Depressive disorders

Over the past decade, researcher at Yale MRRC have found that the concentration of the inhibitory neurotransmitter GABA was reduced in the brains of many patients with epilepsy, using measurements made with ¹H MRS. Then, the investigators found that effective treatments increased the concentration of GABA in those patients.

In the department of Psychiatry, Drs. John Krystal and Gerard Sanacora were interested in the effects of electroconvulsive therapy (ECT) on patients who suffered from major depressive disorder. Because ECT is based on electrically induced seizures in the brain, there was common ground with the epilepsy studies, and they brought patients for GABA scans. The result was surprising: the depressed patients had low brain GABA concentrations before their course of ECT-induced seizures, and what we have found since is that the ECT actually increases the concentration of GABA in the brain.

Since those first studies, we have found that GABA levels depend on a wide variety of parameters, including menstrual cycle (collaboration with Dr. C. Neill Epperson), the presence of anxiety disorder (collaboration with Dr. Andrew Goddard), and the subtype of depression that a patient has.

¹H MRS has been useful for providing concentrations of neurochemicals in psychiatric disorders, and based on those results, we have been able to make hypotheses about reasons for the changes that we see. For further investigation, we are turning to ¹³C MRS.

¹³C MRS lets us detect a naturally occurring, non-radioactive isotope of carbon called carbon-13, or ¹³C. Only 1% of naturally occurring carbon is ¹³C, so there is normally very little signal in the brain. When we inject a ¹³C-labeled substance like glucose (a natural sugar) into the blood, the brain uses it and makes ¹³C-labeled products. With ¹³C MRS we can observe the appearance of these products in the brain and measure rates of metabolism and neurochemicals release by the brain. We are currently using these techniques to investigate why the concentration of GABA is reduced in depressed subjects, and it appears that GABA is made more slowly in people who are depressed.

Researchers :
Graeme F. Mason
John Krystal
Gerard Sanacora
Michael Appel
Douglas L. Rothman
Ognen A. C. Petroff