The Papez Circuit in First-Episode, Treatment-Naive Adults with Major Depressive Disorder: Combined Atlas-Based Tract-Specific Quantification Analysis and Voxel-Based Analysis

PLOS ONE, Dec 2019

Previous findings suggest that the Papez Circuit may have a role in major depressive disorders. We used atlas-based tract-specific quantification analysis and voxel-based analysis to examine the integrity of white matter tracts involved in mood regulation (including tracts in the Papez Circuit). Diffusion tensor imaging acquired from 35 first-episode, treatment-naive adults with major depressive disorders and 34 healthy adult controls were compared. Our statistical approach compared structural integrity of 11 major white matter tracts between the major depressive disorder and adult controls, as well as illness duration influence in patients. Fractional anisotropy was decreased in the hippocampal cingulum and in the anterior thalamic radiation according to both analytical approaches, all of which were important tracts included in the Papez Circuit. Our results support the role of the Papez Circuit in major depressive disorders with the minimal probability of false positive due to similar findings in both analyses that have complementary advantages. Dysfunction of the Papez Circuit may be a potential marker for studying the pathogenesis of major depressive disorders.

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The Papez Circuit in First-Episode, Treatment-Naive Adults with Major Depressive Disorder: Combined Atlas-Based Tract-Specific Quantification Analysis and Voxel-Based Analysis

May The Papez Circuit in First-Episode, Treatment- Naive Adults with Major Depressive Disorder: Combined Atlas-Based Tract-Specific Quantification Analysis and Voxel-Based Analysis Wenyan Jiang 0 1 2 3 Gaolang Gong 0 1 2 3 Feng Wu 0 1 2 3 Lingtao Kong 0 1 2 3 Kaiyuan Chen 0 1 2 3 Wenhui Cui 0 1 2 3 Ling Ren 0 1 2 3 Guoguang Fan 0 1 2 3 Wenge Sun 0 1 2 3 Huan Ma 0 1 2 3 Ke Xu 0 1 2 3 Yanqing Tang 0 1 2 3 Fei Wang 0 1 2 3 0 Funding: This study was supported by the National Natural Science Foundation of China (81071099 and 81271499, Yanqing Tang), the Liaoning Science and Technology Foundation (2008225010-14, Yanqing Tang), National Institute of Health (K01MH086621, Fei Wang), the Liaoning Education Foundation (Pandeng Schoolar, Fei Wang), the National Alliance for Research on Schizophrenia and Depression (Fei Wang) and the Klingenstein Foundation (Fei Wang) 1 Data Availability Statement: All relevant data are within the paper 2 Academic Editor: Yu-Feng Zang, Hangzhou Normal University , CHINA 3 1 Department of Psychiatry, The First Affiliated Hospital, China Medical University , Shenyang 110001, Liaoning , PR China , 2 Department of Radiology, The First Affiliated Hospital, China Medical University , Shenyang 110001, Liaoning , PR China , 3 Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, United States of America, 4 Department of Radiology, The Liaoning Cancer Hospital & Institute , Shenyang 110042, Liaoning , PR China , 5 State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University , Beijing, 100875 , PR China Previous findings suggest that the Papez Circuit may have a role in major depressive disorders. We used atlas-based tract-specific quantification analysis and voxel-based analysis to examine the integrity of white matter tracts involved in mood regulation (including tracts in the Papez Circuit). Diffusion tensor imaging acquired from 35 first-episode, treatment-naive adults with major depressive disorders and 34 healthy adult controls were compared. Our statistical approach compared structural integrity of 11 major white matter tracts between the major depressive disorder and adult controls, as well as illness duration influence in patients. Fractional anisotropy was decreased in the hippocampal cingulum and in the anterior thalamic radiation according to both analytical approaches, all of which were important tracts included in the Papez Circuit. Our results support the role of the Papez Circuit in major depressive disorders with the minimal probability of false positive due to similar findings in both analyses that have complementary advantages. Dysfunction of the Papez Circuit may be a potential marker for studying the pathogenesis of major depressive disorders. - Major depressive disorder (MDD)a common disorder with a chronic and recurring pattern and a lifetime prevalence of 16.2% [1] is a leading cause of disability worldwide [2]. Magnetic resonance imaging (MRI) provides a noninvasive means to measure structural differences among individuals and has significantly advanced our understanding of the neuropathophysiology of MDD. Initial studies have chiefly focused on the use of structural magnetic resonance imaging The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: Co-author Gaolang Gong is a PLOS ONE Editorial Board member, and this does not alter the authors' adherence to PLOS ONE Editorial policies and criteria. (sMRI), but with the discovery of pulsed sequence measurements, such as functional MRI (fMRI) and diffusion tensor imaging (DTI), not only has regional dysregulation been discovered but also the disruption of a neural functional network has been identified [3], [4], [5]. The Papez circuit was postulated by James Papez to be like many other areas of the limbic system involved in emotion. Papez originally speculated that this comprised the anatomical substrate of emotional experience. As one of two major pathways into and out of the hippocampus (the other being the entorhinal cortex, via the cingulate cortex), the fornix connects to the hippocampus and the mammillary bodies of the hypothalamus, and it enters the anterior thalamic nucleus via the mammillothalamic tract. The anterior thalamic nuclei, in turn, connect to the cingulate cortex, which projects back to the entorhinal cortex of the parahippocampal gyrus, completing the Papez circuit [6], [7]. We found that the limbic system (Papez circuit) is activated when emotion is evoked. Emotions are mostly mediated through the Papez circuit of the limbic system to determine the final expression of emotions [8]. Papez circuit disruption is associated with affective processing and cognitive functioning disturbances [9], [10]. It has also been proposed that the Papez circuit is related to depression symptoms [11]. Additional evidence from MRI studies further supports the involvem (...truncated)


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Wenyan Jiang, Gaolang Gong, Feng Wu, Lingtao Kong, Kaiyuan Chen, Wenhui Cui, Ling Ren, Guoguang Fan, Wenge Sun, Huan Ma, Ke Xu, Yanqing Tang, Fei Wang. The Papez Circuit in First-Episode, Treatment-Naive Adults with Major Depressive Disorder: Combined Atlas-Based Tract-Specific Quantification Analysis and Voxel-Based Analysis, PLOS ONE, 2015, Volume 10, Issue 5, DOI: 10.1371/journal.pone.0126673