Abstract

BackgroundAs one of the leading causes of global disability, major depressive disorder (MDD) places a noticeable burden on individuals and society. Despite the great expectation on finding accurate biomarkers and effective treatment targets of MDD, studies in applying functional magnetic resonance imaging (fMRI) are still faced with challenges, including the representational ambiguity, small sample size, low statistical power, relatively high false positive rates, etc. Thus, reviewing studies with solid methodology may help achieve a consensus on the pathology of MDD.MethodsIn this systematic review, we screened fMRI studies on MDD through strict criteria to focus on reliable studies with sufficient sample size, adequate control of head motion, and a proper multiple comparison control strategy.ResultsWe found consistent evidence regarding the dysfunction within and among the default mode network (DMN), the frontoparietal network (FPN), and other brain regions. However, controversy remains, probably due to the heterogeneity of participants and data processing strategies.ConclusionFuture studies are recommended to apply a comprehensive set of neuro‐behavioral measurements, consider the heterogeneity of MDD patients and other potentially confounding factors, apply surface‐based neuroscientific network fMRI approaches, and advance research transparency and open science by applying state‐of‐the‐art pipelines along with open data sharing.

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