ArticleNeuroImage. Clinical2017
Age-dependent, lasting effects of methylphenidate on the GABAergic system of ADHD patients.
Article in NeuroImage. Clinical, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Systematic review of animal studies on the use of herbal medicine for attention-deficit/hyperactivity disorder.Frontiers in psychiatry · 2026Pooled it
- A comprehensive overview of the biological foundations of ADHD.Bioscience reports · 2026Review
- Anterior middle cingulate cortex gamma-aminobutyric acid level is elevated in children with both familial and prenatal alcohol exposure-associated attention deficit hyperactivity disorder.medRxiv : the preprint server for health sciences · 2026Article
- GABA and Glx levels in cortico-subcortical networks predict catecholaminergic effects on response inhibition.Journal of psychopharmacology (Oxford, England) · 2025Article
- Behavioural disorders and sleep problems in Sanfilippo syndrome: overlaps with some other conditions and importance indications.European child & adolescent psychiatry · 2025Review
- Modeling the developing nervous system: a neuroscience perspective on the use of new approach methodologies in developmental neurotoxicity testing.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Novel pharmacological targets for GABAergic dysfunction in ADHD.Neuropharmacology · 2024Review
- Chronic Methylphenidate Effects on Brain Gene Expression: An Exploratory Review.Psychology research and behavior management · 2024Review
- Association of Age and Response to Methylphenidate HCL Treatment in Adult ADHD: A Proton Magnetic Resonance Spectroscopy Study.Neuropsychiatric disease and treatment · 2024Article
- Deficiency of transmembrane AMPA receptor regulatory protein γ-8 leads to attention-deficit hyperactivity disorder-like behavior in mice.Zoological research · 2022Article
- A database of pediatric drug effects to evaluate ontogenic mechanisms from child growth and development.Med (New York, N.Y.) · 2022Article
- No population left behind: Improving paediatric drug safety using informatics and systems biology.British journal of clinical pharmacology · 2022Review
- Effects of Methylphenidate on the Dopamine Transporter and Beyond.Current topics in behavioral neurosciences · 2022Article
- Increased locomotor activity via regulation of GABAergic signalling in foxp2 mutant zebrafish-implications for neurodevelopmental disorders.Translational psychiatry · 2021Article
- Effects of prolonged methylphenidate treatment on amygdala reactivity and connectivity: a randomized controlled trial in stimulant treatment-naive, male participants with ADHD.Psychoradiology · 2021Article
- Precision Medicine Care in ADHD: The Case for Neural Excitation and Inhibition.Brain sciences · 2021Article
- Effects of 12-Week Methylphenidate Treatment on Neurometabolism in Adult Patients with ADHD: The First Double-Blind Placebo-Controlled MR Spectroscopy Study.Journal of clinical medicine · 2020Article
- Integrative proteomics and pharmacogenomics analysis of methylphenidate treatment response.Translational psychiatry · 2019Article
- PharmGKB summary: methylphenidate pathway, pharmacokinetics/pharmacodynamics.Pharmacogenetics and genomics · 2019Review
- Determinants of inter-practice variation in ADHD diagnosis and stimulant prescribing: cross-sectional database study of a national surveillance network.BMJ evidence-based medicine · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Stimulants are the main pharmacological treatment for patients with attention-deficit/hyperactivity disorder (ADHD). Their current prescription rates are rising, both in children, adolescents and adults. Related to the impulse control phenotype, both preclinical and clinical studies have demonstrated lower γ-amino butyric acid (GABA) levels in prefrontal brain regions in ADHD. Whereas stimulant treatment increases GABA levels, preclinical studies have suggested that stimulant treatment effects may be age-dependent. As the long-term consequences of stimulant use in ADHD children and adolescents have so far been poorly studied, we used magnetic resonance spectroscopy to assess GABA+ and glutamate + glutamine (Glx) levels in the medial prefrontal cortex (mPFC) of adult ADHD patients, both before and after an oral methylphenidate (MPH) challenge. Three groups were studied: 1) ADHD patients who were first treated with stimulants before 16 years of age, i.e. during periods of ongoing brain development (early-stimulant-treated, EST); 2) patients first treated with stimulants in adulthood (i.e. > 23 years) (late-stimulant-treated, LST), and 3) stimulant-treatment-naive (STN) ADHD patients. Reduced basal GABA+ levels were found in EST compared to LST patients (p = 0.04), while after an MPH challenge, only the EST patients showed significant increases in GABA+ (p = 0.01). For Glx, no differences were found at baseline, nor after an MPH challenge. First stimulant exposure at a young age is thus associated with lower baseline levels of GABA+ and increased responsivity in adulthood. This effect could not be found in patients that started treatment at an adult age. Hence, while adult stimulant treatment seems to exert no major effects on GABA+ levels in the mPFC, MPH may induce long-lasting alterations in the adult mPFC GABAergic system when treatment was started at a young age.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.