Abstract
Rationale
The dorsolateral prefrontal cortex (DLPFC) participates in the pathophysiology of mania. In particular, left-sided structural and metabolic abnormalities have been described.
Objectives
Clinical symptoms may be due to hyperactivity of cortical glutamatergic neurons, resulting in increased excitatory neurotransmitter flux and thus enhanced Glx levels.
Methods
Glutamate/glutamine (Glx) levels were assessed by proton magnetic resonance spectroscopy (1H-MRS) in eight acute manic patients compared with age- and gender-matched controls.
Results
Manic patients had significantly elevated Glx levels (t-test; t=–3.1, P=0.008) within the left DLPFC.
Conclusions
Our results indicate that the prefrontal cortical glutamatergic system is involved in the pathophysiology of acute mania. This may have implications for the treatment of mania.
Similar content being viewed by others
References
Auer DP, Pütz B, Kraft E, Lipinski B, Schill J, Holsboer F (2000) Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry 47:305–313
Baxter LR, Phelps ME, Mazziotta JC, Schwartz JM, Gerner RH, Selin CE, Sumida RM (1985) Cerebral metabolic rates for glucose in mood disorders. Arch Gen Psychiatry 42:441–447
Bech P, Rafaelsen OJ, Kramp P, Bolwig TG (1978) The mania rating scale: scale construction and inter-observer agreement. Neuropharmacology 17:430–431
Castillo M, Kwock L, Courvoisie H, Hooper SR (2000) Proton MR spectroscopy in children with bipolar affective disorder: preliminary observations. Am J Neuroradiol 21:832–838
Clark L, Iversen SD, Goodwin GM (2001) A neuropsychological investigation of prefrontal cortex involvement in acute mania. Am J Psychiatry 158:1605–1611
de Asis JM, Stern E, Alexopoulos GS, Pan H, Van Gorp W, Blumberg H, Kalayam B, Eidelberg D, Kiosses D, Silbersweig DA (2001) Hippocampal and anterior cingulate activation deficits in patients with geriatric depression. Am J Psychiatry 158:1321–1323
Drevets WC, Price JL, Simpson JR, Todd RD, Reich T, Vannier M, Raichle M (1997) Subgenual prefrontal cortex abnormalities in mood disorders. Nature 386:824–827
Fuster JM (1997) The prefrontal cortex: anatomy, physiology, and neuropsychology of the frontal lobe, 3rd edn. Lippincott-Raven, Philadelphia
Hiller W, Zaudig M, Mombour W (2000) Internationale Diagnosen Checklisten (IDCL) für DSM-IV. Hogrefe Verlag, Göttingen, Bern, Toronto
Knable MB, Barci BM, Bartko JJ, Webster MJ, Torrey EF (2002) Molecular abnormalities in the major psychiatric illnesses: classification and regression tree (CRT) analysis of post-mortem prefrontal markers. Mol Psychiatry 7:392–404
Krystal JH, Sanacora G, Blumberg H, Anand A, Charney DS, Marek G, Epperson CN, Goddard A, Mason GF (2002) Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Mol Psychiatry 7:S71–S80
Michael N, Erfurth A, Ohrmann P, Arolt V, Heindel W, Pfleiderer B (2003) Effects of electroconvulsive therapy on the left dorsolateral prefrontal cortex in patients with treatment resistant depression. Psychol Med (in press)
Michaelis T, Merboldt KD, Bruhn H, Hänicke W, Frahm J (1993) Absolute concentration of metabolites in the adult human brain in vivo: quantification of localized proton MR spectra. Radiology 187:219–227
Nonaka S, Hough CJ, Chuang D-M (1998) Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting N-methyl-d-aspartate receptor-mediated calcium influx. Proc Natl Acad Sci USA 95:2642–2647
Pfleiderer B, Michael N, Erfurth A, Ohrmann P, Homann U, Wolgast M, Fiebich M, Arolt V, Heindel W (2003) Effective electroconvulsive therapy reverses glutamate/glutamine deficit in the left anterior cingulum of unipolar depressed patients. Psychiatr Res Neuroimag (in press)
Provencher SW (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magnet Res Med 30:672–679
Rajkowska G, Goldman-Rakic PS (1995) Cytoarchitectonic definition of prefrontal areas in the normal human cortex: II. variability in locations of area 9 and 46 and relationship to the Talairach coordinate system. Cereb Cortex 45:323–337
Rajkowska G, Halaris A, Selemon LD (2001) Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder. Biol Psychiatry 49:741–752
Sanacora G, Mason GF, Rothman DL, Behar KL, Hyder F, Petroff OA, Berman RM, Charney DS, Krystal JH (1999) Reduced cortical γ-aminobutyric acid levels in depressed patients determined by proton magnetic spectroscopy. Arch Gen Psychiatry 56:1043–1047
Sax KW, Strakowski SM, Zimmerman ME, DelBello MP, Keck PE, Hawkins JM (1999) Frontosubcortical neuroanatomy and the continuous performance test in mania. Am J Psychiatry 156:139–141
Shulman RG (2001) Functional imaging studies: linking mind and basic neuroscience. Am J Psychiatry 158:11–20
Stewart CA, Reid IC (2002) Antidepressant mechanisms: functional and molecular correlates of excitatory amino acid neurotransmission. Mol Psychiatry 7: S15–S22
Wang Y, Li SJ (1998) Differentiation of metabolic concentrations between grey matter and white matter of human brain by in vivo 1H magnetic resonance spectroscopy. Mag Res Med 39:28–33
Acknowledgements
This work was supported by an "innovative medical research" grant (IMF) from the University of Münster, FRG (ER 219918). We wish to thank Professor Martin Fiebich, Department of Biomedical Engineering, University of Applied Sciences, Giessen, Germany, for providing the semiautomatic interactive algorithm to perform segmentation of our voxels.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Michael, N., Erfurth, A., Ohrmann, P. et al. Acute mania is accompanied by elevated glutamate/glutamine levels within the left dorsolateral prefrontal cortex. Psychopharmacology 168, 344–346 (2003). https://doi.org/10.1007/s00213-003-1440-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-003-1440-z