Antidepressant effects of esketamine are associated with functional connectivity in the hippocampal subregion: A resting state magnetic resonance study.

In 29 patients with major depressive disorder, six intravenous infusions of esketamine led to significant reductions in depression, anxiety, and suicidal ideation scores, along with improved cognitive scores. After two weeks, functional connectivity between the right caudal hippocampus and the left cerebellum, precuneus, and middle temporal gyrus increased. The connectivity between the right caudal hippocampus and left middle temporal gyrus negatively correlated with cognitive scores. The altered hippocampal connectivity may reflect esketamine's regulatory mechanism on depressive symptoms, involving the default network and cortico-cerebellar loop.

Study at a glance

Abstract

We aimed to investigate the relationship between changes in resting-state functional connectivity in a subregion of the hippocampus and the antidepressant effects of esketamine as well as to identify potential neuroimaging markers of the treatment outcomes. Twenty-nine patients with major depressive disorder (MDD) received six intravenous infusions of esketamine. All patients completed the Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Baker Suicide Ideation Scale (BSI), and Montreal Cognitive Assessment Scale (MoCA) to assess emotional and cognitive recovery after treatment. At the same time, all participants underwent magnetic resonance imaging using seed point functional connectivity analysis to divide the hippocampus into two subregions (rostral hippocampus (rHipp) and caudal hippocampus (cHipp)). We found that 29 patients with MDD responded favorably to esketamine, with significant reductions in HAMA, HAMD, and BSI scores and significant increases in MoCA scores. After two weeks of treatment with esketamine, we found that the FC between the right cHipp and the left cerebellum_6, precuneus, and middle temporal gyrus (MTG) was significantly increased in patients with MDD. Correlation analysis showed that the FC values between the right cHipp subregion and the left MTG were negatively correlated with MoCA scores. The altered functional connectivity pattern in the hippocampal subregions in patients with MDD may be related to the regulatory mechanism of esketamine in improving depressive symptoms, mainly involving the default network and cortico-cerebellar loop. This study provides new insights into the antidepressant effects of esketamine and potential targets for the treatment of MDD.