Background
Multiple lines of evidence support a role for the glutamatergic system in the pathophysiology
of major depressive disorder (MDD). Ketamine, an N-methyl-D-aspartate antagonist, rapidly improves depressive symptoms in individuals
with treatment-resistant depression. The neural mechanisms underlying this effect
remain unknown.
Methods
In this preliminary study, 20 unmedicated participants with treatment-resistant MDD
underwent positron emission tomography to measure regional cerebral glucose metabolism
at baseline and following ketamine infusion (single dose of .5 mg/kg intravenous over 40 minutes). Metabolic data were compared between conditions using a combination of region-of-interest
and voxelwise analyses, and differences were correlated with the associated antidepressant
response.
Results
Whole-brain metabolism did not change significantly following ketamine. Regional metabolism
decreased significantly under ketamine in the habenula, insula, and ventrolateral
and dorsolateral prefrontal cortices of the right hemisphere. Metabolism increased
postketamine in bilateral occipital, right sensorimotor, left parahippocampal, and
left inferior parietal cortices. Improvement in depression ratings correlated directly
with change in metabolism in right superior and middle temporal gyri. Conversely,
clinical improvement correlated inversely with metabolic changes in right parahippocampal
gyrus and temporoparietal cortex.
Conclusions
Although preliminary, these results indicate that treatment-resistant MDD subjects
showed decreased metabolism in the right habenula and the extended medial and orbital
prefrontal networks in association with rapid antidepressant response to ketamine.
Conversely, metabolism increased in sensory association cortices, conceivably related
to the illusory phenomena sometimes experienced with ketamine. Further studies are
needed to elucidate how these functional anatomical changes relate to the molecular
mechanisms underlying ketamine’s rapid antidepressant effects.
Key Words
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Article info
Publication history
Published online: April 01, 2013
Accepted:
February 1,
2013
Received in revised form:
January 16,
2013
Received:
July 2,
2012
Footnotes
Authors CAZ and WCD contributed equally to this work.
Identification
Copyright
Published by Elsevier Inc.
