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Abnormal intrinsic cerebro-cerebellar functional connectivity in un-medicated patients with bipolar disorder and major depressive disorder

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Abstract

Objective

The cerebellum plays an important role in depression. Cerebro-cerebellar circuits have been found to show aberrance in bipolar disorder (BD) and major depressive disorder (MDD). However, whether the cerebro-cerebellar connectivity contributes equally to the pathologic mechanisms of BD and MDD remains unknown.

Methods

We recruited 33 patients with MDD, 32 patients with BD, and 43 healthy controls (HC). We selected six seed regions (three per hemisphere) in the cerebrum, corresponding to the affective, cognitive control, and default mode networks, to establish cerebro-cerebellar functional connectivity maps.

Results

Relative to the HC, both the BD and MDD patients exhibited weaker negative connectivity between the right subgenual anterior cingulate cortex and the cerebellar vermis IV_V (pBD = 0.03, pMDD = 0.001) and weaker positive connectivity between the left precuneus and the left cerebellar lobule IX (pBD = 0.043, pMDD = 0.000). Moreover, the MDD patients showed weaker positive connectivity in the left precuneus—left cerebellar lobule IX circuit than the BD patients (p = 0.049). In addition, the BD patients showed weaker positive connectivity in the right dorsolateral prefrontal cortex—left cerebellar lobule Crus Ι circuit compared to the HC (p = 0.002) or the MDD patients (p = 0.013). Receiver operating characteristic curves analyses showed that the altered cerebro-cerebellar connectivities could be used to distinguish the patients from the HC with relatively high accuracy.

Conclusions

Our findings suggested that differences in connectivity of cerebro-cerebellar circuits, which are involved in affective or cognitive functioning, significantly contributed to BD and MDD.

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Abbreviations

BD:

Bipolar disorder

MDD:

Major depressive disorder

HC:

Healthy controls

DLPFC:

Dorsolateral prefrontal cortex

SCID-IV:

Structured Clinical Interview for DSM-IV

HDRS:

Hamilton Depression Rating Scale

YMRS:

Young Mania Rating Scale

TR:

Repetition time

TE:

Echo time

FOV:

Field of view

FD-J:

Frame-wise displacement Jenkinson

ROI:

Region of interest

sACC:

Subgenual anterior cingulate cortex

PREC:

Precuneus

M1:

Postcentral gyri

FDR:

False discovery rate

ANCOVA:

One-way analysis of covariance

LSD:

Least significant difference test

ROC:

Receiver operating characteristic

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Acknowledgments

We appreciate the content and English editing assistance of Drs. Rhoda E. and Edmund F. Perozzi.

Funding

This study was supported by the National Natural Science Foundation of China (81671670, 81501456, 81471650, 81371535, 81428013, 81571641, 81628008, and 81471654); Planned Science and Technology Project of Guangdong Province, China (2014B020212022); and Planned Science and Technology Project of Guangzhou, China (1563000653, 155700029, 20160402007, 201604020184). This study was also supported by the National Key Research and Development Program of China (2016YFC0100105). The funding organizations played no further role in the study design, data collection, analysis and interpretation, or the paper writing.

Author information

Author notes

  1. Yuan He and Ying Wang contributed equally to this work.

Authors and Affiliations

  1. Institute for Brain Research and Rehabilitation, Guangdong Key Laboratory of Mental Health and Cognitive Science, Center for Studies of Psychological Application, School of Psychology, South China Normal University, Guangzhou, 510631, China

    Yuan He, Huiyuan Huang, Feng Deng, Xiaoyan Wu, Chen Niu & Ruiwang Huang

  2. Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou, 510630, China

    Ying Wang, Yao Sun & Li Huang

  3. Department of Psychology, Research Center for Mind, Brain & Learning, National Chengchi University, Taipei, Taiwan

    Ting-Ting Chang

  4. Department of Psychiatry, First Affiliated Hospital of Jinan University, Guangzhou, 510630, China

    Yanbin Jia & Shuming Zhong

  5. Department of Applied Psychology, Guangdong University of Foreign Studies, Guangzhou, 510006, China

    Junjing Wang

  6. Department of Radiology, China-Japan Friend Hospital, Yinghua Dongjie 2, Chaoyang District, Beijing, 100029, China

    Guolin Ma

  7. Brain Imaging Center, School of Psychology, South China Normal University, Zhongshan Avenue West 55, Tianhe District, Guangzhou, 510631, China

    Ruiwang Huang

Authors
  1. Yuan He
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  2. Ying Wang
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  3. Ting-Ting Chang
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  4. Yanbin Jia
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  5. Junjing Wang
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  6. Shuming Zhong
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  7. Huiyuan Huang
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  8. Yao Sun
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  9. Feng Deng
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  10. Xiaoyan Wu
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  11. Chen Niu
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  12. Li Huang
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  13. Guolin Ma
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  14. Ruiwang Huang
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Corresponding authors

Correspondence to Ying Wang, Guolin Ma or Ruiwang Huang.

Ethics declarations

This study was approved by the Ethics Committee of First Affiliated Hospital of Jinan University, Guangzhou, China.

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Highlights

• The BD patients showed weaker cerebro-cerebellar positive connectivity between the right dorsolateral prefrontal cortex (DLPFC) and the left cerebellar lobule Crus Ι compared to the HC and MDD groups;

• Cerebro-cerebellar negative connectivity between the right subgenual anterior cingulate cortex (sACC) and the cerebellar vermis IV_V was weaker in both the BD and MDD patients;

• Both the MDD and BD patients showed a weaker positive connectivity between the left precuneus and the left cerebellar lobule IX; in addition, the MDD patients showed a weaker RSFC in that coupling than the BD patients.

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He, Y., Wang, Y., Chang, TT. et al. Abnormal intrinsic cerebro-cerebellar functional connectivity in un-medicated patients with bipolar disorder and major depressive disorder. Psychopharmacology 235, 3187–3200 (2018). https://doi.org/10.1007/s00213-018-5021-6

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  • DOI: https://doi.org/10.1007/s00213-018-5021-6

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