Lithium bidirectionally regulates depression- and mania-related brain functional alterations without worsening cognitive function in patients with bipolar disorder

Chuanjun Zhuo; Guangdong Chen; Jiayue Chen; Hongjun Tian; Xiaoyan Ma; Qianchen Li; Lei Yang; Qiuyu Zhang; Ranli Li; Xueqin Song; Chunhai Huang

doi:10.3389/fpsyt.2022.963005

Lithium bidirectionally regulates depression- and mania-related brain functional alterations without worsening cognitive function in patients with bipolar disorder

Front Psychiatry. 2022 Sep 15:13:963005. doi: 10.3389/fpsyt.2022.963005. eCollection 2022.

Authors

Chuanjun Zhuo^{1

2

3

4}, Guangdong Chen², Jiayue Chen¹, Hongjun Tian¹, Xiaoyan Ma³, Qianchen Li¹, Lei Yang¹, Qiuyu Zhang¹, Ranli Li³, Xueqin Song⁴, Chunhai Huang²

Affiliations

¹ Key Laboratory of Real Time Tracing of Brain Circuits of Neurology and Psychiatry (RTBNP_Lab), Tianjin Fourth Center Hospital Affiliated to Tianjin Medical University, Tianjin Fourth Center Hospital, Tianjin, China.
² Department of Psychiatry, Wenzhou Seventh Peoples Hospital, Wenzhou, China.
³ Key Laboratory of Psychiatric-Neuroimaging-Genetics Laboratory (PNGC_Lab), Tianjin Mental Health Center of Tianjin Medical University, Tianjin Anding Hospital, Tianjin, China.
⁴ Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Lithium monotherapy has been proposed to have antidepressant and antimanic effects in patients with bipolar disorder (BP). However, so far, it is lack of evidence to support this proposition. The main aim of this study was to test the hypothesis that lithium bidirectionally regulates depression- and mania-related brain functional abnormalities in patients with BP. We also assessed the effects of lithium, alone and in combination with other pharmacological treatments, on patients' cognitive performance. We enrolled 149 drug-naïve patients with BP; 99 patients experiencing first depressive episodes were allocated randomly to four treatment groups [lithium (DP/Li), lithium with lamotrigine (LTG; DP/Li+LTG), LTG (DP/LTG), and valproate (VPA) with LTG (DP/VPA+LTG)], and 50 experiencing first hypo-manic episodes were allocated to two treatment groups (MA/Li and MA/VPA). For comparative analysis, 60 age-matched healthy individuals were also recruited. Whole-brain global and regional resting-state cerebral blood flow (rs-CBF) and cognitive alterations were examined before and after 12-week treatment. We have the following findings: DP/Li+LTG, and to a lesser extent DP/Li, alleviated the depression-related reduction in rs-CBF. MA/VPA and MA/Li reversed the mania-related elevation of rs-CBF completely and partially, respectively. Lithium alone improved cognitive performance during depressive and manic episodes; other tested treatments have no such effect or worsened cognitive ability. Our results showed that lithium bidirectionally regulates depression- and mania-associated brain functional abnormalities in patients with BP. Lithium monotherapy has a better antimanic effect than VPA, is superior to other tested treatments in improving cognition during the course of BP, and has satisfactory antidepressant effects in patients with BP.

Keywords: bipolar disorder; cerebral blood flow; cognition; depression; functional magnetic resonance imaging; lithium; mania.