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

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

Yale University, New Haven, CT

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

June 1999, for 3 years

Funding Amount:


Investigator Biographies

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

Associate Professor, Yale University




Cognitive deficits in some learning disability associated syndromes are the consequence of abnormalities in specific neural pathways. In velocardiofacial syndrome (VCFS), several major pathways in the posterior cortical regions seem to be affected, whereas reading disability (RD, dyslexia) specific deficits are related to a more selective involvement of pathways in the left perisylvian region.

To characterize patterns of white matter abnormality in children with velocardiofacial syndrome and reading disabilities, with and without attention deficit hyperactivity disorder (ADHD), through evaluations of white matter architecture as well as fiber bundle integrity by DTI-based fiber bundle direction (color-coded) maps and fiber tracking. To assess the neurobehavioral predictive value of DTI parameters in these children by correlating DTI findings with cognitive variables.

MRI protocol will consist of either a high (zero-filled to 1x1x3mm) or low (zero-filled to 1x1x5mm) resolution diffusion-weighted multishot EPI sequence and a T1- weighted anatomical scan. Post-processing (Stieltjes et al. 2001) will include steps to calculate apparent diffusion coefficients (ADC), coherence index, and fractional anisotropy (FA). DTI measures will be quantified for defined areas and tracking results, and will be correlated with behavioral data.

Our preliminary studies in dyslexia indicate that disruptions of white matter integrity and fiber bundle organization in the perisylvian region may underlie reading disability. Specifically, we observed decreased FA in the left superior longitudinal fasciculus (SLF), a major pathway connecting language-relevant areas of the cortex, as well as changes in the SLF’s orientation in the right hemisphere. Both parameters were directly related to reading ability, with greater tract abnormality being associated with poorer reading performance.

Selected Publications

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.