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BackgroundSerotonin is under-researched in attention deficit hyperactivity disorder (ADHD), despite accumulating evidence for its involvement in impulsiveness and the disorder. Serotonin further modulates temporal discounting (TD), which is typically abnormal in ADHD relative to healthy subjects, underpinned by reduced fronto-striato-limbic activation. This study tested whether a single acute dose of the selective serotonin reuptake inhibitor (SSRI) fluoxetine up-regulates and normalizes reduced fronto-striato-limbic neurofunctional activation in ADHD during TD.MethodTwelve boys with ADHD were scanned twice in a placebo-controlled randomized design under either fluoxetine (between 8 and 15 mg, titrated to weight) or placebo while performing an individually adjusted functional magnetic resonance imaging TD task. Twenty healthy controls were scanned once. Brain activation was compared in patients under either drug condition and compared to controls to test for normalization effects.ResultsRepeated-measures whole-brain analysis in patients revealed significant up-regulation with fluoxetine in a large cluster comprising right inferior frontal cortex, insula, premotor cortex and basal ganglia, which further correlated trend-wise with TD performance, which was impaired relative to controls under placebo, but normalized under fluoxetine. Fluoxetine further down-regulated default mode areas of posterior cingulate and precuneus. Comparisons between controls and patients under either drug condition revealed normalization with fluoxetine in right premotor-insular-parietal activation, which was reduced in patients under placebo.ConclusionsThe findings show that a serotonin agonist up-regulates activation in typical ADHD dysfunctional areas in right inferior frontal cortex, insula and striatum as well as down-regulating default mode network regions in the context of impulsivity and TD. [ABSTRACT FROM PUBLISHER]

Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Despite the increasing diversity of the UK population, we continue to see inequalities in health outcomes in patients of ethnic minorities. Unfortunately, this increasing diversity is not reflected in educational resources, which often continue to feature few images of patients with darker skin tones. Given the lack of diversity in these resources, it is unsurprising that healthcare professionals find it challenging recognising, diagnosing and managing presentations of clinical conditions in darker skinned patients. The development of new online, accessible image banks of medical conditions in different skin tones, such as Skin Deep, aims to facilitate increasing diversity in educational materials and hence improve delivery of equal standards of care to all patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Now more than ever, there is a recognition that the existing racial inequality within healthcare systems around the world must be addressed. Preserving this momentum is vital and every profession and specialty must be held accountable for their own shortcomings. In this article, we place a spotlight on the paediatric medical workforce. We explore key areas of concern including differential attainment and the under-representation of paediatricians from minoritised ethnic groups in leadership roles. We use the recent measures adopted by the Royal College of Paediatrics and Child Health in the United Kingdom as a framework for achieving inclusive work environments and equitable opportunities for all paediatricians., (© 2022 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: The aim of the current paper is to provide the first comparison of computational mechanisms and neurofunctional substrates in adolescents with attention-deficit/hyperactivity disorder (ADHD) and adolescents with obsessive-compulsive disorder (OCD) during decision making under ambiguity., Methods: Sixteen boys with ADHD, 20 boys with OCD, and 20 matched control subjects (12-18 years of age) completed a functional magnetic resonance imaging version of the Iowa Gambling Task. Brain activation was compared between groups using three-way analysis of covariance. Hierarchical Bayesian analysis was used to compare computational modeling parameters between groups., Results: Patient groups shared reduced choice consistency and relied less on reinforcement learning during decision making relative to control subjects, while adolescents with ADHD alone demonstrated increased reward sensitivity. During advantageous choices, both disorders shared underactivation in ventral striatum, while OCD patients showed disorder-specific underactivation in the ventromedial orbitofrontal cortex. During outcome evaluation, shared underactivation to losses in patients relative to control subjects was found in the medial prefrontal cortex and shared underactivation to wins was found in the left putamen/caudate. ADHD boys showed disorder-specific dysfunction in the right putamen/caudate, which was activated more to losses in patients with ADHD but more to wins in control subjects., Conclusions: The findings suggest shared deficits in using learned reward expectancies to guide decision making, as well as shared dysfunction in medio-fronto-striato-limbic brain regions. However, findings of unique dysfunction in the ventromedial orbitofrontal cortex in OCD and in the right putamen in ADHD indicate additional, disorder-specific abnormalities and extend similar findings from inhibitory control tasks in the disorders to the domain of decision making under ambiguity., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) often share phenotypes of repetitive behaviors, possibly underpinned by abnormal decision-making. To compare neural correlates underlying decision-making between these disorders, brain activation of boys with ASD (N = 24), OCD (N = 20) and typically developing controls (N = 20) during gambling was compared, and computational modeling compared performance. Patients were unimpaired on number of risky decisions, but modeling showed that both patient groups had lower choice consistency and relied less on reinforcement learning compared to controls. ASD individuals had disorder-specific choice perseverance abnormalities compared to OCD individuals. Neurofunctionally, ASD and OCD boys shared dorsolateral/inferior frontal underactivation compared to controls during decision-making. During outcome anticipation, patients shared underactivation compared to controls in lateral inferior/orbitofrontal cortex and ventral striatum. During reward receipt, ASD boys had disorder-specific enhanced activation in inferior frontal/insular regions relative to OCD boys and controls. Results showed that ASD and OCD individuals shared decision-making strategies that differed from controls to achieve comparable performance to controls. Patients showed shared abnormalities in lateral-(orbito)fronto-striatal reward circuitry, but ASD boys had disorder-specific lateral inferior frontal/insular overactivation, suggesting that shared and disorder-specific mechanisms underpin decision-making in these disorders. Findings provide evidence for shared neurobiological substrates that could serve as possible future biomarkers., (© The Author 2017. Published by Oxford University Press.)

Both Attention-Deficit/Hyperactivity Disorder (ADHD) and Obsessive-Compulsive Disorder (OCD) are associated with choice impulsivity, i.e. the tendency to prefer smaller immediate rewards over larger delayed rewards. However, the extent to which this impulsivity is mediated by shared or distinct underlying neural mechanisms is unclear. Twenty-six boys with ADHD, 20 boys with OCD and 20 matched controls (aged 12-18) completed an fMRI version of an individually adjusted temporal discounting (TD) task which requires choosing between a variable amount of money now or £100 in one week, one month or one year. Activations to immediate and delayed reward choices were compared between groups using a three-way ANCOVA. ADHD patients had steeper discounting rates on the task relative to controls. OCD patients did not differ from controls or patients with ADHD. Patients with ADHD and OCD showed predominantly shared activation deficits during TD in fronto-striato-insular-cerebellar regions responsible for self-control and temporal foresight, suggesting that choice impulsivity is mediated by overlapping neural dysfunctions in both disorders. OCD patients alone showed dysfunction relative to controls in right orbitofrontal and rostrolateral prefrontal cortex, extending previous findings of abnormalities in these regions in OCD to the domain of choice impulsiveness., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) are often comorbid and share similarities across some cognitive phenotypes, including certain aspects of attention. However, no functional magnetic resonance imaging studies have compared the underlying neural mechanisms contributing to these shared phenotypes., Methods: Age- and IQ-matched boys (11-17 years old) with ASD ( n = 20), boys with OCD ( n = 20), and healthy control boys ( n = 20) performed a parametrically modulated psychomotor vigilance functional magnetic resonance imaging task. Brain activation and performance were compared among adolescents with OCD, adolescents with ASD, and control adolescents., Results: Whereas boys with ASD and OCD were not impaired on task performance, there was a significant group by attention load interaction in several brain regions. With increasing attention load, left inferior frontal cortex/insula and left inferior parietal lobe/pre/post-central gyrus were progressively less activated in boys with OCD relative to the other two groups. In addition, boys with OCD showed progressively increased activation with increasing attention load in rostromedial prefrontal/anterior cingulate cortex relative to boys with ASD and control boys. Shared neurofunctional abnormalities between boys with ASD and boys with OCD included increased activation with increasing attention load in cerebellum and occipital regions, possibly reflecting increased default mode network activation., Conclusions: This first functional magnetic resonance imaging study to compare boys with ASD and OCD showed shared abnormalities in posterior cerebellar-occipital brain regions. However, boys with OCD showed a disorder-specific pattern of reduced activation in left inferior frontal and temporo-parietal regions but increased activation of medial frontal regions, which may potentially be related to neurobiological mechanisms underlying cognitive and clinical phenotypes of OCD.

Patients with Attention-Deficit/Hyperactivity Disorder (ADHD) and obsessive/compulsive disorder (OCD) share problems with sustained attention, and are proposed to share deficits in switching between default mode and task positive networks. The aim of this study was to investigate shared and disorder-specific brain activation abnormalities during sustained attention in the two disorders. Twenty boys with ADHD, 20 boys with OCD and 20 age-matched healthy controls aged between 12 and 18 years completed a functional magnetic resonance imaging (fMRI) version of a parametrically modulated sustained attention task with a progressively increasing sustained attention load. Performance and brain activation were compared between groups. Only ADHD patients were impaired in performance. Group by sustained attention load interaction effects showed that OCD patients had disorder-specific middle anterior cingulate underactivation relative to controls and ADHD patients, while ADHD patients showed disorder-specific underactivation in left dorsolateral prefrontal cortex/dorsal inferior frontal gyrus (IFG). ADHD and OCD patients shared left insula/ventral IFG underactivation and increased activation in posterior default mode network relative to controls, but had disorder-specific overactivation in anterior default mode regions, in dorsal anterior cingulate for ADHD and in anterior ventromedial prefrontal cortex for OCD. In sum, ADHD and OCD patients showed mostly disorder-specific patterns of brain abnormalities in both task positive salience/ventral attention networks with lateral frontal deficits in ADHD and middle ACC deficits in OCD, as well as in their deactivation patterns in medial frontal DMN regions. The findings suggest that attention performance in the two disorders is underpinned by disorder-specific activation patterns.

Background: Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis., Methods: In this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0·0156., Findings: Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohen's d=-0·15), amygdala (d=-0·19), caudate (d=-0·11), hippocampus (d=-0·11), putamen (d=-0·14), and intracranial volume (d=-0·10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0·95) and thalamus (p=0·39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (<15 years) versus adults (>21 years): in the accumbens (Cohen's d=-0·19 vs -0·10), amygdala (d=-0·18 vs -0·14), caudate (d=-0·13 vs -0·07), hippocampus (d=-0·12 vs -0·06), putamen (d=-0·18 vs -0·08), and intracranial volume (d=-0·14 vs 0·01). There was no difference between children and adults for the pallidum (p=0·79) or thalamus (p=0·89). Case-control differences in adults were non-significant (all p>0·03). Psychostimulant medication use (all p>0·15) or symptom scores (all p>0·02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0·5)., Interpretation: With the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes., Funding: National Institutes of Health., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share brain function abnormalities during cognitive flexibility. Serotonin is involved in both disorders, and selective serotonin reuptake inhibitors (SSRIs) can modulate cognitive flexibility and improve behavior in both disorders. Thus, this study investigates shared and disorder-specific brain dysfunctions in these 2 disorders during reward reversal, and the acute effects of an SSRI on these. Age-matched boys with ADHD (15), ASD (18), and controls (21) were compared with functional magnetic resonance imaging (fMRI) during a reversal task. Patients were scanned twice, under either an acute dose of Fluoxetine or placebo in a double-blind, placebo-controlled randomized design. Repeated-measures analyses within patients assessed drug effects. Patients under each drug condition were compared with controls to assess normalization effects. fMRI data showed that, under placebo, ASD boys underactivated medial prefrontal cortex (mPFC), compared with control and ADHD boys. Both patient groups shared decreased precuneus activation. Under Fluoxetine, mPFC activation was up-regulated and normalized in ASD boys relative to controls, but down-regulated in ADHD boys relative to placebo, which was concomitant with worse task performance in ADHD. Fluoxetine therefore has inverse effects on mPFC activation in ASD and ADHD during reversal learning, suggesting dissociated underlying serotonin abnormalities., (© The Author 2014. Published by Oxford University Press.)

Rationale: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are often comorbid and have both performance and brain dysfunctions during motor response inhibition. Serotonin agonists modulate motor response inhibition and have shown positive behavioural effects in both disorders., Aims: We therefore used functional magnetic resonance imaging (fMRI) to investigate the so far unknown shared and disorder-specific inhibitory brain dysfunctions in these two disorders, as well as the effects of a single dose of the selective serotonin reuptake inhibitor fluoxetine., Methods: Age-matched boys with ADHD (18), ASD (19) and healthy controls (25) were compared with fMRI during a stop task measuring motor inhibition. Patients were scanned twice, under either an acute dose of fluoxetine or placebo in a double-blind, placebo-controlled randomised design. Repeated measures analyses within patients assessed drug effects. To test for potential normalisation effects of brain dysfunctions, patients under each drug condition were compared to controls., Results: Under placebo, relative to controls, ASD boys showed overactivation in left and right inferior frontal cortex (IFC), while ADHD boys showed disorder-specific underactivation in orbitofrontal cortex (OFC) and basal ganglia. Under fluoxetine, the prefrontal dysfunctions were no longer observed, due to inverse effects of fluoxetine on these activations: fluoxetine downregulated IFC and OFC activation in ASD but upregulated them in ADHD., Conclusions: The findings show that fluoxetine normalises frontal lobe dysfunctions in both disorders via inverse effects, downregulating abnormally increased frontal activation in ASD and upregulating abnormally decreased frontal activation in ADHD, potentially reflecting inverse baseline serotonin levels in both disorders.

Individuals with autism spectrum disorders (ASD) have difficulty understanding other minds (Theory of Mind; ToM), with atypical processing evident at both behavioural and neural levels. Individuals with conduct problems and high levels of callous-unemotional (CU) traits (CP/HCU) exhibit reduced responsiveness to others' emotions and difficulties interacting with others, but nonetheless perform normally in experimental tests of ToM. The present study aimed to examine the neural underpinnings of ToM in children (aged 10-16) with ASD (N = 16), CP/HCU (N = 16) and typically developing (TD) controls (N = 16) using a non-verbal cartoon vignette task. Whilst individuals with ASD were predicted to show reduced fMRI responses across regions involved in ToM processing, CP/HCU individuals were predicted to show no differences compared with TD controls. The analyses indicated that neural responses did not differ between TD and CP/HCU groups during ToM. TD and CP/HCU children exhibited significantly greater medial prefrontal cortex responses during ToM than did the ASD group. Within the ASD group, responses in medial prefrontal cortex and right temporoparietal junction (TPJ) correlated with symptom severity as measured by the Autism Diagnostic Observation Schedule (ADOS). Findings suggest that although both ASD and CP/HCU are characterized by social difficulties, only children with ASD display atypical neural processing associated with ToM., (© 2014 The Authors. Developmental Science Published by John Wiley & Sons Ltd.)

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share cognitive abnormalities in temporal foresight. A key question is whether shared cognitive phenotypes are based on common or different underlying pathophysiologies and whether comorbid patients have additive neurofunctional deficits, resemble one of the disorders or have a different pathophysiology. We compared age- and IQ-matched boys with non-comorbid ADHD (18), non-comorbid ASD (15), comorbid ADHD and ASD (13) and healthy controls (18) using functional magnetic resonance imaging (fMRI) during a temporal discounting task. Only the ASD and the comorbid groups discounted delayed rewards more steeply. The fMRI data showed both shared and disorder-specific abnormalities in the three groups relative to controls in their brain-behaviour associations. The comorbid group showed both unique and more severe brain-discounting associations than controls and the non-comorbid patient groups in temporal discounting areas of ventromedial and lateral prefrontal cortex, ventral striatum and anterior cingulate, suggesting that comorbidity is neither an endophenocopy of the two pure disorders nor an additive pathology., (Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Objective: Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, but diagnosed by subjective clinical and rating measures. The study's aim was to apply Gaussian process classification (GPC) to grey matter (GM) volumetric data, to assess whether individual ADHD adolescents can be accurately differentiated from healthy controls based on objective, brain structure measures and whether this is disorder-specific relative to autism spectrum disorder (ASD)., Method: Twenty-nine adolescent ADHD boys and 29 age-matched healthy and 19 boys with ASD were scanned. GPC was applied to make disorder-specific predictions of ADHD diagnostic status based on individual brain structure patterns. In addition, voxel-based morphometry (VBM) analysis tested for traditional univariate group level differences in GM., Results: The pattern of GM correctly classified 75.9% of patients and 82.8% of controls, achieving an overall classification accuracy of 79.3%. Furthermore, classification was disorder-specific relative to ASD. The discriminating GM patterns showed higher classification weights for ADHD in earlier developing ventrolateral/premotor fronto-temporo-limbic and stronger classification weights for healthy controls in later developing dorsolateral fronto-striato-parieto-cerebellar networks. Several regions were also decreased in GM in ADHD relative to healthy controls in the univariate VBM analysis, suggesting they are GM deficit areas., Conclusions: The study provides evidence that pattern recognition analysis can provide significant individual diagnostic classification of ADHD patients and healthy controls based on distributed GM patterns with 79.3% accuracy and that this is disorder-specific relative to ASD. Findings are a promising first step towards finding an objective differential diagnostic tool based on brain imaging measures to aid with the subjective clinical diagnosis of ADHD.

Background: Pediatric major depressive disorder (MDD) is associated with deficits in sustained attention, thought to be related to underlying motivation deficits. This hypothesis, however, has never directly been tested using functional magnetic resonance imaging. In this study, we investigated the neurofunctional correlates of the interplay between attention and motivation in medication-naive pediatric MDD using a rewarded sustained attention task., Methods: Functional magnetic resonance imaging was used to compare brain activation between 20 medication-naïve, noncomorbid, first-episode adolescents with MDD aged 13 to 18 years and 21 gender-, age-, and IQ-matched healthy adolescents. Participants performed a sustained attention task with and without a monetary reward to assess the impact of reward on sustained attention networks., Results: During nonrewarded sustained attention, adolescents with MDD showed reduced activation compared with healthy control subjects in occipital cortex. When sustained attention was rewarded, however, the underactivation in adolescents with MDD was in an extensive right hemispheric network of inferior fronto-striato-thalamic attention and limbic hippocampus-anterior cingulate reward processing areas. Major depressive disorder patients showed increased activation in cerebellum, which correlated with reduced frontal activation and depressive symptoms, suggesting compensatory response. Further analysis showed that reward upregulated fronto-striatal and hippocampal/temporal activation in control subjects but deactivated these regions in MDD, with opposite effects in the cerebellum., Conclusions: Medication-naïve MDD adolescents show abnormalities in the regulation in fronto-striato-cerebellar brain regions involved in attention and reward during motivated but not unmotivated attention. This suggests a dysfunctional interplay between motivation and cognition in pediatric MDD, where motivation appears less capable of upregulating attention networks relative to healthy youths., (Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)