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BACKGROUND: It is unknown how much variation in adult mental health problems is associated with differences between societal/cultural groups, over and above differences between individuals. METHODS: To test these relative contributions, a consortium of indigenous researchers collected Adult Self-Report (ASR) ratings from 16 906 18- to 59-year-olds in 28 societies that represented seven culture clusters identified in the Global Leadership and Organizational Behavioral Effectiveness study (e.g. Confucian, Anglo). The ASR is scored on 17 problem scales, plus a personal strengths scale. Hierarchical linear modeling estimated variance accounted for by individual differences (including measurement error), society, and culture cluster. Multi-level analyses of covariance tested age and gender effects. RESULTS: Across the 17 problem scales, the variance accounted for by individual differences ranged from 80.3% for DSM-oriented anxiety problems to 95.2% for DSM-oriented avoidant personality (mean = 90.7%); by society: 3.2% for DSM-oriented somatic problems to 8.0% for DSM-oriented anxiety problems (mean = 6.3%); and by culture cluster: 0.0% for DSM-oriented avoidant personality to 11.6% for DSM-oriented anxiety problems (mean = 3.0%). For strengths, individual differences accounted for 80.8% of variance, societal differences 10.5%, and cultural differences 8.7%. Age and gender had very small effects. CONCLUSIONS: Overall, adults' self-ratings of mental health problems and strengths were associated much more with individual differences than societal/cultural differences, although this varied across scales. These findings support cross-cultural use of standardized measures to assess mental health problems, but urge caution in assessment of personal strengths.
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Salud Mental , Trastornos de la Personalidad , Adulto , Humanos , Trastornos de la Personalidad/psicología , Ansiedad , Trastornos de Ansiedad , IndividualidadRESUMEN
BACKGROUND: Williams syndrome (WS) is a rare genetic disorder caused by a microdeletion at the 7q11.23 region and is characterized by diverse symptoms encompassing physical and cognitive features. WS was reported to be associated to altered DNA methylation (DNAm) patterns. However, due to the limited information from long-term studies, it remains unclear whether WS accelerates aging. Genome-wide DNAm profiles can serve as "epigenetic clocks" to help estimate biological aging along with age-related markers, such as plasma proteins and telomere length. METHODS: We investigated GrimAge, DNAm-based telomere length (DNAmTL), and other epigenetic clocks in blood samples of 32 patients with WS and 32 healthy controls. RESULTS: We observed a significant acceleration in GrimAge, DNAmTL, and other epigenetic clocks in patients with WS as compared with those of controls. In addition, several GrimAge components, such as adrenomedullin, growth differentiation factor-15, leptin and plasminogen activator inhibitor-1, were altered in patients with WS. CONCLUSIONS: This study provides novel evidence supporting the hypothesis that WS may be associated to accelerated biological aging. A better understanding of the overall underlying biological effects of WS can provide new foundations for improved patient care; thus, long-term follow-up studies are still warranted.
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Síndrome de Williams , Humanos , Síndrome de Williams/genética , Envejecimiento/genética , Metilación de ADN/genética , Biomarcadores , Epigénesis GenéticaRESUMEN
OBJECTIVES: To conduct international comparisons of self-reports, collateral reports, and cross-informant agreement regarding older adult psychopathology. PARTICIPANTS: We compared self-ratings of problems (e.g. I cry a lot) and personal strengths (e.g. I like to help others) for 10,686 adults aged 60-102 years from 19 societies and collateral ratings for 7,065 of these adults from 12 societies. MEASUREMENTS: Data were obtained via the Older Adult Self-Report (OASR) and the Older Adult Behavior Checklist (OABCL; Achenbach et al., ). RESULTS: Cronbach's alphas were .76 (OASR) and .80 (OABCL) averaged across societies. Across societies, 27 of the 30 problem items with the highest mean ratings and 28 of the 30 items with the lowest mean ratings were the same on the OASR and the OABCL. Q correlations between the means of the 0-1-2 ratings for the 113 problem items averaged across all pairs of societies yielded means of .77 (OASR) and .78 (OABCL). For the OASR and OABCL, respectively, analyses of variance (ANOVAs) yielded effect sizes (ESs) for society of 15% and 18% for Total Problems and 42% and 31% for Personal Strengths, respectively. For 5,584 cross-informant dyads in 12 societies, cross-informant correlations averaged across societies were .68 for Total Problems and .58 for Personal Strengths. Mixed-model ANOVAs yielded large effects for society on both Total Problems (ES = 17%) and Personal Strengths (ES = 36%). CONCLUSIONS: The OASR and OABCL are efficient, low-cost, easily administered mental health assessments that can be used internationally to screen for many problems and strengths.
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Lista de Verificación , Psicopatología , Anciano , Análisis de Varianza , Humanos , AutoinformeRESUMEN
The purpose of this study was to test whether a syndrome model of elder psychopathology derived from collateral ratings, such as from spouses and adult children, in the United States would be generalizable in 11 other societies. Societies represented South America, Asia, and Europe. The Older Adult Behavior Checklist (OABCL) was completed by collateral informants for 6141 60- to 102-year-olds. The tested model comprised syndromes designated as Anxious/Depressed, Worries, Somatic Complaints, Functional Impairment, Memory/Cognition Problems, Thought Problems, and Irritable/Disinhibited. The model was tested using confirmatory factor analyses in each society separately. The primary model fit index showed a good fit for all societies, while the secondary model fit indices showed acceptable to a good fit for all societies. The items loaded strongly on their respective factors, with a median item loading of 0.69 across the 11 societies. By syndrome, the overall median item loadings ranged from 0.47 for Worries to 0.77 for Functional Impairment. The OABCL syndrome structure was thus generalizable across the tested societies. The OABCL can be used for broad assessment of psychopathology for elders of diverse backgrounds in nursing services and research.
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Lista de Verificación , Internacionalidad , Psicopatología/estadística & datos numéricos , Síndrome , Anciano , Anciano de 80 o más Años , Ansiedad/psicología , Cognición/fisiología , Femenino , Humanos , Masculino , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVES: As the world population ages, psychiatrists will increasingly need instruments for measuring constructs of psychopathology that are generalizable to diverse elders. The study tested whether syndromes of co-occurring problems derived from self-ratings of psychopathology by US elders would fit self-ratings by elders in 19 other societies. METHODS/DESIGN: The Older Adult Self-Report (OASR) was completed by 12 826 adults who were 60 to 102 years old in 19 societies from North and South America, Asia, and Eastern, Northern, Southern, and Western Europe, plus the United States. Individual and multigroup confirmatory factor analyses (CFAs) tested the fit of the seven-syndrome OASR model, consisting of the Anxious/Depressed, Worries, Somatic Complaints, Functional Impairment, Memory/Cognition Problems, Thought Problems, and Irritable/Disinhibited syndromes. RESULTS: In individual CFAs, the primary model fit index showed good fit for all societies, while the secondary model fit indices showed acceptable to good fit. The items loaded strongly on their respective factors, with a median item loading of .63 across 20 societies, and 98.7% of the loadings were statistically significant. In multigroup CFAs, 98% of items demonstrated approximate or full metric invariance. Fifteen percent of items demonstrated approximate or full scalar invariance, and another 59% demonstrated scalar invariance across more than half of societies. CONCLUSIONS: The findings supported the generalizability of OASR syndromes across societies. The seven syndromes offer empirically based clinical constructs that are relevant for elders of different backgrounds. They can be used to assess diverse elders and as a taxonomic framework to facilitate communication, services, research, and training in geriatric psychiatry.
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Comparación Transcultural , Evaluación Geriátrica/métodos , Trastornos Mentales/diagnóstico , Psicopatología , Anciano , Anciano de 80 o más Años , Ansiedad/etnología , Asia , Cognición , Depresión/etnología , Etnicidad , Europa (Continente) , Femenino , Humanos , Masculino , Memoria , Persona de Mediana Edad , Problema de Conducta/psicología , Psicopatología/estadística & datos numéricos , Reproducibilidad de los Resultados , Síndrome , Estados UnidosRESUMEN
BACKGROUND: Williams syndrome (WS) is a neurodevelopmental disorder that has been attributed to heterozygous deletions in chromosome 7q11.23 and exhibits a variety of physical, cognitive, and behavioral features. However, the genetic basis of this phenotypic variability is unclear. In this study, we identified genetic clues underlying these complex phenotypes. METHODS: Neurobehavioral function was assessed in WS patients and healthy controls. Total RNA was extracted from peripheral blood and subjected to microarray analysis, RNA-sequencing, and qRT-PCR. Weighted gene co-expression network analysis was performed to identify specific alterations related to intermediate disease phenotypes. To functionally interpret each WS-related module, gene ontology and disease-related gene enrichment were examined. We also investigated the micro (mi)RNA expression profiles and miRNA co-expression networks to better explain the regulation of the transcriptome in WS. RESULTS: Our analysis identified four significant co-expression modules related to intermediate WS phenotypes. Notably, the three upregulated WS-related modules were composed exclusively of genes located outside the 7q11.23 region. They were significantly enriched in genes related to B-cell activation, RNA processing, and RNA transport. BCL11A, which is known for its association with speech disorders and intellectual disabilities, was identified as one of the hub genes in the top WS-related module. Finally, these key upregulated mRNA co-expression modules appear to be inversely correlated with a specific downregulated WS-related miRNA co-expression module. CONCLUSIONS: Dysregulation of the mRNA/miRNA network involving genes outside of the 7q11.23 region is likely related to the complex phenotypes observed in WS patients.
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Trastorno del Espectro Autista/genética , Perfilación de la Expresión Génica , Expresión Génica/genética , Síndrome de Williams/genética , Niño , Cromosomas Humanos Par 7/genética , Humanos , MicroARNs/genética , ARN Mensajero/genéticaRESUMEN
AIM: The present study aimed to examine the association between copy number variations (CNVs) in parkin (PRKN) and schizophrenia (SCZ) and autism spectrum disorder (ASD) in a large case-control sample. METHOD: Array comparative genomic hybridization was performed on 3111 cases with SCZ, 1236 cases with ASD, and 2713 controls. We systematically prioritized likely pathogenic CNVs (LP-CNVs) in PRKN and examined their association with SCZ and ASD. RESULTS: In total, 3014 SCZ cases (96.9%), 1205 ASD cases (97.5%), and 2671 controls (98.5%) passed quality control. We found that monoallelic carriers of LP-CNVs in PRKN were common (70/6890, 1.02%) and were not at higher risk of SCZ (p = 0.29) or ASD (p = 0.72). We observed that the distribution pattern of LP-CNVs in the Japanese population was consistent with those in other populations. We also identified a patient diagnosed with SCZ and early-onset Parkinson's disease carrying biallelic pathogenic CNVs in PRKN. The absence of Parkinson's symptoms in 10 other monoallelic carriers of the same pathogenic CNV further reflects the lack of effect of monoallelic pathogenic variants in PRKN in the absence of a second hit. CONCLUSION: The present findings suggest that monoallelic CNVs in PRKN do not confer a significant risk for SCZ or ASD. However, further studies to investigate the association between biallelic CNVs in PRKN and SCZ and ASD are warranted.
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Trastorno del Espectro Autista , Esquizofrenia , Humanos , Trastorno del Espectro Autista/genética , Estudios de Casos y Controles , Hibridación Genómica Comparativa , Variaciones en el Número de Copia de ADN , Estudio de Asociación del Genoma Completo , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
The cerebellum plays a vital role in cognition, communication with the cerebral cortex, and fine motor coordination. Near-infrared spectroscopy (NIRS) is a portable, less restrictive, and noninvasive functional brain imaging method that can capture brain activity during movements by measuring the relative oxyhemoglobin (oxy-Hb) concentrations in the blood. However, the feasibility of using NIRS to measure cerebellar activity requires discussion. We compared NIRS responses between areas assumed to be the cerebellum and the occipital lobe during a fine motor task (tying a bow knot) and a visual task. Our results showed that the oxy-Hb concentration increased more in the occipital lobe than in the cerebellum during the visual task (p =.034). In contrast, during the fine motor task, the oxy-Hb concentration decreased in the occipital lobe but increased significantly in the cerebellum, indicating a notable difference (p =.015). These findings suggest that we successfully captured cerebellar activity associated with processing, particularly fine motor coordination. Moreover, the observed responses did not differ between individuals with autism spectrum disorder and those with typical development. Our study demonstrates the meaningful utility of NIRS as a method for measuring cerebellar activity during movements.
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Trastorno del Espectro Autista , Espectroscopía Infrarroja Corta , Humanos , Espectroscopía Infrarroja Corta/métodos , Trastorno del Espectro Autista/diagnóstico por imagen , Oxihemoglobinas/metabolismo , Neuroimagen Funcional/métodos , Cerebelo/metabolismoRESUMEN
The 16-Item Informant Questionnaire on Cognitive Decline for the Elderly (IQCODE 16) has been frequently used to diagnose prestroke dementia, an important determinant of stroke prognosis. We developed the Japanese version of the IQCODE 16 (J-IQCODE 16) using standardized translation methods. We applied the J-IQCODE 16 to 102 patients with stroke (19 with prestroke dementia diagnosed with DSM-5) admitted to the stroke care unit in our hospital. The cohort was randomly divided into a derivation cohort and a validation cohort containing 51 patients each. In the derivation cohort, the median J-IQCODE 16 score was 3.06, and the area under the receiver operating characteristic curve for prestroke dementia was 0.96, with an optimal cutoff value of 3.25 determined using the Youden index. When applied this cut-point to the validation cohort, the sensitivity and specificity of the J-IQCODE 16 for prestroke dementia were 90% and 85%, respectively. The J-IQCODE 16 is considered useful for the diagnosis of prestroke dementia.
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Disfunción Cognitiva , Demencia , Lenguaje , Anciano , Humanos , Disfunción Cognitiva/diagnóstico , Demencia/diagnóstico , Accidente Cerebrovascular , Encuestas y CuestionariosRESUMEN
BACKGROUND: Autism spectrum disorder (ASD) is characterized by impaired social communication and behavioral problems. An increased risk of premature mortality has been observed in individuals with ASD. Therefore, we hypothesized that biological aging is accelerated in individuals with ASD. Recently, several studies have established genome-wide DNA methylation (DNAm) profiles as 'epigenetic clocks' that can estimate biological aging. In addition, ASD has been associated with differential DNAm patterns. METHODS: We used two independent datasets from blood samples consisting of adult patients with high-functioning ASD and controls: the 1st cohort (38 ASD cases and 31 controls) and the 2nd cohort (6 ASD cases and 10 controls). We explored well-studied epigenetic clocks such as HorvathAge, HannumAge, SkinBloodAge, PhenoAge, GrimAge, and DNAm-based telomere length (DNAmTL). In addition, we investigated seven DNAm-based age-related plasma proteins, including plasminogen activator inhibitor-1 (PAI-1), and smoking status, which are the components of GrimAge. RESULTS: Compared to controls, individuals with ASD in the 1st cohort, but not in the 2nd cohort, exhibited a trend for increased GrimAge acceleration and a significant increase of PAI-1 levels. A meta-analysis showed significantly increased PAI-1 levels in individuals with ASD compared to controls. CONCLUSION: Our findings suggest there is no epigenetic age acceleration in the blood of individuals with ASD. However, this study provides novel evidence regarding increased plasma PAI-1 levels in individuals with high-functioning ASD. These findings suggest PAI-1 may be a biomarker for high-functioning ASD, however, larger studies based on epigenetic clocks and PAI-1 will be necessary to confirm these findings.
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Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/metabolismo , Epigénesis Genética , Inhibidor 1 de Activador Plasminogénico/biosíntesis , Adulto , Biomarcadores , Estudios de Casos y Controles , Metilación de ADN , Femenino , Humanos , Masculino , Análisis de Regresión , Riesgo , Telómero/ultraestructura , Adulto JovenRESUMEN
Atypical sensory features are frequently observed in individuals with autism spectrum disorder (ASD) as uncontrollable and less predictable sensory stimuli are thought to be stressful for them. To quantify distal indicators of cardiac vagus nerve activity, which is associated with top-down self-regulatory capacity, during sensory tasks as a stress state in children with ASD, we conducted an exploratory study to measure phasic high-frequency components of heart rate variability (phasic HF-HRV) during less controllable tactile/auditory sensory tasks in 37 children with ASD (aged 6-12 years) and 37 typically developing (TD) children. Only children with ASD showed increased HF-HRV values from the resting state to the task (i.e., phasic HF-HRV augmentation) during both less controllable tactile/auditory sensory tasks. In TD children, decreased phasic HF-HRV values were observed to cope with the task demand during the less-controllable-tactile task. These findings suggest that increased phasic HF-HRV values in response to less controllable sensory stimuli may reflect atypical physiological regulation during sensory stimulation in children with ASD.
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Trastorno del Espectro Autista , Niño , Humanos , Trastorno del Espectro Autista/complicaciones , Tacto , Frecuencia Cardíaca/fisiologíaRESUMEN
Eye movement density (EMD) is an evaluation index of rapid eye movements observed during sleep. This study aimed to investigate the association of fetal EMD with sleeping and developmental problems in infancy. We observed 60 normal singleton pregnancies (gestational age 28-37 weeks) using ultrasonography for 1 h. Fetal eye movements were counted, and EMD was calculated. Participants answered questionnaires regarding their child's sleep and development 1.5 years after their delivery. The outcomes of an infant's sleep were night awakening (yes or no), bedtime (before or after 22:00), and nighttime sleep duration (< 9 or ≥ 9 h). An infant's development was evaluated using the Child Behavior Checklist (CBCL) T-score. We found that decreased fetal EMD was associated with increased night awakening at the age of 1.5 years (odds ratio 0.84, 95% confidence interval 0.69-1.00 per unit decrease in EMD). However, fetal EMD was not associated with bedtime or nighttime sleep duration. In addition, fetal EMD was independently associated with the total problems T-score of the CBCL at the age of 1.5 years in the multivariate model (p = 0.047). In conclusion, fetal EMD may be associated with sleep and developmental problems in infants.
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Movimientos Oculares , Sueño , Niño , Femenino , Movimiento Fetal , Humanos , Lactante , Embarazo , Sueño REM , Encuestas y CuestionariosRESUMEN
This study examined the similarities/differences between the social phenotypes of Williams syndrome (WS) and autism spectrum disorder (ASD). As cultural norms may affect symptom evaluation, this study administered the Social Responsiveness Scale-2 to Japanese individuals with WS (n = 78, 4.4-44.0 years) and ASD (n = 75, 4.7-55.4 years). The scores for Social Motivation and Social Communication were significantly more severe in the ASD than WS group. Overall, the similarities and differences between the social phenotypes of the syndromes were consistent with the findings of a recent study conducted in the UK, except for the social awareness subscale score. This highlights the importance of cross-cultural investigations of WS and ASD.
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Background/Objective: Emotional dysregulation (ED) is a dimensional psychological domain, previously operationalized by instruments of the Achenbach System of Empirically Based Assessment (ASEBA) for children and adolescents; however, its cross-cultural and bottom-up characteristics among adult populations are still unknown. Method: We examined scores obtained on the Adult Self-Report (ASR) by 9,238 18- to 59-year-olds from 10 societies that differed in social, economic, geographic, and other characteristics. A Latent Class Analysis was performed on the data from each society. Results: In each society, a dysregulated class (DYS) was identified, which was characterized by elevated scores on most ASR syndromes. The mean prevalence of DYS was 9.2% (6.1-12.7%). The best models ranged from three to five latent classes in the different societies. Conclusions: Although the number of identified classes and the prevalence of ED varied across societies, a DYS class was found in each society, suggesting the need to adopt a dimensional view of psychopathology and a cross cultural perspective also in adult populations.
Contexto/Objetivo: La desregulación emocional (DE) es un ámbito dimensional en Psicología, previamente operacionalizado por los instrumentos del Sistema de Evaluación Basado Empíricamente de Achenbach (ASEBA, por sus siglas en inglés) para niños y adolescentes; sin embargo, aún se desconocen sus características interculturales y su enfoque ascendente en su aplicación a la población adulta. Método: Examinamos las puntuaciones obtenidas en el Autoinforme de Adultos (ASR, por sus siglas en inglés) por 9.238 personas de 18 a 59 años de edad pertenecientes a 10 sociedades que diferían en cuanto a sus características sociales, económicas, geográficas y de otro tipo. Se realizó un Análisis de Clases Latentes con los datos de cada sociedad. Resultados: En cada sociedad se identificó una clase desregulada (DES), que se caracterizaba por puntuaciones elevadas en la mayoría de los síndromes ASR. La prevalencia media de DES fue del 9,2% (6,1-12,7%). Los mejores modelos oscilaron entre tres y cinco clases latentes en las diferentes sociedades. Conclusiones: Aunque el número de clases identificadas y la prevalencia de DE variaron entre las diversas sociedades, se encontró una clase DES en cada sociedad, lo que sugiere la necesidad de adoptar una visión dimensional de la psicopatología y una perspectiva intercultural también en las poblaciones adultas.
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Individuals with autism spectrum disorder (ASD) often have difficulty with coordinated fine motor skills, but the degree of difficulty significantly varies from person to person. To elucidate the cause of this diversity, we monitored brain activity during fine movement tasks (tying bowknots) by near-infrared spectroscopy in 17 adults with ASD and 18 adults with typical development matched for age, gender, and intelligence quotient (IQ). We also examined the relationship between brain activation and developmental characteristics, including ASD severity, using the Autism-Spectrum Quotient and the Multi-dimensional Scale for Pervasive Developmental Disorder and Attention-Deficit/Hyperactivity Disorder. Although participants in the ASD group did not show significant clumsiness, their right prefrontal cortexes were relatively less activated, particularly in individuals with poor social skills and inattention. Our study indicates that individuals with ASD traits may use different strategies when performing fine movements; that is, they less use the brain areas responsible for processing visual image or planning behaviors.
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Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Adulto , Encéfalo , Humanos , Pruebas de Inteligencia , Corteza PrefrontalRESUMEN
Various attempts have been made to elucidate the development patterns in the spontaneous movements of infants through longitudinal evaluations. Movement complexity has been found to demonstrate u-shaped changes in the measurements focusing on limb movements. However, researchers have not yet clarified how other characteristics, besides movement complexity, change over time. This paper presents a longitudinal evaluation of spontaneous movements in infants using evaluation indices calculated through markerless video analysis. Nine infants with corrected ages from [Formula: see text] to 15 weeks participated in the experiments. We confirmed the change in indices over time using statistical methods. Index changes can be classified as positively correlated, u-shaped, inverted u-shaped, and uncorrelated. We also confirmed that the u-shaped and inverted u-shaped indices are negatively correlated. Furthermore, the principal component analysis revealed that the first principal component had the inverted u-shaped changes with the corrected age. These results suggest that it is important to synchronize the inverted u-shaped variations in the movement and velocity with the u-shaped changes in the movement complexity for infant development.
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Desarrollo Infantil/fisiología , Recién Nacido/fisiología , Movimiento , Grabación en Video/métodos , Humanos , Lactante , Estudios Longitudinales , Posición Supina/fisiologíaRESUMEN
Williams syndrome (WS) is a rare genetic disorder, caused by a microdeletion at the 7q11.23 region. WS exhibits a wide spectrum of features including hypersociability, which contrasts with social deficits typically associated with autism spectrum disorders. The phenotypic variability in WS likely involves epigenetic modifications; however, the nature of these events remains unclear. To better understand the role of epigenetics in WS phenotypes, we integrated DNA methylation and gene expression profiles in blood from patients with WS and controls. From these studies, 380 differentially methylated positions (DMPs), located throughout the genome, were identified. Systems-level analysis revealed multiple co-methylation modules linked to intermediate phenotypes of WS, with the top-scoring module related to neurogenesis and development of the central nervous system. Notably, ANKRD30B, a promising hub gene, was significantly hypermethylated in blood and downregulated in brain tissue from individuals with WS. Most CpG sites of ANKRD30B in blood were significantly correlated with brain regions. Furthermore, analyses of gene regulatory networks (GRNs) yielded master regulator transcription factors associated with WS. Taken together, this systems-level approach highlights the role of epigenetics in WS, and provides a possible explanation for the complex phenotypes observed in patients with WS.
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Trastorno del Espectro Autista , Síndrome de Williams , Trastorno del Espectro Autista/genética , Metilación de ADN , Epigénesis Genética , Humanos , Fenotipo , Síndrome de Williams/genéticaRESUMEN
This study proposes a quantitative evaluation support system for infant motor development and uses the system to analyze hands-and-knees creeping and belly crawling. This system measures movements using two video cameras and extracts movement features via background and inter-frame subtractions of original images. Eight evaluation indices for each crawling cycle are calculated, enabling markerless movement analysis of infants. Cross-sectional analysis of 16 10-month-olds confirmed significant differences between hands-and-knees creeping and belly crawling in five of the eight indices, demonstrating the system capability to quantitatively differentiate between creeping and crawling. Longitudinal analysis of one infant (aged 7-10 months) also suggested that the proposed quantitative indices can follow changes in crawling characteristics and evaluate infants' motor development process. The results from the experiments suggest that the proposed system may enable diagnosis support in clinical practice.
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Desarrollo Infantil , Destreza Motora/fisiología , Grabación en Video , Caminata/fisiología , Calibración , Estudios Transversales , Femenino , Mano/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Lactante , Rodilla/fisiología , Estudios Longitudinales , Masculino , MovimientoRESUMEN
Dysregulation of epigenetic processes involving histone methylation induces neurodevelopmental impairments and has been implicated in schizophrenia (SCZ) and autism spectrum disorder (ASD). Variants in the gene encoding lysine demethylase 4C (KDM4C) have been suggested to confer a risk for such disorders. However, rare genetic variants in KDM4C have not been fully evaluated, and the functional impact of the variants has not been studied using patient-derived cells. In this study, we conducted copy number variant (CNV) analysis in a Japanese sample set (2605 SCZ and 1141 ASD cases, and 2310 controls). We found evidence for significant associations between CNVs in KDM4C and SCZ (p = 0.003) and ASD (p = 0.04). We also observed a significant association between deletions in KDM4C and SCZ (corrected p = 0.04). Next, to explore the contribution of single nucleotide variants in KDM4C, we sequenced the coding exons in a second sample set (370 SCZ and 192 ASD cases) and detected 18 rare missense variants, including p.D160N within the JmjC domain of KDM4C. We, then, performed association analysis for p.D160N in a third sample set (1751 SCZ and 377 ASD cases, and 2276 controls), but did not find a statistical association with these disorders. Immunoblotting analysis using lymphoblastoid cell lines from a case with KDM4C deletion revealed reduced KDM4C protein expression and altered histone methylation patterns. In conclusion, this study strengthens the evidence for associations between KDM4C CNVs and these two disorders and for their potential functional effect on histone methylation patterns.
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Trastorno del Espectro Autista , Esquizofrenia , Trastorno del Espectro Autista/genética , Variaciones en el Número de Copia de ADN , Predisposición Genética a la Enfermedad , Histona Demetilasas/genética , Histonas , Humanos , Histona Demetilasas con Dominio de Jumonji/genética , Esquizofrenia/genéticaRESUMEN
Increasing evidence suggests that epigenetic mechanisms play a role in the etiology of autism spectrum disorder (ASD). To date, several studies have attempted to identify epigenetic biomarkers for ASD. However, reliable markers remain to be established and most of these studies have focused on pediatric patients with ASD. In this study, we sought to find an epigenetic DNA methylation biomarker from peripheral blood for adult patients with high-functioning ASD. DNA methylation profiles were analyzed using the Illumina 450 K methylation array. To identify robust candidate markers, we employed two types of machine-learning algorithms for marker selection. We identified a potential marker (cg20793532) for which is the AUC value was 0.79. Notably, cg20793532 was annotated to the PPP2R2C gene, which was hypermethylated and down-regulated in blood from ASD patients compared to that in the controls. Although requiring careful interpretation, this pilot study seems to provide a potential blood biomarker for identifying individuals with high-functioning ASD.