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

García-Delgar, Blanca; Morer, Àstrid; Luber, Maxwell J.; Coffey, Barbara J.

doi:10.1089/cap.2016.29118.bjc

Cited by 4 publications

(2 citation statements)

References 17 publications

(16 reference statements)

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“…If the trend identified here is confirmed in subsequent studies, the combined treatment with antidepressants and anti-inflammatory drugs like glucocorticoids may be a promising therapy for improving obsessive-compulsive symptoms, as observed in patients with major depressive disorder or schizophrenia [ 51 , 52 ]. In addition, other immune-modulating medications, such as anticytokine agents, may be useful as adjunct therapy in OCD individuals, as observed in a patient with tumor necrosis factor receptor-associated autoinflammatory syndrome (TRAPS), in which psychiatric symptoms, including tics and OCD, showed a remarkable improvement after treatment with the IL-1 blocking agent anakinra [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Inflammatory dysregulation of monocytes in pediatric patients with obsessive-compulsive disorder

Rodríguez

Morer

González-Navarro

et al. 2017

J Neuroinflammation

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BackgroundAlthough the exact etiology of obsessive-compulsive disorder (OCD) is unknown, there is growing evidence of a role for immune dysregulation in the pathophysiology of the disease, especially in the innate immune system including the microglia. To test this hypothesis, we studied inflammatory markers in monocytes from pediatric patients with OCD and from healthy controls.MethodsWe determined the percentages of total monocytes, CD16+ monocytes, and classical (CD14highCD16−), intermediate (CD14highCD16low), and non-classical (CD14lowCD16high) monocyte subsets in 102 patients with early-onset OCD and in 47 healthy controls. Moreover, proinflammatory cytokine production (GM-CSF, IL-1β, IL-6, IL-8, and TNF-α) was measured by multiplex Luminex analysis in isolated monocyte cultures, in basal conditions, after exposure to lipopolysaccharide (LPS) to stimulate immune response or after exposure to LPS and the immunosuppressant dexamethasone.ResultsOCD patients had significantly higher percentages of total monocytes and CD16+ monocytes than healthy controls, mainly due to an increase in the intermediate subset but also in the non-classical monocytes. Monocytes from OCD patients released higher amounts of GM-CSF, IL-1β, IL-6, IL-8, and TNF-α than healthy controls after exposure to LPS. However, there were no significant differences in basal cytokine production or the sensitivity of monocytes to dexamethasone treatment between both groups. Based on monocyte subset distribution and cytokine production after LPS stimulation, patients receiving psychoactive medications seem to have an intermediate inflammatory profile, that is, lower than non-medicated OCD individuals and higher than healthy controls.ConclusionsThese results strongly support the involvement of an enhanced proinflammatory innate immune response in the etiopathogenesis of early-onset OCD.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-1042-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Inflammatory dysregulation of monocytes in pediatric patients with obsessive-compulsive disorder

Rodríguez

Morer

González-Navarro

et al. 2017

J Neuroinflammation

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“…TNFRSF1A and TNFRSF1B expression is upregulated in the striatum of TD patients [ 64 ] and the blood expression of TNFSRF1B is negatively correlated with TD symptom severity [ 67 ]. In addition, a mutation in TNFRSF1A has been linked to persistent tics [ 177 ]. A direct involvement of TNFB in the pathogenesis of TD has not been studied but some evidence for its (putative) role in TD comes from studies on auto-immune disorders.…”

Section: Discussionmentioning

confidence: 99%

Molecular Landscape of Tourette’s Disorder

Widomska

Witte

Buitelaar

et al. 2023

IJMS

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Tourette’s disorder (TD) is a highly heritable childhood-onset neurodevelopmental disorder and is caused by a complex interplay of multiple genetic and environmental factors. Yet, the molecular mechanisms underlying the disorder remain largely elusive. In this study, we used the available omics data to compile a list of TD candidate genes, and we subsequently conducted tissue/cell type specificity and functional enrichment analyses of this list. Using genomic data, we also investigated genetic sharing between TD and blood and cerebrospinal fluid (CSF) metabolite levels. Lastly, we built a molecular landscape of TD through integrating the results from these analyses with an extensive literature search to identify the interactions between the TD candidate genes/proteins and metabolites. We found evidence for an enriched expression of the TD candidate genes in four brain regions and the pituitary. The functional enrichment analyses implicated two pathways (‘cAMP-mediated signaling’ and ‘Endocannabinoid Neuronal Synapse Pathway’) and multiple biological functions related to brain development and synaptic transmission in TD etiology. Furthermore, we found genetic sharing between TD and the blood and CSF levels of 39 metabolites. The landscape of TD not only provides insights into the (altered) molecular processes that underlie the disease but, through the identification of potential drug targets (such as FLT3, NAALAD2, CX3CL1-CX3CR1, OPRM1, and HRH2), it also yields clues for developing novel TD treatments.

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Cotrimoxazole/methylphenidate

2017

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

Cited by 4 publications

References 17 publications

Inflammatory dysregulation of monocytes in pediatric patients with obsessive-compulsive disorder

Inflammatory dysregulation of monocytes in pediatric patients with obsessive-compulsive disorder

Molecular Landscape of Tourette’s Disorder

Cotrimoxazole/methylphenidate

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