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1.
Siglo cero (Madr.) ; 54(4): 65-83, oct.-dic. 2024.
Artículo en Español | IBECS | ID: ibc-EMG-559

RESUMEN

La falta de información sobre el uso de la tecnología en niños con trastorno del espectro autista (TEA) de diferentes perfiles puede dificultar que docentes y alumnos se estén beneficiando del apoyo tecnológico más eficaz y ajustado a sus necesidades. El objetivo de esta revisión fue analizar y sintetizar la evidencia científica sobre la eficacia de los recursos tecnológicos en la mejora de la comprensión emocional de estudiantes con TEA con perfiles de alto y bajo funcionamiento. Para ello se realizó una revisión sistemática de las publicaciones científicas indexadas en algunas de las bases de datos de mayor relevancia siguiendo los criterios establecidos en la declaración PRISMA. En total se analizaron 38 artículos que cumplieron con los criterios de inclusión preestablecidos. Los resultados muestran la importancia de diseñar sistemas versátiles que puedan personalizarse y adaptarse en tiempo real y en contextos naturales con un enfoque claramente inclusivo. Pero también sugieren que la tecnología puede no ser una herramienta de intervención complementaria adecuada para todos los niños con TEA. Lo que subraya la necesidad de ensayos adicionales bien controlados sobre las características que permitan identificar qué estudiantes podrían o no beneficiarse de diferentes modalidades de tecnología. (AU)


The lack of information on the use of technology in children with autism spectrum disorder (ASD) of different profiles can make it difficult for teachers and students to benefit from the most effective technology support tailored to their needs. The aim of this review was to analyze and synthesize scientific evidence on the effectiveness of technological resources in improving the emotional understanding of students with high and low functioning ASD profiles. A systematic review of the scientific publications indexed in some of the most relevant databases was carried out following the criteria established in the PRISMA declaration. A total of 38 articles that met the pre-established inclusion criteria were analyzed. The results show the importance of designing versatile systems that can be customized and adapted in real time and in natural contexts with a clearly inclusive approach. But they also suggest that technology may not be an appropriate complementary intervention tool for all children with ASD. This underlines the need for additional well-controlled tests on the characteristics that would allow identifying which students might or might not benefit from different technology modalities. (AU)


Asunto(s)
Humanos , Preescolar , Niño , Adolescente , Tecnología Educacional , Trastorno del Espectro Autista , Trastorno Autístico
2.
Siglo cero (Madr.) ; 54(4): 65-83, oct.-dic. 2024.
Artículo en Español | IBECS | ID: ibc-229229

RESUMEN

La falta de información sobre el uso de la tecnología en niños con trastorno del espectro autista (TEA) de diferentes perfiles puede dificultar que docentes y alumnos se estén beneficiando del apoyo tecnológico más eficaz y ajustado a sus necesidades. El objetivo de esta revisión fue analizar y sintetizar la evidencia científica sobre la eficacia de los recursos tecnológicos en la mejora de la comprensión emocional de estudiantes con TEA con perfiles de alto y bajo funcionamiento. Para ello se realizó una revisión sistemática de las publicaciones científicas indexadas en algunas de las bases de datos de mayor relevancia siguiendo los criterios establecidos en la declaración PRISMA. En total se analizaron 38 artículos que cumplieron con los criterios de inclusión preestablecidos. Los resultados muestran la importancia de diseñar sistemas versátiles que puedan personalizarse y adaptarse en tiempo real y en contextos naturales con un enfoque claramente inclusivo. Pero también sugieren que la tecnología puede no ser una herramienta de intervención complementaria adecuada para todos los niños con TEA. Lo que subraya la necesidad de ensayos adicionales bien controlados sobre las características que permitan identificar qué estudiantes podrían o no beneficiarse de diferentes modalidades de tecnología. (AU)


The lack of information on the use of technology in children with autism spectrum disorder (ASD) of different profiles can make it difficult for teachers and students to benefit from the most effective technology support tailored to their needs. The aim of this review was to analyze and synthesize scientific evidence on the effectiveness of technological resources in improving the emotional understanding of students with high and low functioning ASD profiles. A systematic review of the scientific publications indexed in some of the most relevant databases was carried out following the criteria established in the PRISMA declaration. A total of 38 articles that met the pre-established inclusion criteria were analyzed. The results show the importance of designing versatile systems that can be customized and adapted in real time and in natural contexts with a clearly inclusive approach. But they also suggest that technology may not be an appropriate complementary intervention tool for all children with ASD. This underlines the need for additional well-controlled tests on the characteristics that would allow identifying which students might or might not benefit from different technology modalities. (AU)


Asunto(s)
Humanos , Preescolar , Niño , Adolescente , Tecnología Educacional , Trastorno del Espectro Autista , Trastorno Autístico
3.
Sci Rep ; 14(1): 8393, 2024 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600134

RESUMEN

Identifying factors linked to autism traits in the general population may improve our understanding of the mechanisms underlying divergent neurodevelopment. In this study we assess whether factors increasing the likelihood of childhood autism are related to early autistic trait emergence, or if other exposures are more important. We used data from 536 toddlers from London (UK), collected at birth (gestational age at birth, sex, maternal body mass index, age, parental education, parental language, parental history of neurodevelopmental conditions) and at 18 months (parents cohabiting, measures of socio-economic deprivation, measures of maternal parenting style, and a measure of maternal depression). Autism traits were assessed using the Quantitative Checklist for Autism in Toddlers (Q-CHAT) at 18 months. A multivariable model explained 20% of Q-CHAT variance, with four individually significant variables (two measures of parenting style and two measures of socio-economic deprivation). In order to address variable collinearity we used principal component analysis, finding that a component which was positively correlated with Q-CHAT was also correlated to measures of parenting style and socio-economic deprivation. Our results show that parenting style and socio-economic deprivation correlate with the emergence of autism traits at age 18 months as measured with the Q-CHAT in a community sample.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Recién Nacido , Humanos , Preescolar , Lactante , Trastorno Autístico/epidemiología , Padres , Escolaridad , Responsabilidad Parental , Composición Familiar , Trastorno del Espectro Autista/epidemiología
4.
Mol Autism ; 15(1): 17, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600595

RESUMEN

BACKGROUND: Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder that can significantly impact an individual's ability to socially integrate and adapt. It's crucial to identify key factors associated with ASD. Recent studies link both birth asphyxia (BA) and febrile seizures (FS) separately to higher ASD prevalence. However, investigations into the interplay of BA and FS and its relationship with ASD are yet to be conducted. The present study mainly focuses on exploring the interactive effect between BA and FS in the context of ASD. METHODS: Utilizing a multi-stage stratified cluster sampling, we initially recruited 84,934 Shanghai children aged 3-12 years old from June 2014 to June 2015, ultimately including 74,251 post-exclusion criteria. A logistic regression model was conducted to estimate the interaction effect after controlling for pertinent covariates. The attributable proportion (AP), the relative excess risk due to interaction (RERI), the synergy index (SI), and multiplicative-scale interaction were computed to determine the interaction effect. RESULTS: Among a total of 74,251 children, 192 (0.26%) were diagnosed with ASD. The adjusted odds ratio for ASD in children with BA alone was 3.82 (95% confidence interval [CI] 2.42-6.02), for FS alone 3.06 (95%CI 1.48-6.31), and for comorbid BA and FS 21.18 (95%CI 9.10-49.30), versus children without BA or FS. The additive interaction between BA and FS showed statistical significance (P < 0.001), whereas the multiplicative interaction was statistically insignificant (P > 0.05). LIMITATIONS: This study can only demonstrate the relationship between the interaction of BA and FS with ASD but cannot prove causation. Animal brain experimentation is necessary to unravel its neural mechanisms. A larger sample size, ongoing monitoring, and detailed FS classification are needed for confirming BA-FS interaction in ASD. CONCLUSION: In this extensive cross-sectional study, both BA and FS were significantly linked to ASD. The coexistence of these factors was associated with an additive increase in ASD prevalence, surpassing the cumulative risk of each individual factor.


Asunto(s)
Trastorno del Espectro Autista , Convulsiones Febriles , Niño , Humanos , Preescolar , Trastorno del Espectro Autista/epidemiología , Convulsiones Febriles/epidemiología , Estudios Transversales , Asfixia , China/epidemiología
5.
Endocr Regul ; 58(1): 105-114, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38656256

RESUMEN

Oxytocin plays an important role in brain development and is associated with various neurotransmitter systems in the brain. Abnormalities in the production, secretion, and distribution of oxytocin in the brain, at least during some stages of the development, are critical for the pathogenesis of neuropsychiatric diseases, particularly in the autism spectrum disorder. The etiology of autism includes changes in local sensory and dopaminergic areas of the brain, which are also supplied by the hypothalamic sources of oxytocin. It is very important to understand their mutual relationship. In this review, the relationship of oxytocin with several components of the dopaminergic system, gamma-aminobutyric acid (GABA) inhibitory neurotransmission and their alterations in the autism spectrum disorder is discussed. Special attention has been paid to the results describing a reduced expression of inhibitory GABAergic markers in the brain in the context of dopaminergic areas in various models of autism. It is presumed that the altered GABAergic neurotransmission, due to the absence or dysfunction of oxytocin at certain developmental stages, disinhibits the dopaminergic signaling and contributes to the autism symptoms.


Asunto(s)
Trastorno Autístico , Encéfalo , Dopamina , Oxitocina , Ácido gamma-Aminobutírico , Oxitocina/metabolismo , Oxitocina/fisiología , Humanos , Dopamina/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Trastorno Autístico/metabolismo , Encéfalo/metabolismo , Animales , Transmisión Sináptica/fisiología , Trastorno del Espectro Autista/metabolismo , Trastorno del Espectro Autista/etiología
6.
Proc Natl Acad Sci U S A ; 121(15): e2317769121, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38564633

RESUMEN

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social and communication deficits and repetitive behaviors. The genetic heterogeneity of ASD presents a challenge to the development of an effective treatment targeting the underlying molecular defects. ASD gating charge mutations in the KCNQ/KV7 potassium channel cause gating pore currents (Igp) and impair action potential (AP) firing of dopaminergic neurons in brain slices. Here, we investigated ASD gating charge mutations of the voltage-gated SCN2A/NaV1.2 brain sodium channel, which ranked high among the ion channel genes with mutations in individuals with ASD. Our results show that ASD mutations in the gating charges R2 in Domain-II (R853Q), and R1 (R1626Q) and R2 (R1629H) in Domain-IV of NaV1.2 caused Igp in the resting state of ~0.1% of the amplitude of central pore current. The R1626Q mutant also caused significant changes in the voltage dependence of fast inactivation, and the R1629H mutant conducted proton-selective Igp. These potentially pathogenic Igp were exacerbated by the absence of the extracellular Mg2+ and Ca2+. In silico simulation of the effects of these mutations in a conductance-based single-compartment cortical neuron model suggests that the inward Igp reduces the time to peak for the first AP in a train, increases AP rates during a train of stimuli, and reduces the interstimulus interval between consecutive APs, consistent with increased neural excitability and altered input/output relationships. Understanding this common pathophysiological mechanism among different voltage-gated ion channels at the circuit level will give insights into the underlying mechanisms of ASD.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Canales de Sodio Activados por Voltaje , Humanos , Trastorno del Espectro Autista/genética , Trastorno Autístico/genética , Encéfalo , Mutación
7.
Mol Biol Rep ; 51(1): 577, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664339

RESUMEN

BACKGROUND: Chromosomal microarray analysis is an essential tool for copy number variants detection in patients with unexplained developmental delay/intellectual disability, autism spectrum disorders, and multiple congenital anomalies. The study aims to determine the clinical significance of chromosomal microarray analysis in this patient group. Another crucial aspect is the evaluation of copy number variants detected in terms of the diagnosis of patients. METHODS AND RESULTS: A Chromosomal microarray analysis was was conducted on a total of 1227 patients and phenotype-associated etiological diagnosis was established in 135 patients. Phenotype-associated copy number variants were detected in 11% of patients. Among these, 77 patients 77 (57%, 77/135) were diagnosed with well-recognized genetic syndromes and phenotype-associated copy number variants were found in 58 patients (42.9%, 58/135). The study was designed to collect data of patients in Kocaeli Derince Training and Research Hospital retrospectively. In our study, we examined 135 cases with clinically significant copy number variability among all patients. CONCLUSIONS: In this study, chromosomal microarray analysis revealed pathogenic de novo copy number variants with new clinical features. Chromosomal microarray analysis in the Turkish population has been reported in the largest patient cohort to date.


Asunto(s)
Anomalías Múltiples , Trastorno del Espectro Autista , Variaciones en el Número de Copia de ADN , Discapacidades del Desarrollo , Humanos , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/diagnóstico , Turquia/epidemiología , Variaciones en el Número de Copia de ADN/genética , Femenino , Masculino , Niño , Preescolar , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/diagnóstico , Anomalías Múltiples/genética , Anomalías Múltiples/diagnóstico , Adolescente , Fenotipo , Lactante , Discapacidad Intelectual/genética , Discapacidad Intelectual/diagnóstico , Aberraciones Cromosómicas , Análisis por Micromatrices/métodos , Estudios Retrospectivos , Adulto
8.
BMC Pediatr ; 24(1): 270, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664754

RESUMEN

BACKGROUND: Recently, studies on behavioral interventions for autism have gained popularity. Naturalistic Developmental Behavior Interventions (NDBIs) are among the most effective, evidence-based, and widely used behavior interventions for autism. However, no research has been conducted on which of the several NDBI methods is most effective for parents and children with autism spectrum disorders. Therefore, we conducted a network meta-analysis to compare the specific effects of each type of parental-mediated NDBI on children's developmental skills and parent fidelity. METHODS: PubMed, Embase, Cochrane Library, Medline, Web of Science, China National Knowledge Infrastructure (CNKI), CINAHL, and Wanfang databases were searched from inception to August 30, 2023. A total of 32 randomized controlled trial studies that examined the efficacy of different NDBIs were included. RESULTS: Parents of children with ASD who received Pivotal Response Treatment (PRT) reported significant improvements in their children's social skills (SUCRA, 74.1%), language skills (SUCRA, 88.3%), and parenting fidelity (SUCRA, 99.5%). Moreover, parents who received Early Start Denver Model (ESDM) reported significant improvements in their children's language (SMD = 0.41, 95% CI: 0.04, 0.79) and motor skills (SMD = 0.44, 95% CI: 0.09, 0.79). In terms of the efficacy of improving parent fidelity, the results showed that the Improving Parents as Communication Teachers (ImPACT) intervention significantly improved parent fidelity when compared with the treatment-as-usual group (TAU) (SMD = 0.90, 95% CI: 0.39, 1.42) and the parental education intervention (PEI) (SMD = 1.10, 95% CI:0.28, 1.91).There was a difference in parent fidelity among parents who received PRT(SMD = 3.53, 95% CI: 2.26, 4.79) or ESDM(SMD = 1.42, 95% CI: 0.76, 2.09) training compared with PEI. CONCLUSION: In conclusion, this study revealed that parents can achieve high fidelity with the ImPACT intervention, and it can serve as an early first step for children newly diagnosed with ASD. It also showed that parent-mediated ESDM is effective in improving language and motor skills for children with ASD and can be used as part of the second stage of parent training. Parent-mediated PRT can also be used as a third stage of parent training with sufficient training intensity to further improve language, social, and motor skills.


Asunto(s)
Trastorno del Espectro Autista , Metaanálisis en Red , Padres , Humanos , Trastorno del Espectro Autista/terapia , Padres/educación , Niño , Terapia Conductista/métodos , Habilidades Sociales , Desarrollo Infantil , Responsabilidad Parental , Preescolar , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
9.
Pediatr Dent ; 46(2): 91-98, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38664910

RESUMEN

Purpose: To evaluate the impact of multisensory room (MSR) use on preoperative anxiety and postoperative outcomes in children with autism spectrum disorder (ASD) undergoing dental treatment with general anesthesia. Methods: Forty children, ages six to 17 years, with ASD re- quiring general anesthesia for dental treatment, participated in this study. Participants were randomized to either the control group (standard pre- operative waiting room) or intervention group (MSR) for 20 minutes prior to general anesthesia induction. Pre- and post-intervention preoperative anxiety were measured. Following surgery, postoperative emergence delirium was assessed. Short- and long-term postoperative pain and adverse behavioral effects were evaluated six hours, 24 hours, one week, and one month post-surgery. Data analysis employed repeated measures analysis of variance with two groups and either two or four time periods. Results: The sample was predominantly male (62.5 percent) and identified as either White or Black (53 percent) and non-Hispanic (60 percent). Preoperative behavioral anxiety levels increased post-intervention in the control group (P<0.05) and decreased in the MSR group (P<0.001). Following surgery, pain intensity was greater in the control group compared to the MSR group at six hours (P<0.05) and 24 hours (P<0.01), and similar at one and four weeks. Pre- and post-intervention measures of preoperative heart rate, postoperative emergence delirium, and behavioral effects were similar between groups and over time. Conclusion: These findings suggest a novel, nonpharmacologic technique that can be utilized by various health care specialties to reduce preoperative anxiety and improve post- operative outcomes in children with autism spectrum disorder.


Asunto(s)
Dolor Postoperatorio , Humanos , Niño , Masculino , Femenino , Adolescente , Dolor Postoperatorio/etiología , Anestesia General , Trastorno del Espectro Autista , Ansiedad , Anestesia Dental/métodos , Delirio del Despertar/prevención & control , Cuidados Preoperatorios , Ansiedad al Tratamiento Odontológico/prevención & control
10.
Lipids Health Dis ; 23(1): 114, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38643132

RESUMEN

Disturbances in cholesterol homeostasis have been associated with ASD. Lipid rafts are central in many transmembrane signaling pathways (including mTOR) and changes in raft cholesterol content affect their order function. Cholesterol levels are controlled by several mechanisms, including endoplasmic reticulum associated degradation (ERAD) of the rate limiting HMGCoA reductase. A new approach to increase cholesterol via temporary ERAD blockade using a benign bacterial toxin-derived competitor for the ERAD translocon is suggested.A new lock and key model for cholesterol/lipid raft dependent signaling is proposed in which the rafts provide both the afferent and efferent 'tumblers' across the membrane to allow 'lock and key' receptor transmembrane signals.


Asunto(s)
Trastorno del Espectro Autista , Humanos , Colesterol/metabolismo , Degradación Asociada con el Retículo Endoplásmico , Microdominios de Membrana/metabolismo
12.
Commun Biol ; 7(1): 485, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649483

RESUMEN

Converging evidence implicates disrupted brain connectivity in autism spectrum disorder (ASD); however, the mechanisms linking altered connectivity early in development to the emergence of ASD symptomatology remain poorly understood. Here we examined whether atypicalities in the Salience Network - an early-emerging neural network involved in orienting attention to the most salient aspects of one's internal and external environment - may predict the development of ASD symptoms such as reduced social attention and atypical sensory processing. Six-week-old infants at high likelihood of developing ASD based on family history exhibited stronger Salience Network connectivity with sensorimotor regions; infants at typical likelihood of developing ASD demonstrated stronger Salience Network connectivity with prefrontal regions involved in social attention. Infants with higher connectivity with sensorimotor regions had lower connectivity with prefrontal regions, suggesting a direct tradeoff between attention to basic sensory versus socially-relevant information. Early alterations in Salience Network connectivity predicted subsequent ASD symptomatology, providing a plausible mechanistic account for the unfolding of atypical developmental trajectories associated with vulnerability to ASD.


Asunto(s)
Trastorno del Espectro Autista , Humanos , Lactante , Masculino , Femenino , Trastorno del Espectro Autista/fisiopatología , Imagen por Resonancia Magnética , Red Nerviosa/fisiopatología , Atención/fisiología , Encéfalo/fisiopatología , Encéfalo/crecimiento & desarrollo , Vías Nerviosas/fisiopatología
13.
Sci Rep ; 14(1): 9230, 2024 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649688

RESUMEN

With its high rate of consanguineous marriages and diverse ethnic population, little is currently understood about the genetic architecture of autism spectrum disorder (ASD) in Pakistan. Pakistan has a highly ethnically diverse population, yet with a high proportion of endogamous marriages, and is therefore anticipated to be enriched for biallelic disease-relate variants. Here, we attempt to determine the underlying genetic abnormalities causing ASD in thirty-six small simplex or multiplex families from Pakistan. Microarray genotyping followed by homozygosity mapping, copy number variation analysis, and whole exome sequencing were used to identify candidate. Given the high levels of consanguineous marriages among these families, autosomal recessively inherited variants were prioritized, however de novo/dominant and X-linked variants were also identified. The selected variants were validated using Sanger sequencing. Here we report the identification of sixteen rare or novel coding variants in fifteen genes (ARAP1, CDKL5, CSMD2, EFCAB12, EIF3H, GML, NEDD4, PDZD4, POLR3G, SLC35A2, TMEM214, TMEM232, TRANK1, TTC19, and ZNF292) in affected members in eight of the families, including ten homozygous variants in four families (nine missense, one loss of function). Three heterozygous de novo mutations were also identified (in ARAP1, CSMD2, and NEDD4), and variants in known X-linked neurodevelopmental disorder genes CDKL5 and SLC35A2. The current study offers information on the genetic variability associated with ASD in Pakistan, and demonstrates a marked enrichment for biallelic variants over that reported in outbreeding populations. This information will be useful for improving approaches for studying ASD in populations where endogamy is commonly practiced.


Asunto(s)
Trastorno del Espectro Autista , Secuenciación del Exoma , Linaje , Humanos , Trastorno del Espectro Autista/genética , Pakistán , Masculino , Femenino , Variaciones en el Número de Copia de ADN/genética , Predisposición Genética a la Enfermedad , Niño , Alelos , Consanguinidad , Preescolar , Mutación , Homocigoto
14.
J Prim Care Community Health ; 15: 21501319241247997, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650542

RESUMEN

BACKGROUND AND OBJECTIVES: Children with autism spectrum disorder (ASD) continue to experience significant delays in diagnosis and interventions. One of the main factors contributing to this delay is a shortage of developmental-behavioral specialists. Diagnostic evaluation of ASD by primary care pediatricians (PCPs) has been shown to be reliable and to decrease the interval from first concern to diagnosis. In this paper, we present the results of a primary care ASD diagnosis program in which the PCP serves as the primary diagnostician and leverages the infrastructure of the primary care medical home to support the child and family during the pre- and post-diagnostic periods, along with data on parental satisfaction with this model. METHODS: Retrospective data from a cohort of patients evaluated through this program were analyzed to determine the mean age at diagnosis and interval from referral for evaluation to diagnosis. We used survey methodology to obtain data from parents regarding their satisfaction with the process. RESULTS: Data from 8 of 20 children evaluated from April 2021 through May 2022 showed a median age of diagnosis of 34.5 months compared to the national average of 49 months. Mean interval from referral for evaluation to diagnosis was 3.5 months. Parental survey responses indicated high satisfaction. CONCLUSIONS: This model was successful in shortening the interval from referral to diagnosis resulting in significant decrease of age at diagnosis compared with the national average. Widespread implementation could improve access to timely diagnostic services and improve outcomes for children with ASD.


Asunto(s)
Trastorno del Espectro Autista , Padres , Atención Primaria de Salud , Humanos , Trastorno del Espectro Autista/diagnóstico , Estudios Retrospectivos , Masculino , Femenino , Preescolar , Niño , Derivación y Consulta , Pediatría , Lactante , Diagnóstico Tardío
15.
ACS Chem Neurosci ; 15(8): 1635-1642, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38557009

RESUMEN

CHD8 is a high penetrance, high confidence risk gene for autism spectrum disorder (ASD), a neurodevelopmental disorder that is substantially more prevalent among males than among females. Recent studies have demonstrated variable sex differences in the behaviors and synaptic phenotypes of mice carrying different heterozygous ASD-associated mutations in Chd8. We examined functional and structural cellular phenotypes linked to synaptic transmission in deep layer pyramidal neurons of the prefrontal cortex in male and female mice carrying a heterozygous, loss-of-function Chd8 mutation in the C57BL/6J strain across development from postnatal day 2 to adulthood. Notably, excitatory neurotransmission was decreased only in Chd8+/- males with no differences in Chd8+/- females, and the majority of alterations in inhibitory transmission were found in males. Similarly, analysis of cellular morphology showed male-specific effects of reduced Chd8 expression. Both functional and structural phenotypes were most prominent at postnatal days 14-20, a stage approximately corresponding to childhood. Our findings suggest that the effects of Chd8 mutation are predominantly seen in males and are maximal during childhood.


Asunto(s)
Corteza Prefrontal , Animales , Femenino , Humanos , Masculino , Ratones , Trastorno del Espectro Autista/genética , Haploinsuficiencia , Ratones Endogámicos C57BL , Fenotipo , Corteza Prefrontal/crecimiento & desarrollo
16.
J Neurodev Disord ; 16(1): 17, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632549

RESUMEN

Monogenic disorders account for a large proportion of population-attributable risk for neurodevelopmental disabilities. However, the data necessary to infer a causal relationship between a given genetic variant and a particular neurodevelopmental disorder is often lacking. Recognizing this scientific roadblock, 13 Intellectual and Developmental Disabilities Research Centers (IDDRCs) formed a consortium to create the Brain Gene Registry (BGR), a repository pairing clinical genetic data with phenotypic data from participants with variants in putative brain genes. Phenotypic profiles are assembled from the electronic health record (EHR) and a battery of remotely administered standardized assessments collectively referred to as the Rapid Neurobehavioral Assessment Protocol (RNAP), which include cognitive, neurologic, and neuropsychiatric assessments, as well as assessments for attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Co-enrollment of BGR participants in the Clinical Genome Resource's (ClinGen's) GenomeConnect enables display of variant information in ClinVar. The BGR currently contains data on 479 participants who are 55% male, 6% Asian, 6% Black or African American, 76% white, and 12% Hispanic/Latine. Over 200 genes are represented in the BGR, with 12 or more participants harboring variants in each of these genes: CACNA1A, DNMT3A, SLC6A1, SETD5, and MYT1L. More than 30% of variants are de novo and 43% are classified as variants of uncertain significance (VUSs). Mean standard scores on cognitive or developmental screens are below average for the BGR cohort. EHR data reveal developmental delay as the earliest and most common diagnosis in this sample, followed by speech and language disorders, ASD, and ADHD. BGR data has already been used to accelerate gene-disease validity curation of 36 genes evaluated by ClinGen's BGR Intellectual Disability (ID)-Autism (ASD) Gene Curation Expert Panel. In summary, the BGR is a resource for use by stakeholders interested in advancing translational research for brain genes and continues to recruit participants with clinically reported variants to establish a rich and well-characterized national resource to promote research on neurodevelopmental disorders.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Discapacidad Intelectual , Trastornos del Neurodesarrollo , Humanos , Masculino , Femenino , Trastorno del Espectro Autista/genética , Encéfalo , Sistema de Registros , Metiltransferasas
17.
Birth Defects Res ; 116(4): e2336, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38624050

RESUMEN

BACKGROUND: According to reports, prenatal exposure to valproic acid can induce autism spectrum disorder (ASD)-like symptoms in both humans and rodents. However, the exact cause and therapeutic method of ASD is not fully understood. Agmatine (AGM) is known for its neuroprotective effects, and this study aims to explore whether giving agmatine hydrochloride before birth can prevent autism-like behaviors in mouse offspring exposed prenatally to valproic acid. METHODS: In this study, we investigated the effects of AGM prenatally on valproate (VPA)-exposed mice. We established a mouse model of ASD by prenatally administering VPA. From birth to weaning, we evaluated mouse behavior using the marble burying test, open-field test, and three-chamber social interaction test on male offspring. RESULTS: The results showed prenatal use of AGM relieved anxiety and hyperactivity behaviors as well as ameliorated sociability of VPA-exposed mice in the marble burying test, open-field test, and three-chamber social interaction test, and this protective effect might be attributed to the activation of the ERK/CREB/BDNF signaling pathway. CONCLUSION: Therefore, AGM can effectively reduce the likelihood of offspring developing autism to a certain extent when exposed to VPA during pregnancy, serving as a potential therapeutic drug.


Asunto(s)
Agmatina , Trastorno del Espectro Autista , Animales , Femenino , Masculino , Ratones , Embarazo , Agmatina/farmacología , Trastorno del Espectro Autista/inducido químicamente , Trastorno del Espectro Autista/tratamiento farmacológico , Trastorno del Espectro Autista/prevención & control , Factor Neurotrófico Derivado del Encéfalo , Carbonato de Calcio , Roedores , Transducción de Señal , Conducta Social , Ácido Valproico/efectos adversos
18.
Cell ; 187(8): 1853-1873.e15, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38574728

RESUMEN

This study has followed a birth cohort for over 20 years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal questionnaires captured infection and antibiotic events, stress, prenatal factors, family history, and more. Biomarkers including cord serum metabolome and lipidome, human leukocyte antigen (HLA) genotype, infant microbiota, and stool metabolome were assessed. Among the 16,440 Swedish children followed across time, 1,197 developed an ND. Significant associations emerged for future ND diagnosis in general and for specific ND subtypes, spanning intellectual disability, speech disorder, attention-deficit/hyperactivity disorder, and autism. This investigation revealed microbiome connections to future diagnosis as well as early emerging mood and gastrointestinal problems. The findings suggest links to immunodysregulation and metabolism, compounded by stress, early-life infection, and antibiotics. The convergence of infant biomarkers and risk factors in this prospective, longitudinal study on a large-scale population establishes a foundation for early-life prediction and intervention in neurodevelopment.


Asunto(s)
Biomarcadores , Microbioma Gastrointestinal , Trastornos del Neurodesarrollo , Niño , Femenino , Humanos , Lactante , Embarazo , Trastorno del Espectro Autista/microbiología , Estudios Longitudinales , Estudios Prospectivos , Heces/microbiología , Trastornos del Humor/microbiología
19.
J Psychiatr Res ; 173: 363-366, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38593694

RESUMEN

In the last decades, growing caseness for Autism Spectrum Disorder (ASD) has been observed, owing to the diagnostic accretion of low-impairment forms, over and above other possible causes. Unrecognized ASD is likely to be mislabeled as a psychotic disorder (PD), as people in the spectrum may show 'pseudopsychotic' symptoms, resembling both negative and positive symptoms. On the other hand, PDs are likely to be overlooked when they arise in people with ASD, due to the 'diagnostic overshadowing' of new-onset conditions by lifelong core autistic symptoms. The three available metanalyses on the occurrence of psychosis in adults with ASD convergently reported a rate of PDs that is at least ten times higher than in the general population. Therefore, the lack of literature addressing risk factors, outcomes, and treatment options for psychosis in the context of ASD is utterly concerning. The present review aims to summarize up-to-date knowledge of PDs with comorbid ASD in terms of clinical features, course, and treatment.


Asunto(s)
Trastorno del Espectro Autista , Trastornos Psicóticos , Adulto , Humanos , Trastorno del Espectro Autista/complicaciones , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/terapia , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/terapia , Trastornos Psicóticos/diagnóstico , Imaginación
20.
Vertex ; 35(163, ene.-mar.): 42-50, 2024 Apr 10.
Artículo en Español | MEDLINE | ID: mdl-38619997

RESUMEN

Introducción: El riesgo de suicidio en el Trastorno del Espectro Autista (TEA) ha emergido como una problemática poco considerada durante mucho tiempo. Esta revisión tiene como objetivo explorar la prevalencia, la evaluación y los tratamientos disponibles para el riesgo de suicidio en los adultos con autismo. Metodología: Se practicó una revisión narrativa sobre tres aspectos relacionados con el riesgo de suicido en la población adulta con TEA: la prevalencia, la evaluación y las intervenciones disponibles basadas en evidencia. La búsqueda bibliográfica fue realizada utilizando los buscadores de Pubmed, Scielo, Dialnet y Psychinfo, limitándose a artículos publicados a partir del año 2010 en adelante. Con el fin de identificar la literatura relevante, se utilizaron diversas combinaciones de palabras clave, tales como "riesgo de suicidio", "trastorno del espectro autista", y "suicidio en autismo", tanto en español como en inglés. Conclusión: Los hallazgos principales sugieren un elevado riesgo de suicidio en la población autista, lo que destaca la necesidad de desarrollar protocolos estandarizados para evaluarlo. Además, la Terapia Dialéctico Conductual se ha establecido como una opción terapéutica prometedora para disminuir la suicidabilidad en esta población, pero aún se requiere de mayor investigación para establecer su eficacia y estandarización como tratamiento.


Asunto(s)
Trastorno del Espectro Autista , Suicidio , Adulto , Humanos , Prevalencia , Estudios Retrospectivos
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