to a variety of neurological disorders, including epilepsy, macrocephaly, hydrocephalus, cerebral palsy, migraine/headaches, and congenital abnormalities of the nervous system. Besides, sleep disorders are a significant problem in individuals with autism, occurring in about 80% of them. Gastrointestinal (GI) disorders are significantly more common in children with ASD; they occur in 46% to 84% of them. The most common GI problems observed in children with ASD are chronic constipation, chronic diarrhoea, gastroesophageal reflux and/or disease, nausea and/or vomiting, flatulence, chronic bloating, abdominal discomfort, ulcers, colitis, inflammatory bowel disease, food intolerance, and/or failure to thrive. Several categories of inborn-errors of metabolism have been observed in some patients with autism including mitochondrial disorders, disorders of creatine metabolism, selected amino acid disorders, disorders of folate or B12 metabolism, and selected lysosomal storage disorders. A significant proportion of children with ASD have evidence of persistent neuroinflammation, altered inflammatory responses, and immune abnormalities. Anti-brain antibodies may play an important pathoplastic mechanism in autism. Allergic disorders are significantly more common in individuals with ASD from all age groups. They influence the development and severity of symptoms. They could cause problematic behaviours in at least a significant subset of affected children. Therefore, it is important to consider the child with autism as a whole and not overlook possible symptoms as part of autism. The physician should rule out the presence of a medical condition before moving on to other interventions or therapies. Children who enjoy good health have a better chance of learning. This can apply to all children including those with autism.
Collapse
Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatrics, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama P.O. Box 26671, Bahrain, Bahrain
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 0000000, Al Gharbia, Egypt
| |
Collapse
|
|
13
|
Al-Beltagi M. Autism medical comorbidities. World J Clin Pediatr 2021. [PMID: 33972922 DOI: 10.5409/wjcp.v10.i3.15.] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Medical comorbidities are more common in children with autism spectrum disorders (ASD) than in the general population. Some genetic disorders are more common in children with ASD such as Fragile X syndrome, Down syndrome, Duchenne muscular dystrophy, neurofibromatosis type I, and tuberous sclerosis complex. Children with autism are also more prone to a variety of neurological disorders, including epilepsy, macrocephaly, hydrocephalus, cerebral palsy, migraine/headaches, and congenital abnormalities of the nervous system. Besides, sleep disorders are a significant problem in individuals with autism, occurring in about 80% of them. Gastrointestinal (GI) disorders are significantly more common in children with ASD; they occur in 46% to 84% of them. The most common GI problems observed in children with ASD are chronic constipation, chronic diarrhoea, gastroesophageal reflux and/or disease, nausea and/or vomiting, flatulence, chronic bloating, abdominal discomfort, ulcers, colitis, inflammatory bowel disease, food intolerance, and/or failure to thrive. Several categories of inborn-errors of metabolism have been observed in some patients with autism including mitochondrial disorders, disorders of creatine metabolism, selected amino acid disorders, disorders of folate or B12 metabolism, and selected lysosomal storage disorders. A significant proportion of children with ASD have evidence of persistent neuroinflammation, altered inflammatory responses, and immune abnormalities. Anti-brain antibodies may play an important pathoplastic mechanism in autism. Allergic disorders are significantly more common in individuals with ASD from all age groups. They influence the development and severity of symptoms. They could cause problematic behaviours in at least a significant subset of affected children. Therefore, it is important to consider the child with autism as a whole and not overlook possible symptoms as part of autism. The physician should rule out the presence of a medical condition before moving on to other interventions or therapies. Children who enjoy good health have a better chance of learning. This can apply to all children including those with autism.
Collapse
Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatrics, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama P.O. Box 26671, Bahrain, Bahrain
| |
Collapse
|
|
14
|
Fombonne E, MacFarlane H, Salem AC. Epidemiological surveys of ASD: advances and remaining challenges. J Autism Dev Disord 2021; 51:4271-4290. [PMID: 33864555 DOI: 10.1007/s10803-021-05005-9] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/01/2021] [Indexed: 12/25/2022]
Abstract
Recent worldwide epidemiological surveys of autism conducted in 37 countries are reviewed; the median prevalence of autism is .97% in 26 high-income countries. Methodological advances and remaining challenges in designing and executing surveys are discussed, including the effects on prevalence of variable case definitions and nosography, of reliance on parental reports only, case ascertainment through mainstream school surveys, innovative approaches to screen school samples more efficiently, and consideration of age in interpreting surveys. Directions for the future of autism epidemiology are discussed, including the need to systematically examine cross-cultural variation in phenotypic expression and developing surveillance programs.
Collapse
Affiliation(s)
- Eric Fombonne
- Department of Psychiatry, Oregon Health & Science University, Mail code: GH254 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.
| | - Heather MacFarlane
- Department of Psychiatry, Oregon Health & Science University, Mail code: GH254 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA
| | - Alexandra C Salem
- Department of Psychiatry, Oregon Health & Science University, Mail code: GH254 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA
| |
Collapse
|
|
15
|
Morris SM, Acosta MT, Garg S, Green J, Legius E, North K, Payne JM, Weiss LA, Constantino JN, Gutmann DH. Autism in neurofibromatosis type 1: misuse of covariance to dismiss autistic trait burden. Dev Med Child Neurol 2021; 63:233-234. [PMID: 32815557 DOI: 10.1111/dmcn.14653] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 07/24/2020] [Indexed: 11/30/2022]
Affiliation(s)
- Stephanie M Morris
- Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
| | - Maria T Acosta
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
| | - Shruti Garg
- Royal Manchester Children's Hospital, Manchester, UK
| | | | - Eric Legius
- Department of Human Genetics, KU Leuven, Leuven, Belgium
| | - Kathryn North
- Department of Pediatrics, Murdoch Children's Research Institute, University of Melbourne, Melbourne, Vic, Australia
| | - Jonathan M Payne
- Department of Pediatrics, Murdoch Children's Research Institute, University of Melbourne, Melbourne, Vic, Australia
| | - Lauren A Weiss
- Department of Psychiatry, Institute for Human Genetics, University of California, San Francisco, CA, USA
| | - John N Constantino
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
| | - David H Gutmann
- Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
| |
Collapse
|
|
16
|
Klein-Tasman BP. Are the autism symptoms in neurofibromatosis type 1 actually autism? Dev Med Child Neurol 2021; 63:132. [PMID: 32614454 DOI: 10.1111/dmcn.14597] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 05/06/2020] [Indexed: 01/07/2023]
|
|
17
|
Fombonne E, Morotti H, Mastel S, Keller K, Barnard RA, Hall T, O'Roak BJ. Autism questionnaire scores do not only rise because of autism. Dev Med Child Neurol 2021; 63:235-236. [PMID: 33118173 DOI: 10.1111/dmcn.14725] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 10/04/2020] [Accepted: 10/06/2020] [Indexed: 11/26/2022]
Affiliation(s)
- Eric Fombonne
- Department of Psychiatry, Oregon Health & Science University (OHSU), Portland, OR, USA.,Department of Pediatrics & Institute on Development & Disability, OHSU, Portland, OR, USA
| | - Hadley Morotti
- Department of Molecular and Medical Genetics, OHSU, Portland, OR, USA
| | - Sarah Mastel
- Department of Psychiatry, Oregon Health & Science University (OHSU), Portland, OR, USA.,Department of Pediatrics & Institute on Development & Disability, OHSU, Portland, OR, USA
| | - Kory Keller
- Department of Molecular and Medical Genetics, OHSU, Portland, OR, USA
| | - Rebecca A Barnard
- Department of Molecular and Medical Genetics, OHSU, Portland, OR, USA
| | - Trevor Hall
- Department of Pediatrics & Institute on Development & Disability, OHSU, Portland, OR, USA
| | - Brian J O'Roak
- Department of Molecular and Medical Genetics, OHSU, Portland, OR, USA
| |
Collapse
|