Precision Medicine in Pediatric Attention-Deficit/Hyperactivity Disorder: A Systematic Review of Behavioral, Neurobiological and Genetic Diagnostic Biomarkers.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common childhood psychiatric disorders and a common presenting concern in primary and developmental pediatric care. However, objective diagnostic tools are currently not available, leading to delayed and missed diagnoses. The current systematic review aimed to determine whether objective indices can serve as diagnostic markers for pediatric ADHD.

Movement-related cortical potentials underlying motor preparation and execution in children with attention-deficit/hyperactivity disorder.

Objective: Motor control difficulties are highly common in Attention-Deficit/Hyperactivity Disorder (ADHD), yet the etiology of this comorbidity remains unclear. We examined (1) whether children with ADHD have atypical movement-related cortical potentials (MRCPs) during movement preparation and/or execution compared to typically developing (TD) children, and (2) whether MRCPs associated with visual-motor performance and ADHD symptoms overlap.

Methods: MRCPs and visual-motor integration (VMI) were measured among 66 right-handed children with ADHD and 30 TD children (ages 7-11 years).

Physical and neurophysiological maturation associated with ADHD among previously institutionalized children: a randomized controlled trial.

Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental outcome among children with a history of early institutional care. Prior research on institutionalized children suggested that accelerated physical growth in childhood is a risk factor for ADHD outcomes.

Methods: The current study examined physical and neurophysiological growth trajectories among institutionalized children randomized to foster care treatment (n = 59) or care as usual (n = 54), and never institutionalized children (n = 64) enrolled in the Bucharest Early Intervention Project (NCT00747396, clinicaltrials.

EEG aperiodic dynamics from early through late childhood: Associations with ADHD, cognition, and development.

Background: Aperiodic resting electroencephalography (EEG) activity is dynamic, reflecting shifting excitatory:inhibitory (E:I) balance with changing environmental conditions. We examined developmental and cognitive correlates of aperiodic and dynamic aperiodic indices in a cross-sequential cohort of early, middle, and late childhood youth with and without attention deficit hyperactivity disorder (ADHD).

Methods: Two-hundred eighty-five children ages 2 - 14 years provided resting EEG during high- and low-visual input conditions.

Diverse clinical presentation of SPTBN1 variants: Complex versus primary attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) belongs to a phenotypically broad class of mental health disorders impacting social and cognitive functioning. Despite heritability estimates of 77%-88% and a global prevalence of up to 1 in 20 children, most of the underlying genetic etiology of the disorder remains undiscovered, making it challenging to obtain a clinical molecular genetic diagnosis and to develop new treatments (Biological Psychiatry, 2005, 57, 1313; Psychological Bulletin, 2009, 135, 608; Psychological Medicine, 2014, 44, 2223). Here we report the identification of a novel ultra-rare heterozygous loss-of-function (p.

Resting EEG correlates of neurodevelopment in a socioeconomically and linguistically diverse sample of toddlers: Wave 1 of the Kia Tīmata Pai best start New Zealand study.

Development of communication and self-regulation skills is fundamental to psychosocial maturation in childhood. The Kia Tīmata 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.

Longitudinal Stability of Neural Correlates of Pediatric Attention Deficit Hyperactivity Disorder: A Pilot Study of Event Related Potentials and Electroencephalography.

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.

Delineating early developmental pathways to ADHD: Setting an international research agenda.

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.

Effortful Control Protects Against Familial Liability for ADHD: Longitudinal Results from the ABCD Study in the United States.

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).

Auditory-Perceptual and Auditory-Motor Timing Abilities in Children with Developmental Coordination Disorder: A Scoping Review.

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.

The role of single trial variability in event related potentials in children with attention deficit hyperactivity disorder.

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).

The role of aperiodic spectral slope in event-related potentials and cognition among children with and without attention deficit hyperactivity disorder.

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.

Neural activation, cognitive control, and attention deficit hyperactivity disorder: Evaluating three competing etiological models.

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.

A framework for characterizing heterogeneity in neurodevelopmental data using latent profile analysis in a sample of children with ADHD.

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.

Absence of dynamic neural oscillatory response to environmental conditions marks childhood attention deficit hyperactivity disorder.

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.

Neural Markers of Methylphenidate Response in Children With Attention Deficit Hyperactivity Disorder.

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.

Heritability and Clinical Characteristics of Neuropsychological Profiles in Youth With and Without Elevated ADHD Symptoms.

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 ( = 2,564) enriched for elevated ADHD symptoms.

Reduced Error Recognition Explains Post-Error Slowing Differences among Children with Attention Deficit Hyperactivity Disorder.

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.

Reflections on the genetics-first approach to advancements in molecular genetic and neurobiological research on neurodevelopmental disorders.

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.

Sensory processing and P300 event-related potential correlates of stimulant response in children with attention-deficit/hyperactivity disorder: A critical review.

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.

Precision Medicine Care in ADHD: The Case for Neural Excitation and Inhibition.

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.

Developmental Predictors of Cognitive and Adaptive Outcomes in Genetic Subtypes of Autism Spectrum Disorder.

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.

Episignatures Stratifying Helsmoortel-Van Der Aa Syndrome Show Modest Correlation with Phenotype.

Helsmoortel-Van der Aa syndrome (HVDAS) is a neurodevelopmental condition associated with intellectual disability/developmental delay, autism spectrum disorder, and multiple medical comorbidities. HVDAS is caused by mutations in activity-dependent neuroprotective protein (ADNP). A recent study identified genome-wide DNA methylation changes in 22 individuals with HVDAS, adding to the group of neurodevelopmental disorders with an epigenetic signature.