Amygdala connectivity predicts response to ketamine treatment in patients with anxious depression

A region of the brain known as the amygdala would, according to new research published in Journal of Affective Disorders.

“Since the antidepressant effects of ketamine in patients with anxiety depression remain unclear, it is necessary to explore potential biomarkers predicting the antidepressant efficacy of ketamine in patients with anxiety depression,” said study author Bin Zhang of the Affiliated Brain Hospital of Guangzhou Medical University. .

“Previous studies have shown that differences in functional connectivity in the amygdala are associated with improvement in depression after ketamine treatment in depressed patients, but their role in anxious depressed patients is uncertain. Therefore, we investigated the correlation between depression improvement after ketamine treatment and amygdala functional connectivity in patients with anxious depression.

For their study, the researchers examined neuroimaging data from 31 patients with anxious depression and 18 patients with non-anxious depression.

The researchers only included participants who had a diagnosis of major depression without comorbid psychotic symptoms, had a score greater than 17 on the Hamilton Depression Rating Scale, had not previously improved from at least two antidepressant therapies, had completed an fMRI brain scan, and had undergone six ketamine infusions.

Among patients with anxious depression, about 60% (20 patients) showed a clinically significant reduction in depressive symptoms after their sixth ketamine infusion. The remaining 11 patients with anxious depression were classified as non-responders.

The researchers found that before the ketamine infusions, responders tended to have greater functional connectivity between the left laterobasal amygdala and left precuneus compared to non-responders. In addition, connectivity between the two brain regions was significantly reduced after treatment in responders.

Anxious depressed patients also tended to have reduced connectivity between the right centriomedial amygdala and right middle temporal gyrus compared to nonanxious depressed patients, which predicted treatment response.

“Consistent with the amygdala’s key role in emotion regulation, especially in negative emotions, our study showed that functional connectivity of the amygdala is associated with improvement in depression upon ketamine infusions in anxious depressed patients,” Zhang told PsyPost.

“The most surprising finding of the current study was that the baseline amygdala-precuneus hyperconnectivity found in responders compared to non-responders was significantly reduced on day 13 compared to baseline after six ketamine infusions. It may point to a potential neural substrate by which ketamine exerts its antidepressant effect in patients with anxiety depression.”

The results provide new insight into the mechanisms underlying the antidepressant effects of ketamine. But like any study, the new research includes limitations. The researchers noted that their sample size was relatively small. Future research with larger samples should be conducted to verify the findings.

“Although the findings in our study may suggest that amygdala functional connectivity is a significant predictor of treatment response to ketamine infusions in patients with anxious depression, further validation is needed,” Zhang said. “Additionally, further studies investigating the potential antidepressant mechanisms of ketamine may help in the treatment of patients with anxious depression.”

“Differences in functional connectivity in the amygdala are related to the antidepressant efficacy of ketamine in patients with anxious depression,” by Shiqi Yuan, Xin Luo, Xiaoyu Chen, Mingqia Wang, Yiru Hu, Yanling Zhou, Yuping Ning, and Bin Zhang.

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