The flow cytometric analysis of depression focusing on modern-type depression and hikikomori: Exploring the link between subtypes of depression and immunological imbalances

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Abstract

Introduction: Depression includes different phenotypes. Modern-type depression (MTD) is a gateway disorder to pathological social withdrawal, known as hikikomori. Adverse childhood experiences (ACEs) are also important aetiologies of depression. Recently, immune imbalance has been proposed as a biological basis of depression. We hypothesised that peripheral immunological characteristics may be involved in subtyping of depression. Methods: 21 patients with major depressive disorder (MDD) and 24 healthy controls (HC) were recruited. Peripheral blood mononuclear cells (PBMCs) were examined for surface antigens by flow cytometry. Participants were administered psychological scales such as Patient Health Questionnaire (PHQ)-9, Modern-Type Depression Trait Scale (TACS-22), Hikikomori Questionnaire (HQ-25), Child Abuse and Trauma Scale (CATS). Results: MDD group showed significantly higher percentage of B cells than HC group (p = 0.032). MDD group presented a negative correlation between: PHQ-9 and CD8 T effector memory cells (r= –0.639, p = 0.002), TACS-22 and monocytes (r= –0.459, p = 0.036), HQ-25 and NK T cells (r= –0.638, p = 0.004), CATS and Intermediate monocytes (r= –0.594, p = 0.009). Conclusions: MTD traits, hikikomori tendencies, and ACEs were correlated with specific characteristics of peripheral immune cells. Our results suggest that immune imbalance influences the diverse presentations of depression. Further validation is warranted by large-scale prospective studies.

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Matsuo, K., Watanabe, M., Inamine, S., Matsushima, T., Kyuragi, S., Maeda, Y., … Kato, T. A. (2025). The flow cytometric analysis of depression focusing on modern-type depression and hikikomori: Exploring the link between subtypes of depression and immunological imbalances. Dialogues in Clinical Neuroscience, 27(1), 13–25. https://doi.org/10.1080/19585969.2025.2452842

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