Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes

Shi-Yi Ye; Yin Zhao; Zhao-Bo Liu; Cui-Pin Luo; Jian-Wen Xiong; Jin-Qiong Zhan; Yi-Heng Li; Bo Wei; Chun-Nuan Chen; Yuan-Jian Yang

doi:10.3389/fpsyt.2024.1354999

Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes

Front Psychiatry. 2024 Mar 18:15:1354999. doi: 10.3389/fpsyt.2024.1354999. eCollection 2024.

Authors

Shi-Yi Ye^#^{1

2}, Yin Zhao^#³, Zhao-Bo Liu^#⁴, Cui-Pin Luo¹, Jian-Wen Xiong^{1

5}, Jin-Qiong Zhan^{1

5}, Yi-Heng Li^{1

5}, Bo Wei^{1

5}, Chun-Nuan Chen⁶, Yuan-Jian Yang^{1

5}

Affiliations

¹ Department of Psychiatry and Biological Psychiatry Laboratory, Jiangxi Mental Hospital & Affiliated Mental Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
² The 3rd Clinical Medical College, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
³ Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Psychiatry, Third People's Hospital of Ji'an City, Ji'an, China.
⁵ Nanchang City Key Laboratory of Biological Psychiatry, Jiangxi Provincial Clinical Research Center on Mental Disorders, Jiangxi Mental Hospital, Nanchang, Jiangxi, China.
⁶ Department of Neurology, The Second Clinical Medical College, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, China.

^# Contributed equally.

Abstract

Objective: Accumulating evidence has indicated that neurodevelopmental defects may underlie the pathophysiology of bipolar disorder (BD). Insulin-like growth factors (IGFs) are a family of neurotrophic factors that are essential for the survival and development of neurons. The present study aims to investigate whether IGF-2 signaling is implicated in the pathophysiological processes of BD.

Method: 50 healthy controls and 78 patients with BD, including 23 patients who diagnosed acute depressive episode and 55 patients who diagnosed acute manic episode, were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) were used to assess the severity of the depressive and manic symptoms, respectively. The serum IGF-2 level was determined by an enzyme-linked immunosorbent assay (ELISA). The Kolmogorov-Smirnov and Mann-Whitney U tests were used for between-group comparisons and spearman analysis was used to analyze correlations.

Results: Patients with BD had lower serum IGF-2 levels (66.08 ± 21.22 ng/ml) when compared to healthy controls (88.72 ± 31.55 ng/ml). BD patients were divided into manic episode and depressive episode subgroups. We found that serum IGF-2 levels were reduced in both the mania and depression subgroups (mania: 67.19 ± 21.52 ng/ml, depression: 63.43 ± 20.67 ng/ml; P < 0.001), while no significant difference was observed between two groups (P > 0.05). Spearman correlation analyses revealed that the levels of serum IGF-2 were negatively correlated with the YMRS scores in BD patients (r = -0.522, P < 0.001). Furthermore, IGF-2 was found to be an independent contributor to the severity of symptoms in patients with manic episodes (B = -0.610, t = -5.299, P < 0.001).

Conclusion: Lower serum IGF-2 levels were found in BD patients and correlated with the severity of the manic symptoms in these patients during manic episodes. These results suggest that reduced IGF-2 levels might be involved in the pathophysiology of BD, and serum IGF-2 could be a peripheral biomarker for the evaluation of the severity of manic symptoms in BD patients.

Keywords: bipolar disorder; insulin-like growth factor-2; manic symptoms; serum; severity.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by grants from the National Natural Science Foundation of China (82271557,82060258,82104317). It was also supported by the Jiangxi Provincial Clinical Research Center Projects (2020BCG74002), the Hubei Provincial Natural Science Foundation (2022CFB254), the Natural Science Foundation of Fujian Province of China (2023J01104), and the Science and Technology Bureau of Quanzhou (Grant number: 2023C005YR).