Relationship between hippocampal volume and inflammatory markers following six infusions of ketamine in major depressive disorder

Abstract

BackgroundEvidences suggest that inflammatory marker-mediated neuroplasticity contributes critically to brain changes following antidepressant treatment. To date, no study has examined the relationship between changes in hippocampal volume, depressive symptoms, and inflammatory markers following repeated ketamine treatment. MethodsForty-four patients with major depressive disorder received six intravenous ketamine (0.5 mg/kg) infusions over 12 days. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to assess depressive symptoms, and peripheral blood was collected to test multiple cytokines and tryptophan (TRP) metabolites at baseline, 24 h and 14 days after the sixth infusion (day 13 and day 26). Magnetic resonance imaging (MRI) scans were carried out at baseline and day13, and FreeSurfer software was used to process the T1 images and analyze hippocampal volume. ResultsFollowing ketamine, a significant improvement in depressive symptoms, a small increase in right hippocampal volume and alterations in inflammatory markers was found. No significant association was found between changes in inflammatory markers and changes in hippocampal volume from baseline to day 13 (P>0.05), while a weak association was found between TRP metabolite changes and other cytokine changes from baseline to day 26 (beta=-0.357, t=−2.600, P = 0.013). LimitationsThe patients continued receiving previous medications during ketamine treatment, which may have impacted hippocampal volume and inflammatory markers. ConclusionsHippocampal volume increase following ketamine was an independent neurobiological effect that was not associated with changes in peripheral inflammatory markers, suggesting a likely complex neurobiological mechanism of the antidepressant effect of ketamine.