Brain Biochemical Effects of Methylphenidate Treatment Using Proton Magnetic Spectroscopy in Youth with Attention‐Deficit Hyperactivity Disorder: A Controlled Pilot Study
Open accessAbstract
SUMMARY: Introduction: This study conducted spectroscopic analyses using proton (1H) Magnetic Resonance Spectroscopy (at 4 Tesla) in a sample of adolescents with Attention Deficit Hyperactivity Disorder (ADHD), before and after treatment with extended release methylphenidate (OROS MPH), as compared to a sample of healthy comparators. Aims: The main aim of this study is to use 1H MRS to measure differences in brain biochemistry between adolescents with and without ADHD, and to assess changes in cerebral biochemistry, before and after stimulant treatment in ADHD youth. Results: Subjects with ADHD were medically healthy adolescents treated in an open label fashion with OROS MPH (mean dose: 54 mg/day; 0.90 mg/kg/day). Subjects with ADHD were scanned before and after OROS MPH treatment. Healthy comparators were scanned once. Magnetic resonance (MR) spectroscopy studies were performed on a 4.0 T Varian Unity/Inova MR scanner; proton spectra were acquired from the Anterior Cingulate Cortex (ACC). Data were analyzed using MANOVA and repeated measurement ANOVA. Higher metabolite ratios (Glutamate/myo‐inositol, Glutamine/myo‐inositol, Glutamate + Glutamine/myo‐inositol) were observed in the ACC in untreated ADHD subjects as compared to controls, and to treated ADHD youth; these group differences did not reach the a priori threshold for statistical significance. Conclusions: These preliminary findings suggest the presence of glutamatergic abnormalities in adolescents with ADHD, which may normalize with MPH treatment. Larger sample, controlled studies are needed to confirm these preliminary findings.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Glutamate signalling is the most common excitatory synapse NT and deficiencies in this signalling have been associated with ADHD symptoms, although it is unknown whether ADHD is associated with differences in glutamate levels.
“Glutamate signalling is the most common excitatory synapse NT [93] and deficiencies in this signalling has been associated with ADHD symptoms [94], although it is unknown whether ADHD is associated with differences in glutamate levels [95–97].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [97]
The Results section reports no statistically significant difference between untreated ADHD participants and controls in this small sample, supporting uncertainty about glutamate-related levels. But the Introduction and Discussion describe earlier studies reporting significant glutamatergic differences in ADHD. The paper therefore does not support an unqualified statement that it is unknown whether any such differences are associated with ADHD; citations [93] and [94] attach to the other clauses. (LLM, conf=0.78)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 31 · Cited by 53
Research works printed but not linked: 25
- [2]Faraone SV Sergeant J Gillberg C Biederman J The worldwide prevalence of ADHD: Is it an American condition? World Psychiatry 2003 2 104 113 16946911 PMC1525089
- [5]Agarwal N Port JD Bazzocchi M Renshaw PF Update on the use of MR for assessment and diagnosis of psychiatric diseases Radiology 2010 255 23 41 20308442
- [6]Carlsson A The neurochemical circuitry of schizophrenia Pharmacopsychiatry 2006 39 Suppl 1 S10 S14 16508890
- [7]MacMaster FP Carrey N Sparkes S Kusumakar V Proton spectroscopy in medication-free pediatric attention-deficit/hyperactivity disorder Biol Psychiatry 2003 53 184 187 12547476
- [8]Courvoisie H Hooper SR Fine C Kwock L Castillo M Neurometabolic functioning and neuropsychological correlates in children with ADHD-H: Preliminary findings J Neuropsychiatry Clin Neurosci 2004 16 63 69 14990761
- [9]Ferreira PE Palmini A Bau CH Differentiating attention-deficit/hyperactivity disorder inattentive and combined types: A (1)H-magnetic resonance spectroscopy study of fronto-striatothalamic regions J Neural Transm 2009 116 623 629 19399368
- [10]Perlov E Tebarzt van Elst L Buechert M H1-MR-spectroscopy of cerebellum in adult attention deficit/hyperactivity disorder J Psychiatr Res 2010 44 938 943 20332052
- [12]Moore CM Frazier JA Glod CA Glutamine and glutamate levels in children and adolescents with bipolar disorder: A 4. 0-T proton magnetic resonance spectroscopy study of the anterior cingulate cortex J Am Acad Child Adolesc Psychiatry 2007 46 524 534 17420688 PMC4090056
- [13]Carrey N MacMaster FP Sparkes SJ Khan SC Kusumakar V Glutamatergic changes with treatment in attention deficit hyperactivity disorder: A preliminary case series J Child Adolesc Psychopharmacol 2002 12 331 336 12625993
- [14]Carrey N MacMaster FP Fogel J Metabolite changes resulting from treatment in children with ADHD: A 1H-MRS study Clin Neuropharmacol 2003 26 218 221 12897644
- [15]Kronenberg G Ende G Alm B Deuschle M Heuser I Colla M Increased NAA and reduced choline levels in the anterior cingulum following chronic methylphenidate. A spectroscopic test-retest study in adult ADHD Eur Arch Psychiatry Clin Neurosci 2008 258 446 450 18330668
- [16]Provencher SW Automatic quantitation of localized in vivo 1H spectra with LCModel NMR Biomed 2001 14 260 264 11410943
- [17]Moore CM Biederman J Wozniak J Differences in brain chemistry in children and adolescents with attention deficit hyperactivity disorder with and without comorbid bipolar disorder: A proton magnetic resonance spectroscopy study Am J Psychiatry 2006 163 316 318 16449488 PMC4068129
- [18]Perlov E Philipsen A Matthies S Spectroscopic findings in attention-deficit/hyperactivity disorder: Review and meta-analysis World J Biol Psychiatry 2009 10 4 Pt 2 355 365 18609427
- [19]Sun L Jin Z Zang YF Differences between attention-deficit disorder with and without hyperactivity: A (1)H-magnetic resonance spectroscopy study Brain Dev 2005 27 340 344 16023548
- [20]Yang P Wu MT Dung SS Ko CW Short-TE proton magnetic resonance spectroscopy investigation in adolescents with attention-deficit hyperactivity disorder Psychiatry Res 2010 181 199 203 20153148
- [21]Jensen JE Licata SC Ongur D Quantification of J-resolved proton spectra in two-dimensions with LCModel using GAMMA-simulated basis sets at 4 Tesla NMR Biomed 2009 22 762 769 19388001
- [22]Russell VA Dopamine hypofunction possibly results from a defect in glutamate-stimulated release of dopamine in the nucleus accumbens shell of a rat model for attention deficit hyperactivity disorder: The spontaneously hypertensive rat Neurosci Biobehav Rev 2003 27 671 682 14624811
- [23]Hyder F Patel AB Gjedde A Rothman DL Behar KL Shulman RG Neuronal-glial glucose oxidation and glutamatergic-GABAergic function J Cereb Blood Flow Metab 2006 26 865 877 16407855
- [24]Struzynska L A glutamatergic component of lead toxicity in adult brain: The role of astrocytic glutamate transporters Neurochem Int 2009 55 151 156 19428820
- [25]Zwingmann C Leibfritz D Hazell AS Nmr spectroscopic analysis of regional brain energy metabolism in manganese neurotoxicity Glia 2007 55 1610 1617 17823966
- [26]Todd RD Botteron KN Is attention-deficit/hyperactivity disorder an energy deficiency syndrome? Biol Psychiatry 2001 50 151 158 11513813
- [27]Meisingset TW Risa O Brenner M Messing A Sonnewald U Alteration of glial-neuronal metabolic interactions in a mouse model of Alexander disease Glia 2010 58 1228 1234 20544858 PMC2908901
- [28]Russell VA Oades RD Tannock R Response variability in Attention-Deficit/Hyperactivity Disorder: A neuronal and glial energetics hypothesis Behav Brain Funct 2006 2 30 16925830 PMC1624838
- [29]Sailasuta N Abulseoud O Hernandez M Haghani P Ross BD Metabolic abnormalities in abstinent methamphetamine dependent subjects Subst Abuse 2010 2010 9 20 20485533 PMC2872246
- Authors
- Hammerness, P., Biederman, J., Petty, C., Henin, A., & Moore, C. M.
- Affiliations
- Harvard University (US)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Hammerness, Paul
- Venue
- CNS Neuroscience & Therapeutics
- Publisher
- Wiley
- Published
- 2010-12-08
- Volume
- 18
- Issue
- 1
- Pages
- 34-40
- ISSN
- 1755-5930 (ISSN-L)
- 1755-5949
- PMC
- PMC4084790
- OpenAlex
- W1535448629
- Cited by
- 53
- References
- 31
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 1 · 2020: 2 · 2019: 5 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 5 · 2014: 4 · 2013: 5 · 2012: 6
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- CNS Neuroscience & Therapeutics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Abbott Laboratories
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Sanofi
- American Academy of Child and Adolescent Psychiatry
- National Alliance for Research on Schizophrenia and Depression
- University of Oxford
- National Institute of Mental Health (R01MH073998)
- National Institute on Drug Abuse
- Janssen Pharmaceuticals
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- attention deficit hyperactivity disorder, methylphenidate, extended-release methylphenidate, 1H NMR, neurochemistry, anterior cingulate cortex, glutamate, glutamine, myo-inositol, stimulant medication, adolescents
- MeSH terms
- Adolescent, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Brain, Female, Glutamine, Humans, Longitudinal Studies, Male, Methylphenidate, Magnetic Resonance Spectroscopy, Pilot Projects, Protons, Psychiatric Status Rating Scales, Radionuclide Imaging, Case-Control Studies, Glutamic Acid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
