Dataset Information

Neural correlates of cognitive function and symptoms in attention-deficit/hyperactivity disorder in adults.

ABSTRACT: While gray matter (GM) anomalies have been reported for attention-deficit/hyperactivity disorder (ADHD), investigating their associations with cognitive deficits and individual symptom domains can help pinpoint the neural underpinnings critical for the pathology of ADHD, particularly the persist form of ADHD. In this work, we performed both independent component analysis and voxel-based morphometry analysis on whole brain GM of 486 adults including 214 patients, 96 unaffected siblings, and 176 healthy controls, in relation to cognition and symptoms. Independent component analysis revealed that higher GM volume in inferior semilunar lobule, inferior frontal gyri, and superior and middle frontal gyri was associated with better working memory performance, and lower GM volume in cerebellar tonsil and culmen was associated with more severe inattention symptoms. Consistently, voxel-based morphometry analysis showed that higher GM volume in multiple regions of frontal lobe, cerebellum and temporal lobe was related to better working memory performance. Focusing on the networks derived from ICA, our results integrated prefrontal regions and cerebellar regions through associations with working memory and inattention symptoms, lending support for the theory of 'cool'-cognition dysfunction being mediated by inferior fronto-striato-cerebellar networks in ADHD. Siblings showed intermediate cognitive impairments between patients and controls but presented GM anomalies in unique focal regions, suggesting they are a separate group potentially affected by the shared genetic and environmental risks with ADHD patients.

SUBMITTER: Duan K

PROVIDER: S-EPMC6044210 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Neural correlates of cognitive function and symptoms in attention-deficit/hyperactivity disorder in adults.

Duan Kuaikuai K Chen Jiayu J Calhoun Vince D VD Lin Dongdong D Jiang Wenhao W Franke Barbara B Buitelaar Jan K JK Hoogman Martine M Arias-Vasquez Alejandro A Turner Jessica A JA Liu Jingyu J

NeuroImage. Clinical 20180502

While gray matter (GM) anomalies have been reported for attention-deficit/hyperactivity disorder (ADHD), investigating their associations with cognitive deficits and individual symptom domains can help pinpoint the neural underpinnings critical for the pathology of ADHD, particularly the persist form of ADHD. In this work, we performed both independent component analysis and voxel-based morphometry analysis on whole brain GM of 486 adults including 214 patients, 96 unaffected siblings, and 176 h ...[more]

PMID: 30013920

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Project description:Symptoms of autism spectrum disorder and attention-deficit/hyperactivity disorder often co-occur. Among these, sensory impairment, which is a core diagnostic feature of autism spectrum disorder, is often observed in children with attention-deficit/hyperactivity disorder. However, the underlying mechanisms of symptoms that are shared across disorders remain unknown. To examine the neural correlates of sensory symptoms that are associated with autism spectrum disorder and attention-deficit/hyperactivity disorder, we analysed resting-state functional MRI data obtained from 113 people with either autism spectrum disorder or attention-deficit/hyperactivity disorder (n = 78 autism spectrum disorder, mean age = 29.5; n = 35 attention-deficit/hyperactivity disorder, mean age = 31.2) and 96 neurotypical controls (mean age = 30.6, range: 20-55 years) using a cross-sectional study design. First, we used a multi-dimensional approach to examine intrinsic brain functional connectivity related to sensory symptoms in four domains (i.e. low registration, sensation seeking, sensory sensitivity and sensation avoidance), after controlling for age, handedness and head motion. Then, we used a partial least squares correlation to examine the link between sensory symptoms related to intrinsic brain functional connectivity and neurodevelopmental symptoms measured using the Autism Spectrum Quotient and Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale, regardless of diagnosis. To test whether observed associations were specific to sensory symptoms related to intrinsic brain functional connectivity, we conducted a control analysis using a bootstrap framework. The results indicated that transdiagnostic yet distinct intrinsic brain functional connectivity neural bases varied according to the domain of the examined sensory symptom. Partial least squares correlation analysis revealed two latent components (latent component 1: q < 0.001 and latent component 2: q < 0.001). For latent component 1, a set of intrinsic brain functional connectivity was predominantly associated with neurodevelopmental symptom-related composite score (r = 0.64, P < 0.001), which was significantly correlated with Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale total T scores (r = -0.99, q < 0.001). For latent component 2, another set of intrinsic brain functional connectivity was positively associated with neurodevelopmental symptom-related composite score (r = 0.58, P < 0.001), which was eventually positively associated with Autism Spectrum Quotient total scores (r = 0.92, q < 0.001). The bootstrap analysis showed that the relationship between intrinsic brain functional connectivity and neurodevelopmental symptoms was relative to sensory symptom-related intrinsic brain functional connectivity (latent component 1: P = 0.003 and latent component 2: P < 0.001). The current results suggest that sensory symptoms in individuals with autism spectrum disorder and those with attention-deficit/hyperactivity disorder have shared neural correlates. The neural correlates of the sensory symptoms were associated with the severity of both autism spectrum disorder and attention-deficit/hyperactivity disorder symptoms, regardless of diagnosis.

Project description:ObjectiveThe purposes of this study were to examine the impact of 3 weeks of amphetamine administration on intrinsic connectome-wide connectivity patterns in adults with attention-deficit/hyperactivity disorder (ADHD) and explore the association between stimulant-induced symptom improvement and functional connectivity alteration.MethodsParticipants included 19 adults (age 20-55 years) diagnosed with ADHD using the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria per the Adult Clinician Diagnostic Scale taking part in amphetamine trials. For each patient, two 6-minute resting-state functional magnetic resonance imaging (R-fMRI) scans were acquired at baseline and after treatment. A fully data-driven multivariate analytic approach (i.e., multivariate distance matrix regression [MDMR]) was applied to R-fMRI data to characterize the distributed pharmacological effects in the entire functional connectome. Clinical efficacy was assessed using ADHD rating scale with adult prompts and the Adult Self-Report Scale v1.1 Symptom Checklist. We linked stimulant-induced functional connectivity changes to symptom amelioration using Spearman's correlation.ResultsThree weeks of administration of a stimulant significantly reduced ADHD symptoms. MDMR-based analyses on R-fMRI data highlighted the left dorsolateral prefrontal cortex (DLPFC, a key cognitive control region) and the medial prefrontal cortex (MPFC, the anterior core of default network) whose distributed patterns of functional connectivity across the entire brain were altered by psychostimulants. Follow-up intrinsic functional connectivity revealed that stimulants specifically decreased the positive functional connectivity between DLPFC-insula, DLPFC-anterior cingulate cortex, and MPFC-insula. Importantly, these functional connectivity changes are associated with symptom improvement.ConclusionThese results suggested that ADHD is associated with increased functional integration or decreased functional segregation between core regions of cognitive control, default, and salience networks. The apparent normalization of intrinsic functional interaction in these circuits (i.e., increased functional segregation) may underlie the clinical benefits produced by 3 weeks of amphetamine treatment.

Project description:BACKGROUND:Previous studies have reported associations between attention-deficit/hyperactivity disorder symptoms and DNA methylation in children. We report the first epigenome-wide association study meta-analysis of adult attention-deficit/hyperactivity disorder symptoms, based on peripheral blood DNA methylation (Infinium HumanMethylation450K array) in three population-based adult cohorts. METHODS:An epigenome-wide association study was performed in the Netherlands Twin Register (N = 2258, mean age 37 years), Dunedin Multidisciplinary Health and Development Study (N = 800, age 38 years), and Environmental Risk Longitudinal Twin Study (N = 1631, age 18 years), and results were combined through meta-analysis (total sample size N = 4689). Region-based analyses accounting for the correlation between nearby methylation sites were also performed. RESULTS:One epigenome-wide significant differentially methylated position was detected in the Dunedin study, but meta-analysis did not detect differentially methylated positions that were robustly associated across cohorts. In region-based analyses, six significant differentially methylation regions (DMRs) were identified in the Netherlands Twin Register, 19 in the Dunedin study, and none in the Environmental Risk Longitudinal Twin Study. Of these DMRs, 92% were associated with methylation quantitative trait loci, and 68% showed moderate to large blood-brain correlations for DNA methylation levels. DMRs included six nonoverlapping DMRs (three in the Netherlands Twin Register, three in the Dunedin study) in the major histocompatibility complex, which were associated with expression of genes in the major histocompatibility complex, including C4A and C4B, previously implicated in schizophrenia. CONCLUSIONS:Our findings point at new candidate loci involved in immune and neuronal functions that await further replication. Our work also illustrates the need for further research to examine to what extent epigenetic associations with psychiatric traits depend on characteristics such as age, comorbidities, exposures, and genetic background.

Project description:BackgroundFor the diagnosis of attention-deficit/hyperactivity disorder (ADHD), the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) proposes that adherence to six symptoms in either group (inattention and hyperactivity/impulsivity) will lead to the diagnosis of one of three presentations of the disorder. Underlying this diagnostic algorithm is the assumption that the 18 symptoms have equal relevance for the diagnosis of ADHD, all are equally severe, and all have the same power to detect the presence of the disorder in all its degrees of severity, without considering the possibility of using marker symptoms. However, several studies have suggested that ADHD symptoms differ in both their power to discriminate the presence of the disorder and the degree of severity they represent. The aim of the present study was to replicate the results of previous research by evaluating the discriminative capacity and relative severity of ADHD symptoms, as well as to extend the investigation of this topic to Spanish-speaking Latin American samples.MethodsThe properties of ADHD symptoms rated by the parents of 474 Chilean children were analyzed. Symptom parameters were estimated using the graded response model.ResultsThe results suggest that symptoms of ADHD differ substantially in both the accuracy with which they reflect the presence of the disorder, and their relative severity. Symptoms "easily distracted by extraneous stimuli" and "have difficulty sustaining attention in tasks" (inattention) and "is on the go, acting as if driven by motor" (hyperactivity/impulsivity) were the most informative, and those with relatively lower severity thresholds.DiscussionThe fact that symptoms differ substantially in the probability of being observed conditionally to the trait level suggests the need to refine the diagnostic process by weighting the severity of the symptom, and even to assess the possibility of defining ADHD marker symptoms, as has been done in other disorders.

Dataset Information

Neural correlates of cognitive function and symptoms in attention-deficit/hyperactivity disorder in adults.

Publications

Neural correlates of cognitive function and symptoms in attention-deficit/hyperactivity disorder in adults.

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