Publications by authors named "Jan K Buitelaar"

559 Publications

Parental rejection in early adolescence predicts a persistent ADHD symptom trajectory across adolescence.

Eur Child Adolesc Psychiatry 2021 Jul 17. Epub 2021 Jul 17.

Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Lübeckweg 2, NL-9723 HE, Groningen, The Netherlands.

Despite a general decrease of attention-deficit/hyperactivity disorder (ADHD) symptoms during adolescence, these may persist in some individuals but not in others. Prior cross-sectional studies have shown that parenting style and their interaction with candidate genes are associated with ADHD symptoms. However, there is a lack of longitudinal research examining the independent and interactive effects of parenting and plasticity genes in predicting the course of attention-deficit/hyperactivity disorder (ADHD) symptoms across adolescence. Here, we investigated how children perceived their parents' parenting style (i.e., rejection, overprotection, and emotional warmth) at the age of 11, and their interaction with DRD4, MAOA, and 5-HTTLPR genotypes on parent-reported ADHD symptoms at three time points (mean ages 11.1, 13.4, and 16.2 years) in 1730 adolescents from the TRacking Adolescents' Individual Lives Survey (TRAILS). Growth Mixture Modeling in Mplus identified four ADHD symptom trajectories: low, moderate stable, high decreasing, and high persistent. Perceived parental rejection predicted class membership in the high persistent trajectory compared to the other classes (p < 0.001, odds ratios between 2.14 and 3.74). Gene-environment interactions were not significantly related to class membership. Our results indicate a role of perceived parental rejection in the persistence of ADHD symptoms. Perceived parental rejection should, therefore, be taken into consideration during prevention and treatment of ADHD in young adolescents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00787-021-01844-0DOI Listing
July 2021

Implicit learning in 3-year-olds with high and low likelihood of autism shows no evidence of precision weighting differences.

Dev Sci 2021 Jul 12:e13158. Epub 2021 Jul 12.

Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands.

Predictive Processing accounts of autism claim that autistic individuals assign higher precision to their prediction errors than non-autistic individuals, that is, autistic individuals update their predictions more readily when faced with unexpected sensory input. Since setting the level of precision is a fundamental part of perception and learning, we propose that such differences should be detectable in various domains at a very early age, before clinical symptoms have fully emerged. We therefore tested 3-year-old younger siblings of autistic children, with a high likelihood of later receiving an autism diagnosis themselves, and low-likelihood children with an older sibling without autism. We used a novel implicit learning paradigm to examine the effect of sensory noise on the predictions participants built. In order to learn a sequence, our participants had to select which visual information to attend to and disregard low-level prediction errors caused by the sensory noise, which the theory claims is more difficult for autistic individuals. Contrary to the proposed higher precision-weighting of prediction errors in autism, the high-likelihood children did not show signs of updating their predictions more readily when we added sensory noise compared to the low-likelihood children, either in their reaction times or in the recurrence and determinism of their response locations. These results raise challenges for Predictive Processing theories of autism, specifically for the notion that prediction errors are inflexibly highly weighted by individuals with autism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/desc.13158DOI Listing
July 2021

Structural Degradation in Midcingulate Cortex Is Associated with Pathological Aggression in Mice.

Brain Sci 2021 Jun 29;11(7). Epub 2021 Jun 29.

Donders Institute for Brain, Cognition and Behavior, Radboudumc, 6525 EN Nijmegen, The Netherlands.

Pathological aggression is a debilitating feature of many neuropsychiatric disorders, and cingulate cortex is one of the brain areas centrally implicated in its control. Here we explore the specific role of midcingulate cortex (MCC) in the development of pathological aggression. To this end, we investigated the structural and functional degeneration of MCC in the BALB/cJ strain, a mouse model for pathological aggression. Compared to control animals from the BALB/cByJ strain, BALB/cJ mice expressed consistently heightened levels of aggression, as assessed by the resident-intruder test. At the same time, immunohistochemistry demonstrated stark structural degradation in the MCC of aggressive BALB/cJ mice: Decreased neuron density and widespread neuron death were accompanied by increased microglia and astroglia concentrations and reactive astrogliosis. cFos staining indicated that this degradation had functional consequences: MCC activity did not differ between BALB/cJ and BALB/cByJ mice at baseline, but unlike BALB/cByJ mice, BALB/cJ mice failed to activate MCC during resident-intruder encounters. This suggests that structural and functional impairments of MCC, triggered by neuronal degeneration, may be one of the drivers of pathological aggression in mice, highlighting MCC as a potential key area for pathologies of aggression in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/brainsci11070868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301779PMC
June 2021

Pivotal Response Treatment with and without robot-assistance for children with autism: a randomized controlled trial.

Eur Child Adolesc Psychiatry 2021 Jun 3. Epub 2021 Jun 3.

Karakter Child and Adolescent Psychiatry University Centre, Reinier Postlaan 12, 6525 GC, Nijmegen, The Netherlands.

Pivotal response treatment (PRT) is a promising intervention focused on improving social communication skills in children with autism spectrum disorder (ASD). Since robots potentially appeal to children with ASD and may contribute to their motivation for social interaction, this exploratory randomized controlled trial (RCT) was conducted comparing PRT (PRT and robot-assisted PRT) with treatment-as-usual (TAU). Seventy-three children (PRT: n = 25; PRT + robot: n = 25; TAU: n = 23) with ASD, aged 3-8 years were assessed at baseline, after 10 and 20 weeks of intervention, and at 3-month follow-up. There were no significant group differences on parent- and teacher-rated general social-communicative skills and blindly rated global functioning directly after treatment. However, at follow-up largest gains were observed in robot-assisted PRT compared to other groups. These results suggest that robot-assistance may contribute to intervention efficacy for children with ASD when using game scenarios for robot-child interaction during multiple sessions combined with motivational components of PRT. This trial is registered at https://www.trialregister.nl/trial/4487 ; NL4487/NTR4712 (2014-08-01).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00787-021-01804-8DOI Listing
June 2021

Effects of substance misuse on inhibitory control in patients with attention-deficit/hyperactivity disorder.

Addict Biol 2021 Jun 7:e13063. Epub 2021 Jun 7.

Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.

Patients with attention-deficit/hyperactivity disorder (ADHD) are often diagnosed with comorbid substance misuse (SM), which is associated with poor treatment efficacy. Although literature indicates similar inhibitory control deficits in both conditions, it is unclear whether SM in ADHD exaggerates pre-existing deficits, with additive or distinct impairments in patients. Our aim was to examine SM effects on inhibitory control in ADHD. Behavioural and functional magnetic resonance imaging (fMRI) data from a stop-signal task were compared across ADHD patients with and without SM (ADHD + SM and ADHD-only, respectively) and controls (n = 33/group; 79 males, mean age 18.02 ± 2.45). To limit substance use disorder (SUD) trait effects, groups were matched for parental SUD. Overall, we found worse performance for ADHD-only and/or ADHD + SM compared with controls but no difference between the ADHD groups. Moreover, the ADHD groups showed decreased frontostriatal and frontoparietal activity during successful and failed stop trials. There were no differences between the ADHD groups in superior frontal nodes, but there was more decreased activation in temporal/parietal nodes in ADHD-only compared with ADHD + SM. During go-trials, ADHD + SM showed decreased activation in inferior frontal nodes compared with ADHD-only and controls. Findings during response inhibition showed deficits in inhibition and attentional processes for ADHD patients with and without SM. Despite no evidence for SM effects during response inhibition, results during go-trials suggest distinct effects on nodes that are associated with several executive functions. Future studies should investigate whether distinct deficits in ADHD + SM relate to poor treatment results and can direct development of distinct ADHD treatment strategies for these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/adb.13063DOI Listing
June 2021

A randomised controlled trial (MindChamp) of a mindfulness-based intervention for children with ADHD and their parents.

J Child Psychol Psychiatry 2021 May 24. Epub 2021 May 24.

Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, The Netherlands.

Background: Family mindfulness-based intervention (MBI) for child attention-deficit/hyperactivity disorder (ADHD) targets child self-control, parenting and parental mental health, but its effectiveness is still unclear.

Methods: MindChamp is a pre-registered randomised controlled trial comparing an 8-week family MBI (called 'MYmind') in addition to care-as-usual (CAU) (n = 55) with CAU-only (n = 48). Children aged 8-16 years with remaining ADHD symptoms after CAU were enrolled together with a parent. Primary outcome was post-treatment parent-rated child self-control deficits (BRIEF); post hoc, Reliable Change Indexes were explored. Secondary child outcomes included ADHD symptoms (parent/teacher-rated Conners' and SWAN; teacher-rated BRIEF), other psychological symptoms (parent/teacher-rated), well-being (parent-rated) and mindfulness (self-rated). Secondary parent outcomes included self-ratings of ADHD symptoms, other psychological symptoms, well-being, self-compassion and mindful parenting. Assessments were conducted at post-treatment, 2- and 6-month follow-up.

Results: Relative to CAU-only, MBI+CAU resulted in a small, statistically non-significant post-treatment improvement on the BRIEF (intention-to-treat: d = 0.27, p = .18; per protocol: d = 0.33, p = .11). Significantly more children showed reliable post-treatment improvement following MBI+CAU versus CAU-only (32% versus 11%, p < .05, Number-Needed-to-Treat = 4.7). ADHD symptoms significantly reduced post-treatment according to parent (Conners' and SWAN) and teacher ratings (BRIEF) per protocol. Only parent-rated hyperactivity impulsivity (SWAN) remained significantly reduced at 6-month follow-up. Post-treatment group differences on other secondary child outcomes were consistently favour of MBI+CAU, but mostly non-significant; no significant differences were found at follow-ups. Regarding parent outcomes, significant post-treatment improvements were found for their own ADHD symptoms, well-being and mindful parenting. At follow-ups, some significant effects remained (ADHD symptoms, mindful parenting), some additional significant effects appeared (other psychological symptoms, self-compassion) and others disappeared/remained non-significant.

Conclusions: Family MBI+CAU did not outperform CAU-only in reducing child self-control deficits on a group level but more children reliably improved. Effects on parents were larger and more durable. When CAU for ADHD is insufficient, family MBI could be a valuable addition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcpp.13430DOI Listing
May 2021

COVID-19 health and social care access for autistic people: European policy review.

BMJ Open 2021 05 17;11(6):e045341. Epub 2021 May 17.

Department of Forensic and Neurodevelopmental Sciences, King's College London, London, UK.

Background: The global COVID-19 pandemic has had an unprecedented impact on European health and social care systems, with demands on testing, hospital and intensive care capacity exceeding available resources in many regions. This has led to concerns that some vulnerable groups, including autistic people, may be excluded from services.

Methods: We reviewed policies from 15 European member states, published in March-July 2020, pertaining to (1) access to COVID-19 tests; (2) provisions for treatment, hospitalisation and intensive care units (ICUs); and (3) changes to standard health and social care. In parallel, we analysed survey data on the lived experiences of 1301 autistic people and caregivers.

Results: Autistic people experienced significant barriers when accessing COVID-19 services. First, despite being at elevated risk of severe illness due to co-occurring health conditions, there was a lack of accessibility of COVID-19 testing. Second, many COVID-19 outpatient and inpatient treatment services were reported to be inaccessible, predominantly resulting from individual differences in communication needs. Third, ICU triage protocols in many European countries (directly or indirectly) resulted in discriminatory exclusion from lifesaving treatments. Finally, interruptions to standard health and social care left over 70% of autistic people without everyday support.

Conclusions: The COVID-19 pandemic has further exacerbated existing healthcare inequalities for autistic people, probably contributing to disproportionate increases in morbidity and mortality, mental health and behavioural difficulties, and reduced quality of life. An urgent need exists for policies and guidelines on accessibility of COVID-19 services to be updated to prevent the widespread exclusion of autistic people from services, which represents a violation of international human rights law.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-045341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130751PMC
May 2021

Maternal serotonin transporter genotype and offsprings' clinical and cognitive measures of ADHD and ASD.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Aug 15;110:110354. Epub 2021 May 15.

Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Center, Kapittelweg 29, 6525 EN Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center, Reinier Postlaan 12, 6525 GC Nijmegen, the Netherlands. Electronic address:

Serotonin (5-HT) is an important factor for prenatal neurodevelopment whereby its neurotrophic actions can be regulated through maternal-fetal interactions. We explored if maternal 5-HTTLPR genotype is associated with clinical and cognitive measures of attention-deficit/hyperactivity disorder (ADHD) and comorbid autism spectrum disorder (ASD) in typically-developing and ADHD-diagnosed offspring, beyond classical inheritance and environmental- and comorbidity-mediators/confounders. Family-based variance decomposition analyses were performed incorporating 6-31 year-old offsprings' as well as parental genotypes of 462 ADHD and control families from the NeuroIMAGE cohort. Dependent measures were offsprings' ADHD symptom- and ASD trait-scores and cognitive measures including executive functioning (including response inhibition and cognitive flexibility), sustained attention, reward processing, motor control, and emotion recognition. Offsprings' stereotyped behavior was predicted by an interaction between maternal 5-HTTLPR genotype and offsprings' sex. Furthermore, offspring of mothers with low-expressing genotypes demonstrated larger reward-related reductions in reaction time. While specifically adult male offspring of these mothers reported a faster reversal learning with less errors, specifically young female offspring of these mothers were more accurate in identifying happy faces. Adult offspring from the mothers with low-expressing 5-HTTLPR genotypes were also slower in identifying happy faces. However, this association seemed to be mediated by offsprings' high anxiety levels. In sum, we found some support for a role of the maternal 5-HT system in modulating fetal brain development and behavior. Offsprings' cognitive measures might be more sensitive to small alterations within the maternal 5-HT system than their ADHD and ASD clinical phenotypes. Further studies are needed to specify the association between maternal genotype and risk for neurodevelopmental disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pnpbp.2021.110354DOI Listing
August 2021

Imbalanced social-communicative and restricted repetitive behavior subtypes of autism spectrum disorder exhibit different neural circuitry.

Commun Biol 2021 May 14;4(1):574. Epub 2021 May 14.

Roche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, Basel, Switzerland.

Social-communication (SC) and restricted repetitive behaviors (RRB) are autism diagnostic symptom domains. SC and RRB severity can markedly differ within and between individuals and may be underpinned by different neural circuitry and genetic mechanisms. Modeling SC-RRB balance could help identify how neural circuitry and genetic mechanisms map onto such phenotypic heterogeneity. Here, we developed a phenotypic stratification model that makes highly accurate (97-99%) out-of-sample SC = RRB, SC > RRB, and RRB > SC subtype predictions. Applying this model to resting state fMRI data from the EU-AIMS LEAP dataset (n = 509), we find that while the phenotypic subtypes share many commonalities in terms of intrinsic functional connectivity, they also show replicable differences within some networks compared to a typically-developing group (TD). Specifically, the somatomotor network is hypoconnected with perisylvian circuitry in SC > RRB and visual association circuitry in SC = RRB. The SC = RRB subtype show hyperconnectivity between medial motor and anterior salience circuitry. Genes that are highly expressed within these networks show a differential enrichment pattern with known autism-associated genes, indicating that such circuits are affected by differing autism-associated genomic mechanisms. These results suggest that SC-RRB imbalance subtypes share many commonalities, but also express subtle differences in functional neural circuitry and the genomic underpinnings behind such circuitry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42003-021-02015-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121854PMC
May 2021

An Individual Participant Data Meta-analysis: Behavioral Treatments for Children and Adolescents With Attention-Deficit/Hyperactivity Disorder.

J Am Acad Child Adolesc Psychiatry 2021 Apr 28. Epub 2021 Apr 28.

Objective: Behavioral interventions are well established treatments for children with attention-deficit/hyperactivity disorder (ADHD). However, insight into moderators of treatment outcome is limited.

Method: We conducted an individual participant data meta-analysis (IPDMA), including data of randomized controlled behavioral intervention trials for individuals with ADHD <18 years of age. Outcomes were symptoms of ADHD, oppositional defiant disorder (ODD), and conduct disorder (CD) and impairment. Moderators investigated were symptoms and impairment severity, medication use, age, IQ, sex, socioeconomic status, and single parenthood.

Results: For raters most proximal to treatment, small- to medium-sized effects of behavioral interventions were found for symptoms of ADHD, inattention, hyperactivity/impulsivity (HI), ODD and CD, and impairment. Blinded outcomes were available only for small preschool subsamples and limited measures. CD symptoms and/or diagnosis moderated outcome on ADHD, HI, ODD, and CD symptoms. Single parenthood moderated ODD outcome, and ADHD severity moderated impairment outcome. Higher baseline CD or ADHD symptoms, a CD diagnosis, and single parenthood were related to worsening of symptoms in the untreated but not in the treated group, indicating a protective rather than an ameliorative effect of behavioral interventions for these children.

Conclusion: Behavioral treatments are effective for reducing ADHD symptoms, behavioral problems, and impairment as reported by raters most proximal to treatment. Those who have severe CD or ADHD symptoms, a CD diagnosis, or are single parents should be prioritized for treatment, as they may evidence worsening of symptoms in the absence of intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaac.2021.02.024DOI Listing
April 2021

Action predictability is reflected in beta power attenuation and predictive eye movements in adolescents with and without autism.

Neuropsychologia 2021 07 19;157:107859. Epub 2021 Apr 19.

Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands.

Most theoretical accounts of autism posit difficulties in predicting others' actions, and this difficulty has been proposed to be at the root of autistic individuals' social communication differences. Empirical results are mixed, however, with autistic individuals showing reduced action prediction in some studies but not in others. It has recently been proposed that this effect might be observed primarily when observed actions are less predictable, but this idea has yet to be tested. To assess the influence of predictability on neural and behavioural action prediction, the current study employed an action observation paradigm with multi-step actions that become gradually more predictable. Autistic and non-autistic adolescents showed similar patterns of motor system activation during observation, as seen in attenuated mu and beta power compared to baseline, with beta power further modulated by predictability in both groups. Bayesian statistics confirmed that action predictability influenced beta power similarly in both groups. The groups also made similar behavioural predictions, as seen in three eye-movement measures. We found no evidence that autistic adolescents responded differently than non-autistic adolescents to the predictability of an observed action. These findings show that autistic adolescents do spontaneously predict others' actions, both neurally and behaviourally, which calls into question the role of action prediction as a key mechanism underlying autism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuropsychologia.2021.107859DOI Listing
July 2021

Early detection of young children at risk of autism spectrum disorder at well-baby clinics in the Netherlands: Perspectives of preventive care physicians.

Autism 2021 Apr 22:13623613211009345. Epub 2021 Apr 22.

Karakter Child and Adolescent Psychiatry University Centre, The Netherlands.

Lay Abstract: To improve early detection of autism spectrum disorder in preventive care, a Dutch guideline was developed 5 years ago. The guideline provides preventive care physicians at well-baby clinics action-oriented advice and describes a step-by-step approach for children identified at an increased risk for autism spectrum disorder during general healthcare surveillance. The present qualitative study evaluated adherence to the guideline and studied barriers regarding early detection of autism spectrum disorder at well-baby clinics. Interviews were undertaken with 12 preventive care physicians (one representative per province). It was found that the vast majority of participants did not follow-up general surveillance with an autism spectrum disorder -specific screener as prescribed by the guideline. Six barriers (limited knowledge about autism spectrum disorder symptoms in infant and toddlerhood, professional attitude toward early detection, problems in discussing initial worries with parents, limited use of screening instruments, perceptions toward cultural and language differences and constraints regarding availability of healthcare services) were found. The results of this study highlight the importance of an integrative approach, raising awareness of the benefits regarding early detection of autism spectrum disorder in preventive care, the need of continuous investment in easy and accessible training and active screening, and a closer collaboration between preventive care organizations and autism spectrum disorder experts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/13623613211009345DOI Listing
April 2021

A central role for anterior cingulate cortex in the control of pathological aggression.

Curr Biol 2021 Jun 14;31(11):2321-2333.e5. Epub 2021 Apr 14.

Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Nijmegen, the Netherlands; Department of Cognitive Neuroscience, Radboudumc, Nijmegen, the Netherlands.

Controlling aggression is a crucial skill in social species like rodents and humans and has been associated with anterior cingulate cortex (ACC). Here, we directly link the failed regulation of aggression in BALB/cJ mice to ACC hypofunction. We first show that ACC in BALB/cJ mice is structurally degraded: neuron density is decreased, with pervasive neuron death and reactive astroglia. Gene-set enrichment analysis suggested that this process is driven by neuronal degeneration, which then triggers toxic astrogliosis. cFos expression across ACC indicated functional consequences: during aggressive encounters, ACC was engaged in control mice, but not BALB/cJ mice. Chemogenetically activating ACC during aggressive encounters drastically suppressed pathological aggression but left species-typical aggression intact. The network effects of our chemogenetic perturbation suggest that this behavioral rescue is mediated by suppression of amygdala and hypothalamus and activation of mediodorsal thalamus. Together, these findings highlight the central role of ACC in curbing pathological aggression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2021.03.062DOI Listing
June 2021

Characterizing the heterogeneous course of inattention and hyperactivity-impulsivity from childhood to young adulthood.

Eur Child Adolesc Psychiatry 2021 Apr 3. Epub 2021 Apr 3.

Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

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, their 665 siblings, and 399 typically developing children. Trajectories were based on scores of the Conners Parent Rating Scale Revised and estimated over seven homogeneous age bins (from 5 to 28 years) using parallel process latent class growth analysis on data collected across 2-4 time points. Multilevel multinomial logistic regression was used to identify characteristics that differentiated between the derived classes. A seven-class solution revealed "severe combined stable" (4.8%), "severe combined decreasing" (13%), "severe inattentive stable" (4.8%), "moderate combined increasing" (7.5%), "moderate combined decreasing" (12.7%), "stable mild" (12.9%), and "stable low" (44.3%) classes. Polygenic risk for depression, ADHD diagnosis, ADHD medication use, IQ, comorbid symptom levels (foremost oppositional behaviour), and functional impairment levels differentiated classes with similar ADHD symptom levels in childhood but a diverging course thereafter. The course of ADHD is highly heterogeneous, with stable, decreasing, and increasing trajectories. Overall, severe symptom levels in childhood are associated with elevated-to-severe symptom levels in adolescence and young adulthood, despite substantial symptom reductions. Beyond symptom severity in childhood, genetic, demographic, and clinical characteristics distinguish the heterogeneous course.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00787-021-01764-zDOI Listing
April 2021

Characterizing neuroanatomic heterogeneity in people with and without ADHD based on subcortical brain volumes.

J Child Psychol Psychiatry 2021 Mar 30. Epub 2021 Mar 30.

Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. Neuroanatomic heterogeneity limits our understanding of ADHD's etiology. This study aimed to parse heterogeneity of ADHD and to determine whether patient subgroups could be discerned based on subcortical brain volumes.

Methods: Using the large ENIGMA-ADHD Working Group dataset, four subsamples of 993 boys with and without ADHD and to subsamples of 653 adult men, 400 girls, and 447 women were included in analyses. We applied exploratory factor analysis (EFA) to seven subcortical volumes in order to constrain the complexity of the input variables and ensure more stable clustering results. Factor scores derived from the EFA were used to build networks. A community detection (CD) algorithm clustered participants into subgroups based on the networks.

Results: Exploratory factor analysis revealed three factors (basal ganglia, limbic system, and thalamus) in boys and men with and without ADHD. Factor structures for girls and women differed from those in males. Given sample size considerations, we concentrated subsequent analyses on males. Male participants could be separated into four communities, of which one was absent in healthy men. Significant case-control differences of subcortical volumes were observed within communities in boys, often with stronger effect sizes compared to the entire sample. As in the entire sample, none were observed in men. Affected men in two of the communities presented comorbidities more frequently than those in other communities. There were no significant differences in ADHD symptom severity, IQ, and medication use between communities in either boys or men.

Conclusions: Our results indicate that neuroanatomic heterogeneity in subcortical volumes exists, irrespective of ADHD diagnosis. Effect sizes of case-control differences appear more pronounced at least in some of the subgroups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcpp.13384DOI Listing
March 2021

Effects of methylphenidate on executive functioning in children and adolescents with ADHD after long-term use: a randomized, placebo-controlled discontinuation study.

J Child Psychol Psychiatry 2021 Mar 28. Epub 2021 Mar 28.

Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Background: Methylphenidate may improve executive functioning in children with attention-deficit/hyperactivity disorder (ADHD). However, it is unclear if there are still acute effects of methylphenidate on executive functioning after long-term use.

Methods: In a randomized double-blind, placebo-controlled discontinuation study, 94 children and adolescents (ages 8-18 years) who used methylphenidate beyond two years were either assigned to seven weeks of continued treatment with 36 or 54 mg of extended-release methylphenidate or to gradual withdrawal over three weeks to placebo for four weeks. Performance on neuropsychological tasks, measuring working memory, response inhibition, attentional flexibility and psychomotor speed was compared between both groups using mixed models for repeated measures. Additionally, we investigated within the discontinuation group if a deterioration on the investigator-rated Clinical Global Impressions Improvement scale after withdrawing to placebo was related to a worse performance on the neuropsychological tasks. This study was registered in the Netherlands Trial Register (www. Trialregister.nl) with identifier 5252.

Results: After withdrawal of methylphenidate, the discontinuation group made more errors on working memory (β = -1.62, SD = 0.56, t = -2.88, p = .01, Cohen's f2 = .14), independent from reaction time compared to baseline, in contrast to the continuation group. We did not find differences in changes in response inhibition, attentional flexibility and psychomotor speed between the two groups. Also, there were no significant differences in task measures between the participants who deteriorated clinically and those who did not.

Conclusions: Our study shows that methylphenidate has a beneficial effect on working memory after two years of use. Future studies should explore whether cognitive outcomes may aid clinical decision-making on the continued use of methylphenidate, given dissociation between cognitive and behavioural effects of stimulant medication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcpp.13419DOI Listing
March 2021

Gray matter networks associated with attention and working memory deficit in ADHD across adolescence and adulthood.

Transl Psychiatry 2021 03 25;11(1):184. Epub 2021 Mar 25.

Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University Georgia Institute of Technology and Emory University, Atlanta, GA, USA.

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neuropsychiatric disorder and may persist into adulthood. Working memory and attention deficits have been reported to persist from childhood to adulthood. How neuronal underpinnings of deficits differ across adolescence and adulthood is not clear. In this study, we investigated gray matter of two cohorts, 486 adults and 508 adolescents, each including participants from ADHD and healthy controls families. Two cohorts both presented significant attention and working memory deficits in individuals with ADHD. Independent component analysis was applied to the gray matter of each cohort, separately, to extract cohort-inherent networks. Then, we identified gray matter networks associated with inattention or working memory in each cohort, and projected them onto the other cohort for comparison. Two components in the inferior, middle/superior frontal regions identified in adults and one component in the insula and inferior frontal region identified in adolescents were significantly associated with working memory in both cohorts. One component in bilateral cerebellar tonsil and culmen identified in adults and one component in left cerebellar region identified in adolescents were significantly associated with inattention in both cohorts. All these components presented a significant or nominal level of gray matter reduction for ADHD participants in adolescents, but only one showed nominal reduction in adults. Our findings suggest although the gray matter reduction of these regions may not be indicative of persistency of ADHD, their persistent associations with inattention or working memory indicate an important role of these regions in the mechanism of persistence or remission of the disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41398-021-01301-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994833PMC
March 2021

Developmental changes in fronto-striatal glutamate and their association with functioning during inhibitory control in autism spectrum disorder and obsessive compulsive disorder.

Neuroimage Clin 2021 10;30:102622. Epub 2021 Mar 10.

Department of Cognitive Neuroscience, Donders Institute of Brain, Cognition and Behaviour, Radboud University Medical Center, the Netherlands; Donders Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, the Netherlands. Electronic address:

Autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) show overlapping symptomatology and deficits in inhibitory control, which are associated with altered functioning and glutamatergic signaling in fronto-striatal circuitry. These parameters have never been examined together. The purpose of the current study was to investigate functioning during inhibitory control and its association with fronto-striatal glutamate concentrations across these disorders using a multi-center, longitudinal approach. Adolescents with ASD (n = 24), OCD (n = 15) and controls (n = 35) underwent two magnetic resonance imaging (MRI) sessions with a one-year interval. This included proton magnetic resonance spectroscopy (H-MRS; n = 74) and functional MRI during an inhibitory control task (n = 53). We investigated H-MRS data and fMRI data separately as well as integrated in a multimodal analysis using linear models focusing on diagnosis and continuous measures of overlapping compulsivity symptoms. ACC glutamate was reduced over time in the ASD group compared with controls, while striatal glutamate decreased over time independent of diagnosis. Increased compulsive behavior seemed to be associated with increased striatal activity during failed inhibitory control. The integrated analyses showed differential involvement of increased striatal glutamate during failed but decreased striatal glutamate during successful inhibitory control in the OCD group compared to controls and ASD, suggesting different underlying mechanisms for OCD compared to ASD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2021.102622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022251PMC
March 2021

Task-generic and task-specific connectivity modulations in the ADHD brain: an integrated analysis across multiple tasks.

Transl Psychiatry 2021 03 10;11(1):159. Epub 2021 Mar 10.

Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.

Attention-deficit/hyperactivity disorder (ADHD) is associated with altered functioning in multiple cognitive domains and neural networks. This paper offers an overarching biological perspective across these. We applied a novel strategy that extracts functional connectivity modulations in the brain across one (P), two (P) or three (P) cognitive tasks and compared the pattern of modulations between participants with ADHD (n-89), unaffected siblings (n = 93) and controls (n = 84; total N = 266; age range = 8-27 years). Participants with ADHD had significantly fewer P connections (modulated regardless of task), but significantly more task-specific (P) connectivity modulations than the other groups. The amplitude of these P modulations was significantly higher in ADHD. Unaffected siblings showed a similar degree of P connectivity modulation as controls but a similar degree of P connectivity modulation as ADHD probands. P connections were strongly reproducible at the individual level in controls, but showed marked heterogeneity in both participants with ADHD and unaffected siblings. The pattern of reduced task-generic and increased task-specific connectivity modulations in ADHD may be interpreted as reflecting a less efficient functional brain architecture due to a reduction in the ability to generalise processing pathways across multiple cognitive domains. The higher amplitude of unique task-specific connectivity modulations in ADHD may index a more "effortful" coping strategy. Unaffected siblings displayed a task connectivity profile in between that of controls and ADHD probands, supporting an endophenotype view. Our approach provides a new perspective on the core neural underpinnings of ADHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41398-021-01284-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943764PMC
March 2021

Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets.

J Child Psychol Psychiatry 2021 Mar 22. Epub 2021 Mar 22.

Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.

Objective: Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.

Methods: We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.

Results: There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.

Conclusion: Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcpp.13396DOI Listing
March 2021

Towards robust and replicable sex differences in the intrinsic brain function of autism.

Mol Autism 2021 03 1;12(1):19. Epub 2021 Mar 1.

Autism Center, The Child Mind Institute, 101 E 56 Street, New York City, New York, 10026, USA.

Background: Marked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data.

Methods: We addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7-18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z > 3.1, cluster-level P < 0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research.

Results: Discovery analyses in ABIDE revealed significant main effects of diagnosis and sex across the intrinsic functional connectivity of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples-EU-AIMS LEAP.

Limitations: Given the lack of a priori harmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability.

Conclusions: Atypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13229-021-00415-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923310PMC
March 2021

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 17. Epub 2021 Feb 17.

Laboratory of Psychiatric Neuroimaging, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25364DOI Listing
February 2021

Reward and Punishment Sensitivity are Associated with Cross-disorder Traits.

Psychiatry Res 2021 Apr 8;298:113795. Epub 2021 Feb 8.

Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands; Radboud University, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands.

Reversal learning deficits following reward and punishment processing are observed across disruptive behaviors (DB) and attention-deficit/hyperactivity disorder (ADHD), and have been associated with callous-unemotional (CU) traits. However, it remains unknown to what extent these altered reinforcement sensitivities are linked to the co-occurrence of oppositional traits, ADHD symptoms, and CU traits. Reward and punishment sensitivity and perseverative behavior were therefore derived from a probabilistic reversal learning task to investigate reinforcement sensitivity in participants with DB (n=183, ODD=62, CD=10, combined=57, age-range 8-18), ADHD (n=144, age-range 11-28), and controls (n=191, age-range 8-26). The SNAP-IV and Conners rating scales were used to assess oppositional and ADHD traits. The Inventory of CU traits was used to assess CU traits. Decreased reward sensitivity was associated with ADHD symptom severity (p=0.018) if corrected for oppositional symptoms. ADHD symptomatology interacted with oppositional behavior on perseveration (p=0.019), with the former aggravating the effect of oppositional behavior on perseveration and vice versa. Within a pooled sample, reversal learning alterations were associated with the severity of ADHD symptoms, underpinned by hyposensitivity to reward and increased perseveration. These results show ADHD traits, as opposed to oppositional behavior and CU traits, is associated with decreased reward-based learning in adolescents and adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psychres.2021.113795DOI Listing
April 2021

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 11. Epub 2021 Feb 11.

Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25320DOI Listing
February 2021

Pivotal Response Treatment for School-Aged Children and Adolescents with Autism Spectrum Disorder: A Randomized Controlled Trial.

J Autism Dev Disord 2021 Feb 9. Epub 2021 Feb 9.

Karakter Child and Adolescent Psychiatry University Centre, Reinier Postlaan 12, 6525 GC, Nijmegen, The Netherlands.

Pivotal Response Treatment (PRT) is promising for children with Autism Spectrum Disorder (ASD), but more methodologically robust designed studies are needed. In this randomized controlled trial, forty-four children with ASD, aged 9-15 years, were randomly allocated to PRT (n = 22) or treatment-as-usual (TAU; n = 22). Measurements were obtained after 12- and 20-weeks treatment, and 2-month follow-up. PRT resulted in significant greater improvements on parent-rated social-communicative skills after 12 weeks treatment (p = .004, partial η = 0.22), compared to TAU. Furthermore, larger gains in PRT compared to TAU were observed on blindly rated global functioning, and parent-rated adaptive socialization skills and attention problems. Implications for clinical practice and suggestions for future research are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10803-021-04886-0DOI Listing
February 2021

The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder.

Neurosci Biobehav Rev 2021 Feb 4. Epub 2021 Feb 4.

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wuerzburg, Wuerzburg, Germany. Electronic address:

Background: Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base.

Methods: We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder.

Results: We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents.

Conclusions: Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neubiorev.2021.01.022DOI Listing
February 2021

Structural brain imaging studies offer clues about the effects of the shared genetic etiology among neuropsychiatric disorders.

Mol Psychiatry 2021 Jan 17. Epub 2021 Jan 17.

Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.

Genomewide association studies have found significant genetic correlations among many neuropsychiatric disorders. In contrast, we know much less about the degree to which structural brain alterations are similar among disorders and, if so, the degree to which such similarities have a genetic etiology. From the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium, we acquired standardized mean differences (SMDs) in regional brain volume and cortical thickness between cases and controls. We had data on 41 brain regions for: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), epilepsy, major depressive disorder (MDD), obsessive compulsive disorder (OCD), and schizophrenia (SCZ). These data had been derived from 24,360 patients and 37,425 controls. The SMDs were significantly correlated between SCZ and BD, OCD, MDD, and ASD. MDD was positively correlated with BD and OCD. BD was positively correlated with OCD and negatively correlated with ADHD. These pairwise correlations among disorders were correlated with the corresponding pairwise correlations among disorders derived from genomewide association studies (r = 0.494). Our results show substantial similarities in sMRI phenotypes among neuropsychiatric disorders and suggest that these similarities are accounted for, in part, by corresponding similarities in common genetic variant architectures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41380-020-01002-zDOI Listing
January 2021

Guideline Adherence of Monitoring Antipsychotic Use for Nonpsychotic Indications in Children and Adolescents: A Patient Record Review.

J Clin Psychopharmacol 2021 Jan/Feb 01;41(1):13-18

From the Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen.

Background: Antipsychotics are frequently prescribed to children and adolescents for nonpsychotic indications. Guidelines recommend regularly assessing treatment response and adverse effects and the ongoing need for their use. We aimed to assess adherence to recommendations of available guidelines regarding monitoring antipsychotic use and to test the influence of children's age, sex, intelligence quotient, and diagnosis on adherence.

Methods: We reviewed 426 medical records from 26 centers within 3 large Dutch child and adolescent psychiatry organizations, excluding children with schizophrenia, psychosis, mania, or an intelligence quotient below 70. We investigated whether there was regular assessment of treatment response, adverse events (physical and laboratory), and at least annual discussion of the need of continued use.

Results: On average, treatment response was assessed in 69.3% of the recommended treatment periods, height in 25.6%, weight in 30.6%, blood pressure in 20.6%, evaluation of adverse events in 19.4%, and cardiometabolic measures in 13.7%; discontinuation and/or continued need was discussed at least annually in 36.2%. Extrapyramidal and prolactin-related adverse effects, waist circumference, glucose, and lipids were rarely investigated. Higher age was associated with lower rates of assessment of treatment response. Most antipsychotics were prescribed long-term. In those children with sufficient documentation of the course of treatment, 57.7% was still using an antipsychotic 3 years after initiation.

Conclusions: Our findings indicate insufficient adherence to guideline recommendations for monitoring antipsychotic use in children and adolescents, as well as long duration of use in the majority of children. Especially, older children are at higher risk of receiving suboptimal care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JCP.0000000000001322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752226PMC
December 2020

Effects of substance misuse on reward-processing in patients with attention-deficit/hyperactivity disorder.

Neuropsychopharmacology 2021 02 12;46(3):622-631. Epub 2020 Nov 12.

Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.

Attention-Deficit/Hyperactivity Disorder (ADHD) and Substance Use Disorder (SUD) often co-occur and are associated with treatment resistance. Both disorders are characterized by similar reward-processing deficits with decreased striatal responses to reward anticipation, though literature is inconsistent. It is unclear whether substance misuse exaggerates reward-processing deficits observed in ADHD. The aim of this study was to examine substance misuse effects on reward-processing in ADHD. Functional MRI data in a Monetary Incentive Delay (MID) task from a multi-site study were compared across ADHD groups with and without substance misuse (ADHD + SM and ADHD-only, respectively) and healthy controls (n = 40/group, 74 males and 46 females, aged 13.7-25.9 years). Substance misuse was defined as misuse of alcohol, nicotine, or drugs. Groups were matched with presence/absence of parental SUD to avoid interference with SUD trait effects. Compared to ADHD-only and controls, ADHD + SM showed hyperactivation in putamen during reward anticipation. Compared to controls, the ADHD groups showed hypoactivation in motor/sensory cortices and hyperactivation in frontal pole and OFC during reward outcome. ADHD + SM also showed hyperactivation in frontal pole during neutral outcome. Moreover, ADHD + SM patients showed higher callous-unemotional (CU) traits that were positively correlated with putamen responses to reward anticipation. Our results show distinct condition-independent neural activation profile for ADHD + SM compared to ADHD-only and controls. Effects of comorbid substance misuse and variability of its prevalence across ADHD studies might have contributed to inconsistencies in ADHD literature. Contrasted with findings for reward-processing in SUD literature, results potentially suggest distinct underlying mechanisms for SUD subgroups with different characteristics, like antisocial/psychopathic traits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41386-020-00896-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027205PMC
February 2021

Fractionating autism based on neuroanatomical normative modeling.

Transl Psychiatry 2020 11 6;10(1):384. Epub 2020 Nov 6.

Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands.

Autism is a complex neurodevelopmental condition with substantial phenotypic, biological, and etiologic heterogeneity. It remains a challenge to identify biomarkers to stratify autism into replicable cognitive or biological subtypes. Here, we aim to introduce a novel methodological framework for parsing neuroanatomical subtypes within a large cohort of individuals with autism. We used cortical thickness (CT) in a large and well-characterized sample of 316 participants with autism (88 female, age mean: 17.2 ± 5.7) and 206 with neurotypical development (79 female, age mean: 17.5 ± 6.1) aged 6-31 years across six sites from the EU-AIMS multi-center Longitudinal European Autism Project. Five biologically based putative subtypes were derived using normative modeling of CT and spectral clustering. Three of these clusters showed relatively widespread decreased CT and two showed relatively increased CT. These subtypes showed morphometric differences from one another, providing a potential explanation for inconsistent case-control findings in autism, and loaded differentially and more strongly onto symptoms and polygenic risk, indicating a dilution of clinical effects across heterogeneous cohorts. Our results provide an important step towards parsing the heterogeneous neurobiology of autism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41398-020-01057-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648836PMC
November 2020