Increased densities of T and B lymphocytes indicate neuroinflammation in subgroups of schizophrenia and mood disorder patients.
Abstract
An increasing number of clinical, epidemiological and genetic studies as well as investigations of CSF and blood suggests that neuroinflammation plays an essential role in the etiology of schizophrenia and mood disorders. However, direct neuropathological evidence of inflammation within the brain tissue remains sparse and the regional distribution of lymphocytes as surrogate markers of blood-brain barrier (BBB) impairment has not yet been investigated in this context. Densities of T and B lymphocytes were assessed in coronal whole brain sections of 22 patients with schizophrenia and 20 patients suffering from major depression or bipolar disorder, compared to 20 individuals without neuropsychiatric disorders from the Magdeburg Brain Collection. Cell densities were determined by immunohistochemical staining (anti-CD3 for T cells, anti-CD20 for B cells), followed by automated microscopic image acquisition and analysis. Hierarchical clustering and detailed cluster analysis were performed to detect possible subgroups of patients. Regional distribution was assessed by analysis of color coded mappings based on microsopic scans. Elevated lymphocyte density was found in 7 out of 20 mood disorder patients (adj. p = 0.022; Fisher's exact test, FET), 9 out of 22 schizophrenic patients (adj. p = 0.014; FET) and in 1 of 20 controls (p < 0.005; FET). Several cases showed different patterns of infiltration affecting cortical regions or subcortical white matter, while some presented diffuse infiltration. In two thirds of patients, no increased lymphocyte density could be found. The current findings indicate that lymphocyte infiltration occurs in a greater proportion of schizophrenia and mood disorder patients as compared to healthy controls. Under healthy conditions lymphocytes rarely cross the BBB. Thus, higher densities are considered indicators of neuroinflammation associated with an impairment of the BBB.
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T cell function degradation in MMD could be due to inflammatory substances such as tumor necrosis factor-α destroying T cell function.
“T cell function degradation could be due to inflammatory substances such as tumor necrosis factor-α destroying T cell function.”
In MMD patients, immunological function is compromised, with increased T cell apoptosis, increased neutrophils, and decreased total lymphocytes.
“In MMD patients, the immunological function was compromised, for T cell apoptosis increased, neutrophils rose, and total lymphocytes decreased.”
B cells mediate humoral immunity via antibodies, and as the number of B cells falls, the rate of transformation falls.
“B cells mediate humoral immunity via antibodies; as the number of B cells falls, so does the rate of transformation [57].”
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- Authors
- Schlaaff, K., Dobrowolny, H., Frodl, T., Mawrin, C., Gos, T., Steiner, J., & Bogerts, B.
- Affiliations
- Otto-von-Guericke-Universität Magdeburg (DE)
- German Center for Neurodegenerative Diseases (DE)
- Center for Behavioral Brain Sciences (DE)
- Gdańsk Medical University (PL)
- Corresponding author
- Schlaaff, Konstantin
- Venue
- Brain Behavior and Immunity
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 88
- Pages
- 497-506
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W3015654719
- Cited by
- 107
- References
- 58
- Citations by year
- 2026: 10 · 2025: 24 · 2024: 20 · 2023: 19 · 2022: 23 · 2021: 9 · 2020: 2
- FWCI
- 4.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- DZNE Pub (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Stanley Foundation (07R-1832)
- Bundesministerium für Bildung und Forschung (NBL-3/2, 01ZZ0407)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- neuroinflammation, schizophrenia, mood disorders, major depressive disorder, bipolar disorder, T cells, B cells, lymphocyte infiltration, blood-brain barrier disruption, brain tissue, patient subgroups
- MeSH terms
- B-Lymphocytes, Bipolar Disorder, Brain, Humans, Schizophrenia, T-Lymphocytes, Mood Disorders
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