Adult attention-deficit/hyperactivity disorder is associated with reduced norepinephrine transporter availability in right attention networks: a (S,S)-O-[11C]methylreboxetine positron emission tomography study

Ulke, Christine; Rullmann, Michael; Huang, Jue; Luthardt, Julia; Becker, Georg-Alexander; Patt, Marianne; Meyer, Philipp; Tiepolt, Solveig; Hesse, Swen; Sabri, Osama; Strauß, Maria

doi:10.1038/s41398-019-0619-y

Cited by 30 publications

(31 citation statements)

References 58 publications

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“…Brain imaging studies have shown that dopamine and norepinephrine pathways are involved in the pathology of ADHD. Dopamine and norepinephrine pathways are also involved in other comorbid disorders such as depression, anxiety, and panic (27)(28)(29)(30)(31)(32)(33). Therefore, it is not surprising that by regulating these pathways some improvements occur in mood and concentration of ADHD patients; they also show why MPH is effective for the treatment of ADHD (34).…”

Section: Discussionmentioning

confidence: 99%

A Comparison of Methylphenidate (MPH) and Combined Methylphenidate with Crocus sativus (Saffron) in the Treatment of Children and Adolescents with ADHD: A Randomized, Double-blind, Parallel-Group, Clinical Trial

Khaksarian

Ahangari

Masjedi-Arani

et al. 2021

Iran J Psychiatry Behav Sci

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Background: Attention-deficit/hyperactivity disorder (ADHD) is characterized by behavioral and neurodevelopmental problems. It is estimated that 3 - 7% of children and adolescents suffer from this problem. Apart from synthetic drugs, other effective types of medication like herbal medicines are of great importance. Objectives: This study aimed to evaluate the effectiveness of methylphenidate (MPH) and its combination with Crocus sativus (saffron) in the treatment of children suffering from ADHD. Methods: The sample included 70 children aged between 6 and 16 years who had been diagnosed with ADHD. The patients were randomly assigned into two equal groups (n = 35 in each group). While both groups received 20 or 30 mg/d of MPH (20 and 30 mg/d for < 30 and > 30, respectively), one of them also received 20 or 30 mg/d of saffron in a capsule based on BMI (20 and 30 mg/d for < 30 and > 30, respectively). To collect data, parents and teachers completed Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV). Also, for analyzing the data, the repeated measures analysis of variance (RMANOVA) was used. Results: The results of general linear model (GLM) repeated measures indicated that in both groups, the patients had less symptoms after eight weeks of treatment. However, after four weeks, the average score assigned by the parents and teachers in the MPH with saffron group was lower than the average total score in the MPH group (P < 0.05). Conclusions: Using MPH combined with saffron proved to be more effective in the treatment of patients suffering from ADHD compared to separate treatments. It seems that the duration of therapy can be reduced and the effectiveness be improved by prescribing proposed combined treatment.

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Section: Discussionmentioning

confidence: 99%

A Comparison of Methylphenidate (MPH) and Combined Methylphenidate with Crocus sativus (Saffron) in the Treatment of Children and Adolescents with ADHD: A Randomized, Double-blind, Parallel-Group, Clinical Trial

Khaksarian

Ahangari

Masjedi-Arani

et al. 2021

Iran J Psychiatry Behav Sci

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“…Dopamine and noradrenaline play important roles in high-level executive functions in attention-deficit/hyperactivity disorder (ADHD) by influencing the fronto-striato-cerebellar circuits [ 6 ]. ADHD is associated with reduced noradrenaline (norepinephrine) transporter availability in right attention networks [ 38 ]: noradrenaline (norepinephrine) reuptake inhibitors inhibit the uptake of primarily norepinephrine by presynaptic nerve terminals and increase its availability in the synaptic cleft by blocking the human norepinephrine transporter [ 17 ]. Dopamine influences the attention, concentration and motivation.…”

Section: Discussionmentioning

confidence: 99%

Brain activation patterns in medicated versus medication-naïve adults with attention-deficit hyperactivity disorder during fMRI tasks of motor inhibition and cognitive switching

Berberat

Huggenberger²,

Montali

et al. 2021

BMC Med Imaging

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Background Adult-attention-deficit-hyperactive-disorder (ADHD) is often unrecognized condition. FMRI examination along with neuropsychological testing might strengthen the diagnosis. We hypothesized that ADHD-adults with and without medication would show different fMRI pattern compared to healthy controls while testing tasks of motor inhibition and cognitive switching. Methods 45 subjects in three age-matched groups: (1) controls, (2) ADHD-adults under medication (ADHD+) and (3) medication-naïve adults with ADHD (ADHD−) underwent fMRI and neuropsychological testing. Group analysis and population-based statistics were performed. Results DTVP-A, intellectual ability as well as attention capability, visual-perceptual and visual-motor abilities showed no significant differences between the groups. However, fMRI revealed statistically significant differences between the ADHD+, ADHD− and control groups on tasks of motor inhibition and cognitive switching on adults in bilateral fronto-striatal brain regions, inferior fronto-frontal, fronto-cingulate and fronto-parietal networks as well as in the parietal lobe (p < 0.05). Conclusions fMRI offers the potential to differentiate between the ADHD+, ADHD− and control groups. FMRI possibly opens a new window for monitoring the therapeutic effect of ADHD medication. Trial registration NCT02578342, registered at August 2015 to clinical trial registry (https://ichgcp.net/clinical-trials-registry/NCT02578342).

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“…This implies that MPH could still affect noradrenergic transmission through DAT inhibition. Moreover, we cannot exclude that some NETrelated FC changes that do not reach statistical significance at rest may emerge during a paradigm preferentially engaging attentional networks [73,74]. Finally, we acquired data on a single time-interval post-dosing with a single low dose.…”

Section: Discussionmentioning

confidence: 99%

Unravelling the effects of methylphenidate on the dopaminergic and noradrenergic functional circuits

Dipasquale

Martins

Sethi

et al. 2020

Neuropsychopharmacol.

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Functional magnetic resonance imaging (fMRI) can be combined with drugs to investigate the system-level functional responses in the brain to such challenges. However, most psychoactive agents act on multiple neurotransmitters, limiting the ability of fMRI to identify functional effects related to actions on discrete pharmacological targets. We recently introduced a multimodal approach, REACT (Receptor-Enriched Analysis of functional Connectivity by Targets), which offers the opportunity to disentangle effects of drugs on different neurotransmitters and clarify the biological mechanisms driving clinical efficacy and side effects of a compound. Here, we focus on methylphenidate (MPH), which binds to the dopamine transporter (DAT) and the norepinephrine transporter (NET), to unravel its effects on dopaminergic and noradrenergic functional circuits in the healthy brain at rest. We then explored the relationship between these target-enriched resting state functional connectivity (FC) maps and inter-individual variability in behavioural responses to a reinforcement-learning task encompassing a novelty manipulation to disentangle the molecular systems underlying specific cognitive/behavioural effects. Our main analysis showed a significant MPH-induced FC increase in sensorimotor areas in the functional circuit associated with DAT. In our exploratory analysis, we found that MPH-induced regional variations in the DAT and NET-enriched FC maps were significantly correlated with some of the inter-individual differences on key behavioural responses associated with the reinforcement-learning task. Our findings show that main MPH-related FC changes at rest can be understood through the distribution of DAT in the brain. Furthermore, they suggest that when compounds have mixed pharmacological profiles, REACT may be able to capture regional functional effects that are underpinned by the same cognitive mechanism but are related to engagement of distinct molecular targets.

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Adult attention-deficit/hyperactivity disorder is associated with reduced norepinephrine transporter availability in right attention networks: a (S,S)-O-[11C]methylreboxetine positron emission tomography study

Cited by 30 publications

References 58 publications

A Comparison of Methylphenidate (MPH) and Combined Methylphenidate with Crocus sativus (Saffron) in the Treatment of Children and Adolescents with ADHD: A Randomized, Double-blind, Parallel-Group, Clinical Trial

A Comparison of Methylphenidate (MPH) and Combined Methylphenidate with Crocus sativus (Saffron) in the Treatment of Children and Adolescents with ADHD: A Randomized, Double-blind, Parallel-Group, Clinical Trial

Brain activation patterns in medicated versus medication-naïve adults with attention-deficit hyperactivity disorder during fMRI tasks of motor inhibition and cognitive switching

Unravelling the effects of methylphenidate on the dopaminergic and noradrenergic functional circuits

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