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Tuesday, August 14, 2007

Brain perfusion and electroconvulsive therapy (ECT)

Hypoperfusion of parts of the brain in depressive disorder largely normalizes after response to antidepressants. Perfusion changes after response to electroconvulsive therapy (ECT) follows a different course. This interesting conclusion is recently published in the Journal of Nuclear Medicine. The design of this study delivers interesting results besides those already mentioned.

First they compared healthy controls with depressed patients without medication for at least 2 weeks before undergoing SPECT. Single photon emission computed tomography (SPECT) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information. Usually the gamma-emitting tracer used in functional brain imaging is 99mTc-HMPAO (hexamethylpropylene amine oxime). 99mTc is a metastable nuclear isomer which emits gamma rays which can be detected by a gamma camera. When it is attached to HMPAO, this allows 99mTc to be taken up by brain tissue in a manner proportial to brain blood flow, in turn allowing brain blood flow to be assessed with the nuclear gamma camera. Because blood flow in the brain is tightly coupled to local brain metabolism and energy use, the 99mTc-HMPAO tracer (as well as the similar 99mTc-EC tracer) is used to assess brain metabolism regionally.

Compared with healthy controls depressed patients had a significant lower regional cerebral blood flow (rCBF) before treatment over the frontal lobes and the subcortical nuclei (amygdala, caudate, thalamus and hypothalamus).
The effect of antidepressants and ECT were compared with these baseline measures after treatment. Another SPECT was performed after 6 weeks of medication or completion of the ECT course.
For those patients who responded to antidepressants, a significant increase in rCBF was found in the right parietal lobe of depressed patients. No perfusion changes were found in non-responders. No perfusion differences were found between medication responders and controls. In other words, responders on antidepressants had regained normal cerebral blood flow comparable to normal controls.

In contrast, rCBF was still lower in ECT responders than in controls, in the same region as before treatment as well as in the occipital and cerebellar regions. Especially this last finding is of interest since previous studies used the cerebellum as reference region for data analysis assuming the cerebellum had nothing to do with depression. The cerebellum was not traditionally considered a major contributor to the neurocircuitry of mood regulation. This assumption has to be refuted, cerebellar dysfunction is known to have an impact on cognition and affect.
The fact that further reduction in rCBF in posterior brain regions occur after response to ECT could be a state phenomenon or a trait phenomenon. Long term studies are needed to document the course of rCBF changes.

This is the Talairach under-surface view showing the Prefrontal Inferior Orbital area at the top of the picture and the Temporal lobes in the middle of the picture. With Major Depression we see significant decreased blood flow to both of these areas of the Brain as is shown here.

Reduced perfusion to the frontotemporal cortex bilaterally.

99mTc-HMPAO SPECT Study of Cerebral Perfusion After Treatment with Medication and Electroconvulsive Therapy in Major Depression
Yoav Kohn,Nanette Freedman,Hava Lester,Yodphat Krausz,Roland Chisin,Bernard Lerer,and Omer Bonne.
J Nucl Med 2007;48:1273–1278.

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