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The Rise and Fall of MRI Studies in Major Depressive Disorder

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The Rise and Fall of MRI Studies in Major Depressive Disorder Zhuo et al. Translational Psychiatry (2019) 9:335 https://doi.org/10.1038/s41398-019-0680-6 Translational Psychiatry REVIEW ARTICLE Open Access The rise and fall of MRI studies in major depressive disorder Chuanjun Zhuo 1,2,3,4,5,6,7,8, Gongying Li2, Xiaodong Lin3, Deguo Jiang3,YongXu 4,5, Hongjun Tian6, Wenqiang Wang7 and Xueqin Song1 Abstract Structural and functional brain alterations are common in patients with major depressive disorder (MDD). In this review, we assessed the recent literature (1995–2018) on the structural and functional magnetic resonance imaging (MRI) studies of MDD. Despite the growing number of MRI studies on MDD, reverse inference is not possible as MRI scans cannot be used to aid in the diagnosis or treatment planning of patients with MDD. Hence, researchers must develop “bridges” to overcome the reverse inference fallacy in order to build effective tools for MDD diagnostics. From our findings, we proposed that the “bridges” may be built using multidisciplinary technologies, such as artificial intelligence, multimodality imaging, and nanotheranostics, allowing for the further study of MDD at the biological level. In return, the “bridges” will aid in the development of future diagnostics for MDD and other mental disorders. Introduction (CNS) disorders, endocrine disorders, infectious diseases, During the last three decades, magnetic resonance and sleep disorders, which further complicates the timely 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; imaging (MRI) has played a critical role in deciphering the diagnosis of MDD in the clinic. pathogenesis of major depressive disorder (MDD)1. MDD Currently, the diagnosis of MDD is based on behavioral is a mood disorder lasting six months or longer that is observations and patient-reported symptoms, in associa- characterized by feelings of persistent sadness or dimin- tion with the Hamilton Scale for Depression and DSM-V ished interest in daily activities. MDD is one of the most criteria2. There are no molecular or imaging biomarkers commonly diagnosed mental disorder in most first world widely accepted for the assessment of clinical depression. countries, including Europe, China, and the United States. However, researchers have used diagnostic imaging Due to the similarities between the symptoms of MDD techniques to study the core aspects of MDD over the and other mental disorders, such as schizophrenia and past thirty years, primarily focusing on structural and bipolar disorder, the differentiation between the condi- functional brain alterations3. Specifically, MRI has played tions can be difficult and often requires highly-trained an important role in uncovering the etiology and patho- psychiatrists. However, the timely diagnosis and treat- genesis of depression, schizophrenia, and other psychia- ment of patients with MDD is of critical importance. tric disorders. Depressive-like symptoms can also be associated with The majority of findings from structural and functional non-psychiatric disorders, such as central nervous system MRI (fMRI) studies have shown excellent potential as reliable indexes to aid in the diagnosis and treatment planning of MDD. However, to the best of our knowledge, Correspondence: Chuanjun Zhuo ([email protected])or there has been minimal translation of these important Xueqin Song ([email protected]) 1Department of Psychiatry, The First Affiliated Hospital of Zhengzhou findings into the clinic. For this reason, there is an urgent University, 450000 Zhengzhou, China need for a comprehensive review article summarizing 2 Department of Psychiatry Pattern Recognition, Department of Genetics previous findings from MRI studies to explore the Laboratory of Schizophrenia, School of Mental Health, Jining Medical University, 272119 Jining, China Full list of author information is available at the end of the article. © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a linktotheCreativeCommons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Zhuo et al. Translational Psychiatry (2019) 9:335 Page 2 of 14 possible indexes that may aid in the diagnosis and treat- affected by different diseases. Structural brain alterations ment planning of MDD. have been associated with MDD and many other neuro- A critical barrier to the clinical translation of many findings logical disorders. Some structural alterations are involved is the reverse inference fallacy. While forward inference in the etiology of a disease, while others may result from allows for the identification of brain activity or regions the disease. associated with specific experimental conditions, reverse Despite the growing number of MRI studies in MDD, inference attempts to uncover the specificcognitivepro- the clinical impact of these findings has been hindered, in cesses or behaviors that may be associated with specific part, by the heterogeneity of findings, which may include structural or functional brain alteration. However, reasoning both imaging- and study-related differences. For example, backward from brain activity is problematic as neurological imaging-related factors that commonly differ between disorders are multifaceted and can be influenced by many studies include scanner strength, slice thickness, imaging other factors, such as concurrent diseases, disease history, sequences, and image post-processing procedures. In and artifacts. Hence, it is unlikely that a single alteration or terms of study-related differences, group-specificdefini- biomarker will ever be identified for the detection or treat- tions of healthy controls, disease classification (e.g., ment planning of MDD or other psychiatric disorders. chronic vs. acute), and statistical methods can also vary In this review, our team has summarized the recent between studies and can strongly impact the conclusions. literature (1995–2018) on the utilization of MRI for the In return, it can be challenging to compare the findings diagnosis and treatment planning of MDD. The first from different MRI studies in the literature. Despite these section focuses on structural MRI and examines the limitations, many important findings from the past thirty common and distinct structural brain alterations asso- years of studies have supported the development of ciated with MDD, the consistency of structural brain diagnostics and treatments still in use in the clinic today. alterations between first-episode and chronic MDD, the structural brain network alterations associated with Structural brain alterations associated with MDD MDD, and the effects of antidepressants on these findings. Structural MRI is used to assess anatomical alterations The second section focuses on fMRI and examines the in the brain, which are commonly denoted as volume common and distinct functional brain alterations asso- differences. The common and distinct structural brain ciated with MDD, the consistency of functional brain alterations associated with MDD are shown in Table 1. alterations between first-episode and chronic MDD, the Many of the structural alterations associated with MDD functional brain network alterations associated with are also associated with other psychiatric disorders. MDD, and the effects of antidepressants on these findings. While changes in total brain volumes and whole gray Lastly, we discuss the advent and implementation of matter volumes have been described in patients with potential research “bridges” to advance the study of MRI MDD, these findings have been deemed insignificant in MDD and other psychiatric disorders. when compared with the general healthy population2. Similar to many other psychiatric disorders, MDD has Literature search been commonly associated with ventricular alterations. The Web of Science database was searched using the The first study that detected lateral ventricular enlarge- following terms: MRI, structural MRI, functional MRI, ment in patients with MDD was conducted at the Uni- depression, major depressive disorder, first-episode versity of Nebraska Medical Center in 19833. However, depression, chronic depression, and others as deemed these early studies that found ventricular alterations in necessary. The inclusion criteria were: (1) articles pub- MDD employed computed tomography (CT) as MRI was lished since 1995, and (2) articles published in journals a relatively new technology not widely accessible at that with an impact factor greater than 4. The exclusion cri- time. Recently, ventricular enlargement was assessed in a teria included: (1) articles not published in English, (2) meta-analysis conducted by Kempton and colleagues4.In articles published before 1995, (3) studies that lacked patients with MDD, MRI revealed lateral ventricular healthy control groups, (4) articles with missing human enlargement, along with increased cerebrospinal fluid study approval information, and (5) articles
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