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Journal of Affective Disorders
journal homepage: www.elsevier.com/locate/jad
Subthreshold depression may exist on a spectrum with major depressive
disorder: Evidence from gray matter volume and morphological brain
network
Tianhao Zhang
a,b,#
, Bingcong Zhao
c,d,#
, Chuan Shi
e
, Binbin Nie
a,b
, Hua Liu
a,b
, Xinjing Yang
f
,
Yang Sun
c
, Panlong Li
a,g
, Lei Lin
h
, Xiuyan Yang
i
, Jing Li
j
, Xingzhou Gao
c
, Shixing Feng
c
,
Xiang Li
c
, Xi Sun
a,g
, Tingting Pan
a,g
, Ting Feng
a,g
, Tuya Bao
c,
⁎
, Baoci Shan
a,b,k,
⁎⁎
a
Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China
b
School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, China
c
School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
d
Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture
Neuromodulation, Beijing, China
e
Peking University Six Hospital, Beijing, China
f
School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
g
Department of Physics, Zhengzhou University, Zhengzhou, Henan, China
h
Department of Acupuncture, Beijing Hospital, Beijing, China
i
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
j
Center on Aging Psychology Institute of Psychology, Chinese Academy of Sciences, Beijing, China
k
CAS center for Excellence in Brain Science and Intelligence Technology, Shanghai, China
ARTICLE INFO
Keywords:
Subthreshold depression
Major depressive disorder
Magnetic resonance imaging
Voxel-based morphometry
Morphological brain networks
Depressive spectrum
ABSTRACT
Background: Subthreshold depression (StD) is a prevalent condition that may increase the risk of incident major
depressive disorder (MDD). However, the relationship between StD and MDD remains unclear.
Methods: A total of 153 adult subjects, including 53 drug-naive MDD, 50 StD and 50 healthy control (HC) subjects,
underwent a T1-weighted magnetic resonance imaging scan, and the gray matter volume (GMV) alterations among
the three groups were quantitatively analyzed using voxel-based morphometry (VBM). Then, to capture the whole-
brain connectivity characteristics, we constructed morphological brain networks (MBN) based on the similarity among
brain regions of individual VBM images and compared the network connection strengths among the three groups.
Results: The StD and MDD subjects had similar patterns of GMV reductions in the orbitofrontal cortex and left
temporal gyrus, although the magnitude of the reductions was smaller in StD subjects. Moreover, a total of 21
morphological connections were significantly different among the three groups. For the majority of the different
connections (15/21), the connection strength of the StD group took an intermediate position between that of the
MDD and HC groups.
Limitations: There is still a lack of a consistent definition of StD, and the age range of the subjects in this study
was wide. Meanwhile the mechanisms and biological significance of the MBN remains to be clarified.
Conclusions: These results may support the hypothesis that depression is better expressed as a spectrum and that
StD exists on a spectrum with MDD.
https://doi.org/10.1016/j.jad.2020.01.135
Received 21 June 2019; Received in revised form 6 December 2019; Accepted 12 January 2020
Abbreviations: StD, Subthreshold depression; MDD, major depressive disorder; HC, healthy control; VBM, Voxel-based morphometry; MRI, magnetic resonance
imaging; GMV, gray matter volumes; fMRI, functional magnetic resonance imaging; DTI, diffusion tensor imaging; MBN, morphological brain network; ICD-10,
International Classification of Disease 10th Edition; CES-D, Center for Epidemiologic Studies Depression Scale; HAMD-17, 17-item Hamilton Depression Rating Scale;
ANOVA, analysis of variance; TIV, total intracranial volume; GRF, Gaussian random field; DMN, default mode network
⁎
Corresponding author: School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, No.11 Bei San Huan Dong Lu, Chaoyang District,
Beijing, 100029, China.
⁎⁎
Corresponding author at: Institute of High Energy Physics, Chinese Academy of Sciences, 19B Yuquan Road, Shijingshan District. Beijing 100049, China.
E-mail addresses: tuyab@bucm.edu.cn (T. Bao), shanbc@ihep.ac.cn (B. Shan).
#
Authors contributed equally to this work.
Journal of Affective Disorders 266 (2020) 243–251
Available online 27 January 2020
0165-0327/ © 2020 Elsevier B.V. All rights reserved.
T