Adults with Attention-Deficit/Hyperactivity Disorder ? A Brain Magnetic Resonance Spectroscopy Study
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BACKGROUND: Impaired cognitive control in individuals with attention-deficit/hyperactivity disorder (ADHD) may be related to a prefrontal cortical glutamatergic deficit. We assessed the glutamate level in the left and the right midfrontal region including the anterior cingulate cortex in adults with ADHD and healthy controls. METHODS: Twenty-nine adults with ADHD and 38 healthy controls were included. We used Proton Magnetic Resonance Imaging with single voxel point-resolved spectroscopy to measure the ratio of glutamate to creatine (Glu/Cre) in the left and the right midfrontal region in the two groups. RESULTS: The ADHD group showed a significant reduction of Glu/Cre in the left midfrontal region compared to the controls. CONCLUSION: The reduction of Glu/Cre in the left midfrontal region in the ADHD group may reflect a glutamatergic deficit in prefrontal neuronal circuitry in adults with ADHD, resulting in problems with cognitive control.
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Proton MRI studies have reported glutamatergic deficits in frontal cortical and striatal regions in individuals with ADHD that may be related to cognitive control and symptom severity.
“Studies examining neurometabolism using proton MRIs have reported glutamatergic deficits in the frontal cortical and striatal regions in individuals with ADHD that may be related to cognitive control and symptom severity (12, 222, 223).”
From The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities (2018) · cites this paper as [222]
The Abstract and Results report reduced glutamate-to-creatine ratio in the left midfrontal region of adults with ADHD, and the Discussion links this finding to possible impaired cognitive control. The study does not report a striatal deficit. Its Results also found no significant correlation with symptom severity among participants with ADHD, although an exploratory correlation with inattentive symptoms appeared when controls were included. (LLM, conf=0.87)
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Willcutt, E. G., Doyle, A. E., Nigg, J. T., Faraone, S. V., & Pennington, B. F. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.02.006 · Cited by 3,568 · see citing works
KESSLER, R. C., ADLER, L., AMES, M., DEMLER, O., FARAONE, S., HIRIPI, E., HOWES, M. J., JIN, R., SECNIK, K., SPENCER, T., et al. (2005) · Psychological Medicine · doi:10.1017/s0033291704002892 · Cited by 3,452 · see citing works
FARAONE, S. V., BIEDERMAN, J., & MICK, E. (2006) · Psychological Medicine · doi:10.1017/s003329170500471x · Cited by 2,267 · see citing works
The activation of attentional networks
FAN, J., MCCANDLISS, B., FOSSELLA, J., FLOMBAUM, J., & POSNER, M. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.02.004 · Cited by 1,737 · see citing works
Bush, G., Valera, E. M., & Seidman, L. J. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.01.034 · Cited by 714 · see citing works
Testing the behavioral interaction and integration of attentional networks
Fan, J., Gu, X., Guise, K. G., Liu, X., Fossella, J., Wang, H., & Posner, M. I. (2009) · Brain and Cognition · doi:10.1016/j.bandc.2009.02.002 · Cited by 458 · see citing works
Potential Psychiatric Applications of Metabotropic Glutamate Receptor Agonists and Antagonists
Krystal, J. H., Mathew, S. J., DʼSouza, D. C., Garakani, A., Gunduz-Bruce, H., & Charney, D. S. (2010) · CNS Drugs · doi:10.2165/11533230-000000000-00000 · Cited by 180 · see citing works
Sonuga-Barke, E. J. S., Wiersema, J. R., van der Meere, J. J., & Roeyers, H. (2010) · Neuropsychology Review · doi:10.1007/s11065-009-9115-0 · Cited by 142 · see citing works
Cornforth, C., Sonuga-Barke, E., & Coghill, D. (2010) · Current Pharmaceutical Design · doi:10.2174/138161210791959827 · Cited by 41 · see citing works
Flagged first, then by citations
Research works printed but not linked: 46
- Bozkurt A. Zilles K. Schleicher A. Kamper L. Arigita E. S. Uylings H. B. Kotter R. (2005). Distributions of transmitter receptors in the macaque cingulate cortex. Neuroimage 25, 219– 229 10.1016/j.neuroimage.2004.10.040 15734357 · DOI
- Bush G. Luu P. Posner M. I. (2000). Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn. Sci. (Regul. Ed.) 4, 215– 222 10.1016/S1364-6613(00)01483-2 10827444 · DOI · Paper page
- Capizzano A. A. Jorge R. E. Acion L. C. Robinson R. G. (2007). In vivo proton magnetic resonance spectroscopy in patients with mood disorders: a technically oriented review. J. Magn. Reson. Imaging 26, 1378– 1389 10.1002/jmri.21144 17968885 · DOI
- Carlsson M. L. (2001). On the role of prefrontal cortex glutamate for the antithetical phenomenology of obsessive compulsive disorder and attention deficit hyperactivity disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry 25, 5– 26 10.1016/S0278-5846(00)00146-9 11263758 · DOI
- Carter C. S. Van Veen V. (2007). Anterior cingulate cortex and conflict detection: an update of theory and data. Cogn. Affect. Behav. Neurosci. 7, 367– 379 10.3758/CABN.7.4.367 18189010 · DOI · Paper page
- Challman T. D. Lipsky J. J. (2000). Methylphenidate: its pharmacology and uses. Mayo Clin. Proc. 75, 711– 721 10.4065/75.7.711 10907387 · DOI
- Colla M. Ende G. Alm B. Deuschle M. Heuser I. Kronenberg G. (2008). Cognitive MR spectroscopy of anterior cingulate cortex in ADHD: elevated choline signal correlates with slowed hit reaction times. J. Psychiatr. Res. 42, 587– 595 10.1016/j.jpsychires.2007.06.006 17698080 · DOI
- Dager S. R. Corrigan N. M. Richards T. L. Posse S. (2008). Research applications of magnetic resonance spectroscopy to investigate psychiatric disorders. Top. Magn. Reson. Imaging 19, 81– 96 10.1097/RMR.0b013e318181e0be 19363431 PMC2669689 · DOI
- Dennis M. Francis D. J. Cirino P. T. Schachar R. Barnes M. A. Fletcher J. M. (2009). Why IQ is not a covariate in cognitive studies of neurodevelopmental disorders. J. Int. Neuropsychol. Soc. 15, 331– 343 10.1017/S1355617709090481 19402919 PMC3075072 · DOI · Paper page
- Doyle A. E. (2006). Executive functions in attention-deficit/hyperactivity disorder. J. Clin. Psychiatry 67(Suppl. 8), 21– 26 16961426
- Ferreira P. E. Palmini A. Bau C. H. Grevet E. H. Hoefel J. R. Rohde L. A. Anes M. Ferreira E. E. Belmonte-De-Abreu P. (2009). Differentiating attention-deficit/hyperactivity disorder inattentive and combined types: a (1)H-magnetic resonance spectroscopy study of fronto-striato-thalamic regions. J. Neural Transm. 116, 623– 629 10.1007/s00702-009-0191-3 19399368 · DOI
- Fornito A. Wood S. J. Whittle S. Fuller J. Adamson C. Saling M. M. Velakoulis D. Pantelis C. Yucel M. (2008). Variability of the paracingulate sulcus and morphometry of the medial frontal cortex: associations with cortical thickness, surface area, volume, and sulcal depth. Hum. Brain Mapp. 29, 222– 236 10.1002/hbm.20381 17497626 PMC6870636 · DOI
- Genro J. P. Kieling C. Rohde L. A. Hutz M. H. (2010). Attention-deficit/hyperactivity disorder and the dopaminergic hypotheses. Expert Rev. Neurother. 10, 587– 601 10.1586/ern.10.17 20367210 · DOI
- Graaf R. A. D. (2007). In vivo NMR Spectroscopy: Principles and Techniques. Chichester: Wiley
- Halleland H. Lundervold A. J. Halmoy A. Haavik J. Johansson S. (2009). Association between catechol O-methyltransferase (COMT) haplotypes and severity of hyperactivity symptoms in adults. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 403– 410 10.1002/ajmg.b.30831 18802928 · DOI
- Halmoy A. Fasmer O. B. Gillberg C. Haavik J. (2009). Occupational outcome in adult ADHD: impact of symptom profile, comorbid psychiatric problems, and treatment: a cross-sectional study of 414 clinically diagnosed adult ADHD patients. J. Atten. Disord. 13, 175– 187 10.1177/1087054708329777 19372500 · DOI · Paper page
- Hesslinger B. Thiel T. Tebartz Van Elst L. Hennig J. Ebert D. (2001). Attention-deficit disorder in adults with or without hyperactivity: where is the difference? A study in humans using short echo (1)H-magnetic resonance spectroscopy. Neurosci. Lett. 304, 117– 119 10.1016/S0304-3940(01)01730-X 11335068 · DOI
- Hugdahl K. Westerhausen R. Alho K. Medvedev S. Laine M. Hamalainen H. (2009). Attention and cognitive control: unfolding the dichotic listening story. Scand. J. Psychol. 50, 11– 22 10.1111/j.1467-9450.2009.00775.x 18705670 · DOI
- Huster R. J. Westerhausen R. Kreuder F. Schweiger E. Wittling W. (2007). Morphologic asymmetry of the human anterior cingulate cortex. Neuroimage 34, 888– 895 10.1016/j.neuroimage.2006.10.023 17161625 · DOI
- Javitt D. C. (2004). Glutamate as a therapeutic target in psychiatric disorders. Mol. Psychiatry 9, 984– 997 10.1038/sj.mp.4001551 15278097 · DOI
- Johansson S. Halleland H. Halmoy A. Jacobsen K. K. Landaas E. T. Dramsdahl M. Fasmer O. B. Bergsholm P. Lundervold A. J. Gillberg C. Hugdahl K. Knappskog P. M. Haavik J. (2008). Genetic analyses of dopamine related genes in adult ADHD patients suggest an association with the DRD5-microsatellite repeat, but not with DRD4 or SLC6A3 VNTRs. Am. J. Med. Genet. B Neuropsychiatr. Genet. 147B, 1470– 1475 10.1002/ajmg.b.30662 18081165 · DOI · Paper page
- Karaszewski B. Thomas R. G. Chappell F. M. Armitage P. A. Carpenter T. K. Lymer G. K. Dennis M. S. Marshall I. Wardlaw J. M. (2010). Brain choline concentration. Early quantitative marker of ischemia and infarct expansion? Neurology 75, 850– 856 10.1212/WNL.0b013e3181f11bf1 20819997 · DOI
- Kaufman J. Birmaher B. Brent D. Rao U. Flynn C. Moreci P. Williamson D. Ryan N. (1997). Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J. Am. Acad. Child Adolesc. Psychiatry 36, 980– 988 10.1016/S0890-8567(09)66571-0 9204677 · DOI
- Kronenberg G. Ende G. Alm B. Deuschle M. Heuser I. Colla M. (2008). 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. 258, 446– 450 10.1007/s00406-008-0810-2 18330668 · DOI
- Lesage A. Steckler T. (2010). Metabotropic glutamate mGlu1 receptor stimulation and blockade: therapeutic opportunities in psychiatric illness. Eur. J. Pharmacol. 639, 2– 16 10.1016/j.ejphar.2009.12.043 20371230 · DOI
- Ludolph A. G. Udvardi P. T. Schaz U. Henes C. Adolph O. Weigt H. U. Fegert J. M. Boeckers T. M. Fohr K. J. (2010). Atomoxetine acts as an NMDA receptor blocker in clinically relevant concentrations. Br. J. Pharmacol. 160, 283– 291 10.1111/j.1476-5381.2010.00707.x 20423340 PMC2874851 · DOI
- O’neill M. J. Dix S. (2007). AMPA receptor potentiators as cognitive enhancers. IDrugs 10, 185– 192 17351873
- Parsons C. G. Danysz W. Zieglgansberger W. (2005). Excitatory amino acid neurotransmission. Handb. Exp. Pharmacol. 169, 249– 303 10.1007/3-540-28082-0_10 16594262 · DOI
- Perlov E. Philipsen A. Hesslinger B. Buechert M. Ahrendts J. Feige B. Bubl E. Hennig J. Ebert D. Tebartz Van Elst L. (2007). Reduced cingulate glutamate/glutamine-to-creatine ratios in adult patients with attention deficit/hyperactivity disorder – a magnet resonance spectroscopy study. J. Psychiatr. Res. 41, 934– 941 10.1016/j.jpsychires.2006.12.007 17303167 · DOI
- Perlov E. Philipsen A. Matthies S. Drieling T. Maier S. Bubl E. Hesslinger B. Buechert M. Henning J. Ebert D. Tebartz Van Elst L. (2009). Spectroscopic findings in attention-deficit/hyperactivity disorder: review and meta-analysis. World J. Biol. Psychiatry 10, 355– 365 10.1080/15622970802176032 18609427 · DOI
- Perlov E. Tebarzt Van Elst L. Buechert M. Maier S. Matthies S. Ebert D. Hesslinger B. Philipsen A. (2010). H(1)-MR-spectroscopy of cerebellum in adult attention deficit/hyperactivity disorder. J. Psychiatr. Res. 44, 938– 943 10.1016/j.jpsychires.2010.02.016 20332052 · DOI
- Polanczyk G. De Lima M. S. Horta B. L. Biederman J. Rohde L. A. (2007). The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am. J. Psychiatry 164, 942– 948 10.1176/appi.ajp.164.6.942 17541055 · DOI · Paper page
- Posner M. I. Rothbart M. K. (2007). Research on attention networks as a model for the integration of psychological science. Annu. Rev. Psychol. 58, 1– 23 10.1146/annurev.psych.58.110405.085516 17029565 · DOI · Paper page
- Provencher S. W. (1993). Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn. Reson. Med. 30, 672– 679 10.1002/mrm.1910300604 8139448 · DOI
- Provencher S. W. (2001). Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR. Biomed. 14, 260– 264 10.1002/nbm.698 11410943 · DOI
- Rusch N. Boeker M. Buchert M. Glauche V. Bohrmann C. Ebert D. Lieb K. Hennig J. Tebartz Van Elst L. (2010). Neurochemical alterations in women with borderline personality disorder and comorbid attention-deficit hyperactivity disorder. World J. Biol. Psychiatry 11, 372– 381 10.3109/15622970801958331 20218799 · DOI
- Saunders D. E. Howe F. A. Van Den Boogaart A. Griffiths J. R. Brown M. M. (1999). Aging of the adult human brain: in vivo quantitation of metabolite content with proton magnetic resonance spectroscopy. J. Magn. Reson. Imaging 9, 711– 716 10.1002/(SICI)1522-2586(199905)9:5<711::AID-JMRI14>3.0.CO;2-3 10331768 · DOI
- Schubert F. Gallinat J. Seifert F. Rinneberg H. (2004). Glutamate concentrations in human brain using single voxel proton magnetic resonance spectroscopy at 3 Tesla. Neuroimage 21, 1762– 1771 10.1016/j.neuroimage.2003.11.014 15050596 · DOI
- Shaw P. Eckstrand K. Sharp W. Blumenthal J. Lerch J. P. Greenstein D. Clasen L. Evans A. Giedd J. Rapoport J. L. (2007). Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proc. Natl. Acad. Sci. U.S.A. 104, 19649– 19654 10.1073/pnas.0703280104 18024590 PMC2148343 · DOI
- Solanto M. V. (1998). Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration. Behav. Brain Res. 94, 127– 152 10.1016/S0166-4328(97)00175-7 9708845 · DOI · Paper page
- Staller J. A. Faraone S. V. (2007). Targeting the dopamine system in the treatment of attention-deficit/hyperactivity disorder. Expert Rev. Neurother. 7, 351– 362 10.1586/14737175.7.4.351 17425490 · DOI · Paper page
- Van Wageningen H. Jorgensen H. A. Specht K. Eichele T. Hugdahl K. (2009). The effects of the glutamate antagonist memantine on brain activation to an auditory perception task. Hum. Brain Mapp. 30, 3616– 3624 10.1002/hbm.20789 19449331 PMC6870652 · DOI
- Van Wageningen H. Jorgensen H. A. Specht K. Hugdahl K. (2010). A 1H-MR spectroscopy study of changes in glutamate and glutamine (Glx) concentrations in frontal spectra after administration of memantine. Cereb. Cortex 20, 798– 803 10.1093/cercor/bhp145 19605521 · DOI
- Vogt B. A. (2009). Cingulate Neurobiology and Disease. Oxford: Oxford University Press
- Yang J. W. Shih H. C. Shyu B. C. (2006). Intracortical circuits in rat anterior cingulate cortex are activated by nociceptive inputs mediated by medial thalamus. J. Neurophysiol. 96, 3409– 3422 10.1152/jn.00623.2006 16956990 · DOI
- Yerli H. Agildere A. M. Ozen O. Geyik E. Atalay B. Elhan A. H. (2007). Evaluation of cerebral glioma grade by using normal side creatine as an internal reference in multi-voxel 1H-MR spectroscopy. Diagn. Interv. Radiol. 13, 3– 9 17354186
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Glutamate/glutamine and neuronal integrity in adults with ADHD: a proton MRS study
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- Authors
- Dramsdahl, M., Ersland, L., Plessen, K. J., Haavik, J., Hugdahl, K., & Specht, K.
- Affiliations
- Haukeland University Hospital (NO)
- University of Copenhagen (DK)
- Corresponding author
- Dramsdahl, Margaretha
- Venue
- Frontiers in Psychiatry
- Publisher
- Frontiers Media SA
- Published
- 2011
- Volume
- 2
- Pages
- 65-65
- ISSN
- 1664-0640 (ISSN-L)
- PMC
- PMC3222884
- OpenAlex
- W2062525177
- Cited by
- 43
- References
- 9
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 3 · 2015: 6 · 2014: 5 · 2013: 1
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- other-oa
- Locations
- Frontiers in Psychiatry (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Norges Forskningsråd
- Haukeland Universitetssjukehus
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- attention deficit hyperactivity disorder, adult ADHD, glutamate, prefrontal cortex, anterior cingulate cortex, cognitive control, 1H NMR
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