The Flow Cytometric Analysis of Depression Focusing on Modern-type Depression and Hikikomori: Exploring the Link Between Subtypes of Depression and Immunological Imbalances

Overview

Journal Dialogues Clin Neurosci

Date 2025 Jan 20

PMID 39831784

Authors

Keitaro Matsuo

Mitsuru Watanabe

Shogo Inamine

Toshio Matsushima

Sota Kyuragi

Yasuhiro Maeda

Ryoko Katsuki

Masahiro Ohgidani

Ryo Yamasaki

Noriko Isobe

Tomohiro Nakao

Takahiro A Kato

Affiliations

Soon will be listed here.

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 ( = 0.032). MDD group presented a negative correlation between: PHQ-9 and CD8 T effector memory cells (r= -0.639, = 0.002), TACS-22 and monocytes (r= -0.459, = 0.036), HQ-25 and NK T cells (r= -0.638, = 0.004), CATS and Intermediate monocytes (r= -0.594, = 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.

References

Hashioka S, Klegeris A, Monji A, Kato T, Sawada M, McGeer P . Antidepressants inhibit interferon-gamma-induced microglial production of IL-6 and nitric oxide. Exp Neurol. 2007; 206(1):33-42. DOI: 10.1016/j.expneurol.2007.03.022. View

Harald B, Gordon P . Meta-review of depressive subtyping models. J Affect Disord. 2011; 139(2):126-40. DOI: 10.1016/j.jad.2011.07.015. View

Suzuki H, Ohgidani M, Kuwano N, Chretien F, de la GrandMaison G, Onaya M . Suicide and Microglia: Recent Findings and Future Perspectives Based on Human Studies. Front Cell Neurosci. 2019; 13:31. PMC: 6381042. DOI: 10.3389/fncel.2019.00031. View

Al-Sibani N, Chan M, Al-Huseini S, Al Kharusi N, Guillemin G, Al-Abri M . Exploring Hikikomori-like idiom of distress a year into the SARS-CoV-2 pandemic in Oman: Factorial validity of the 25-item Hikikomori Questionnaire, prevalence and associated factors. PLoS One. 2023; 18(8):e0279612. PMC: 10406187. DOI: 10.1371/journal.pone.0279612. View

Su M, Ouyang X, Song Y . Neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and monocyte to lymphocyte ratio in depression: A meta-analysis. J Affect Disord. 2022; 308:375-383. DOI: 10.1016/j.jad.2022.04.038. View

Gold P . The organization of the stress system and its dysregulation in depressive illness. Mol Psychiatry. 2014; 20(1):32-47. DOI: 10.1038/mp.2014.163. View

Teo A, Horie K, Kurahara K, Kato T . The Hikikomori Diagnostic Evaluation (HiDE): a proposal for a structured assessment of pathological social withdrawal. World Psychiatry. 2023; 22(3):478-479. PMC: 10503919. DOI: 10.1002/wps.21123. View

Orsolini L, Longo G, Bellagamba S, Kato T, Volpe U . Could the Construct of Modern-Type Depression Predict Internet Gaming Disorder in Italian Video Gamers? A Case-Control Study. Brain Sci. 2024; 14(1). PMC: 10813306. DOI: 10.3390/brainsci14010048. View

Koyama A, Miyake Y, Kawakami N, Tsuchiya M, Tachimori H, Takeshima T . Lifetime prevalence, psychiatric comorbidity and demographic correlates of "hikikomori" in a community population in Japan. Psychiatry Res. 2010; 176(1):69-74. DOI: 10.1016/j.psychres.2008.10.019. View

10.

Malagon-Amor A, Martin-Lopez L, Corcoles D, Gonzalez A, Bellsola M, Teo A . Family Features of Social Withdrawal Syndrome (Hikikomori). Front Psychiatry. 2020; 11:138. PMC: 7061609. DOI: 10.3389/fpsyt.2020.00138. View

11.

Schiweck C, Valles-Colomer M, Arolt V, Muller N, Raes J, Wijkhuijs A . Depression and suicidality: A link to premature T helper cell aging and increased Th17 cells. Brain Behav Immun. 2020; 87:603-609. DOI: 10.1016/j.bbi.2020.02.005. View

12.

Irwin M, Miller A . Depressive disorders and immunity: 20 years of progress and discovery. Brain Behav Immun. 2007; 21(4):374-83. DOI: 10.1016/j.bbi.2007.01.010. View

13.

Kato T, Katsuki R, Kubo H, Shimokawa N, Sato-Kasai M, Hayakawa K . Development and validation of the 22-item Tarumi's Modern-Type Depression Trait Scale: Avoidance of Social Roles, Complaint, and Low Self-Esteem (TACS-22). Psychiatry Clin Neurosci. 2019; 73(8):448-457. PMC: 6850625. DOI: 10.1111/pcn.12842. View

14.

Kato T, Yamauchi Y, Horikawa H, Monji A, Mizoguchi Y, Seki Y . Neurotransmitters, psychotropic drugs and microglia: clinical implications for psychiatry. Curr Med Chem. 2012; 20(3):331-44. DOI: 10.2174/0929867311320030003. View

15.

Kato T, Kanba S . Modern-Type Depression as an "Adjustment" Disorder in Japan: The Intersection of Collectivistic Society Encountering an Individualistic Performance-Based System. Am J Psychiatry. 2017; 174(11):1051-1053. DOI: 10.1176/appi.ajp.2017.17010059. View

16.

Kato T, Kanba S, Teo A . Hikikomori : Multidimensional understanding, assessment, and future international perspectives. Psychiatry Clin Neurosci. 2019; 73(8):427-440. DOI: 10.1111/pcn.12895. View

17.

Kato T, Hashimoto R, Hayakawa K, Kubo H, Watabe M, Teo A . Multidimensional anatomy of 'modern type depression' in Japan: A proposal for a different diagnostic approach to depression beyond the DSM-5. Psychiatry Clin Neurosci. 2015; 70(1):7-23. PMC: 5560068. DOI: 10.1111/pcn.12360. View

18.

Andrews J, Neises K . Cells, biomarkers, and post-traumatic stress disorder: evidence for peripheral involvement in a central disease. J Neurochem. 2011; 120(1):26-36. DOI: 10.1111/j.1471-4159.2011.07545.x. View

19.

Teo A, Fetters M, Stufflebam K, Tateno M, Balhara Y, Choi T . Identification of the hikikomori syndrome of social withdrawal: Psychosocial features and treatment preferences in four countries. Int J Soc Psychiatry. 2014; 61(1):64-72. PMC: 5573567. DOI: 10.1177/0020764014535758. View

20.

Hayashi F, Isobe N, Glanville J, Matsushita T, Maimaitijiang G, Fukumoto S . A new clustering method identifies multiple sclerosis-specific T-cell receptors. Ann Clin Transl Neurol. 2021; 8(1):163-176. PMC: 7818280. DOI: 10.1002/acn3.51264. View