Methylphenidate Effects on Cortical Thickness in Children and Adults with Attention-Deficit/Hyperactivity Disorder: A Randomized Clinical Trial

Walhovd, Kristine B.; Amlien, Inge K.; Schrantee, Anouk; Rohani, Darius Adam; Groote, Inge Rasmus; Bjørnerud, Atle; Fjell, Anders Martin; Reneman, Liesbeth

doi:10.3174/ajnr.a6560

Cited by 12 publications

(12 citation statements)

References 42 publications

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“…Despite these limitations, the following two advantages enhance the reliability of the results. Previous studies have outlined that stimulants can change the brain structure and function of patients with ADHD ( An et al, 2013 ; Querne et al, 2017 ; Walhovd et al, 2020 ) and the dose of the stimulant correlates with the size of the amygdala ( Becker et al, 2015 ). The participants selected for this study were not on any stimulants.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Functional Connectivity Reveals Abnormal Variability in the Amygdala Subregions of Children With Attention-Deficit/Hyperactivity Disorder

Yang

Zhang

et al. 2021

Front. Neurosci.

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Objective: This study investigates whether the dynamic functional connectivity (dFC) of the amygdala subregions is altered in children with attention-deficit/hyperactivity disorder (ADHD).Methods: The dFC of the amygdala subregions was systematically calculated using a sliding time window method, for 75 children with ADHD and 20 healthy control (HC) children.Results: Compared with the HC group, the right superficial amygdala exhibited significantly higher dFC with the right prefrontal cortex, the left precuneus, and the left post-central gyrus for children in the ADHD group. The dFC of the amygdala subregions showed a negative association with the cognitive functions of children in the ADHD group.Conclusion: Functional connectivity of the amygdala subregions is more unstable among children with ADHD. In demonstrating an association between the stability of functional connectivity of the amygdala and cognitive functions, this study may contribute by providing a new direction for investigating the internal mechanism of ADHD.

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Section: Discussionmentioning

confidence: 99%

Dynamic Functional Connectivity Reveals Abnormal Variability in the Amygdala Subregions of Children With Attention-Deficit/Hyperactivity Disorder

Yang

Zhang

et al. 2021

Front. Neurosci.

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Section: Structural and Functional Neuroimagingmentioning

confidence: 82%

“…Both acute and longer-term treatment effects on brain patterns have been documented using structural and functional magnetic resonance imaging in ADHD samples (Table 4 ). Changes in structural neuroimaging markers following treatment with MPH have been studied as part of a 16-week double-blind, randomized, placebo-controlled trial of boys and young men with ADHD [ 69 , 70 ]. One report from this trial showed wide-spread time-by-medication-by-age interaction effects in left hemisphere white matter, which were driven by increases in fractional anisotropy among medicated children [ 69 ].…”

Section: Monitoring and Response/pharmacodynamic Biomarkersmentioning

confidence: 99%

“…A report from the same trial described increasing cortical thickness in medicated children within right medial frontal cortex, which contrasted with the cortical thinning that was observed in the placebo group. No significant results were found for the adult groups, and structural brain changes were not associated with clinical improvement [ 70 ]. Similarly, a double-blind randomized placebo-controlled trial of N = 131 adults with ADHD who underwent 12 months of MPH treatment reported no significant treatment-related changes in gray matter volume [ 71 ].…”

Section: Monitoring and Response/pharmacodynamic Biomarkersmentioning

confidence: 99%

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Treatment biomarkers for ADHD: Taking stock and moving forward

et al. 2022

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The development of treatment biomarkers for psychiatric disorders has been challenging, particularly for heterogeneous neurodevelopmental conditions such as attention-deficit/hyperactivity disorder (ADHD). Promising findings are also rarely translated into clinical practice, especially with regard to treatment decisions and development of novel treatments. Despite this slow progress, the available neuroimaging, electrophysiological (EEG) and genetic literature provides a solid foundation for biomarker discovery. This article gives an updated review of promising treatment biomarkers for ADHD which may enhance personalized medicine and novel treatment development. The available literature points to promising pre-treatment profiles predicting efficacy of various pharmacological and non-pharmacological treatments for ADHD. These candidate predictive biomarkers, particularly those based on low-cost and non-invasive EEG assessments, show promise for the future stratification of patients to specific treatments. Studies with repeated biomarker assessments further show that different treatments produce distinct changes in brain profiles, which track treatment-related clinical improvements. These candidate monitoring/response biomarkers may aid future monitoring of treatment effects and point to mechanistic targets for novel treatments, such as neurotherapies. Nevertheless, existing research does not support any immediate clinical applications of treatment biomarkers for ADHD. Key barriers are the paucity of replications and external validations, the use of small and homogeneous samples of predominantly White children, and practical limitations, including the cost and technical requirements of biomarker assessments and their unknown feasibility and acceptability for people with ADHD. We conclude with a discussion of future directions and methodological changes to promote clinical translation and enhance personalized treatment decisions for diverse groups of individuals with ADHD.

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“…The effects of MPH are usually attributed to its ability to block the reuptake of dopamine, noradrenaline, and (in low affinity) serotonin to potentiate the effects of monoamines in the synaptic cleft ( Quintero et al, 2022 ). Nevertheless, accumulating evidence suggests that the ability of MPH to stimulate cortical maturation [responsible for its long-term effects ( Shaw et al, 2009 ; Walhovd et al, 2020 )] may be mediated by a separate mechanism not related to the inhibition of monoamine transporters ( Bartl et al, 2010 , 2013b , 2017 ; Grünblatt et al, 2018 ; Yde Ohki et al, 2020 ). It has been reported that MPH can inhibit proliferation and enhance neuronal differentiation both in vitro ( Bartl et al, 2013b ; Grünblatt et al, 2018 ) and in vivo ( Lee et al, 2012 ; Oakes et al, 2019 ) via an unknown molecular mechanism.…”

Section: Methylphenidate In Attention-deficit Hyperactivity Disorder ...mentioning

confidence: 99%

From attention-deficit hyperactivity disorder to sporadic Alzheimer’s disease—Wnt/mTOR pathways hypothesis

et al. 2023

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Alzheimer’s disease (AD) is the most common neurodegenerative disorder with the majority of patients classified as sporadic AD (sAD), in which etiopathogenesis remains unresolved. Though sAD is argued to be a polygenic disorder, apolipoprotein E (APOE) ε4, was found three decades ago to pose the strongest genetic risk for sAD. Currently, the only clinically approved disease-modifying drugs for AD are aducanumab (Aduhelm) and lecanemab (Leqembi). All other AD treatment options are purely symptomatic with modest benefits. Similarly, attention-deficit hyperactivity disorder (ADHD), is one of the most common neurodevelopmental mental disorders in children and adolescents, acknowledged to persist in adulthood in over 60% of the patients. Moreover, for ADHD whose etiopathogenesis is not completely understood, a large proportion of patients respond well to treatment (first-line psychostimulants, e.g., methylphenidate/MPH), however, no disease-modifying therapy exists. Interestingly, cognitive impairments, executive, and memory deficits seem to be common in ADHD, but also in early stages of mild cognitive impairment (MCI), and dementia, including sAD. Therefore, one of many hypotheses is that ADHD and sAD might have similar origins or that they intercalate with one another, as shown recently that ADHD may be considered a risk factor for sAD. Intriguingly, several overlaps have been shown between the two disorders, e.g., inflammatory activation, oxidative stress, glucose and insulin pathways, wingless-INT/mammalian target of rapamycin (Wnt/mTOR) signaling, and altered lipid metabolism. Indeed, Wnt/mTOR activities were found to be modified by MPH in several ADHD studies. Wnt/mTOR was also found to play a role in sAD and in animal models of the disorder. Moreover, MPH treatment in the MCI phase was shown to be successful for apathy including some improvement in cognition, according to a recent meta-analysis. In several AD animal models, ADHD-like behavioral phenotypes have been observed indicating a possible interconnection between ADHD and AD. In this concept paper, we will discuss the various evidence in human and animal models supporting the hypothesis in which ADHD might increase the risk for sAD, with common involvement of the Wnt/mTOR-pathway leading to lifespan alteration at the neuronal levels.

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Methylphenidate Effects on Cortical Thickness in Children and Adults with Attention-Deficit/Hyperactivity Disorder: A Randomized Clinical Trial

Cited by 12 publications

References 42 publications

Dynamic Functional Connectivity Reveals Abnormal Variability in the Amygdala Subregions of Children With Attention-Deficit/Hyperactivity Disorder

Dynamic Functional Connectivity Reveals Abnormal Variability in the Amygdala Subregions of Children With Attention-Deficit/Hyperactivity Disorder

Treatment biomarkers for ADHD: Taking stock and moving forward

From attention-deficit hyperactivity disorder to sporadic Alzheimer’s disease—Wnt/mTOR pathways hypothesis

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