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Genes Jan 2022Fragile X syndrome (FXS) causes intellectual disability and is the known leading cause of autism. Common problems in FXS include behavior and social problems. Along with... (Review)
Review
Fragile X syndrome (FXS) causes intellectual disability and is the known leading cause of autism. Common problems in FXS include behavior and social problems. Along with syndromic characteristics and autism comorbidity, environmental factors might influence these difficulties. This systematic review focuses on the last 20 years of studies concerning behavior and social problems in FXS, considering environmental and personal variables that might influence both problems. Three databases were reviewed, leading to fifty-one studies meeting the inclusion criteria. Attention deficit hyperactivity disorder (ADHD) problems remain the greatest behavior problems, with behavioral problems and social competence being stable during the 20 years. Some developmental trajectories might have changed due to higher methodological control, such as aggressive behavior and attention problems. The socialization trajectory from childhood to adolescence remains unclear. Comorbidity with autism in individuals with FXS increased behavior problems and worsened social competence profiles. At the same time, comparisons between individuals with comorbid FXS and autism and individuals with autism might help define the comorbid phenotype. Environmental factors and parental characteristics influenced behavior problems and social competence. Higher methodological control is needed in studies including autism symptomatology and parental characteristics. More studies comparing autism in FXS with idiopathic autism are needed to discern differences between conditions.
Topics: Autistic Disorder; Child; Fragile X Syndrome; Humans; Intellectual Disability; Problem Behavior; Social Skills
PubMed: 35205326
DOI: 10.3390/genes13020280 -
Neuroscience and Biobehavioral Reviews Jul 2022Individuals with syndromic intellectual disability are at increased risk of experiencing anxiety. Comparing prevalence estimates of anxiety will allow the identification... (Meta-Analysis)
Meta-Analysis Review
Individuals with syndromic intellectual disability are at increased risk of experiencing anxiety. Comparing prevalence estimates of anxiety will allow the identification of at-risk groups and inform causal pathways of anxiety. No known study has explored estimates of anxiety symptomatology and diagnosis, including specific anxiety profiles, across groups whilst accounting for methodological quality of studies. This systematic review and meta-analysis aimed to fill this gap. Prior to review completion, methodology and analysis plans were registered and documented in a protocol (CRD42019123561). Data from 83 papers, involving a pooled sample of 13,708 across eight syndromes were synthesised using a random effects model. Anxiety prevalence ranged from 9 % (95 % CI: 4-14) in Down syndrome to 73% in Rett syndrome (95 % CI: 70-77). Anxiety prevalence across syndromic intellectual disability was higher than for intellectual disability of mixed aetiology and general population estimates. Substantial variability between syndromes identified groups at higher risk than others. The identification of high-risk groups is crucial for early intervention, allowing us to refine models of risk and identify divergent profiles.
Topics: Anxiety; Anxiety Disorders; Down Syndrome; Humans; Intellectual Disability; Prevalence
PubMed: 35661754
DOI: 10.1016/j.neubiorev.2022.104719 -
Neurological Sciences : Official... Jun 2024The diagnostic criteria for adult-onset Alzheimer's disease (AD) in patients with Down syndrome (DS) have not been standardised. This study investigated the specific... (Meta-Analysis)
Meta-Analysis Review
The diagnostic criteria for adult-onset Alzheimer's disease (AD) in patients with Down syndrome (DS) have not been standardised. This study investigated the specific symptoms of AD in the prodromal stage of DS, the mean age at diagnosis at each stage of dementia, and the relationship between intellectual disability (ID) and dementia. PubMed, Web of Science, and Embase were searched for studies on DS, AD, early-stage disease, initial symptoms, and prodromal dementia registered between January 2012 and January 2022. We also performed a meta-analysis of the differences between the mean age at prodromal symptoms and AD diagnosis and the proportion of mild cognitive impairment in patients with mild and moderately abnormal ID. We selected 14 articles reporting the behavioural and psychological symptoms of dementia (BPSD) and memory- and language-related impairments as early symptoms of AD in patients with DS. The specific symptoms of BPSD were classified into five categories: irritability (agitation), apathy, abnormal behaviour, adaptive functioning, and sleep disturbance. The mean age at the diagnosis of prodromal symptoms and AD dementia was 52.7 and 56.2 years, respectively (mean difference, + 3.11 years; 95% CI 1.82-4.40) in the meta-analysis. The diagnosis of mild dementia tended to correlate with ID severity (odds ratio [OR], 1.38; 95% CI 0.87-2.18). The features of behaviour-variant frontotemporal dementia may be clinically confirmed in diagnosing early symptoms of DS-associated AD (DSAD). Moreover, age-appropriate cognitive assessment is important. Further studies are required to evaluate DSAD using a combination of biomarkers and ID-related data.
Topics: Down Syndrome; Humans; Alzheimer Disease; Prodromal Symptoms; Cognitive Dysfunction
PubMed: 38228941
DOI: 10.1007/s10072-023-07292-9 -
Annals of Medicine Dec 2022Psychotropic medications are commonly prescribed among adults with intellectual disability, often in the absence of a psychiatric diagnosis. The aim of this scoping...
BACKGROUND/OBJECTIVE(S)
Psychotropic medications are commonly prescribed among adults with intellectual disability, often in the absence of a psychiatric diagnosis. The aim of this scoping review is to provide an overview of the extent, range, and nature of the available research on medication use and practices and medication management in people with intellectual disability taking psychotropic medications for behaviours that challenge.
MATERIALS AND METHODS
A scoping review of research studies (qualitative, quantitative, and mixed design) and Grey Literature (English) was carried out. Databases included: Ovid MEDLINE, Embase, CINAHL, JBI Evidence Synthesis, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PsycINFO, and Scopus. A three-step search strategy was followed, with results screened by two independent reviewers. Data was extracted independently by two reviewers using a data extraction tool with results mapped and presented using a narrative form supported by tables and diagrams to the research questions.
RESULTS
Following the removal of duplicates, records were screened, full texts assessed, and 49 studies were included. Medication outcomes included reduced repetitive, stereotypic, and/or aggressive behaviours. High dosing/prescribing in the setting of an absent/unclear clinical indication was associated with worsening of symptoms for which psychotropics were prescribed. While psychotropics had a role in managing behaviours that challenge, reducing or discontinuing psychotropics is sometimes warranted. Study designs were frequently pragmatic resulting in small sample sizes and heterogeneous cohorts receiving different doses and combinations of medications. Access to multidisciplinary teams, guidelines, medication reviews, staff training, and enhanced roles for carers in decision-making were warranted to optimize psychotropic use.
CONCLUSIONS
These findings can inform prescribing interventions and highlight the need for timely and comprehensive patient outcome data, especially on long-term use of high doses of psychotropics and what happens when reduce or stop prescribing these doses.KEY MESSAGESPsychotropic medications are frequently prescribed for people with intellectual disabilities, often at high doses and these medications are associated with both positive and negative patient outcomes.Work to rationalize psychotropic use has been reported with interventions aiming to reduce polypharmacy or deprescribe a single psychotropic medicine. These interventions had mixed success and risk of relapse was documented in some studies.Limitations in sample size and heterogenous patient cohorts make it challenging to understand the risks and benefits associated with reducing or stopping psychotropic medicines.Patient, carer, and clinician partnerships are critical to advance medication management.
Topics: Adult; Databases, Factual; Humans; Intellectual Disability; Polypharmacy; Psychotropic Drugs; Systematic Reviews as Topic
PubMed: 36120887
DOI: 10.1080/07853890.2022.2121853 -
International Journal of Psychiatry in... Mar 2017Background Subjects with intellectual disability are at increased risk of having comorbid psychiatric disorders and worse response to psychotherapeutic and... (Review)
Review
Background Subjects with intellectual disability are at increased risk of having comorbid psychiatric disorders and worse response to psychotherapeutic and psychopharmacological treatment interventions. On the other hand, available data on best treatment approach in this population are scarce and lack scientific evidence due to methodological limitations. The present study aims to perform a systematic review of the literature to facilitate the use of psychotropic drugs in clinical practice and better establish future research targets in this field. Objectives To review the available psychopharmacological strategies for patients with intellectual disabilities, psychiatric disorders, and behavioural disturbances. Serve as a quick guide for clinicians working in the field of intellectual disability. Methods We conducted a selective evidence-based review of the literature using Pubmed and EMBASE databases and selected most recent and relevant papers for this review. Results There are several available psychotropic drugs for the treatment of patients with intellectual disability and comorbid psychiatric disorders, although scientific evidence is limited. Treatment should be individualized according to risk-benefit balance. Discussion Further studies are needed and new available drugs should be considered to gain knowledge in effectiveness of different therapeutic approaches available in this population.
Topics: Adult; Humans; Intellectual Disability; Mental Disorders; Psychotropic Drugs
PubMed: 28792289
DOI: 10.1177/0091217417720896 -
Molecular Genetics and Metabolism 2022Arginase 1 Deficiency (ARG1-D) is a rare, progressive, metabolic disorder that is characterized by devastating manifestations driven by elevated plasma arginine levels.... (Review)
Review
BACKGROUND
Arginase 1 Deficiency (ARG1-D) is a rare, progressive, metabolic disorder that is characterized by devastating manifestations driven by elevated plasma arginine levels. It typically presents in early childhood with spasticity (predominately affecting the lower limbs), mobility impairment, seizures, developmental delay, and intellectual disability. This systematic review aims to identify and describe the published evidence outlining the epidemiology, diagnosis methods, measures of disease progression, clinical management, and outcomes for ARG1-D patients.
METHODS
A comprehensive literature search across multiple databases such as MEDLINE, Embase, and a review of clinical studies in ClinicalTrials.gov (with results reported) was carried out per PRISMA guidelines on 20 April 2020 with no date restriction. Pre-defined eligibility criteria were used to identify studies with data specific to patients with ARG1-D. Two independent reviewers screened records and extracted data from included studies. Quality was assessed using the modified Newcastle-Ottawa Scale for non-comparative studies.
RESULTS
Overall, 55 records reporting 40 completed studies and 3 ongoing studies were included. Ten studies reported the prevalence of ARG1-D in the general population, with a median of 1 in 1,000,000. Frequently reported diagnostic methods included genetic testing, plasma arginine levels, and red blood cell arginase activity. However, routine newborn screening is not universally available, and lack of disease awareness may prevent early diagnosis or lead to misdiagnosis, as the disease has overlapping symptomology with other diseases, such as cerebral palsy. Common manifestations reported at time of diagnosis and assessed for disease progression included spasticity (predominately affecting the lower limbs), mobility impairment, developmental delay, intellectual disability, and seizures. Severe dietary protein restriction, essential amino acid supplementation, and nitrogen scavenger administration were the most commonly reported treatments among patients with ARG1-D. Only a few studies reported meaningful clinical outcomes of these interventions on intellectual disability, motor function and adaptive behavior assessment, hospitalization, or death. The overall quality of included studies was assessed as good according to the Newcastle-Ottawa Scale.
CONCLUSIONS
Although ARG1-D is a rare disease, published evidence demonstrates a high burden of disease for patients. The current standard of care is ineffective at preventing disease progression. There remains a clear need for new treatment options as well as improved access to diagnostics and disease awareness to detect and initiate treatment before the onset of clinical manifestations to potentially enable more normal development, improve symptomatology, or prevent disease progression.
Topics: Infant, Newborn; Humans; Child, Preschool; Arginase; Intellectual Disability; Hyperargininemia; Seizures; Muscle Spasticity; Arginine; Amino Acids, Essential; Disease Progression; Nitrogen
PubMed: 36049366
DOI: 10.1016/j.ymgme.2022.08.005 -
BMC Psychiatry Jun 2022Migration has been implicated as a risk factor for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), but evidence is still limited and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Migration has been implicated as a risk factor for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), but evidence is still limited and inconsistent. We aim to investigate the relationship between migration status and risk of ASD and ADHD.
METHODS
Electronic databases including PubMed, EMBASE, Web of Science, and PsychINFO were searched to identify observational studies on this topic, from inception to February 2021. Random-effects meta-analysis models were used to pool the summary odds ratio (OR) and 95% confidence interval (95% CI), and subgroup analyses were conducted to detect possible discrepancies in associations. Certainty of evidence was assessed as per the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines.
RESULTS
A total of 13 studies (6,532,546 participants) for ASD, five studies (2,875,070 participants) for ADHD, and six studies (31,158 participants) for hyperactivity were included. Overall, the pooled results indicated that migration was associated with increased risk of ASD (pooled OR: 1.32; 95% CI: 1.07-1.63; P for Z test = 0.010), but no association was found between migration and ADHD (pooled OR: 0.84; 95% CI: 0.53-1.32; P for Z test = 0.452) or hyperactivity (pooled standardized mean difference: -0.073; 95% CIs: - 0.383-0.236; P for Z test = 0.642). Subgroup analyses further demonstrated that maternal migration was ASD risk factor (pooled OR: 1.49; 95% CI: 1.19-1.87), and migrant children were more likely to develop ASD with comorbid intellectual disability (ID) (pooled OR: 1.21, P for interaction = 0.006) than ASD without ID. After standardized the origin of migrants, European migrant children from Americas were at higher risk of ASD and ADHD (pooled OR were 4.13 and 1.26), and increased ASD risk was also observed in African children (pooled OR: 2.72). The GRADE of evidence was very low.
CONCLUSIONS
Maternal migration is a risk factor for ASD, and migrant ASD children are more likely comorbid ID. The role of migration on ADHD remains controversial, more studies are needed to assess the association between migration status and ADHD. Health care practitioners should consider screening and providing extra resources for migrant children.
Topics: Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Child; Comorbidity; Humans; Intellectual Disability; Prevalence
PubMed: 35698047
DOI: 10.1186/s12888-022-04037-4 -
Developmental Medicine and Child... May 2019In an attempt to clarify the debate surrounding the diagnostic validity of childhood disintegrative disorder (CDD), we systematically reviewed its characteristics and... (Review)
Review
AIM
In an attempt to clarify the debate surrounding the diagnostic validity of childhood disintegrative disorder (CDD), we systematically reviewed its characteristics and compared it with autism spectrum disorder (ASD).
METHOD
Four databases were searched (PubMed, PsycINFO, Embase, and Web of Science). Included articles had participants with CDD, as defined by symptoms present in the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision and the International Classification of Diseases, 10th Revision. Comparison groups were those with ASD and ASD with regression. Case studies were excluded.
RESULTS
Twenty articles, comprising 96 participants with CDD (80 males, 16 females), were included. Most studies were cross-sectional. The prevalence of CDD was 1.1 to 9.2 per 100 000, with a mean age at regression of 3 years 2 months (SD 1y 1mo), with a range of 2 years to 7 years. In addition to core CDD symptoms, most had intellectual impairment, anxiety, challenging behaviours, and regressed in toileting skills. Participants with CDD and ASD shared core diagnostic and extra-diagnostic features. However, participants with CDD seemed to have more severe symptoms and a different symptom profile, including apparently typical development before regression, faster regression, more affective symptoms, and more global developmental deficit. Possible genetic and autoimmune neurobiological mechanisms were identified.
INTERPRETATION
There is limited high-quality evidence describing the aetiology and outcomes of CDD. However, given the qualitative and prognostic differences between ASD and CDD, we recommend that future diagnostic criteria should distinguish late-onset regression.
Topics: Autism Spectrum Disorder; Child; Child, Preschool; Humans; Intellectual Disability; Language Disorders; Social Behavior Disorders
PubMed: 30548847
DOI: 10.1111/dmcn.14126 -
Human Genetics Dec 2021ATR-X, an acronym for alpha thalassemia and mental retardation X-linked, syndrome is a congenital condition predominantly affecting males, characterized by mild to...
ATR-X, an acronym for alpha thalassemia and mental retardation X-linked, syndrome is a congenital condition predominantly affecting males, characterized by mild to severe intellectual disability, facial, skeletal, urogenital, and hematopoietic anomalies. Less common are heart defects, eye anomalies, renal abnormalities, and gastrointestinal dysfunction. ATR-X syndrome is caused by germline variants in the ATRX gene. Until recently, the diagnosis of the ATR-X syndrome had been guided by the classical clinical manifestations and confirmed by molecular techniques. However, our new systematic analysis shows that the only clinical sign shared by all affected individuals is intellectual disability, with the other manifestations varying even within the same family. More than 190 different germline ATRX mutations in some 200 patients have been analyzed. With improved and more frequent analysis by molecular technologies, more subtle deletions and insertions have been detected recently. Moreover, emerging technologies reveal non-classic phenotypes of ATR-X syndrome as well as the description of a new clinical feature, the development of osteosarcoma which suggests an increased cancer risk in ATR-X syndrome. This review will focus on the different types of inherited ATRX mutations and their relation to clinical features in the ATR-X syndrome. We will provide an update of the frequency of clinical manifestations, the affected organs, and the genotype-phenotype correlations. Finally, we propose a shift in the diagnosis of ATR-X patients, from a clinical diagnosis to a molecular-based approach. This may assist clinicians in patient management, risk assessment and genetic counseling.
Topics: Animals; Humans; Intellectual Disability; Mental Retardation, X-Linked; Molecular Diagnostic Techniques; Mutation; alpha-Thalassemia
PubMed: 34524523
DOI: 10.1007/s00439-021-02361-5 -
Journal of Intellectual Disability... May 2023Multiple measures of mental health problems and mental wellbeing for adults with intellectual disabilities are available, but investigations into their reliability and... (Review)
Review
BACKGROUND
Multiple measures of mental health problems and mental wellbeing for adults with intellectual disabilities are available, but investigations into their reliability and validity are still in the early stages. The aim of this systematic review was to provide an update to previous evaluations of measures of common mental health problems and wellbeing in adults with mild to moderate intellectual disabilities (ID).
METHODS
A systematic search was performed across three databases (MEDLINE, PsycINFO and SCOPUS). The literature search was limited to the years from 2009 to 2021 and to the original English versions. Ten papers evaluating nine measures were reviewed, and the psychometric properties of these measures were discussed using the Characteristics of Assessment Instructions for Psychiatric Disorders in Persons with Intellectual Developmental Disorders as a framework.
RESULTS
Four measures had at least one rating of 'good' across both dimensions of reliability and at least one dimension of validity and were deemed to have promising psychometric properties: the Clinical Outcomes in Routine Evaluation-Learning Disabilities, Impact of Events Scale-Intellectual Disabilities, Lancaster and Northgate Trauma Scales and Self-Assessment and Intervention (self-report section). Additionally, these measures were developed through consultations with mental health professionals and/or people with IDs and thus were deemed to have good content validity.
CONCLUSIONS
This review informs measurement choice for researchers and clinicians while highlighting a need for continued research efforts into the quality of measures available for people with IDs. The results were limited by incomplete psychometric evaluations of measures available. A paucity of psychometrically robust measures of mental wellbeing was observed.
Topics: Adult; Humans; Mental Health; Psychometrics; Intellectual Disability; Reproducibility of Results; Learning Disabilities
PubMed: 36808653
DOI: 10.1111/jir.13018