A pilot study on immuno-psychiatry in the 22q11.2 deletion syndrome: A role for Th17 cells in psychosis?

Abstract

Background: A growing body of evidence supports a role for immune alterations in Schizophrenia Spectrum Disorders (SSD). A high prevalence (25–40%) of SSD has been found in patients with 22q11.2 deletion syndrome (22q11.2DS), which is known for T-cell deficits due to thymus hypoplasia. This study is the first to explore the association between the T-cell subsets and psychotic symptoms in adults with 22q11.2DS. Methods: 34 individuals (aged 19–38 yrs.) with 22q11.2DS and 34 healthy age- and gender matched control individuals were included. FACS analysis of the blood samples was performed to define T-cell subsets. Ultra-high risk for psychosis or diagnosis of SSD was determined based on CAARMS interviews and DSM-5 criteria for SSD. Positive psychotic symptom severity was measured based on the PANSS positive symptoms subscale. Results: A partial T-cell immune deficiency in 22q11.2DS patients was confirmed by significantly reduced percentages of circulating T and T-helper cells. Significantly higher percentages of inflammatory Th1, Th17, and memory T-helper cells were found in adults with 22q11.2DS. Most importantly an increased Th17 percentage was found in adults with psychotic symptoms as compared to non-psychotic adults with 22q11.2DS, and Th17 percentage were related to the presence of positive psychotic symptoms. Conclusions: Given the literature on the role of T cells and in particular of Th17 cells and IL-17 in hippocampus development, cognition and behavior, these results support the hypothesis for a role of Th17 cells in the development and/or regulation of psychotic symptoms in 22q11.2DS. This pilot study underlines the importance to further study the role of T-cell defects and of Th17 cells in the development of psychiatric symptoms. It also supports the possibility to use 22q11.2DS as a model to study T-cell involvement in the development of SSD.

Disruption of the Blood-Brain Barrier in 22q11.2 Deletion Syndrome

“…Fundamental to this hypothesis is the clinical data indicating peripheral inflammation in a subpopulation of SZ patients, including elevated peripheral 30 cytokines (most notably IL-6) and immune cell activation (especially of Th17 cells) (Debnath & Berk, 2014;Potvin et al, 2008;Subbanna et al, 2018b). Interestingly, 22qDS patients present with a similar inflammatory profile, as they also have elevated peripheral IL-6 and increased percentages of circulating Th17 cells (Mekori-Domachevsky et al, 2015;O'Rourke & Murphy, 2019;Vergaelen et al, 2018). Furthermore, a key component to the association between this reported immune activation and SZ is that BBB disruption facilitates CNS inflammation and neuronal dysfunction.…”

Genetic and environmental influences on circulating NK and T cells and their relation to bipolar disorder

“…Mild deficiencies of T cells per se could explain disturbances in mood state, since T cells are indispensable for a proper structure and function of the hippocampus (Lewitus et al 2008; Niebling 2004). Mild to severe T cell deficiencies can be due to genetic defects/polymorphisms, such as to the 22q11 deletion syndrome (Vergaelen et al 2018). On the other hand environmental influences, such as virus infections (e.g.…”

A Gut Feeling: The Importance of the Intestinal Microbiota in Psychiatric Disorders

“…Although family history is a risk for the disease, environmental factors, including viral and parasitic infections, are under scrutiny (98). Neuroinflammation has also been recently proposed to play a role in the pathology of schizophrenic brains (99, 100), including the impact of Th17 cells in 22q11.2 deletion syndrome (22q11.2DS) patients suffering from schizophrenia spectrum disorders (SSD) and psychotic symptoms (101). A positive correlation between IgG levels to dietary wheat gluten and bovine milk casein in serum and cerebrospinal fluid of schizophrenic patients was found (102).…”