Open Access Research article

Abnormalities of cortical-limbic-cerebellar white matter networks may contribute to treatment-resistant depression: a diffusion tensor imaging study

Hong-jun Peng12, Hui-rong Zheng3, Yu-ping Ning2, Yan Zhang1, Bao-ci Shan4, Li Zhang1, Hai-chen Yang1, Jun Liu5, Ze-xuan Li1, Jian-song Zhou1, Zhi-jun Zhang6 and Ling-jiang Li17*

  • * Corresponding author: Ling-jiang Li

  • † Equal contributors

Author affiliations

1 Mental Health Institute, The 2nd Xiangya Hospital, Central South University, No. 139 Renmin Zhong Road, Changsha, 410011, China

2 Guangzhou Psychiatric Hospital, Affiliated Hospital of Guangzhou Medical College, Guangzhou, China

3 Guangdong Mental Health Institute, Guangdong General Hospital, Guangzhou, China

4 Key Laboratory of Nuclear Analysis, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, People’s Republic of China

5 Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China

6 The Department of Neuropsychiatry and Institute of Neuropsychiatric Research, Affiliated ZhongDa Hospital of Southeast University, Nanjing, China

7 Chinese University of Hong Kong, Hong Kong, China

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Citation and License

BMC Psychiatry 2013, 13:72  doi:10.1186/1471-244X-13-72

Published: 2 March 2013



White matter abnormalities can cause network dysfunction that underlies major depressive disorder (MDD). Diffusion tensor imaging (DTI) is used to examine the neural connectivity and integrity of the white matter. Previous studies have implicated frontolimbic neural networks in the pathophysiology of MDD. Approximately 30% of MDD patients demonstrate treatment-resistant depression (TRD). However, the neurobiology of TRD remains unclear.


We used a voxel-based analysis method to analyze DTI data in young patients with TRD (n = 30; 19 males, 11 females) compared with right-handed, age- and sex-matched healthy volunteers (n = 25; 14 males, 11 females).


We found a significant decrease in fractional anisotropy (FA) (corrected, cluster size >50) in the left middle frontal gyrus (peak coordinates [−18 46–14]), left limbic lobe uncus (peak coordinates [−18 2–22]), and right cerebellum posterior lobe (peak coordinates [26–34 -40]). There was no increase in FA in any brain region in patients. We also found a significant negative correlation between mean regional FA values in the three areas and Beck Depression Inventory symptom scores.


We found significant differences in white matter FA in the frontal lobe, limbic lobe and cerebellum between TRD patients and controls. These data suggest that abnormalities of cortical-limbic-cerebellar white matter networks may contribute to TRD in young patients.

Treatment-resistant depression; Diffusion tensor imaging; Fractional anisotropy; Voxel-based analysis method