Jan Buitelaar

• Radboud University

It has been proposed that autistic perception may be marked by a reduced influence of temporal context. Following this theory, prior exposure to a stimulus should lead to a weaker or absent alteration of the behavioral and neural response to the stimulus in autism, compared with a typical population. To examine these hypotheses, we recruited two sa...

While impaired response inhibition has been reported in attention-deficit/hyperactivity disorder (ADHD), findings in disruptive behavior disorders (DBDs) have been inconsistent, probably due to unaccounted effects of co-occurring ADHD in DBD. This study investigated the associations of behavioral and neural correlates of response inhibition with DB...

Alzheimer’s disease (AD) is a multifactorial disease with both genetic and environmental factors contributing to its etiology. Previous evidence has implicated disturbed insulin signaling as a key mechanism that plays a role in both neurodegenerative diseases such as AD and comorbid somatic diseases such as diabetes mellitus type 2 (DM2). In this s...

Atypical functional connectivity (FC) in autism is a common finding, but the results of individual studies are often inconsistent and sometimes contradictory. Classical reliance on case-control comparisons of group means that ignore the inter-individual heterogeneity autism may be a key drive of this inconsistency. Here, we used normative modelling...

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon)...

Importance In the neurotypical brain, regions develop in coordinated patterns, providing a fundamental scaffold for brain function and behavior. Whether altered patterns contribute to clinical profiles in neurodevelopmental conditions, including autism, remains unclear. Objectives To examine if, in autism, brain regions develop differently in rela...

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. We performed GWAS meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and, for the first time, the ventral diencephalon) in 74,898...

Low medication-adherence and persistence may reduce the effectiveness of ADHD-medication. This preregistered systematic review (PROSPERO CRD42020218654) on medication-adherence and persistence in children and adolescents with ADHD focuses on clinically relevant questions and extends previous reviews by including additional studies. We included a to...

Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and a...

Many youths with attention‐deficit/hyperactivity disorder (ADHD) experience significant long‐term impairment and may develop concurrent mental and somatic health difficulties as adults. This is associated with burden and costs for the individual and society which could be prevented through continued support in youth. Yet, only few young people tran...

Background An Elimination Diet (ED) or Healthy Diet (HD) may be effective in reducing symptoms of Attention‐Deficit/Hyperactivity Disorder (ADHD), but long‐term maintenance effects and feasibility have never been examined. Methods One‐year prospective follow‐up of a sample of 165 children (5–12 years) with ADHD randomized (unblinded; 1:1) to 5 wee...

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain‐age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain‐age has highlighted the need for robust and publicly available brain‐age model...

Introduction Parents of children with a neurodevelopmental disorder (NDD) experience more stress than parents of typically developing children. In a cocreation process with experts and parents, a low-threshold application that uses exercises based on the principles of positive psychology and mindfulness was developed. This application, called “Adap...

Background The neurobiology of autism remains poorly understood. Brain sulcation is a promising proxy to assess the cortical developmental trajectory in autism spectrum disorders. We aimed to explore this neurodevelopmental marker in children with autism and its association with symptoms in a large multicentric dataset. Methods 841 children with a...

Objectives: Risperidone is commonly prescribed off-label in children and adolescents to manage disruptive behavior. This study aimed to investigate continued benefits of risperidone after at least 1 year of treatment and effects of discontinuation on physical health. Methods: Thirty-five youths (aged 6-18 years, intelligence quotient [IQ] >70) who...

Depression is common in attention-deficit/hyperactivity disorder (ADHD), but preventive behavioural interventions are lacking. This randomised controlled, pilot phase-IIa trial aimed to study a physical exercise intervention (EI) and bright light therapy (BLT)—both implemented and monitored in an individual, naturalistic setting via a mobile health...

Predictive processing accounts of autism posit that autistic individuals' perception is less biased by expectations than nonautistic individuals', perhaps through stronger precision‐weighting of prediction errors. Since precision‐weighting is fundamental to all information processing, under this theory, the differences between autistic and nonautis...

Attention-deficit/hyperactivity disorder (ADHD; also known as hyperkinetic disorder) is a common neurodevelopmental condition that affects children and adults worldwide. ADHD has a predominantly genetic aetiology that involves common and rare genetic variants. Some environmental correlates of the disorder have been discovered but causation has been...

White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, w...

Background Autism spectrum disorder (henceforth autism) is a complex neurodevelopmental condition associated with differences in gray matter (GM) volume covariations, as reported in our previous study of the Longitudinal European Autism Project (LEAP) data. To make progress on the identification of potential neural markers and to validate the robus...

Background Differences in face processing are commonly reported in case/control studies of autism. Their neural correlates have been explored extensively across single neuroimaging modalities within key regions of the face processing network, such as the fusiform gyrus (FFG). Nonetheless, it is poorly understood how different variation(s) in brain...

Objectives As part of the ‘Suicidality: Treatment Occurring in Paediatrics (STOP)’ study, we developed and performed psychometric validation of an electronic-clinical-outcome-assessment (eCOA), which included a patient-reported-outcome (ePRO), an observer-rated-outcome (eObsRO) for parents/carers and a clinician-reported-outcome (eClinRO) that allo...

Background Disruptive behavior in children and adolescents can manifest as reactive aggression and proactive aggression and is modulated by callous-unemotional traits and other comorbidities. Neural correlates of these aggression dimensions or subtypes and comorbid symptoms remain largely unknown. This multi-center study investigated the relationsh...

Neuroimaging analyses of brain structure and function in autism have typically been conducted in isolation, missing the sensitivity gains of linking data across modalities. Here we focus on the integration of structural and functional organisational properties of brain regions. We aim to identify novel brain-organisation phenotypes of autism. We ut...

Environmental adversities constitute potent risk factors for psychiatric disorders. Evidence suggests the brain adapts to adversity, possibly in an adversity-type and region-specific manner. However, the long-term effects of adversity on brain structure and the association of individual neurobiological heterogeneity with behavior have yet to be elu...

Sensory atypicalities are particularly common in autism spectrum disorders (ASD). Nevertheless, our knowledge about the divergent functioning of the underlying somatosensory region and its association with ASD phenotype features is limited. We applied a data-driven approach to map the fine-grained variations in functional connectivity of the primar...

An Elimination Diet (ED) may be effective in reducing symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD), but has never been compared to an active control condition [i.e., Healthy Diet (HD)]. In a two-armed RCT, a total of N = 165 children (5–12 years) with ADHD were randomized by means of minimization (1:1) to either an ED (N = 84) or HD...

Introduction Mindfulness-based programmes (MBPs) are widely used to prevent mental ill-health that is becoming the leading global cause of morbidity. Evidence suggests beneficial average effects but wide variability. We aimed to confirm the effect of MBPs on psychological distress, and to understand whether and how baseline distress, gender, age, e...

Impaired response inhibition is commonly present in individuals with attention-deficit/hyperactivity disorder (ADHD) and their unaffected relatives, suggesting impaired response inhibition as a candidate endophenotype in ADHD. Therefore, we explored whether behavioral and neural correlates of response inhibition are related to polygenic risk scores...

Background: Working memory training (WMT) can offer therapeutic benefits to patients with neurodevelopmental disorders (NDD) and mild to borderline intellectual disability (MBID). However, consistent evidence for treatment benefits of WMT over placebo training is missing. So far, participants in double-blind research designs did receive non-specif...

Background: Guideline adherence is important to ensure optimal and safe use of methylphenidate for children and adolescents with attention-deficit/hyperactivity disorder (ADHD). We investigated adherence to Dutch guidelines regarding dosing and monitoring of methylphenidate in child and adolescent mental health care and pediatric treatment settings...

Background: Autism is a heterogenous neurodevelopmental condition accompanied by differences in brain connectivity. Structural connectivity in autism has mainly been investigated within the white matter. However, many genetic variants associated with autism highlight genes related to synaptogenesis and axonal guidance, thus also implicating differ...

Background: Despite much research on socioeconomic status (SES) from global health perspectives, surprisingly little has focused on autistic individuals. As this gap is integral to address the cognitive and mental health vulnerability of the vast majority of autistic people living in middle-to-low income settings (Lord, Charman, Havdal et al., 2022...

Neuroimaging analyses of brain structure and function in autism have typically been conducted in isolation, missing the sensitivity gains of linking data across modalities. Here we focus on the integration of structural and functional organisational properties of brain regions. We aim to identify novel brain-organisation phenotypes of autism. We ut...

It has been proposed that autistic perception may be marked by a reduced influence of temporal context. Under this hypothesis, prior exposure to a stimulus should lead to a weaker or absent alteration of the behavioral and neural response to the stimulus in autism, compared to a typical population. To examine this hypothesis, we recruited two sampl...

Individuals with autism spectrum disorder (henceforth referred to as autism) display significant variation in clinical outcome. For instance, across age, some individuals’ adaptive skills naturally improve or remain stable, while others’ decrease. To pave the way for ‘precision-medicine’ approaches, it is crucial to identify the cross-sectional and...

Investigating the impact of gut microbiome on human health is a rapidly growing area of research. A significant limiting factor in the progress in this field is the lack of consistency between study results, which hampers the correct biological interpretation of findings. One of the reasons is variation of the applied bioinformatics analysis pipeli...

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder, with onset in childhood and a considerable likelihood to persist into adulthood. Our previous work has identified that across adults and adolescents with ADHD, gray matter volume (GMV) alteration in the frontal cortex was consistently associated with...

Background Attenuated social attention is a key marker of autism spectrum disorder (ASD). Recent neuroimaging findings also emphasize an altered processing of sensory salience in ASD. The locus coeruleus–norepinephrine system (LC-NE) has been established as a modulator of this sensory salience processing (SSP). We tested the hypothesis that altered...

We present an empirically benchmarked framework for sex-specific normative modeling of brain morphometry that can inform about the biological and behavioral significance of deviations from typical age-related neuroanatomical changes and support future study designs. This framework was developed using regional morphometric data from 37,407 healthy i...

Background: Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD. Aims: Utilising a large sample, we aimed to assess reward processing in...

The excitatory/inhibitory (E/I) imbalance hypothesis posits that imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) mechanisms underlies the behavioral characteristics of autism. However, how E/I imbalance arises and how it may differ across autism symptomatology and brain regions is not well understood. We used innovative anal...

Tourette’s disorder (TD) is a highly heritable childhood-onset neurodevelopmental disorder and is caused by a complex interplay of multiple genetic and environmental factors. Yet, the molecular mechanisms underlying the disorder remain largely elusive. In this study, we used the available omics data to compile a list of TD candidate genes, and we s...

Background: Autism spectrum disorder (autism) is a complex neurodevelopmental condition with pronounced behavioral, cognitive, and neural heterogeneities across individuals. Here, our goal was to characterize heterogeneity in autism by identifying patterns of neural diversity as reflected in BOLD fMRI in the way individuals with autism engage with...

Background Although the importance of early detection and early intervention of autism spectrum disorders (ASD) is widely recognized, multiple barriers exist in accessing early intervention services. As an alternative to these barriers, the SCOPE project presents a new, easy accessible and blended intervention called BEAR (Blended E-health for chil...

Background Neuroimaging studies on functional connectivity (FC) in autism have been hampered by small sample sizes and inconsistent findings with regard to whether connectivity is increased or decreased in autistic individuals, whether these alterations affect focal systems or reflect a brain-wide pattern, and whether these are age- and/or sex-depe...

Objective: The male preponderance in prevalence of autism is among the most pronounced sex ratios across neurodevelopmental conditions. The authors sought to elucidate the relationship between autism and typical sex-differential neuroanatomy, cognition, and related gene expression. Methods: Using a novel deep learning framework trained to predic...

Background Difficulties in social communication are a defining clinical feature of autism. However, the underlying neurobiological heterogeneity has impeded targeted therapies and requires new approaches to identifying clinically relevant bio-behavioural subgroups. In the largest autism cohort to date, we comprehensively examined difficulties in fa...

Young people with attention deficit hyperactivity disorder (ADHD) are now being treated with psychostimulant medication for longer than was previously the case and are increasingly likely to remain on methylphenidate into adolescence and adulthood. This study was designed to determine whether the long-term use of methylphenidate (MPH, immediate rel...

Aims: Between 2008 and 2012, the number of children and adolescents in the Netherlands who received methylphenidate prescriptions increased by 35.6%. We determined guideline adherence regarding the assessment of attention-deficit/hyperactivity disorder (ADHD) and rates of off-label use in those 2 years. We also compared adherence to guidelines betw...

Little is known about factors contributing to perceived stigma in parents of children and adolescents with behavioral and emotional problems in outpatient mental healthcare. We aimed to identify the most relevant factors related to perceived parental stigma using least absolute shrinkage and selection operator (LASSO) regression including a broad r...

Youth with disruptive behavior showing high callous-unemotional (CU) traits and proactive aggression are often assumed to exhibit distinct impairments in emotion recognition from those showing mainly reactive aggression. Yet, reactive and proactive aggression and CU traits may co-occur to varying degrees across individuals. We aimed to investigate...

Network modeling of the social, communication and restrictive/repetitive behaviors (RRBs) included in the definition of Autism Spectrum Disorder was performed. The Autism Diagnostic Interview-Revised (ADI-R) assessed behaviors in 139 pre-school cases at two cross-sections that averaged 34.8 months apart. Cross-sectional networks were based on the c...

In the last two decades, there has been a growing body of research that identified sex-related differences in attention-deficit hyperactivity disorder (ADHD). Our objective was to quantify whether these sex differences are based on altered functional brain connectivity profiles. In addition, we investigated whether the presence of comorbid disorder...

Antisocial and aggressive behaviors show considerable heritability and are central to disruptive behavior disorders (DBDs), but are also frequently observed in attention deficit hyperactivity disorder (ADHD). While the amygdala is implicated as a key neural structure, it remains unclear whether common genetic variants underlie this brain-behavior a...

Background Although many studies have explored atypicalities in gray and white matter (GM, WM) morphology of autism, most of them rely on unimodal analyses that do not benefit from the likelihood that different imaging modalities may reflect common neurobiology. We aimed to establish brain patterns of modalities that differentiate between autism an...

Background Behavioral studies have shown that individuals with autism spectrum disorder (ASD) have problems coordinating their own motor actions (meta-analysis: Fournier et al., 2010). There is also evidence that delays and atypical patterns of development emerge early in the onset of ASD (Iverson et al., 2019). One hypothesis is that motor impairm...

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties in social communication, but also great heterogeneity. To offer individualized medicine approaches, we need to better target interventions by stratifying autistic people into subgroups with different biological profiles and/or prognoses. We sought to vali...

To advance understanding of the heterogeneity in the course of ADHD, joint symptom trajectories of inattention and hyperactivity-impulsivity from childhood to young adulthood were modelled and associated with genetic, demographic, and clinical characteristics. Data were obtained from the NeuroIMAGE cohort which includes 485 individuals with ADHD, t...

Whereas it is well documented how parents experience the diagnostic process of their child with autism spectrum disorder (ASD), less is known about parental experiences with the course of the early identification process and first steps in receiving care for their child with ASD symptoms. This mixed-method study investigated these experiences as we...

Background Dietary patterns have been associated with variations in behavior. However, evidence has been limited and mixed, and the underlying mechanism remains unclear. Objective Extend a previous study reporting significant associations between food patterns and behavioral disinhibition and explore whether low-grade inflammation is linked to dis...

Background Studying the neural processing of faces can illuminate the mechanisms of compromised social expertise in autism. To resolve a longstanding debate, we examined whether differences in configural face processing in autism are underpinned by quantitative differences in the activation of typical face processing pathways, or the recruitment of...

Schizophrenia is a severely debilitating neurodevelopmental disorder that requires continuous multidisciplinary treatment. Early onset schizophrenia (EOS, onset before 18) is associated with poorer outcomes than the adult-onset type. The transition from adolescent to adult mental healthcare services (AMHS) poses various challenges for maintaining c...

Iron and zinc have been associated with attention-deficit/hyperactivity disorder (ADHD), executive functioning, and response to methylphenidate, given their link with the dopaminergic system. This study aimed to investigate the effect of withdrawing methylphenidate after long-term treatment on serum levels of ferritin and zinc; and if baseline (pre...

Background Social attention affords learning opportunities across development and may contribute to individual differences in developmental trajectories, such as between male and female individuals, and in neurodevelopmental conditions, such as autism. Methods Using eye‐tracking, we measured social attention in a large cohort of autistic (n = 123)...

The excitatory/inhibitory (E/I) imbalance hypothesis posits that an imbalance between glutamatergic and GABAergic neurotransmission contributes to autism symptomatology. Whether this is due to altered GABAergic or glutamatergic functioning, or both, remains largely unknown. We integrated genetic, brain structure and brain chemistry data to investig...

Background Variation in the longitudinal course of childhood attention deficit/hyperactivity disorder (ADHD) coincides with neurodevelopmental maturation of brain structure and function. Prior work has attempted to determine how alterations in white matter (WM) relate to changes in symptom severity, but much of that work has been done in smaller cr...

Pivotal Response Treatment (PRT) is a promising intervention addressing core symptoms of autism spectrum disorder (ASD), with parent involvement as key component. Parent group-delivered PRT may be an effective treatment model, but currently the evidence is limited. Also, little attention has been paid to therapeutic involvement of multiple importan...

Background: Recent evidence has shown distinct profiles of autistic features in females, including domains such as social communication, with a more relevant use of social attention (i.e., the tendency to look at other people and parts of the body expressing social cues) compared to autistic males. Establishing a link between social attention in fe...

Background: Understanding the development of the neuronal circuitry underlying autism spectrum disorder (ASD) is critical to shed light into its etiology and for the development of treatment options. Resting state EEG provides a window into spontaneous local and long-range neuronal synchronization and has been investigated in many ASD studies, but...

Background The cerebellum contains more than 50% of the brain neurons and is involved in social cognition. Cerebellar anatomical atypicalities have repeatedly been reported in individuals with autism. However, studies have yielded inconsistent findings, likely because of a lack of statistical power, and did not capture the clinical and neuroanatomi...

BACKGROUND Sensory atypicalities are particularly common in autism spectrum disorders (ASD). Nevertheless, our knowledge about the divergence of the underlying somatosensory region and its association with ASD phenotype features is limited. METHODS We applied a data-driven approach to map the fine-grained variations in functional connectivity of t...

Rationale: Compulsivity often develops during childhood and is associated with elevated glutamate levels within the frontostriatal system. This suggests that anti-glutamatergic drugs, like memantine, may be an effective treatment. Objective: Our goal was to characterize the acute and chronic effect of memantine treatment on compulsive behavior a...

Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously bee...

Exercise interventions in mental disorders have evidenced a mood-enhancing effect. However, the association between physical activity and affect in everyday life has not been investigated in adult individuals with ADHD, despite being important features of this disorder. As physical activity and affect are dynamic processes in nature, assessing thos...

Objective: Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition that is associated with significant difficulties in adaptive behavior and variation in clinical outcomes across the life span. Some individuals with ASD improve, whereas others may not change significantly, or regress. Hence, the development of "personalized medic...

Mechanisms underpinning age-related variations in cortical thickness in the human brain remain poorly understood. We investigated whether inter-regional age-related variations in cortical thinning (in a multicohort neuroimaging dataset from the ENIGMA Lifespan Working Group totalling 14,248 individuals, aged 4-89 years) depended on cell-specific ma...

Objectives The male preponderance in autism spectrum conditions (ASC) prevalence is among the most pronounced sex ratios across different neurodevelopmental conditions. Here, we aimed to elucidate the relationship between autism and typical sex-differential neuroanatomy, cognition, and related gene expression. Methods Using a novel deep learning f...

Patients with attention-deficit/hyperactivity disorder (ADHD) often develop early onset substance use disorder (SUD) and show poor treatment outcomes. Both disorders show similar reward-processing alterations, but it is unclear whether these are associated with familial vulnerability to SUD. Our aim was to investigate effects of family history of S...