Dataset Information

Neural Correlates of Symptom Improvement Following Stimulant Treatment in Adults with Attention-Deficit/Hyperactivity Disorder.

ABSTRACT: The 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.Participants 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.Three 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.These 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.

SUBMITTER: Yang Z

PROVIDER: S-EPMC4991601 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Neural Correlates of Symptom Improvement Following Stimulant Treatment in Adults with Attention-Deficit/Hyperactivity Disorder.

Yang Zhen Z Kelly Clare C Castellanos Francisco X FX Leon Terry T Milham Michael P MP Adler Lenard A LA

Journal of child and adolescent psychopharmacology 20160330 6

<h4>Objective</h4>The 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.<h4>Methods</h4>Participants included 19 adults (age 20-55 years) diagnosed with ADHD using the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., ...[more]

PMID: 27027541

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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:ObjectiveBecause models of attention-deficit/hyperactivity disorder (ADHD) therapeutics emphasize benefits of both enhanced dopaminergic and noradrenergic signaling, strategies to enhance D1 and α2A agonism may yield enhanced clinical and cognitive responses. This study tested the hypothesis that combined effects of a dopamine and noradrenergic agonist, d-methylphenidate extended-release (DMPH) with guanfacine (GUAN), an α2A receptor agonist, would be clinically superior to either monotherapy and would have equal tolerability.MethodAn 8-week, double-blind, 3-arm, comparative trial randomized 7- to 14-year-olds with DSM-IV ADHD to GUAN (1-3 mg/day), DMPH (5-20 mg/day), or a combination (COMB) with fixed-flexible dosing. Outcome measures were the ADHD Rating Scale IV (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale. Data on adverse events and safety measures were obtained.ResultsA total of 207 participants were randomized and received drug. Analyses showed significant treatment group main effects for ADHD-RS-IV ADHD total (p = .0001) and inattentive symptoms (p = .0001). COMB demonstrated small but consistently greater reductions in ADHD-RS-IV Inattentive subscale scores versus monotherapies (DMPH: p = .05; f(2) = .02; and GUAN: p = .02; f(2) = .02), and was associated with a greater positive response rate by CGI-I (p = .01). No serious cardiovascular events occurred. Sedation, somnolence, lethargy, and fatigue were greater in both guanfacine groups. All treatments were well tolerated.ConclusionCOMB showed consistent evidence of clinical benefits over monotherapies, possibly reflecting advantages of greater combined dopaminergic and α2A agonism. Adverse events were generally mild to moderate, and COMB treatment showed no differences in safety or tolerability.Clinical trial registration informationSingle Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder (Project1); http://clinicaltrials.gov/; NCT00429273.

Dataset Information

Neural Correlates of Symptom Improvement Following Stimulant Treatment in Adults with Attention-Deficit/Hyperactivity Disorder.

Publications

Neural Correlates of Symptom Improvement Following Stimulant Treatment in Adults with Attention-Deficit/Hyperactivity Disorder.

Similar Datasets

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