title: Quetiapine Extended Release Open-Label Treatment Associated Changes in Amygdala Activation and Connectivity in Anxious Depression: An fMRI Study.
abstract: 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]).
  
  
  CONCLUSIONS
  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.
authors: From the Center for Behavioral Health, Cleveland Clinic Foundation, Cleveland, OH.
authors: Murat
authors: M
authors: Altinay
authors: Harish
authors: H
authors: Karne
authors: Erik
authors: E
authors: Beall
authors: Amit
authors: A
authors: Anand
mesh_terms: D000328:Adult; D000359:Aftercare; D000679:Amygdala / Q000187:drug effects* / Q000503:physiopathology; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D015897:Comorbidity; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000187:drug effects* / Q000503:physiopathology; D000069348:Quetiapine Fumarate / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D000069348:Quetiapine Fumarate