Impaired lipid homeostasis and elevated lipid oxidation of erythrocyte membrane in adolescent depression

Jinfeng Wang; Xiaowen Hu; Ya Li; Shuhui Li; Tianqi Wang; Dandan Wang; Yan Gao; Qian Wang; Jiansong Zhou; Chunling Wan

doi:10.1016/j.redox.2025.103491

Impaired lipid homeostasis and elevated lipid oxidation of erythrocyte membrane in adolescent depression

Redox Biol. 2025 Jan 8:80:103491. doi: 10.1016/j.redox.2025.103491. Online ahead of print.

Authors

Jinfeng Wang¹, Xiaowen Hu², Ya Li³, Shuhui Li⁴, Tianqi Wang⁵, Dandan Wang⁶, Yan Gao⁷, Qian Wang⁸, Jiansong Zhou⁹, Chunling Wan¹⁰

Affiliations

¹ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China. Electronic address: wangjinfeng@sjtu.edu.cn.
² Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China. Electronic address: xiaowen@sjtu.edu.cn.
³ School of Rehabilitation Medicine, Shandong Second Medical University, Weifang, Shandong, China. Electronic address: liya_ay@163.com.
⁴ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China. Electronic address: 925365231@qq.com.
⁵ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China. Electronic address: 814863602@qq.com.
⁶ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China. Electronic address: wangdandan26@126.com.
⁷ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China. Electronic address: gy_1001_sim@163.com.
⁸ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China. Electronic address: is_wangq@163.com.
⁹ Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. Electronic address: zhoujs2003@csu.edu.cn.
¹⁰ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China; Shanghai Mental Health Center, Shanghai Key Laboratory of Psychiatry Disorders, Shanghai Jiao Tong University, Shanghai, China. Electronic address: clwan@sjtu.edu.cn.

PMID: 39809016
DOI: 10.1016/j.redox.2025.103491

Abstract

Adolescent depression is a globally concerned mental health issue, the pathophysiological mechanisms of which remain elusive. Membrane lipids play a crucial role in brain development and function, potentially serving as a crossroad for the abnormalities in neurotransmitters, neuroendocrine, inflammation, oxidative stress, and energy metabolism observed in depressed adolescents. The primary aim of this study was to investigate the erythrocyte membrane lipid profile in adolescent depression. A total of 2838 erythrocyte membrane lipids were detected and quantified in 81 adolescents with depression and 67 matched healthy adolescents using ultra-high performance liquid chromatography-mass spectrometry. Depressed adolescents exhibited significantly different membrane lipid characteristics compared to healthy controls. Specifically, the levels of cholesterol, sphingomyelins, and ceramides were increased, while ether lipids were decreased in patients. Moreover, the patients showed reduced polyunsaturated fatty acids and elevated lipophilic index in membrane, suggesting diminished membrane fluidity. The higher oxidized membrane lipids and plasma malondialdehyde were observed in adolescent depression, indicating the presence of oxidative stress. Importantly, membrane lipid damage was associated with more severe depressive symptoms and worse cognitive function in patients. In addition, reduced polyunsaturated fatty acids and membrane fluidity may be partly responsible for the blunted niacin skin flushing response found in depressed adolescents. In conclusion, our results reveal impaired erythrocyte membrane lipid homeostasis in adolescents with depression, which may implicate membrane dysfunction in the brain. These findings offer new insights into the underlying molecular mechanisms of adolescent depression, highlighting the potential of counteracting membrane damage as a promising avenue for future therapeutic interventions.

Keywords: Adolescent depression; Cognitive function; Lipidome; Membrane fluidity; Niacin skin flushing response; Oxidative stress.