Ketamine Normalizes the Structural Alterations of Inferior Frontal Gyrus in Depression.

Background: Ketamine is a novel fast-acting antidepressant. Acute ketamine treatment can reverse microstructure deficits and normalize functional alterations in the brain, but little is known about the impacts of ketamine on brain volumes in individuals with depression.

Methods: We used 3 T magnetic resonance imaging (MRI) and tensorbased morphological methods to investigate the regional volume differences for 29 healthy control (HC) subjects and 21 subjects with major depressive disorder (MDD), including 10 subjects with comorbid post-traumatic stress disorder (PTSD). All the subjects participated in MRI scanning before and 24 h post intravenous ketamine infusion. The effects of acute ketamine administration on HC, MDD, and MDD/PTSD groups were examined separately by whole-brain voxel-wise t-tests.

Results: Our data showed smaller volume of inferior frontal gyrus (IFG, opercular part) in MDD and MDD/PTSD subjects compared to HC, and a significant correlation between opercular IFG volume and depressive severity in MDD subjects only. Ketamine administration normalized the structural alterations of opercular IFG in both MDD and MDD/PTSD groups, and significantly improved depressive and PTSD symptoms. Twenty-four hours after a single ketamine infusion, there were two clusters of voxels with volume changes in MDD subjects, including significantly increased volumes of opercular IFG. No significant structural alterations were found in the MDD/PTSD or HC groups.

Conclusion: These findings provide direct evidence that acute ketamine administration can normalize structural alterations associated with depression and highlight the importance of IFG in the guidance of future therapeutic targets.