Meta-analysis of cortical thickness abnormalities in medication-free patients with major depressive disorder

Qian Li,Jing Dai,Qiyong Gong,Ziqi Chen,Eduard Vieta,Jingyi Long,Su Lui,Xiaoqi Huang,Graham J Kemp,John A Sweeney,Youjin Zhao,Joaquim Radua,Fei Li

doi:10.1038/s41386-019-0563-9

Abstract

Alterations in cortical thickness have been identified in major depressive disorder (MDD), but findings have been variable and inconsistent. To date, no reliable tools have been available for the meta-analysis of surface-based morphometric (SBM) studies to effectively characterize what has been learned in previous studies, and drug treatments may have differentially impacted findings. We conducted a comprehensive meta-analysis of magnetic resonance imaging (MRI) studies that explored cortical thickness in medication-free patients with MDD, using a newly developed meta-analytic mask compatible with seed-based d mapping (SDM) meta-analytic software. We performed the meta-regression to explore the effects of demographics and clinical characteristics on variation in cortical thickness in MDD. Fifteen studies describing 529 patients and 586 healthy controls (HCs) were included. Medication-free patients with MDD, relative to HCs, showed a complex pattern of increased cortical thickness in some areas (posterior cingulate cortex, ventromedial prefrontal cortex, and anterior cingulate cortex) and decreased cortical thickness in others (gyrus rectus, orbital segment of the superior frontal gyrus, and middle temporal gyrus). Most findings in the whole sample analysis were confirmed in a meta-analysis of studies recruiting medication-naive patients. Using the new mask specifically developed for SBM studies, this SDM meta-analysis provides evidence for regional cortical thickness alterations in MDD, mainly involving increased cortical thickness in the default mode network and decreased cortical thickness in the orbitofrontal and temporal cortex.

Highlights

Major depressive disorder (MDD) is a major cause of disability and contributor to the global burden of disease affecting more than 300 million people worldwide [1, 2]
The minimum time off medication in the studies of patients off medication included in our current study was at least 1 week (1 week, 1 study; 2 weeks, 1 study; 1 month, 1 study; 6 weeks, 1 study; 2 months, 1 study; and 6 months, 1 study) according to the six studies that reported the duration of the medication-free period before scanning [10, 11, 14, 16, 18, 30]
We identified replicable increased cortical thickness in the default mode network (DMN) (PCC, ventromedial prefrontal cortex (vmPFC), and anterior cingulate cortex (ACC)), and decreased cortical thickness in orbitofrontal cortex (OFC) and temporal cortex in medication-free patients with major depressive disorder (MDD)

Summary

Introduction

Major depressive disorder (MDD) is a major cause of disability and contributor to the global burden of disease affecting more than 300 million people worldwide [1, 2]. Magnetic resonance imaging (MRI) research has a significantly advanced understanding of brain changes associated with depression [3]. Many advances in clinical brain imaging research in recent years have been made possible by improvements in the measurement of distinct aspects of brain anatomy and function. Advances in the measurement of cortical thickness, which reflects the size, arrangement, and density of neurons, nerve fibers and neuroglia, can be performed with minimal partial volume effects that complicate brain volume estimates [4]. Cortical thickness abnormalities can be especially sensitive to regional disease-specific effects, including both neuroinflammation and other factors that can increase cortical thickness, and decreases in cortical thickness resulting from factors such as exuberant synaptic pruning and other causes of neuropil reduction [4, 6]

Methods

Results

Discussion

Conclusion