Amygdala connectivity predicts response to ketamine treatment among anxious depressed patients

A brain region known as the amygdala could play a key role in predicting symptom improvement after ketamine treatment in patients with treatment-resistant anxiety depression, according to new research published in Journal of Affective Disorders.

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

“Previous studies have indicated that functional connectivity differences 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 association between depression improvement after ketamine treatment and amygdala functional connectivity in anxious depressed patients.’

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

The researchers included only participants who had a diagnosis of major depression without comorbid psychotic symptoms, had a score greater than 17 on the Hamilton Depression Scale, had previously failed to improve after at least two antidepressant treatments, had completed fMRI brain scans, and had undergone six ketamine infusions.

Among patients with anxious depression, approximately 60% (20 patients) experienced clinically significant reductions in depressive symptoms after the sixth ketamine infusion. The remaining 11 patients with anxious depression were classified as non-responders.

The researchers found that, prior to the ketamine infusions, responders tended to have greater functional connectivity between the left lateral base of the amygdala and the left precum when compared to non-responders. Additionally, connectivity between the two brain regions was significantly reduced after treatment among responders.

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

“Consistent with the amygdala’s critical role in emotion regulation, especially negative emotion, our study showed that functional connectivity of the amygdala is associated with amelioration of depression in ketamine infusions in anxiety-depressed patients,” Zhang told PsyPost.

“The most surprising finding of the current study was that the basal amygdala-precuneus hyperconnectivity found in responders relative to nonresponders was significantly reduced at day 13 compared to baseline after six ketamine infusions. It may suggest a possible neural basis through which ketamine exerts its antidepressant effect in patients with anxiety depression.”

The results provide new insights into the mechanisms underlying ketamine’s antidepressant effect. But as with any study, the new research has limitations. The researchers noted that their sample size was relatively small. Future research with larger samples should be conducted to validate the findings.

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

The study, “Functional connectivity differences in the amygdala is associated with the antidepressant efficacy of ketamine in anxious depressed patients,” was authored by Shiqi Yuan, Xin Luo, Xiaoyu Chen, Mingqia Wang, Yiru Hu, Yanling Zhou, Yuping Ning, and Bin Zhang .

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