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Magnetic resonance (MR) spectroscopic measurement of γ-aminobutyric acid (GABA) in major depression before and after electroconvulsive therapy

Published online by Cambridge University Press:  06 August 2018

Marie Krøll Knudsen*
Affiliation:
Center of Functionally Integrative Neuroscience, Aarhus University Hospital, Aarhus, Denmark
Jamie Near
Affiliation:
Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Canada Department of Biomedical Engineering, McGill University, Montreal, Canada
Anne Bastholm Blicher
Affiliation:
Department of Psychiatry, Aarhus University Hospital Risskov, Aarhus, Denmark
Poul Videbech
Affiliation:
Mental Health Centre Glostrup, Copenhagen University Hospital, Glostrup, Denmark
Jakob Udby Blicher
Affiliation:
Center of Functionally Integrative Neuroscience, Aarhus University Hospital, Aarhus, Denmark
*
*Author for correspondence: Dr. Marie Krøll Knudsen, Center of Functionally Integrative Neuroscience, Aarhus University Hospital, Nørrebrogade 44, building 10G, 5th floor, 8000 Aarhus C, Denmark. Tel: +45 4114 2216; Fax: +45 7846 4400; E-mail: maeknu@rm.dk

Abstract

Objective

Prior studies suggest that a dysregulation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) is involved in the pathophysiology of major depression. We aimed to elucidate changes in cortical GABA content in relation to depression and electroconvulsive therapy (ECT) using magnetic resonance spectroscopy (MRS).

Methods

In total, 11 patients with major depression or depressive episode of bipolar disorder (mean pre-ECT Ham-17 of 26) and 11 healthy subjects were recruited. GABA was quantified using short-TE MRS in prefrontal and occipital cortex. Other neurometabolites such as glutathione (GSH), N-acetylaspartate (NAA) and glutamate (Glu) were secondary outcome measures.

Results

No significant differences in GABA/Cr levels were observed between patients at baseline and healthy subjects in prefrontal cortex, t(20)=0.089, p=0.93 or occipital cortex t(21)=0.37, p=0.72. All patients improved on Ham-17 (mean post-ECT Ham-17 of 9). No significant difference was found in GABA, Glu, glutamine, choline or GSH between pre- and post-ECT values. However, we observed a significant decrease in NAA levels following ECT t(22)=3.89, p=0.0038, and a significant correlation between the NAA decline and the number of ECT sessions p=0.035.

Conclusions

Our study does not support prior studies arguing for GABA as a key factor in the treatment effect of ECT on major depression. The reduction in NAA levels following ECT could be due to neuronal loss or a transient dysfunction in prefrontal cortex. As no long-term follow-up scan was performed, it is unknown whether NAA levels will normalise over time.

Type
Original Article
Copyright
© Scandinavian College of Neuropsychopharmacology 2018 

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References

1. Brambilla, P, Perez, J, Barale, F, Schettini, G Soares, JC (2003) GABAergic dysfunction in mood disorders. Mol Psychiatry 715, 721737.Google Scholar
2. Luscher, B Fuchs, T (2015) GABAergic control of depression-related brain states. Adv Pharmacol 73, 97144.Google Scholar
3. Pehrson, AL Sanchez, C (2015) Altered gamma-aminobutyric acid neurotransmission in major depressive disorder: a critical review of the supporting evidence and the influence of serotonergic antidepressants. Drug Des Devel Ther 9, 603624.Google Scholar
4. Luscher, B, Shen, Q Sahir, N (2011) The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry 16, 383406.Google Scholar
5. Sanacora, G, Mason, GF, Rothman, DL, Hyder, F, Ciarcia, JJ, Ostroff, RB, Berman, RM Krystal, JH (2011) Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Arch Gen Psychiatry 56, 10431047.Google Scholar
6. Esel, E, Kose, K Hacimusalar, Y , Ozsoy S, Kula M, Candan Z and Turan T (2008) The effects of electroconvulsive therapy on GABAergic function in major depressive patients. J ECT 24, 224228.Google Scholar
7. Gold, BI, Bowers, MB Jr, Roth, RH Sweeney, DW (1980) GABA levels in CSF of patients with psychiatric disorders. Am J Psychiatry 137, 362364.Google Scholar
8. Bhagwagar, Z, Wylezinska, M, Taylor, M, Jezzard, P, Matthews, PM Cowen, PJ (2004) Increased brain GABA concentrations following acute administration of a selective serotonin reuptake inhibitor. Am J Psychiatry 161, 368370.Google Scholar
9. Sanacora, G, Mason, GF, Rothman, DL Krystal, JH (2002) Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors. Am J Psychiatry 159, 663665.Google Scholar
10. Bolwig, TG (2014) Neuroimaging and electroconvulsive therapy: a review. J ECT 30, 138142.Google Scholar
11. Sanacora, G, Mason, GF, Rothman, DL, Hyder, F, Ciarcia, JJ, Ostroff, RB, Berman, RM Krystal, JH (2003) Increased cortical GABA concentrations in depressed patients receiving ECT. Am J Psychiatry 160, 577579.Google Scholar
12. Near, J, Ho, YC, Sandberg, K, Kumaragamage, C Blicher, JU (2014) Long-term reproducibility of GABA magnetic resonance spectroscopy. Neuroimage 99, 191196.Google Scholar
13. Bertholdo, D, Watcharakorn, A Castillo, M (2013) Brain proton magnetic resonance spectroscopy: introduction and overview. Neuroimaging Clin N Am 23, 359380.Google Scholar
14. Godlewska, BR, Near, J Cowen, PJ (2015) Neurochemistry of major depression: a study using magnetic resonance spectroscopy. Psychopharmacology 232, 501507.Google Scholar
15. Sanacora, G, Gueorguieva, R, Epperson, CN, Wu, YT, Appel, M, Rothman, DL, Krystal, JH Mason, GF (2004) Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry 61, 705713.Google Scholar
16. Bhagwagar, Z, Wylezinska, M, Jezzard, P, Evans, J, Ashworth, F, Sule, A, Matthews, PM Cowen, PJ et al. (2007) Reduction in occipital cortex gamma-aminobutyric acid concentrations in medication-free recovered unipolar depressed and bipolar subjects. Biol Psychiatry 61, 806812.Google Scholar
17. Hasler, G, van der Veen, JW, Tumonis, T, Meyers, N, Shen, J Drevets, WC (2007) Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry 64, 193200.Google Scholar
18. Bhagwagar, Z, Wylezinska, M, Jezzard, P, Evans, J, Boorman, E Matthews, PM (2008) Low GABA concentrations in occipital cortex and anterior cingulate cortex in medication-free, recovered depressed patients. Int J Neuropsychopharmacol 11, 255260.Google Scholar
19. Price, RB, Shungu, DC, Mao, X, Kang, G, Cheema, R, Coplan, JD, Mathew, SJ Shungu, DC (2009) Amino acid neurotransmitters assessed by proton magnetic resonance spectroscopy: relationship to treatment resistance in major depressive disorder. Biol Psychiatry 65, 792800.Google Scholar
20. Lei, H, Xin, L, Gruetter, R Mlynarik, V (2014) Localized single-voxel magnetic resonance spectroscopy, water supression, and novel approaches for ultrashort echo-time measurements. In: Stagg CJ and Rothman D editors Magnetic resonance spectroscopy tools for neuroscience research and emerging clinical applications. Amsterdam: Elsevier, p. 15.Google Scholar
21. Cusin, C, Yang, H, Yeung, A Fava, M (2009) Rating scales for depression. In: Baer L and Blais MA editors Handbook of clinical rating scales and assessment in psychiatry and mental health, Current clinical psychiatry. New York: Humana Press, p. 2.Google Scholar
22. Gruetter, R Tkac, I (2000) Field mapping without reference scan using asymmetric echo-planar techniques. Magn Reson Med 43, 319324.Google Scholar
23. Simpson, R, Devenyi, GA, Jezzard, P, Hennessy, TJ Near, J (2015) Advanced processing and simulation of MRS data using the FID appliance (FID-A)-An open source, MATLAB-based toolkit. Magn Reson Med 77, 2333.Google Scholar
24. Provencher, S (2015) LCModel. Available at http://www.s-provencher.com/pages/lcm-manual.shtml. Accessed February 2014.Google Scholar
25. Kirkwood, BR Sterne, JA (2003) Essential medical statistics, 2nd edn. Malden, MA: John Wiley & Sons Ltd.Google Scholar
26. Hasler, G, Neumeister, A, van der Veen, JW , Tumonis T, Bain EE, Shen J, Drevets WC and Charney DS (2005) Normal prefrontal gamma-aminobutyric acid levels in remitted depressed subjects determined by proton magnetic resonance spectroscopy. Biol Psychiatry 58, 969973.Google Scholar
27. Nobler, MS, Oquendo, MA, Kegeles, LS , Malone KM, Campbell, CC, Sackeim HA and Mann JJ (2001) Decreased regional brain metabolism after ECT. Am J Psychiatry 158, 305308.Google Scholar
28. Ende, G, Braus, DF, Walter, S , Weber-Fahr W and Henn FA (2000) The hippocampus in patients treated with electroconvulsive therapy: a proton a proton magnetic resonance spectroscopic imaging study. Arch Gen Psychiatry 57, 937943.Google Scholar
29. de Graaf, RA ed. (2007) In vivo NMR spectroscopy, 2nd edn. Chichester, England: John Wiley & Sons Ltd.Google Scholar
30. Merkl, A, Schubert, F, Quante, A, Luborzewski A, Brakemeier EL, Grimm S, Heuser I and Bajbouj M (2011) Abnormal cingulate and prefrontal cortical neurochemistry in major depression after electroconvulsive therapy. Biol Psychiatry 69, 772779.Google Scholar
31. Michael, N, Erfurth, A, Ohrmann, P, Arolt V, Heindel W and Pfleiderer B (2003) Neurotrophic effects of electroconvulsive therapy: a proton magnetic resonance study of the left amygdalar region in patients with treatment-resistant depression. Neuropsychopharmacology 28, 720725.Google Scholar
32. Jorgensen, A, Magnusson, P, Hanson, LG, Kirkegaard T, Benveniste H, Lee H, Svarer C, Mikkelsen JD, Fink-Jensen A, Knudsen GM, Paulson OB, Bolwig TG and Jorgensen MB (2015) Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression. Acta Psychiatry Scand 133, 154.Google Scholar
33. Njau, S, Joshi, SH, Espinoza, R, Leaver AM, Vasavada M, Marquina A, Woods RP and Narr KL (2017) Neurochemical correlates of rapid treatment response to electroconvulsive therapy in patients with major depression. J Psychiatry Neurosci 42, 616.Google Scholar
34. Fava, M, McCall, WV, Krystal, A, Wessel, T, Rubens, R, Caron, J, Amato D and Roth T (2006) Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder. Biol Psychiatry 59, 10521060.Google Scholar