Proton Magnetic Resonance Spectroscopy Studies of ECT Effects on Cortical GABA Concentrations in Major Depression

Gerard Sanacora, M.D., Ph.D.

Yale University

Funded in June, 1999: $100000 for 3 years
LAY SUMMARY . BIOGRAPHY . HYPOTHESIS . SELECTED PUBLICATIONS .

INVESTIGATOR BIOGRAPHIES

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Gerard Sanacora, M.D., Ph.D.

Associate Professor
Yale University

HYPOTHESIS

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Hypothesis: 
GABAergic deficits, as reflected by decreased cortical GABA concentrations, are associated with major depressive illness. Electroconvulsive therapy (ECT), which is believed to increase GABAergic tone, appears to increase cortical GABA levels. The researchers thus propose that the elevated cortical GABA levels resulting from ECT are associated with the clinical benefit of the treatment modality.

Goals: 
The goal of this project is to define the relationship between cortical GABA concentrations, major depressive illness, and the clinical efficacy of ECT. In order to achieve this, the researchers will use non-invasive in vivo proton magnetic resonance spectroscopy (1H-MRS) to determine GABA concentrations in the frontal and occipital cortex of depressed individuals, at several time points during a course of ECT. They will also collect measures reflecting the severity of depression in all patients during the course of treatment. This information will allow the researchers to determine if ECT effects on the GABAergic system are related to the clinical efficacy.

Methods: 
To specifically determine if cortical GABA concentrations are elevated by a course of ECT, the researchers employed proton magnetic resonance spectroscopy (1H-MRS) methods described by Rothman et al. [Rothman, 1993 #89]. Using a 2.1 Oxford Magnet with a 1-m bore, equipped with a Bruker Avance spectrometer (Bruker Instruments, Billerica MA), the researchers measured occipital cortex GABA concentrations in depressed patients before and after a course of ECT. Eight patients with major depressive disorder that were referred for ECT treatment, were invited to participate in the study after providing written informed consent. All subjects had an initial pre-ECT 1H-MRS study after completing a two-week period free of psychotropic medications. A second 1H-MRS study was obtained following completion of the initial index course of ECT treatment (1-14 days after last treatment).

SELECTED PUBLICATIONS

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Sanacora G., Gueorguieva R., Epperson C.N., Wu Y.T., Appel M., Rothman D.L., Krystal J.H., and Mason G.F.  Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression.  Arch Gen Psychiatry. 2004 Jul;61(7):705-13.

Sanacora G., Mason G.F., Rothman D.L., Hyder F., Ciarcia J.J., Ostroff R.B., Berman R.M., and Krystal J.H.  Increased cortical GABA concentrations in depressed patients receiving ECT.   Am J Psychiatry. 2003 Mar;160(3):577-9

Chen A.C-H., Shin K-H., Duman R.S., and Sanacora G.  ECS-induced mossy fiber sprouting and BDNF expression are attenuated by ketamine pretreatment.  J ECT. 2001 Mar;17(1):27-32.

Sanacora G., Mason G.F., and Krystal J.H. Impairment of GABAergic transmission in depression: New insights from neuroimaging studies. Crit Rev Neurobiol. 2000;14(1):23-45.