Brain Imaging and Behavior

, Volume 13, Issue 5, pp 1255–1264 | Cite as

Cortical thickness and subcortical volumes alterations in euthymic bipolar I patients treated with different mood stabilizers

  • Linling Li
  • Erni Ji
  • Xue Han
  • Fei Tang
  • Yuanhan Bai
  • Daihui Peng
  • Yiru Fang
  • Shengli Zhang
  • Zhiguo ZhangEmail author
  • Haichen YangEmail author
Original Research


Reported structural abnormalities of patients with bipolar disorder (BD) are inconsistent and the use of psychotropic medication is one of the sources of heterogeneity. A fairly small number of morphometric studies have involved comparison of BD on different mood stabilizers. Here in this study, we aimed to investigate the cortical thickness and subcortical volumes in euthymic BD patients on lithium and valproate and healthy controls (HC), and to elucidate the relationship between the use of medication and brain structure variations. We acquired structural magnetic resonance imaging data from 35 BD patients (19/valproate;16/lithium) and 30 HC subjects. Cortical thickness was compared in multiple locations across the continuous cortical surface, and subcortical volumes were compared on a structure-by-structure basis. Group analyses revealed widespread thinning of the prefrontal cortex in BD. Compared with BD on valproate, BD on lithium showed significant increased cortical thickness of the left rostral middle frontal cortex and right superior frontal cortex, while cortical thickness was not significantly different between BD on lithium and HC in the bilateral rostral middle frontal cortex. Moreover, no significant difference was observed in subcortical volume. Limitations of this study comprise the possible effect of other psychotropic drugs, small sample size and the cross-sectional design. Therefore, the results suggest medication-related neurobiological difference between BD patients on different mood stabilizers, but no casual role can be proposed. Our findings provided new evidence about the effects of psychotropic medication upon neuroanatomy in BD, and could help to explain the inconsistency of existing studies as well as contribute to the extraction of reliable neuroimaging biomarkers in BD.


Bipolar disorder Euthymia Mood stabilizers MRI Prefrontal cortex 



This work was supported by the Science and Technology Bureau of Shenzhen city (grant number JCYJ20150402093137765 and 20170814183413357), the Sanming Project of Medicine in Shenzhen (grant number SZSM201612006), the National Natural Science Foundation of China (grant number 81871443), and the Shenzhen Peacock Plan (grant number KQTD2016053112051497).

Compliance with ethical standards

Conflict of interest

Linling Li, Erni Ji, Xue Han, Fei Tang, Yuanhan Bai, Daihui Peng, Yiru Fang, Shengli Zhang, Zhiguo Zhang and Haichen Yang declare that they have no conflicts of interest.

Ethical approval

All procedures performed in this study were approved by the Human Research Ethics Committee of the Shenzhen Mental Health Centre, and were conducted in accordance with the 1964 Helsinki declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11682_2018_9950_MOESM1_ESM.docx (22 kb)
ESM 1 (DOCX 22 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Linling Li
    • 1
    • 2
    • 3
  • Erni Ji
    • 2
  • Xue Han
    • 4
    • 5
  • Fei Tang
    • 1
    • 3
  • Yuanhan Bai
    • 2
  • Daihui Peng
    • 6
  • Yiru Fang
    • 6
  • Shengli Zhang
    • 7
  • Zhiguo Zhang
    • 1
    • 3
    Email author
  • Haichen Yang
    • 2
    Email author
  1. 1.School of Biomedical Engineering, Health Science CenterShenzhen UniversityShenzhen 518060China
  2. 2.Department for Affective Disorders, Shenzhen Mental Health CentreShenzhen Key Lab for Psychological HealthcareShenzhen 518020China
  3. 3.Guangdong Provincial Key Laboratory of Biomedical Measurements and Ultrasound ImagingShenzhen UniversityShenzhen 518060China
  4. 4.Mental Health Institute of the Second Xiangya Hospital, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan ProvinceCentral South UniversityChangsha 410011China
  5. 5.Department of Mental HealthShenzhen Nanshan Center for Chronic Disease ControlShenzhen 518060China
  6. 6.Department for Mood Disorders, Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China
  7. 7.Department of Communication EngineeringShenzhen UniversityShenzhen 518060China

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