Cytokine Correlations in Youth with Tic Disorders

Abstract

Background: Studies have noted immunological disruptions in patients with tic disorders, including increased serum cytokine levels. This study aimed to determine whether or not cytokine levels could be correlated with tic symptom severity in patients with a diagnosed tic disorder. Methods: Twenty-one patients, ages 4-17 years (average 10.63 -2.34 years, 13 males), with a clinical diagnosis of Tourette's syndrome (TS) or chronic tic disorder (CTD), were selected based on having clinic visits that coincided with a tic symptom exacerbation and a remission. Ratings of tic severity were assessed using the Yale Global Tic Severity Scale (YGTSS) and serum cytokine levels (interleukin [IL]-2, IL-4, IL-5, IL-10, IL-12p70, IL-13, interferon [IFN]-c, tumor necrosis factor [TNF]-a, and granulocyte macrophage-colony stimulating factor [GM-CSF]) were measured using Luminex xMAP technology. Results: During tic symptom exacerbation, patients had higher median serum TNF-a levels (z = -1.962, p = 0.05), particularly those on antipsychotics (U = 9.00, p = 0.033). Increased IL-13 was also associated with antipsychotic use during exacerbation (U = 4.00, p = 0.043) despite being negatively correlated to tic severity scores (q = -0.599, p = 018), whereas increased IL-5 was associated with antibiotic use (U = 6.5, p = 0.035). During tic symptom remission, increased serum IL-4 levels were associated with antipsychotic (U = 6.00, p = 0.047) and antibiotic (U = 1.00, p = 0.016) use, whereas increased IL-12p70 (U = 4.00, p = 0.037) was associated with antibiotic use. Conclusions: These findings suggest a role for cytokine dysregulation in the pathogenesis of tic disorders. It also points toward the mechanistic involvement and potential diagnostic utility of cytokine monitoring, particularly TNF-a levels. Larger, systematic studies are necessary to further delineate the role of cytokines and medication influences on immunological profiling in tic disorders.

Immune function changes of the IDPN‐induced Tourette syndrome rat model

“…This may be due to a homeostasis effect under toxic stress. In a balanced system, increased IL‐4 may help fight the physical and psychological disorders (Parker‐Athill et al., 2015; Pranzatelli et al., 2017). Intuitively, acute IDPN treatment may cause impairment in the Treg cells and hence immune dysfunction.…”

Regulatory effects of Ningdong granule on microglia-mediated neuroinflammation in a rat model of Tourette's syndrome

“…After intervention with NDG, tics were alleviated, and the levels of TNF-α and IL-6in the striatum and serum of rats with TS decreased. TNF-α plays an integral role in immunological responses to infection as a potent regulator of the immune system and inflammatory processes, recruiting macrophages, activating T-cells, and inducing the expression of downstream cytokines and other immune mediators during infection (28). IL-6 is an important mediator of neuroinflammation and is involved in microglial priming under neuroinflammatory conditions.…”

Obsessive-Compulsive Disorder, Tics, and Autoinflammatory Diseases: Beyond PANDAS

“…Recent studies have described increased levels of proinflammatory markers in children and adolescents with neuropsychiatric disorders, including OCD and tics (Mitchell and Goldstein 2014;Gariup et al 2015). Studies have also reported higher levels of serum TNF-a during periods of tic exacerbation (Leckman et al 2005;Parker-Athill et al 2015). Although the correlation between tic severity and high cytokine levels does not imply causation, it seems plausible to hypothesize that psychiatric symptoms could attenuate with the remission of inflammation.…”