title: Assessment of abnormal brain structures and networks in major depressive disorder using morphometric and connectome analyses.
abstract: It is hypothesized that the phenomenology of major depressive disorder (MDD) is subserved by disturbances in the structure and function of brain circuits; however, findings of structural abnormalities using MRI have been inconsistent. Generalized q-sampling imaging (GQI) methodology provides an opportunity to assess the functional integrity of white matter tracts in implicated circuits.
  
  
  
  The study population was comprised of 16 outpatients with MDD (mean age 44.81±2.2 years) and 30 age- and gender-matched healthy controls (mean age 45.03±1.88 years). We excluded participants with any other primary mental disorder, substance use disorder, or any neurological illnesses. We used T1-weighted 3D MRI with voxel-based morphometry (VBM) and vertex-wise shape analysis, and GQI with voxel-based statistical analysis (VBA), graph theoretical analysis (GTA) and network-based statistical (NBS) analysis to evaluate brain structure and connectivity abnormalities in MDD compared to healthy controls correlates with clinical measures of depressive symptom severity, Hamilton Depression Rating Scale 17-item (HAMD) and Hospital Anxiety and Depression Scale (HADS).
  
  
  
  Using VBM and vertex-wise shape analyses, we found significant volumetric decreases in the hippocampus and amygdala among subjects with MDD (p<0.001). Using GQI, we found decreases in diffusion anisotropy in the superior longitudinal fasciculus and increases in diffusion probability distribution in the frontal lobe among subjects with MDD (p<0.01). In GTA and NBS analyses, we found several disruptions in connectivity among subjects with MDD, particularly in the frontal lobes (p<0.05). In addition, structural alterations were correlated with depressive symptom severity (p<0.01).
  
  
  
  Small sample size; the cross-sectional design did not allow us to observe treatment effects in the MDD participants.
  
  
  
  Our results provide further evidence indicating that MDD may be conceptualized as a brain disorder with abnormal circuit structure and connectivity.
authors.affiliation: School of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Vincent Chin-Hung
authors.initials: VC
authors.lastname: Chen
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chao-Yu
authors.initials: CY
authors.lastname: Shen
authors.affiliation: School of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Psychiatry, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Sophie Hsin-Yi
authors.initials: SH
authors.lastname: Liang
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Zhen-Hui
authors.initials: ZH
authors.lastname: Li
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Yeu-Sheng
authors.initials: YS
authors.lastname: Tyan
authors.affiliation: Department of Psychiatry, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yin-To
authors.initials: YT
authors.lastname: Liao
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Yin-Chen
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada.
authors.forename: Yena
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada.
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan. Electronic address: jcweng@csmu.edu.tw.
authors.forename: Jun-Cheng
authors.initials: JC
authors.lastname: Weng
mesh_terms: D000328:Adult; D000679:Amygdala / Q000473:pathology; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D063132:Connectome; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000473:pathology*; D066127:White Matter / Q000503:physiopathology
keywords: Generalized q-sampling imaging (GQI); Graph theoretical analysis (GTA); Major depressive disorder (MDD); Network-based statistical analysis (NBS); Vertex-wise shape analysis; Voxel-based morphometry (VBM)