Wenbin Li1, Du Lei2, Maxwell J Tallman2, Yuan Ai3, Jeffrey A Welge2, Thomas J Blom2, David E Fleck2, Christina C Klein2, Luis R Patino2, Jeffrey R Strawn2, Qiyong Gong4, Stephen M Strakowski5, John A Sweeney3, Caleb M Adler2, Melissa P DelBello2. 1. Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Ohio; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 2. Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Ohio. 3. Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Ohio. 4. Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, Sichuan, China; Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, Fujian Province, China. Electronic address: qiyonggong@hmrrc.org.cn. 5. Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Ohio; Dell Medical School, University of Texas at Austin, Texas.
Abstract
OBJECTIVE: Disruptions in cognition are a clinically significant feature of bipolar disorder (BD). The effects of different treatments on these deficits and the brain systems that support them remain to be established. METHOD: A continuous performance test was administered to 55 healthy controls and 71 acutely ill youths with mixed/manic BD to assess vigilance and working memory during task-based functional magnetic resonance imaging studies. Patients, who were untreated for at least 7 days at baseline, and controls were scanned at pretreatment baseline and at weeks 1 and 6. After baseline testing, patients (n = 71) were randomly assigned to 6-week double-blind treatment with lithium (n = 26; 1.0-1.2 mEq/L) or quetiapine (n = 45; 400-600 mg). Weighted seed-based connectivity (wSBC) was used to assess regional brain interactions during the attention task compared with the control condition. RESULTS: At baseline, youths with BD showed reduced connectivity between bilateral anterior cingulate cortex and both left ventral lateral prefrontal cortex and left insula and increased connectivity between left ventral lateral prefrontal cortex and left temporal pole, left orbital frontal cortex and right postcentral gyrus, and right amygdala and right occipital pole compared with controls. At 1-week follow-up, quetiapine, but not lithium, treatment led to a significant shift of connectivity patterns toward those of the controls. At week 6, compared with baseline, there was no difference between treatment conditions, at which time both patient groups showed significant normalization of brain connectivity toward that of controls. CONCLUSION: Functional alterations in several brain regions associated with cognitive processing and the integration of cognitive and affective processing were demonstrated in untreated youths with BD before treatment. Treatment reduced several of these alterations, with significant effects at week 1 only in the quetiapine treatment group. Normalization of functional connectivity might represent a promising biomarker for early target engagement in youth with BD. CLINICAL TRIAL REGISTRATION INFORMATION: Multimodal Neuroimaging of Treatment Effects in Adolescent Mania; https://clinicaltrials.gov/; NCT00893581. Published by Elsevier Inc.
OBJECTIVE: Disruptions in cognition are a clinically significant feature of bipolar disorder (BD). The effects of different treatments on these deficits and the brain systems that support them remain to be established. METHOD: A continuous performance test was administered to 55 healthy controls and 71 acutely ill youths with mixed/manic BD to assess vigilance and working memory during task-based functional magnetic resonance imaging studies. Patients, who were untreated for at least 7 days at baseline, and controls were scanned at pretreatment baseline and at weeks 1 and 6. After baseline testing, patients (n = 71) were randomly assigned to 6-week double-blind treatment with lithium (n = 26; 1.0-1.2 mEq/L) or quetiapine (n = 45; 400-600 mg). Weighted seed-based connectivity (wSBC) was used to assess regional brain interactions during the attention task compared with the control condition. RESULTS: At baseline, youths with BD showed reduced connectivity between bilateral anterior cingulate cortex and both left ventral lateral prefrontal cortex and left insula and increased connectivity between left ventral lateral prefrontal cortex and left temporal pole, left orbital frontal cortex and right postcentral gyrus, and right amygdala and right occipital pole compared with controls. At 1-week follow-up, quetiapine, but not lithium, treatment led to a significant shift of connectivity patterns toward those of the controls. At week 6, compared with baseline, there was no difference between treatment conditions, at which time both patient groups showed significant normalization of brain connectivity toward that of controls. CONCLUSION: Functional alterations in several brain regions associated with cognitive processing and the integration of cognitive and affective processing were demonstrated in untreated youths with BD before treatment. Treatment reduced several of these alterations, with significant effects at week 1 only in the quetiapine treatment group. Normalization of functional connectivity might represent a promising biomarker for early target engagement in youth with BD. CLINICAL TRIAL REGISTRATION INFORMATION: Multimodal Neuroimaging of Treatment Effects in Adolescent Mania; https://clinicaltrials.gov/; NCT00893581. Published by Elsevier Inc.
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