According to new research published in the Journal of Affective Disorders.
“As the antidepressant effects of ketamine in patients with anxious depression remain unclear, it is imperative to investigate the potential biomarkers predicting the antidepressant efficacy of ketamine in patients with anxious depression,” said study author Bin Zhang of the Affiliated Brain Hospital of the Guangzhou Medical University. .
“Previous studies have shown that functional connectivity differences in the amygdala are associated with improvement in depression following ketamine treatment in depressed patients, but their role in anxious depressed patients is uncertain. Therefore, we investigated the correlation between improvement in depression after ketamine treatment and functional connectivity of the amygdala 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 with no comorbid psychotic symptoms, a score of more than 17 on the Hamilton Depression Rating Scale, who had previously failed to improve after taking at least two antidepressants, fMRI brain scans, and taking six ketamine infusions.
Of patients with anxious depression, approximately 60% (20 patients) showed clinically significant reductions in depression symptoms after their sixth ketamine infusion. The remaining 11 patients with anxious depression were classified as non-responders.
The researchers found that those who responded to treatment, prior to the ketamine infusions, had greater functional connectivity between the left laterobasal amygdala and the left precuneus compared to non-responders. In addition, connectivity between the two brain regions was significantly reduced after treatment among responders.
Patients with anxious depression also tended to have reduced connectivity between the right centriomedial amgydala and right middle temporal gyrus compared to patients with non-anxiety depression, predicting treatment response.
“Corresponding to the critical role of the amygdala in emotion regulation, especially in negative emotion, our study showed that the functional connectivity of the amygdala is associated with improvement from depression to ketamine infusions in patients with anxious depression,” Zhang told PsyPost.
“The most surprising finding of the present study was that the baseline hyperconnectivity of the amygdala precuneus found in responders relative to non-responders was significantly reduced at day 13 compared to baseline after six ketamine infusions. It may point to a possible neural underpinning through which ketamine exerts its antidepressant effect in patients with anxious depression.”
The results provide new insights into the mechanisms underlying ketamine’s antidepressant effects. 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.
“While the findings in our study may suggest that the functional connectivity of the amygdala is a significant predictor of treatment response to ketamine infusions in patients with anxious depression, further validation is required,” Zhang said. “In addition, further studies exploring ketamine’s potential antidepressant mechanisms may aid in the treatment of patients with anxious depression.”
The study, “Functional Connectivity Differences in the Amygdala Are Related to the Antidepressant Efficacy of Ketamine in Patients with Anxious Depression,” is authored by Shiqi Yuan, Xin Luo, Xiaoyu Chen, Mingqia Wang, Yiru Hu, Yanling Zhou, Yuping Ning, and Bin Zhang.