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Effortful control, the ability to regulate complex and goal-directed behavior, may protect individuals from developing mental health symptoms. This study tested the potential for child effortful control and executive functioning to buffer the effects of familial liability for attention deficit hyperactivity disorder (ADHD) problems across a one-year timeframe. Data from the prospectively-collected Adolescent Brain Cognitive Development (ABCD)® study were used to examine whether caregiver-rated child effortful control and executive functioning moderated the association between familial ADHD risk and later ADHD symptoms in a sample of children (N = 6,133; ages 9-10 years at baseline). Two independent variables were considered to compare the predictive powers of specific (family ADHD) and broad (family psychopathology) risk factors. Two additional moderating variables (surgency, negative affect) were tested to examine specificity of effortful control and executive functioning as moderators. All variables of interest were measured on a continuum and via caregiver report. At high levels of effortful control and executive functioning, there was no association between familial liability for ADHD or broad psychopathology and later child ADHD problems. The moderator effects were specific to effortful control and executive functioning domains. Etiological models of heritable psychiatric disorders, such as ADHD, should consider the risk and protective contributions of individual traits, such as effortful control and executive functioning. Clinical prevention and intervention efforts may target self-regulation skills in children to buffer against familial liability for ADHD problems.
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Trastorno por Déficit de Atención con Hiperactividad , Niño , Adolescente , Humanos , Estados Unidos/epidemiología , Temperamento/fisiología , Función Ejecutiva/fisiología , Salud Mental , PsicopatologíaRESUMEN
This case-control study examines the prevalence of rare de novo and inherited sequence variations among children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and siblings and parents without ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , Humanos , Niño , Trastorno por Déficit de Atención con Hiperactividad/genética , Padres , HermanosRESUMEN
Development of communication and self-regulation skills is fundamental to psychosocial maturation in childhood. The Kia Timata Pai Best Start (KTP) longitudinal study aims to promote these skills through interventions delivered at early childcare centers across New Zealand. In addition to evaluating effects of the interventions on behavioral and cognitive outcomes, the study utilizes electroencephalography (EEG) to characterize cortical development in a subsample of participating children. Here, we present results of the baseline resting EEG assessment with 193 children aged 15 to 33 months. We identified EEG correlates of individual differences in demographics, communication abilities, and temperament. We obtained communication and behavior ratings from multiple informants, and we applied contemporary analytic methods to the EEG data. Periodic spectral power adjusted for aperiodic activity was most closely associated with demographic, language, and behavioral measures. As in previous studies, gamma power was positively associated with verbal language. Alpha power was positively associated with effortful control. Nonverbal and verbal language measures showed distinct associations with EEG indices, as did the three temperament domains. Our results identified a number of candidate EEG measurements for use as longitudinal markers of optimal cortical development and response to interventions in the KTP cohort.
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Electroencefalografía , Lenguaje , Humanos , Preescolar , Estudios Longitudinales , Nueva Zelanda , Electroencefalografía/métodos , Temperamento/fisiologíaRESUMEN
OBJECTIVE: Stability and developmental effects of electroencephalography (EEG) and event related potential (ERP) correlates of ADHD are understudied. This pilot study examined stability and developmental changes in ERP and EEG metrics of interest. METHODS: Thirty-seven 7 to 11-year-old children with ADHD and 15 typically developing (TD) children completed EEG twice, 11 to 36 months apart. A series of mixed effects linear models were run to examine stability and developmental effects of EEG and ERP metrics. RESULTS: Stability and developmental effects of EEG and ERP correlates of ADHD varied considerably across metrics. P3 amplitude was stable over time and showed diverging developmental trajectories across groups. Developmental differences were apparent in error related ERPs and resting aperiodic exponent. Theta-beta ratio was stable over time among all children. CONCLUSIONS: Developmental trajectories of EEG and ERP correlates of ADHD are candidate diagnostic markers. Replication with larger samples is needed.
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Trastorno por Déficit de Atención con Hiperactividad , Humanos , Niño , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Proyectos Piloto , Electroencefalografía , Potenciales Evocados , DescansoRESUMEN
Background: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent, impairing, and highly heritable condition typically diagnosed in middle childhood. However, it is now recognized that symptoms emerge much earlier in development. Research focused on understanding-using multiple units of analysis-the cascade of early-life (i.e., prenatal-infant-toddler) developmental changes that will later emerge as ADHD has the potential to transform early identification, prevention, and intervention. To this end, we introduce the recently established Early ADHD Consortium, an international network of investigators engaged in prospective, longitudinal studies of risk for ADHD beginning early in life, conducted within a developmental framework, and which incorporate multimethod approaches. This network seeks to harmonize measures and methodological approaches to increase the potential for data sharing and subsequent impact. Methods: This perspective paper highlights the importance of investigating pre-diagnostic markers of ADHD, and potential models and mechanisms of ADHD risk and development, with the long-term objective of facilitating development of preemptive interventions that will minimize the impact of ADHD symptoms on everyday functioning and maximize health and developmental outcomes. Results: We selectively describe key challenges and questions for this field related to theoretical models and developmental mechanisms in ADHD and recommend next steps for the science, including methodological, measurement, and study design considerations. We then describe potential implications for preemptive intervention development. We conclude by considering other issues including ethical concerns and the critical value of incorporating stakeholder input. Conclusions: It is hoped that this perspective puts forth a research agenda that will enhance collaborative efforts and accelerate progress in understanding developmental mechanisms and the early ADHD phenotype, with implications for early intervention enhancement of healthy development for infants, young children, and their families.
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Attention-deficit/hyperactivity disorder (ADHD) and developmental coordination disorder (DCD) co-occur in approximately 50% of cases. This study aimed to characterize the behavioral, cognitive, and neurobiological profiles of co-occurring ADHD and DCD diagnoses by mapping, synthesizing, and providing a critical appraisal of the existing literature. A systematic search was conducted across four databases (MEDLINE, PsycINFO, Embase, and Scopus) to identify studies comparing a coexisting ADHD+DCD diagnosis to ADHD and DCD alone. From 2353 screened articles, 15 behavioral and 10 neuroimaging studies were included. Collectively, these studies suggest that the comorbid ADHD+DCD presentation constitutes a more severe phenotype characterized by neurocognitive differences associated with both conditions. Despite sharing some common neural features, our findings support the separate etiology hypothesis indicating that neural network alterations in individuals with ADHD+DCD represent a unique neural pattern rather than a sum of ADHD and DCD characteristics. Considering the heterogeneity inherent to both ADHD and DCD, future studies should involve rigorous and comprehensive assessment procedures to delineate how different subtypes of each diagnosis relate to distinct performance characteristics.
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Developmental coordination disorder (DCD) remains largely underdiagnosed and masked by other co-occurring conditions. The aim of this study was to (1) provide the first review of research regarding auditory-motor timing and synchronization abilities in children with DCD and (2) examine whether reduced motor performance may be associated with difficulties in auditory perceptual timing. The scoping review was carried out across five major databases (MEDLINE, Embase, PsycINFO, CINAHL, and Scopus) in accordance with the PRISMA-ScR guidelines. Studies were screened by two independent reviewers against the inclusion criteria, without publication date restrictions. From an initial return of 1673 records, 16 articles were included in the final review and synthesized based on the timing modality studied (i.e., auditory-perceptual, motor, or auditory-motor). Results suggest that children with DCD have difficulties with rhythmic movements both with and without external auditory cues and further indicate that variability in and slowness of motor response are key characteristics of DCD, regardless of the experimental task. Importantly, our review highlights a significant gap in the literature regarding auditory perceptual abilities in DCD. In addition to testing auditory perception, future studies should compare the performance of children with DCD on paced and unpaced tasks to determine whether auditory stimuli contribute to a more or less stable performance. This knowledge may inform future therapeutic interventions.
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OBJECTIVE: Children with attention deficit hyperactivity disorder (ADHD) show attenuated mean P3 component amplitudes compared to typically developing (TD) children. This finding may be the result of individual differences in P3 amplitudes, P3 latencies, and/or greater single trial variability (STV) in amplitude or latency, suggesting neural "noise." METHODS: Event related potentials (ERPs) from 75 children with ADHD and 29 TD children were recorded with electroencephalography (EEG). Caregivers provided ratings on child ADHD symptoms. Single-trial ERP amplitudes and latencies were extracted from the P3 component time window during a visual oddball task. Additionally, we computed individual-centered and trial-centered P3 amplitudes to account for inter-individual and inter-trial variability in the timing of the P3 peak. RESULTS: In line with prior research, greater ADHD symptom severity was associated with reduced mean P3 amplitude. This correlation was no longer significant after correcting for inter-trial differences in P3 latency. In contrast, greater ADHD symptom severity was associated with reduced STV in P3 amplitude. CONCLUSIONS: Our results suggest that attenuated average P3 amplitude in ADHD samples is due to a consistent reduction in strength of the neurophysiological signal at the single trial level, as well as increased inter-trial variability in the timing of P3 peak amplitudes. The traditional method of extracting P3 amplitudes based on a single time window for all trials may not adequately capture variability in P3 latencies associated with ADHD. SIGNIFICANCE: Inter- and intra-individual differences in brain signatures should be considered in models of neurobiological differences in neurodevelopmental samples.
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Trastorno por Déficit de Atención con Hiperactividad , Niño , Humanos , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Encéfalo , Electroencefalografía/métodos , Potenciales Relacionados con Evento P300/fisiología , Potenciales Evocados/fisiología , Tiempo de Reacción/fisiologíaRESUMEN
BACKGROUND: Cognitive control impairments are observed across several psychiatric conditions, highlighting their role as a transdiagnostic marker. Individuals with attention deficit hyperactivity disorder (ADHD) have difficulties with inhibition, working memory, processing speed, and attention regulation. These cognitive control impairments may either mediate or moderate the association between neurobiological vulnerabilities and phenotypic presentation in neurodevelopmental disorders. Alternately, neurocognitive vulnerabilities in ADHD may be additive, akin to a multiple deficit model. We tested the mediation, moderation, and additive models using neurocognitive data in youth with ADHD. METHODS: 7-11 year-old children diagnosed with ADHD (n = 75) and control children (n = 29) completed EEG recordings and neuropsychological testing (full scale IQ; cognitive control). Caregivers provided ADHD symptom ratings. Correlations and linear regression analyses were completed to examine the associations among cortical functioning (aperiodic slope), cognitive control, and ADHD symptoms. RESULTS: We found support for an additive model wherein vulnerabilities in aperiodic slope, event-related potentials, and cognitive control each explained unique variance in ADHD symptoms. There was some evidence that cognitive control moderates the effect of atypical cortical development on ADHD symptoms. There was no support for the mediation model. CONCLUSIONS: The etiology of ADHD symptoms is multifaceted and involves multiple "hits" across neurological and cognitive-behavioral factors.
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Aperiodic spectral slope is a measure of spontaneous neural oscillatory activity that is believed to support regulation of brain responses to environmental stimuli. Compared to typically developing (TD) control participants, children with attention deficit hyperactivity disorder (ADHD) have been shown to have flatter aperiodic spectral slope at rest as well as attenuated event-related potential (ERP) amplitudes in response to environmental stimuli. A small body of research suggests that aperiodic slope may also explain differences in behavioral responses. In this study, we examine associations between prestimulus aperiodic slope, stimulus characteristics, environmental demands, and neural as well as behavioral responses to these stimuli. Furthermore, we evaluate whether ADHD diagnostic status moderates these associations. Seventy-nine children with ADHD and 27 TD school-age children completed two visual ERP experiments with predictable alternating presentations of task-relevant and task-irrelevant stimuli. Aperiodic slope was extracted from prestimulus time windows. Prestimulus aperiodic slope was steeper for the TD relative to ADHD group, driven by task-relevant rather than task-irrelevant stimuli. For both groups, the aperiodic slope was steeper during a task with lower cognitive demand and before trials in which they responded correctly. Aperiodic slope did not mediate the association between ADHD diagnosis and attenuated P300 amplitude. The aperiodic spectral slope is dynamic and changes in anticipation of varying stimulus categories to support performance. The aperiodic slope and P300 amplitude reflect distinct cognitive processes. Background neural oscillations, captured via aperiodic slope, support cognitive behavioral control and should be included in etiological models of ADHD.NEW & NOTEWORTHY This study constitutes the first investigation of associations between aperiodic spectral slope and three aspects of neurocognition: event-related potential (ERP) amplitudes, cognitive load, and task performance. We find that background oscillatory activity is dynamic, shifting in anticipation of varying levels of task relevance and in response to increasing cognitive load. Moreover, we report that aperiodic activity and ERPs constitute distinct neurophysiological processes. Children with attention deficit hyperactivity disorder (ADHD) show reduced aperiodic dynamics in addition to attenuated ERP amplitudes.
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Trastorno por Déficit de Atención con Hiperactividad , Niño , Humanos , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Electroencefalografía , Potenciales Evocados/fisiología , Cognición , EncéfaloRESUMEN
BACKGROUND: Heterogeneity in neurodevelopmental disorders, and attention deficit hyperactivity disorder (ADHD) in particular, is increasingly identified as a barrier to identifying biomarkers and developing standards for clinical care. Clustering analytic methods have previously been used across a variety of data types with the goal of identifying meaningful subgroups of individuals with ADHD. However, these analyses have often relied on algorithmic approaches which assume no error in group membership and have not made associations between patterns of behavioral, neurocognitive, and genetic indicators. More sophisticated latent classification models are often not utilized in neurodevelopmental research due to the difficulty of working with these models in small sample sizes. METHODS: In the current study, we propose a framework for evaluating mixture models in sample sizes typical of neurodevelopmental research. We describe a combination of qualitative and quantitative model fit evaluation procedures. We test our framework using latent profile analysis (LPA) in a case study of 120 children with and without ADHD, starting with well-understood neuropsychological indicators, and building toward integration of electroencephalogram (EEG) measures. RESULTS: We identified a stable five-class LPA model using seven neuropsychological indicators. Although we were not able to identify a stable multimethod indicator model, we did successfully extrapolate results of the neuropsychological model to identify distinct patterns of resting EEG power across five frequency bands. CONCLUSIONS: Our approach, which emphasizes theoretical as well as empirical evaluation of mixture models, could make these models more accessible to clinical researchers and may be a useful approach to parsing heterogeneity in neurodevelopmental disorders.
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Trastorno por Déficit de Atención con Hiperactividad , Trastornos del Neurodesarrollo , Trastorno por Déficit de Atención con Hiperactividad/psicología , Niño , Electroencefalografía , Humanos , Trastornos del Neurodesarrollo/complicacionesRESUMEN
Background: Despite widespread use of stimulants to treat ADHD, individual responses vary considerably and few predictors of response have been identified. The identification of reliable and clinically feasible biomarkers would facilitate a precision medicine approach to pharmacological treatment of ADHD. We test the hypothesis that two electroencephalography (EEG) based neural signatures of ADHD, resting aperiodic slope exponent and novelty P3 amplitude, are markers of methylphenidate response in children. We hypothesize that positive response to methylphenidate treatment will be associated with greater abnormality of both neural markers. Methods: Twenty-nine 7-11 year-old children with ADHD and a history of methylphenidate treatment, and 30 controls completed resting EEG and visual oddball event related potential (ERP) paradigms. ADHD participants were characterized as methylphenidate responders (n = 16) or non-responders (n = 13) using the clinical global improvement (CGI-I) scale during blinded retrospective interview. All participants abstained from prescribed medications for at least 48 hours prior to the EEG. Results: As expected, methylphenidate responders (CGI-I rating < 3) demonstrated attenuated P3 amplitude relative to controls. Unexpectedly, methylphenidate non-responders showed atypically flat aperiodic spectral slope relative to controls, while responders did not differ on this measure. Conclusion: ADHD symptoms associated with atypical patterns of intrinsic neural activity may be less responsive to methylphenidate. In contrast, ADHD symptoms associated with abnormal frontal-striatal neural network excitation may be correctable with methylphenidate. Altogether, EEG is a feasible and promising candidate methodology for identifying biomarkers of stimulant response.
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BACKGROUND: Prior research suggests that symptoms of attention deficit hyperactivity disorder (ADHD) and related neurodevelopmental disorders may derive from alterations in the brain's ability to flexibly tune the balance between information integration and segregation and global versus local processing. This balance allows the brain to optimally filter salient stimuli in the environment and can be measured with electroencephalography (EEG) via calculation of the aperiodic spectral slope. A steeper aperiodic slope increases the capacity of global neural networks to process low-salience stimuli, while a flatter aperiodic slope reflects an emphasis on local neural networks that respond preferentially to high-salience input. Although aperiodic slope differences have been reported in ADHD, prior studies have not accounted for differing levels of stimulus input in experimental paradigms. There is evidence to suggest that dynamic shifts in neural oscillation patterns in response to changing environmental conditions could be critical for attention regulation. METHODS: Using high-density resting EEG, we measured aperiodic spectral slope during low contrast (lights off) and high contrast (lights on) environmental conditions in a sample of 88 7-11-year-old children diagnosed with ADHD and 29 controls (30% female). RESULTS: While controls showed a flatter aperiodic slope during the high contrast (lights on) as compared to low contrast (lights off) environmental condition, children with ADHD did not show any change in aperiodic slope across conditions. CONCLUSIONS: This study presents a novel etiological model of biological mechanisms associated with ADHD. Children with ADHD show suboptimal modulation of intrinsic neural activity in response to changing environmental input. The dynamic spectral slope is a promising candidate biomarker for ADHD. The possibility that dynamic spectral slope is associated with cognitive-behavioral regulation more broadly merits further investigation.
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Trastorno por Déficit de Atención con Hiperactividad , Niño , Femenino , Humanos , Masculino , Electroencefalografía , EncéfaloRESUMEN
OBJECTIVE: In the last decade, there has been an increase in research that aims to parse heterogeneity in attention deficit hyperactivity disorder (ADHD). The current study tests heritability of latent class neuropsychological subtypes. METHOD: Latent class analysis was used to derive subtypes in a sample of school-age twins (N = 2,564) enriched for elevated ADHD symptoms. RESULTS: Five neuropsychological profiles replicated across twin 1 and twin 2 datasets. Latent class membership was heritable overall, but heritability varied by profile and was lower than heritability of ADHD status. Variability in neuropsychological performance across domains was the strongest predictor of elevated ADHD symptoms. Neuropsychological profiles showed distinct associations with age, psychiatric symptoms and reading ability. CONCLUSION: Neuropsychological profiles are associated with unique neurocognitive presentations, but are not strong candidate endophenotypes for ADHD diagnosis.
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Trastorno por Déficit de Atención con Hiperactividad , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/psicología , Cognición , Humanos , Gemelos/genéticaRESUMEN
OBJECTIVE: Youth with attention deficit hyperactivity disorder (ADHD) often show reduced post-error slowing (PES) compared to typically developing controls. This finding has been interpreted as evidence that children with ADHD have error recognition and adaptive control impairments. However, several studies report mixed results regarding PES differences in ADHD, and among healthy controls, there is considerable debate about the cognitive-behavioral origin of PES. METHODS: We tested competing hypotheses aimed at clarifying whether reduced PES in children with ADHD is due to impaired error detection, deficits in adaptive control, and/or attention orienting to novelty. Children aged 7-11 years with a diagnosis of ADHD (n = 74) and controls (n = 30) completed four laboratory-based computer tasks with variable cognitive loads and error types. RESULTS: ADHD diagnosis was associated with shorter PES only on a task with high cognitive load and low error-cuing, consistent with impaired error recognition. In contrast, there was no evidence of impaired adaptive control or heightened novelty orienting among children with ADHD. CONCLUSIONS: The cognitive-behavioral origin of PES is multifactorial, but reduced PES among children with an ADHD diagnosis is due to impaired error recognition during cognitively demanding tasks. Behavioral interventions that scaffold error recognition may facilitate improved performance among children with ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Niño , Humanos , Pruebas Neuropsicológicas , Tiempo de Reacción , Reconocimiento en PsicologíaRESUMEN
BACKGROUND: Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and intellectual disability (ID), are common diagnoses with highly heterogeneous phenotypes and etiology. The genetics-first approach to research on NDDs has led to the identification of hundreds of genes conferring risk for ASD, ID, and related symptoms. MAIN BODY: Although relatively few individuals with NDDs share likely gene-disruptive (LGD) mutations in the same gene, characterization of overlapping functions, protein networks, and temporospatial expression patterns among these genes has led to increased understanding of the neurobiological etiology of NDDs. This shift in focus away from single genes and toward broader gene-brain-behavior pathways has been accelerated by the development of publicly available transcriptomic databases, cell type-specific research methods, and sequencing of non-coding genomic regions. CONCLUSIONS: The genetics-first approach to research on NDDs has advanced the identification of critical protein function pathways and temporospatial expression patterns, expanding the impact of this research beyond individuals with single-gene mutations to the broader population of patients with NDDs.
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Trastorno del Espectro Autista , Discapacidad Intelectual , Trastornos del Neurodesarrollo , Trastorno del Espectro Autista/genética , Genómica , Humanos , Discapacidad Intelectual/genética , Biología Molecular , Trastornos del Neurodesarrollo/genéticaRESUMEN
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with considerable impairment in psychiatric and functional domains. Although stimulant medication can reduce core symptoms of inattention, hyperactivity, and impulsivity, a subgroup of patients does not respond to this intervention. A precision medicine approach has been proposed, whereby biomarkers are used to identify an effective treatment approach for a given individual. This review synthesizes the existing literature on event-related potential (ERP) correlates of stimulant response in children diagnosed with ADHD, with the goal of evaluating the potential for ERP to inform precision medicine care in this population. Forty-three articles were examined and results tentatively suggest that stimulant medications normalize the amplitude of the P300 component, and this is also associated with behavioral improvement. In contrast, results generally indicate that stimulants do not significantly alter early processing components, although there are some exceptions to this finding. Implications for research, theory, and clinical work are considered and concrete recommendations for future directions are provided. While recognizing limitations of existing literature (e.g., homogenous samples, variable methodologies), we conclude that ERP methods represent a promising approach for precision medicine care of patients with ADHD.
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Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Encéfalo/fisiopatología , Estimulantes del Sistema Nervioso Central/uso terapéutico , Potenciales Relacionados con Evento P300/fisiología , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Niño , Humanos , Resultado del TratamientoRESUMEN
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that has become increasingly prevalent worldwide. Its core symptoms, including difficulties regulating attention, activity level, and impulses, appear in early childhood and can persist throughout the lifespan. Current pharmacological options targeting catecholamine neurotransmissions have effectively alleviated symptoms in some, but not all affected individuals, leaving clinicians to implement trial-and-error approach to treatment. In this review, we discuss recent experimental evidence from both preclinical and human studies that suggest imbalance of excitation/inhibition (E/I) in the fronto-striatal circuitry during early development may lead to enduring neuroanatomical abnormality of the circuitry, causing persistence of ADHD symptoms in adulthood. We propose a model of precision medicine care that includes E/I balance as a candidate biomarker for ADHD, development of GABA-modulating medications, and use of magnetic resonance spectroscopy and scalp electrophysiology methods to monitor the effects of treatments on shifting E/I balance throughout the lifespan.
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Objective: Among children with ADHD, coexisting psychiatric disorders are common and associated with greater impairment and symptom persistence. Given that temperament traits are easily measured, developmentally stable, and variable among youth with ADHD, temperament profiles may be clinically useful for predicting liability for coexisting psychiatric symptoms in this population. Methods: Eighty-three children with ADHD symptoms participated. Caregivers rated their child's surgency, negative emotionality, and effortful control, as well as severity of internalizing and externalizing psychiatric symptoms. Hierarchical linear regressions were conducted to estimate associations between temperament traits and psychiatric symptoms, controlling for severity of ADHD. Results: Temperament ratings explained significant variance in psychiatric symptoms above and beyond ADHD symptoms alone. Symptoms of each coexisting psychiatric disorder was associated with a distinct temperament and ADHD symptom profile. Conclusion: Temperament ratings appear to have clinical utility for predicting coexisting psychiatric symptoms in children with elevated ADHD symptoms.
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Trastorno por Déficit de Atención con Hiperactividad , Temperamento , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Niño , HumanosRESUMEN
Approximately one-fourth of autism spectrum disorder (ASD) cases are associated with a disruptive genetic variant. Many of these ASD genotypes have been described previously, and are characterized by unique constellations of medical, psychiatric, developmental, and behavioral features. Development of precision medicine care for affected individuals has been challenging due to the phenotypic heterogeneity that exists even within each genetic subtype. In the present study, we identify developmental milestones that predict cognitive and adaptive outcomes for five of the most common ASD genotypes. Sixty-five youth with a known pathogenic variant involving ADNP, CHD8, DYRK1A, GRIN2B, or SCN2A genes participated in cognitive and adaptive testing. Exploratory linear regressions were used to identify developmental milestones that predicted cognitive and adaptive outcomes within each gene group. We hypothesized that the earliest and most predictive milestones would vary across gene groups, but would be consistent across outcomes within each genetic subtype. Within the ADNP group, age of walking predicted cognitive outcomes, while age of first words predicted adaptive behaviors. Age of phrases predicted adaptive functioning in the CHD8 group, but cognitive outcomes were not clearly associated with early developmental milestones. Verbal milestones were the strongest predictors of cognitive and adaptive outcomes for individuals with mutations to DYRK1A, GRIN2B, or SCN2A. These trends inform decisions about treatment planning and long-term expectations for affected individuals, and they add to the growing body of research linking molecular genetic function to brain development and phenotypic outcomes. LAY SUMMARY: Researchers have found many genetic causes of autism including mutations to ADNP, CHD8, DYRK1A, GRIN2B, and SCN2A genes. We found that each genetic cause had different early developmental milestones that explained the overall functioning of the children when they were older. Depending on the genetic cause, the age that a child first starts walking and/or talking may help to better understand and support a child's development who has a mutation to one of the above genes. Autism Res 2020, 13: 1659-1669. © 2020 International Society for Autism Research and Wiley Periodicals LLC.