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Quetiapine Extended Release Open-Label Treatment Associated Changes in Amygdala Activation and Connectivity in Anxious Depression: An fMRI Study

Altinay, Murat MD; Karne, Harish MS; Beall, Erik PhD; Anand, Amit MD

Journal of Clinical Psychopharmacology: December 2016 - Volume 36 - Issue 6 - p 562–571
doi: 10.1097/JCP.0000000000000600
Original Contributions

Background This study investigated extended release quetiapine (quetiapine XR) associated changes in functional MRI (fMRI) measures of task-induced amygdalar activation and resting state connectivity in anxious unipolar major depressive disorder (AMDD).

Methods Anxious unipolar major depressive disorder patients (n = 15) (17-item Hamilton Depression Rating Scale (HAM-D) >18 and Hamilton Anxiety Scale (HAM-A) >18) and closely matched healthy control (HC) subjects were compared at baseline for task induced amygdala activation and resting state connectivity on fMRI. Subsequently, AMDD patients were treated for 8 weeks with open-label quetiapine XR. Weekly HAM-D and HAM-A ratings were obtained, and the fMRI scan was repeated at weeks 2 and 8. Changes in fMRI measures were calculated using repeated-measures analysis of variance and correlation with decrease in HAM-D and HAM-A scores was examined.

Results At baseline, AMDD compared with HC exhibited increased task-induced left amygdalar activation (P = 0.05 clusterwise corrected) and decreased resting state amygdala-cortical and amygdala-pons connectivity (P < 0.05 clusterwise corrected). Quetiapine XR treatment was associated with significant decrease in HAM-D (df = 1,28; female [F] = 39; P = 0.001) and HAM-A scores (df = 1,28; F = 55; P = 0.001). The AMDD group showed increased amygdala-cortical connectivity (P < 0.05 [clusterwise corrected]) at week 2, which was maintained at week 8. At week 8, additional areas showed increased connectivity including insula and putamen. At 8 weeks, decrease in HAM-D scores correlated with increase in amygdala-mid cingulate and amygdala-cuneus connectivity (P = 0.05 [clusterwise corrected]). Decrease in HAM-A scores correlated with increase in amygdala-cuneus and parietal cortex connectivity (P = 0.05 [clusterwise corrected]).

Limitations Small sample-size, open-label single-arm design, HC only tested at baseline, focused only on amygdala.

Conclusions Quetiapine XR effects in the treatment of AMDD are associated with modulation of amygdala connectivity.

Supplemental digital content is available in the text.

From the Center for Behavioral Health, Cleveland Clinic Foundation, Cleveland, OH.

Received October 2, 2015; accepted after revision September 6, 2016.

Reprints: Amit Anand, MD, Cleveland Clinic Foundation, 9500 Euclid Avenue, P-57 Mailbox, Cleveland, OH 44195 (e-mail:

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