Voxel-wise meta-analyses of brain blood flow and local synchrony abnormalities in medication-free patients with major depressive disorder

Voxel-wise meta-analyses of brain blood flow and local synchrony abnormalities in medication-free patients with major depressive disorder

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J Psychiatry Neurosci 2015;40(6):401-11

Zi-Qi Chen, MD*; Ming-Ying Du, MD*; You-Jin Zhao, MD; Xiao-Qi Huang, MD, PhD; Jing Li, MD; Su Lui, MD, PhD; Jun-Mei Hu, MD; Huai-Qiang Sun, PhD; Jia Liu, MD; Graham J. Kemp, MA, DM; Qi-Yong Gong, MD, PhD

Abstract

Background: Published meta-analyses of resting-state regional cerebral blood flow (rCBF) studies of major depressive disorder (MDD) have included patients receiving antidepressants, which might affect brain activity and thus bias the results. To our knowledge, no meta-analysis has investigated regional homogeneity changes in medication-free patients with MDD. Moreover, an association between regional homogeneity and rCBF has been demonstrated in some brain regions in healthy controls. We sought to explore to what extent resting-state rCBF and regional homogeneity changes co-occur in the depressed brain without the potential confound of medication.

Methods: Using the effect-size signed differential mapping method, we conducted 2 meta-analyses of rCBF and regional homogeneity studies of medication-free patients with MDD.

Results: Our systematic search identified 14 rCBF studies and 9 regional homogeneity studies. We identified conjoint decreases in resting-state rCBF and regional homogeneity in the insula and superior temporal gyrus in medication-free patients with MDD compared with controls. Other changes included altered resting-state rCBF in the precuneus and in the frontal–limbic–thalamic–striatal neural circuit as well as altered regional homogeneity in the uncus and parahippocampal gyrus. Meta-regression revealed that the percentage of female patients with MDD was negatively associated with resting-state rCBF in the right anterior cingulate cortex and that the age of patients with MDD was negatively associated with rCBF in the left insula and with regional homogeneity in the left uncus.

Limitations: The analysis techniques, patient characteristics and clinical variables of the included studies were heterogeneous.

Conclusion: The conjoint alterations of rCBF and regional homogeneity in the insula and superior temporal gyrus may be core neuropathological changes in medication-free patients with MDD and serve as a specific region of interest for further studies on MDD.


*These authors contributed equally to this work.

Submitted May 6, 2014; Revised Sept. 23, 2014; Accepted Dec. 6, 2014; Early-released Apr. 8, 2015.

Acknowledgments: This study was supported by the National Natural Science Foundation (grants # 81227002 and 81220108013) and Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT, grant # IRT1272) of China. Q. Gong acknowledges support from his Changjiang Scholar Professorship Award (#T2014190) of China and the CMB Distinguished Professorship Award (# F510000/G16916411) administered by the Institute of International Education, USA.

Affiliations: Huaxi MR Research Center, Department of Radiology, West China Hospital of Sichuan University, Chengdu, China (Chen, Du, Zhao, Huang, Lui, Sun, Liu, Gong); Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, China (Li, Hu); Magnetic Resonance and Image Analysis Research Centre and Institute of Ageing and Chronic Disease, University of Liverpool, United Kingdom (Kemp).

Competing interests: None declared.

Contributors: Z. Chen, M. Du and Q. Gong designed the study. Z. Chen, M. Du, Y. Zhao, J. Li and S. Lui acquired the data, which Z. Chen, M. Du, X. Huang, J. Hu, H. Sun, J. Liu, G. Kemp and Q. Gong analyzed. Z. Chen and M. Du wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.140119

Correspondence to: Q.Y. Gong, Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, No. 37 GuoXue Xiang, Chengdu, China; qiyonggong@hmrrc.org.cn