Functional connectivity between the amygdala and subgenual cingulate gyrus predicts the antidepressant effects of ketamine in patients with treatment‐resistant depression

• Published in: Neuropsychopharmacology reports Vol. 41; no. 2; pp. 168 - 178
• Main Authors: Nakamura, Tomoyuki, Tomita, Masaru, Horikawa, Naoki, Ishibashi, Masatoshi, Uematsu, Ken, Hiraki, Teruyuki, Abe, Toshi, Uchimura, Naohisa
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.06.2021; John Wiley and Sons Inc; Wiley
• Subjects: Amygdala - diagnostic imaging; Antidepressants; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Decomposition; Depression; Depressive Disorder, Major - diagnostic imaging; Depressive Disorder, Major - drug therapy; functional connectivity; Gyrus Cinguli - diagnostic imaging; Humans; Ketamine; Ketamine - pharmacology; Ketamine - therapeutic use; Magnetic resonance imaging; Medical imaging; Mental depression; Original; Pathophysiology; Psychotropic drugs; resting‐state functional MRI; Software; treatment response prediction; treatment‐resistant depression; treatment-resistant depression; functional connectivity; ketamine; resting-state functional MRI; treatment response prediction
• ISSN: 2574-173X; 2574-173X
• DOI: 10.1002/npr2.12165

Aim Approximately one‐third of patients with major depressive disorder develop treatment‐resistant depression. One‐third of patients with treatment‐resistant depression demonstrate resistance to ketamine, which is a novel antidepressant effective for this disorder. The objective of this study was to examine the utility of resting‐state functional magnetic resonance imaging for the prediction of treatment response to ketamine in treatment‐resistant depression. Methods An exploratory seed‐based resting‐state functional magnetic resonance imaging analysis was performed to examine baseline resting‐state functional connectivity differences between ketamine responders and nonresponders before treatment with multiple intravenous ketamine infusions. Results Fifteen patients with treatment‐resistant depression received multiple intravenous subanesthetic (0.5 mg/kg/40 minutes) ketamine infusions, and nine were identified as responders. The exploratory resting‐state functional magnetic resonance imaging analysis identified a cluster of significant baseline resting‐state functional connectivity differences associating ketamine response between the amygdala and subgenual anterior cingulate gyrus in the right hemisphere. Using anatomical region of interest analysis of the resting‐state functional connectivity, ketamine response was predicted with 88.9% sensitivity and 100% specificity. The resting‐state functional connectivity of significant group differences between responders and nonresponders retained throughout the treatment were considered a trait‐like feature of heterogeneity in treatment‐resistant depression. Conclusion This study suggests the possible clinical utility of resting‐state functional magnetic resonance imaging for predicting the antidepressant effects of ketamine in treatment‐resistant depression patients and implicated resting‐state functional connectivity alterations to determine the trait‐like pathophysiology underlying treatment response heterogeneity in treatment‐resistant depression. This study illustrates that the alteration in the RSFC within the right AN in TRD patients reflects the antidepressant response to ketamine at baseline. The alteration remained throughout the 2‐week treatment with multiple ketamine infusions and seemed to reflect the trait‐like features underlying treatment heterogeneity in TRD. By employing an anatomical ROI of the sc/sgACC, the present study also suggests the possible clinical utility of the rsfMRI to predict the treatment response to ketamine in TRD patients.