Amygdala connectivity predicts response to ketamine treatment among patients with anxious depression
A brain region known as the amygdala may play a key role in predicting improvement in symptoms after ketamine therapy in patients with treatment-resistant anxious 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 of the Affiliated Brain Hospital of Guangzhou Medical University. .
“Previous studies have indicated that differences in amygdala functional connectivity 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 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 included only 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 previously failed to improve after at least two antidepressant treatments, had completed an fMRI brain scan, and had undergone six infusions ketamine.
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 anxiety depression were classified as non-responders.
The researchers found that, prior to the ketamine infusion, responders had greater functional connectivity between the left laterobasal amygdala and left precuneus compared to nonresponders. 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 centriomedial amygdala and right middle temporal gyrus compared to non-anxious-depressed patients, which predicted treatment response.
“Consistent with the amygdala’s key role in emotion regulation, especially negative emotions, our study showed that functional connectivity of the amygdala was associated with improvement in depression with ketamine infusions in patients with anxious depression,” Zhang told PsyPost.
“The most surprising finding of the current study is that the baseline amygdala-precuneus hyperconnectivity found in responders versus nonresponders was significantly reduced at day 13 compared to baseline after six ketamine infusions. This may indicate a potential neural basis by which ketamine exerts its antidepressant effect in patients with anxious depression.”
The results provide new insights into the mechanisms underlying the antidepressant effects of ketamine. But as with any study, the new research comes with limitations. The researchers noted that their sample size was relatively small. Future studies with larger samples should be conducted to confirm the findings.
“Although the findings in our study may suggest that amygdala functional connectivity is a significant predictor of response to ketamine infusion treatment in patients with anxious depression, 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, “Differences in functional connectivity of the amygdala are associated with the antidepressant efficacy of ketamine in patients with anxious depression“, authored by Shiqi Yuan, Xin Luo, Xiaoyu Chen, Mingqia Wang, Yiru Hu, Yanling Zhou, Yuping Ning and Bin Zhang.