Persistent Attention-deficit/hyperactivity Disorder Research Articles

Changes in MRI head motion across development: typical development and ADHD

Head motion is a major confounding variable for magnetic resonance imaging (MRI) analysis, and is commonly seen in individuals with neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD). This study investigated the trajectory of change in head motion in typically developing children and children with ADHD, and examined possible altered trajectories in head motion between children with remitted and persistent ADHD. 105 children with ADHD and 84 controls completed diffusion and resting-state functional MRI scans at up to three waves over ages 9–14 years. In-scanner head motion was calculated using framewise displacement, and longitudinal trajectories analyzed using generalized additive mixed modelling. Results revealed a significant age effect on framewise displacement where head motion decreased as age increased during both diffusion (p < .001) and resting-state functional MRI (p < .001). A significant effect of group was also observed; children with ADHD displayed greater framewise displacement than controls over the age range (diffusion MRI p = .036, functional MRI p = .004). Further analyses revealed continued elevation in head motion in children in remission from ADHD (diffusion MRI p = .020, functional MRI p = .011) compared to controls. Rates of change in head motion did not significantly differ between diagnostic groups. Findings indicate a critical link between in-scanner head motion and developmental age within children regardless of ADHD diagnosis, important to consider in studies of neurodevelopment. Findings also suggest change in head motion with age does not differ between individuals with remitted and persistent ADHD, adding further evidence that behavioral manifestations of ADHD may continue despite clinical remission.

Assessing Brain Iron and Its Relationship to Cognition and Comorbidity in Children With Attention-Deficit/Hyperactivity Disorder With Quantitative Susceptibility Mapping

BackgroundQuantitative susceptibility mapping is a neuroimaging technique that detects local changes in magnetic susceptibility induced by brain iron. Brain iron and the dopaminergic system are linked because iron is an important cofactor for dopamine synthesis. Attention-deficit/hyperactivity disorder (ADHD) is associated with dysregulation of dopaminergic transmission. Therefore, we applied quantitative susceptibility mapping on subcortical structures to study potential alterations in brain iron and its impact on cognition and mental health in children with ADHD. MethodsQuantitative susceptibility mapping data (3T) of 111 participants (nADHD = 58, mean [SD] age = 13.2 [0.63] years; nControl = 53, mean [SD] age = 13.2 [0.51] years) were analyzed. Subcortical regional brain iron values were extracted. Analysis of variance was used to examine group differences for each region of interest. For dimensional approaches, Pearson correlation analysis was performed across the cohort to examine the association of brain iron with symptoms, mental health, and cognition. ResultsNo significant differences were found in iron susceptibility between participants with ADHD and control participants, between participants with persistent ADHD and those with remitted ADHD, or between participants treated with medication and medication-naïve participants. An unexpected finding was that children with an internalizing disorder had significantly higher iron susceptibility, but the result did not survive multiple comparison correction. Higher brain iron was associated with sustained attention, but not inhibition, IQ, or working memory. ConclusionsThis is the first study to address brain iron susceptibility and its association with comorbidities and cognition in ADHD. Alterations in brain iron may not fully account for a diagnosis of ADHD but may be an indicator of internalizing problems in children. Alterations in brain iron content in children were linked to detrimental sustained attention and may represent developmental variation in cognition.

Mendelian randomization analysis of the brain, cerebrospinal fluid, and plasma proteome identifies potential drug targets for attention deficit hyperactivity disorder

The need for new therapeutics for attention deficit hyperactivity disorder (ADHD) is evident. Brain, cerebrospinal fluid (CSF), and plasma protein biomarkers with causal genetic evidence could represent potential drug targets. However, a comprehensive screen of the proteome has not yet been conducted. We employed a three-pronged approach using Mendelian Randomization (MR) and Bayesian colocalization analysis. Firstly, we studied 608 brains, 214 CSF, and 612 plasma proteins as potential causal mediators of ADHD using MR analysis. Secondly, we analysed the consistency of the discovered biomarkers across three distinct subtypes of ADHD: childhood, persistent, and late-diagnosed ADHD. Finally, we extended our analysis to examine the correlation between identified biomarkers and Tourette syndrome and pervasive autism spectrum disorder (ASD), conditions often linked with ADHD. To validate the MR findings, we conducted sensitivity analysis. Additionally, we performed cell type analysis on the human brain to identify risk genes that are notably enriched in various brain cell types. After applying Bonferroni correction, we found that the risk of ADHD was increased by brain proteins GMPPB, NAA80, HYI, CISD2, and HYI, TIE1 in CSF and plasma. Proteins GMPPB, NAA80, ICA1L, CISD2, TIE1, and RMDN1 showed overlapped loci with ADHD risk through Bayesian colocalization. Overexpression of GMPPB protein was linked to an increase in the risk for all three ADHD subtypes. While ICA1L provided protection against both ASD and ADHD, CISD2 increased the probability of both disorders. Cell-specific studies revealed that GMPPB, NAA80, ICA1L, and CISD2 were predominantly present on the surface of excitatory-inhibitory neurons. Our comprehensive MR investigation of the brain, CSF, and plasma proteomes revealed seven proteins with causal connections to ADHD. Particularly, GMPPB and TIE1 emerged as intriguing targets for potential ADHD therapy. This work was partly funded by the Key R & D Program of Zhejiang (T.L. 2022C03096); the National Natural Science Foundation of China Project (C.Z. 82001413); Postdoctoral Foundation of West China Hospital (C.Z. 2020HXBH163).

Cumulative Effects of Resting-State Connectivity Across All Brain Networks Significantly Correlate with Attention-Deficit Hyperactivity Disorder Symptoms.

Identification of replicable neuroimaging correlates of attention-deficit hyperactivity disorder (ADHD) has been hindered by small sample sizes, small effects, and heterogeneity of methods. Given evidence that ADHD is associated with alterations in widely distributed brain networks and the small effects of individual brain features, a whole-brain perspective focusing on cumulative effects is warranted. The use of large, multisite samples is crucial for improving reproducibility and clinical utility of brain-wide MRI association studies. To address this, a polyneuro risk score (PNRS) representing cumulative, brain-wide, ADHD-associated resting-state functional connectivity was constructed and validated using data from the Adolescent Brain Cognitive Development (ABCD, N = 5,543, 51.5% female) study, and was further tested in the independent Oregon-ADHD-1000 case-control cohort (N = 553, 37.4% female). The ADHD PNRS was significantly associated with ADHD symptoms in both cohorts after accounting for relevant covariates (p < 0.001). The most predictive PNRS involved all brain networks, though the strongest effects were concentrated among the default mode and cingulo-opercular networks. In the longitudinal Oregon-ADHD-1000, non-ADHD youth had significantly lower PNRS (Cohen's d = -0.318, robust p = 5.5 × 10-4) than those with persistent ADHD (age 7-19). The PNRS, however, did not mediate polygenic risk for ADHD. Brain-wide connectivity was robustly associated with ADHD symptoms in two independent cohorts, providing further evidence of widespread dysconnectivity in ADHD. Evaluation in enriched samples demonstrates the promise of the PNRS approach for improving reproducibility in neuroimaging studies and unraveling the complex relationships between brain connectivity and behavioral disorders.

The causal impact of maternal smoking around birth on offspring ADHD: A two-sample Mendelian randomization study

BackgroundThe previous literature highlights a relationship between maternal smoking around birth (MSAB) and offspring attention-deficit/hyperactivity disorder (ADHD). These studies have focused on the causal effects of MSAB on offspring ADHD. MethodA Mendelian randomization analysis was conducted using summary statistics. Data on MSAB were obtained from a recent study including 391,992 participants. ADHD data were obtained from six sources for 246,888 participants. The present study used five methods to examine the causal impact from outcomes on exposures. The inverse variance weighted (IVW) was the main method of analysis, while the other four methods were supplementary methods. ResultThe IVW revealed that MSAB was a risk factor for offspring ADHD (OR: 2.54; 95 % confidence interval [CI]: 1.61–4.00, p = 6.04 × 10−5). Concerning ADHD in both sexes, MSAB was associated with females (OR = 3.96, 95 % CI: 1.99–7.90, p = 8.98 × 10−5) and males (OR = 3.74, 95 % CI: 1.74–5.72, p = 1.48 × 10−4). In different diagnosis periods for ADHD, MSAB increased the risk of childhood (OR = 3.63, 95 % CI: 2.25–5.87, p = 1.31 × 10−7), late-diagnosed (OR = 2.99, 95 % CI: 1.74–5.14, p = 7.33 × 10−5), and persistent (OR = 4.77, 95 % CI: 1.88–12.14, p = 1.03 × 10−3) ADHD. The final analysis did not reveal heterogeneity. ConclusionsA causal impact of MSAB on offspring ADHD was observed. These findings highlight the need for careful consideration of prenatal exposure (MSAB) during the assessment of offspring ADHD. Additionally, it can provide targeted guidance for prenatal interventions. Future studies should analyze the effects of different doses of maternal smoking on ADHD.

Working Memory-Related Neurofunctional Correlates Associated with the Frontal Lobe in Children with Familial vs. Non-Familial Attention Deficit/Hyperactivity Disorder.

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high prevalence, heritability, and heterogeneity. Children with a positive family history of ADHD have a heightened risk of ADHD emergence, persistence, and executive function deficits, with the neural mechanisms having been under investigated. The objective of this study was to investigate working memory-related functional brain activation patterns in children with ADHD (with vs. without positive family histories (ADHD-F vs. ADHD-NF)) and matched typically developing children (TDC). Voxel-based and region of interest analyses were conducted on two-back task-based fMRI data of 362 subjects, including 186, 96, and 80 children in groups of TDC, ADHD-NF, and ADHD-F, respectively. Relative to TDC, both ADHD groups had significantly reduced activation in the left inferior frontal gyrus (IFG). And the ADHD-F group demonstrated a significant positive association of left IFG activation with task reaction time, a negative association of the right IFG with ADHD symptomatology, and a negative association of the IFG activation laterality index with the inattention symptom score. These results suggest that working memory-related functional alterations in bilateral IFGs may play distinct roles in ADHD-F, with the functional underdevelopment of the left IFG significantly informing the onset of ADHD symptoms. Our findings have the potential to assist in tailored diagnoses and targeted interventions in children with ADHD-F.

Bibliometric analysis of publications on attention deficit hyperactivity disorder (ADHD) in France since 1974

BackgroundThe predominance of the psychodynamic approach is often put forward to explain the delay in diagnosis and treatment of attention-deficit disorder with hyperactivity (ADHD) reported in France. ObjectiveA bibliometric study of abstracts, articles, or letters authored by French researchers may provide objective insight into this issue. MethodsOnline electronic databases were searched without any date limits for documents related to ADHD, and allocated to the AllFR group when all authors had an affiliation in France or to the notAllFR group when at least one author had an affiliation in France. Publications expressing any psychodynamic point of view on the causes and/or treatment of ADHD were identified. ResultsA total of 747 documents were analyzed: 417 were exclusively indexed in SCOPUS, and 418 were allocated to the AllFR group. Compared with documents in the notAllFR group, documents in the AllFR group were written by a smaller number of authors (median 3 vs. 6, p<0.002), more frequently evoked psychodynamic concepts (10.45% vs. 1.67%, p<0.001), and less frequently acknowledged the persistence of ADHD in adulthood (29.10% vs. 42.14%). The psychodynamic approach was likely to rely on case reports of fewer than three children. ConclusionsAny serious review of the literature should pool documents from several online databases, especially SCOPUS. In publications by only French authors, the psychodynamic approach seems predominant and the persistence of ADHD in adulthood is overlooked. This may concur with the excessive delay observed in the diagnosis and treatment of children and adults in France compared to other European countries.

Early and repeated screening detects children with persistent attention-deficit/hyperactivity disorder

Preschool screening of attention-deficit/hyperactivity disorder (ADHD) has been found too inaccurate to be clinically useful. This may be due to the known instability of ADHD symptoms from preschool onwards, and the use of a single screening only. We hypothesized that by identifying a group of children with persistent ADHD from preschool to school age and repeating the screening, the clinical usefulness of screening would increase. This study is part of the prospective longitudinal, population-based Norwegian Mother, Father and Child Cohort Study, with a diagnostic parent interview at 3.5 years and follow-up with parent questionnaires at ages 5 and 8 years (n = 707). We identified a group classified with ADHD at all three time points (persistent ADHD). We then used the Child Behavior Checklist ADHD DSM-oriented scale at ages 3.5 and 5 years to investigate the accuracies of single- and two-stage screening at different thresholds to identify children with persistent ADHD. About 30% of the children were classified with ADHD at least once across time (at ages 3.5, 5, and/or 8 years), but only 4% (n = 30) had persistent ADHD. At all thresholds, the two-stage screening identified children with persistent ADHD more accurately than single screening, mainly due to a substantial reduction in false positives. Only a small group of children were classified with persistent ADHD from preschool to school age, underlining that future screening studies should distinguish this group from those with fluctuating symptoms when estimating screening accuracies. We recommend a two-stage screening process to reduce false positives.

Risk factors of suicidal spectrum behaviors in adults and adolescents with attention-deficit / hyperactivity disorder – a systematic review

IntroductionAdolescents and adults with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of suicidal spectrum behaviors (SSBs). However, there is limited knowledge about risk factors triggering SSBs in this group of people.ObjectiveTo explore published literature concerning factors that may increase the risk of SSBs in adults and adolescents with ADHD.MethodsA systematic literature search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted on 22nd of February 2022 using the Ovid MEDLINE and Web of Science databases. Three categories of search terms were used: (1) self-harm, self-injury, self-mutilation, suicide, self-poisoning; (2) adults, adolescents; and (3) attention-deficit hyperactivity disorder/ADHD. Studies with data concerning mediating factors of SSBs in relation to a clinical diagnosis of ADHD in participants above 16 years of age were included.ResultsThe literature search identified 604 articles, of which 40 were included in the final study selection. Factors found to increase the likelihood of SSBs included ADHD symptom severity and persistence, female gender, family history of ADHD, childhood and parental influences, and social functioning. Even when adjusting for psychiatric comorbidities, most studies showed that adults and adolescents with ADHD have an elevated risk of SSBs.ConclusionThis systematic review has documented that several demographic and clinical features are associated with an increased risk of SSBs in adolescents and adults with ADHD. Notably, ADHD emerges as an independent risk factor for SSBs. This information ought to have clinical implications in terms of screening and suicide prevention strategies. Further longitudinal studies are needed to investigate the outcome of preventive strategies in individuals along the full spectrum of ADHD symptom severity.

Longitudinal Trajectories of White Matter Development in Attention-Deficit/Hyperactivity Disorder

BackgroundFew longitudinal studies have investigated whether white matter development reflects differential outcomes for children with and without attention-deficit/hyperactivity disorder (ADHD). To examine whether deviations from typical trajectories of white matter development were associated with the persistence or remission of ADHD symptoms, this study examined microstructural and morphological properties of 71 white matter tracts from 390 high angular diffusion scans acquired prospectively for 62 children with persistent ADHD, 37 children remitted from ADHD, and 85 children without ADHD. MethodsParticipants (mean age at wave 1 = 10.39 years, scan interval = 18 months) underwent up to 3 magnetic resonance imaging assessments. White matter tracts were reconstructed using TractSeg, a semiautomated method. For each tract, we derived measures of fiber density (microstructure) and fiber bundle cross-section (morphology) using fixel-based analysis. Linear mixed models were used to compare trajectories of fiber development between the persistent ADHD, remitted ADHD, and non-ADHD groups. ResultsCompared with the non-ADHD group, the remitted and persistent ADHD groups showed accelerated fiber development in thalamic pathways, striatal pathways, and the superior longitudinal fasciculus. In the remitted ADHD group, accelerated fiber development in corticospinal, frontopontine, striatal-premotor, and thalamo-premotor pathways was associated with greater reductions in ADHD symptom severity. The persistent ADHD group showed ongoing white matter alterations along sensorimotor pathways. ConclusionsThese results suggest that variations in white matter development are associated with different clinical trajectories in ADHD. The findings advance our understanding of the neurobiological mechanisms underpinning ADHD symptom progression and provide novel evidence in support of developmental models of ADHD.

Unimodal Versus Multimodal Treatment in the Context of ADHD Symptom Persistence into Adulthood

As more children and adults are diagnosed with attention-deficit hyperactivity disorder (ADHD), it is important to inform the general population about the extensive yet complex nature of the disorder. If left untreated, ADHD can negatively impact the academic, social, and economical aspects of a person’s life. The concept of ADHD has historically shifted from decade to decade, each time focusing on a different etiology as well as symptoms. The main piece of literature examined in this paper is the Multimodal Treatment Study of Children with ADHD (MTA), a 14-month randomized clinical trial funded by the National Institute of Mental Health (NIMH) to determine the most effective method of treatment for ADHD. Four methods were introduced: medication, behavioral, combined (medication and behavioral), and community (already available) treatment. Results from the study indicated medication to be the most efficient treatment due to its convenience and cost-effectiveness. However, contemporary research revealed the persistence of ADHD symptoms into adulthood, and how they can negatively affect the educational, occupational, and emotional aspects of adult life. Further supplementary research showcases people’s willingness to expend more resources to prevent greater losses in the future. Along with newly found efficacy of behavioral therapy in ADHD with anxiety comorbidity which is a leading predictor in ADHD persistence into adulthood, this paper suggests the multimodal combined treatment to be the most optimal mode of treatment. In summary, the purpose of this review is to inform the reader of ADHD as well as propose a novel and optimal treatment for those with persistence of ADHD symptoms into adulthood.

Genomic patterns linked to gray matter alterations underlying working memory deficits in adults and adolescents with attention-deficit/hyperactivity disorder

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 working memory underperformance, and GMV alteration in the cerebellum was associated with inattention. Recent knowledge regarding ADHD genetic risk loci makes it feasible to investigate genomic factors underlying these persistent GMV alterations, potentially illuminating the pathology of ADHD persistence. Based on this, we applied a sparsity-constrained multivariate data fusion approach, sparse parallel independent component analysis, to GMV variations in the frontal and cerebellum regions and candidate risk single nucleotide polymorphisms (SNPs) data from 341 unrelated adult participants, including 167 individuals with ADHD, 47 unaffected siblings, and 127 healthy controls. We identified one SNP component significantly associated with one GMV component in superior/middle frontal regions and replicated this association in 317 adolescents from ADHD families. The association was stronger in individuals with ADHD than in controls, and stronger in adults and older adolescents than in younger ones. The SNP component highlights 93 SNPs in long non-coding RNAs mainly in chromosome 5 and 21 protein-coding genes that are significantly enriched in human neuron cells. Eighteen identified SNPs have regulation effects on gene expression, transcript expression, isoform percentage, or methylation level in frontal regions. Identified genes highlight MEF2C, CADM2, and CADPS2, which are relevant for modulating neuronal substrates underlying high-level cognition in ADHD, and their causality effects on ADHD persistence await further investigations. Overall, through a multivariate analysis, we have revealed a genomic pattern underpinning the frontal gray matter variation related to working memory deficit in ADHD.

Young-Adult Social Outcomes of Attention-Deficit/Hyperactivity Disorder.

Attention Deficit Hyperactivity Disorder (ADHD) is associated with a range of adverse outcomes in adult life. However it is unclear whether the risk pathways to adverse adult outcomes are established during childhood or whether associations are driven by concurrent ADHD symptoms that have persisted to adulthood. We examined associations between broadly defined child-limited (remitted) and persistent ADHD (assessed using the ADHD subscale of the Strengths and Difficulties Questionnaire) with social outcomes (low emotional and instrumental support, antisocial behaviour, employment, receipt of state benefits as an indicator of socio-economic disadvantage, homelessness) at age 25 years in a UK longitudinal population sample ALPSAC (the Avon Longitudinal Study of Parents and Children, age 25 data collected between years 2017 and 2018): total N=6439. Up to 20% of young-people with less favourable social outcomes at age 25 had persistent ADHD. Persistent ADHD was associated with an increased likelihood of being not in education, employment or training (NEET: OR=3.71, 95% CI=2.06 to 6.67, p=1x10-05) and receiving state benefits (OR=2.72, 95% CI=1.62 to 4.57, p=2x10-04) at age 25 years compared to those without ADHD. We did not find strong evidence of associations between child-limited ADHD and social outcomes (NEET OR=1.20, 95% CI=0.54 to 2.69, p=0.65; state benefits OR=1.38, 95% CI=0.76 to 2.51, p=0.29). Persistent ADHD associations with negative social outcomes were observed across family-of-origin income groups, sex and were not explained by comorbidity. Our findings highlight the importance of continued monitoring and management of ADHD symptoms and related social as well as clinical outcomes across development into adulthood. Future research is needed to identify what factors promote positive social outcomes, including effective treatment of adult ADHD symptoms.

Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with onset in childhood (childhood ADHD); two-thirds of affected individuals continue to have ADHD in adulthood (persistent ADHD), and sometimes ADHD is diagnosed in adulthood (late-diagnosed ADHD). We evaluated genetic differences among childhood (n = 14,878), persistent (n = 1,473) and late-diagnosed (n = 6,961) ADHD cases alongside 38,303 controls, and rare variant differences in 7,650 ADHD cases and 8,649 controls. We identified four genome-wide significant loci for childhood ADHD and one for late-diagnosed ADHD. We found increased polygenic scores for ADHD in persistent ADHD compared with the other two groups. Childhood ADHD had higher genetic overlap with hyperactivity and autism compared with late-diagnosed ADHD and the highest burden of rare protein-truncating variants in evolutionarily constrained genes. Late-diagnosed ADHD had a larger genetic overlap with depression than childhood ADHD and no increased burden in rare protein-truncating variants. Overall, these results suggest a genetic influence on age at first ADHD diagnosis, persistence of ADHD and the different comorbidity patterns among the groups.

Brain Signatures During Reward Anticipation Predict Persistent Attention-Deficit/Hyperactivity Disorder Symptoms.

Children experiencing attention-deficit/hyperactivity disorder (ADHD) symptoms may retain symptoms into adulthood, but little is known about the underlying mechanism. To identify biomarkers of persistent ADHD symptom development, we carried out whole-brain analyses of neuroimaging data during the anticipation phase of the Monetary-Incentive-Delay (MID) task in 1,368 adolescents recruited by the IMAGEN Consortium at age 14 years, whose behavioral measurements were followed up longitudinally at age 16. In particular, we focused on comparing individuals with persistent high ADHD symptoms at both ages 14 and 16 years to unaffected control individuals, but also exploring which individuals demonstrating symptom remission (with high ADHD symptoms at age 14 but much reduced at age 16). We identified reduced activations in the medial frontal cortex and the thalamus during reward anticipation as neuro-biomarkers for persistent ADHD symptoms across time. The genetic relevance of the above findings was further supported by the associations of the polygenic risk scores of ADHD with both the persistent and control status and the activations of both brain regions. Furthermore, in an exploratory analysis, the thalamic activation might also help to distinguish persons with persistent ADHD from those remitted in both an exploratory sample (odds ratio= 9.43, p< .001) and an independent generalization sample (odds ratio= 4.64, p= .003). Using a well-established and widely applied functional magnetic resonance imaging task, we have identified neural biomarkers that could discriminate ADHD symptoms that persist throughout adolescence from controls and potentially those likely to remit during adolescent development as well.

Neural Correlates of Reactive Aggression in Adult Attention-Deficit/Hyperactivity Disorder.

Despite not being part of the core diagnostic criteria for attention-deficit/hyperactivity disorder (ADHD), emotion dysregulation is a highly prevalent and clinically important component of (adult) ADHD. Emotionally dysregulated behaviors such as reactive aggression have a significant impact on the functional outcome in ADHD. However, little is known about the mechanisms underlying reactive aggression in ADHD. In this study, we aimed to identify the neural correlates of reactive aggression as a measure of emotionally dysregulated behavior in adults with persistent ADHD during implicit emotion regulation processes. We analyzed associations of magnetic resonance imaging-based whole-brain activity during a dynamic facial expression task with levels of reactive aggression in 78 adults with and 78 adults without ADHD, and also investigated relationships of reactive aggression with symptoms and impairments. While participants with ADHD had higher reactive aggression scores than controls, the neural activation patterns of both groups to processing of emotional faces were similar. However, investigating the brain activities associated with reactive aggression in individuals with and without ADHD showed an interaction of diagnosis and reactive aggression scores. We found high levels of activity in the right insula, the hippocampus, and middle and superior frontal areas to be particularly associated with high reactive aggression scores within the ADHD group. Furthermore, the limbic activity was associated with more hyperactivity/impulsivity symptoms. These results suggest a partly differential mechanism associated with reactive aggression in ADHD as compared to controls. Emotional hyper-reactivity in the salience network as well as more effortful top–down regulation from the self-regulation network might contribute to emotionally dysregulated behavior as measured by reactive aggression.

Review: Adult Outcome as Seen Through Controlled Prospective Follow-up Studies of Children With Attention-Deficit/Hyperactivity Disorder Followed Into Adulthood.

To describe adult outcome of people with attention-deficit/hyperactivity disorder (ADHD) diagnosed in childhood and its several key predictors via a review of 7 North American controlled prospective follow-up studies: Montreal, New York, Milwaukee, Pittsburgh, Massachusetts General Hospital (MGH), Berkeley, and 7-site Multimodal Treatment Study of Children With ADHD (MTA). All studies were prospective and followed children with a diagnosis of ADHD and an age- and gender-matched control group at regular intervals from childhood (6-12 years of age) through adolescence into adulthood (20-40 years of age), evaluating symptom and syndrome persistence, functional outcomes, and predictors of these outcomes. The rates of ADHD syndrome persistence ranged from 5.7% to 77%, likely owing to varying diagnostic criteria and the source of information (self-report vs informant report) across the studies. However, all studies observed high rates of symptomatic persistence ranging from 60% to 86%. The 7 studies were largely consistent in finding that relative to control groups, research participants with childhood-diagnosed ADHD had significant impairments in the areas of educational functioning, occupational functioning, mental health, and physical health as well as higher rates of substance misuse, antisocial behavior, and unsafe driving. The most consistently observed predictors of functional outcomes included ADHD persistence and comorbidity, especially with disruptive behavior disorders. Childhood ADHD has high rates of symptomatic persistence, which is associated with negative functional outcomes. Characteristics that predict these negative outcomes, such as comorbid disruptive behavior disorders, may be important targets for intervention.

Associations between attention-deficit hyperactivity disorder (ADHD) symptom remission and white matter microstructure: A longitudinal analysis.

Background:Attention-deficit hyperactivity disorder (ADHD) is associated with white matter (WM) microstructure. Our objective was to investigate how WM microstructure is longitudinally related to symptom remission in adolescents and young adults with ADHD.Methods:We obtained diffusion-weighted imaging (DWI) data from 99 participants at two timepoints (mean age baseline: 16.91 years, mean age follow-up: 20.57 years). We used voxel-wise Tract-Based Spatial Statistics (TBSS) with permutation-based inference to investigate associations of inattention (IA) and hyperactivity-impulsivity (HI) symptom change with fractional anisotropy (FA) at baseline, follow-up, and change between time-points.Results:Remission of combined HI and IA symptoms was significantly associated with reduced FA at follow-up in the left superior longitudinal fasciculus and the left corticospinal tract (CST; PFWE = 0.038 and PFWE = 0.044, respectively), mainly driven by an association between HI remission and follow-up CST FA (PFWE = 0.049). There was no significant association of combined symptom decrease with FA at baseline or with changes in FA between the two assessments.Conclusions:In this longitudinal DWI study of ADHD using dimensional symptom scores, we show that greater symptom decrease is associated with lower follow-up FA in specific WM tracts. Altered FA thus may appear to follow, rather than precede, changes in symptom remission. Our findings indicate divergent WM developmental trajectories between individuals with persistent and remittent ADHD, and support the role of prefrontal and sensorimotor tracts in the remission of ADHD.

Variable Patterns of Remission From ADHD in the Multimodal Treatment Study of ADHD.

It is estimated that childhood attention deficit hyperactivity disorder (ADHD) remits by adulthood in approximately 50% of cases; however, this conclusion is typically based on single endpoints, failing to consider longitudinal patterns of ADHD expression. The authors investigated the extent to which children with ADHD experience recovery and variable patterns of remission by adulthood. Children with ADHD (N=558) in the Multimodal Treatment Study of ADHD (MTA) underwent eight assessments over follow-ups ranging from 2 years (mean age, 10.44 years) to 16 years (mean age, 25.12 years) after baseline. The authors identified participants with fully remitted, partially remitted, and persistent ADHD at each time point on the basis of parent, teacher, and self-reports of ADHD symptoms and impairment, treatment utilization, and substance use and mental disorders. Longitudinal patterns of remission and persistence were identified that considered context and timing. Approximately 30% of children with ADHD experienced full remission at some point during the follow-up period; however, a majority of them (60%) experienced recurrence of ADHD after the initial period of remission. Only 9.1% of the sample demonstrated recovery (sustained remission) by study endpoint, and only 10.8% demonstrated stable ADHD persistence across study time points. Most participants with ADHD (63.8%) had fluctuating periods of remission and recurrence over time. The MTA findings challenge the notion that approximately 50% of children with ADHD outgrow the disorder by adulthood. Most cases demonstrated fluctuating symptoms between childhood and young adulthood. Although intermittent periods of remission can be expected in most cases, 90% of children with ADHD in MTA continued to experience residual symptoms into young adulthood.

Children and adolescents with ADHD followed up to adulthood: a systematic review of long-term outcomes.

The objective is to highlight the clinical and social outcomes among adults who suffered from Attention-Deficit Hyperactivity Disorder (ADHD) in their childhood/adolescence. PubMed, PsycINFO, and Scopus databases were searched for prospective studies published during the last 5 years addressing patients with ADHD in childhood/adolescence followed-up to adulthood. We also included studies published before 2015 reported in other reviews with similar outcomes. Thousand four-hundred and eighty-five studies were identified, but only 39 were included for qualitative analysis and 27 for quantitative analysis. Overall, we found that ADHD persisted into adulthood with a mean rate of 43% and was mainly associated with both substance/alcohol use disorders and antisocial behavior and, less frequently, with anxiety and depressive disorders. The prevalence of persistent ADHD in adulthood reported by studies published after 2011 (55%) was higher than that reported by studies published previously from 1985 to 2011 (34%), suggesting a greater focus on ADHD in recent years. Our results highlight that ADHD can be considered not only a neurodevelopmental disorder, but also a persistent and complex condition, with detrimental consequences for quality of life in adulthood.