Meng-Xuan Qiao,1,2 Hua Yu,1,3– 5 Zheng Fu,1,2 Wei Wei,1,3– 5 Xiao-Jing Li,1,3– 5 Wei Deng,1,3– 5 Wan-Jun Guo,1,3– 5 Tao Li1– 5 

1Affiliated Mental Health Center and Hangzhou Seventh People’s Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China; 2School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 3Zhejiang Key Laboratory of Clinical and Basic Research on Mental Disorders, Hangzhou, People’s Republic of China; 4Zhejiang Engineering Research Center for Intelligent Diagnosis and Treatment of Mental Disorders, Hangzhou, People’s Republic of China; 5Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, Hangzhou, 311121, People’s Republic of China

Correspondence: Tao Li, Affiliated Mental Health Center and Hangzhou Seventh People’s Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China, Email litaozjusc@zju.edu.cn Hua Yu, Affiliated Mental Health Center and Hangzhou Seventh People’s Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China, Email ashelychongqing@163.com

Background: Numerous studies suggest that hyperactivation of the immuno-inflammatory system, as reflected in cytokine levels, is associated with more severe symptoms in mood and anxiety disorders and weaker response to treatment. Here we examined whether the efficacy of a combination of bright light therapy, repetitive transcranial magnetic stimulation and medication is associated with another immuno-inflammatory index, white blood cell count, before and/or after treatment, in a retrospective observational study.
Methods: We retrospectively analyzed 467 inpatients with major depressive, bipolar, or generalized anxiety disorder who were treated with combination therapy for at least one week at Hangzhou Seventh People’s Hospital between April 2022 and April 2024. Potential associations between remission incidences within four weeks after treatment and white blood cell count both before treatment and post-treatment were explored. We used mixed-effects linear modeling to examine the association between treatment characteristics and changes in white blood cell count and depressive symptoms.
Results: Bipolar and major depressive disorders were associated with significantly higher white blood cell counts at baseline than generalized anxiety disorder as well as with significantly lower remission incidences. Bright light therapy’s effects depended on baseline inflammation, more sessions led to greater reductions in the Hamilton Depression Rating Scale score with low baseline white blood cell count, and greater decreases in white blood cell count with high baseline count. In contrast, repetitive transcranial magnetic stimulation sessions showed no association with white blood cell count.
Conclusion: These results highlight the need to account for an individual’s immuno-inflammatory state when personalizing treatment for mental health disorders.

Keywords: depressive symptoms, white blood cell count, bright light therapy, inflammation