Monthly Archives:
January 2021

Rare Disease Day 2021
January 21, 2021
Rare Disease Day 2021

Whether you think PANS/PANDAS is a Rare Disease or actually just rarely diagnosed, it is a day to educate people about PANS/PANDAS. The main objective of Rare Disease Day is to raise awareness...

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Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum

Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum

Frick LR, Rapanelli M, Jindachomthong K, et al. Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum. Brain Behav Immun. 2018;69:304-311. doi:10.1016/j.bbi.2017.12.004

“In summary, our in vivo approach to characterizing antibody reactivity in patients with PANDAS has identified a novel candidate pathophysiology: specific autoantibody binding to striatal cholinergic interneurons. This focus on cholinergic interneurons fits well with the developing appreciation of the role of these cells in tic disorders. Identification of the specific antigens on these cells and the functional consequences of antibody binding may open new avenues for the understanding and treatment of PANDAS and related conditions.”

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Maternal Autoimmunity and Inflammation are Associated with Childhood Tics and Obsessive-Compulsive Disorder: Transcriptomic Data show Common Enriched Innate Immune Pathways

Maternal Autoimmunity and Inflammation are Associated with Childhood Tics and Obsessive-Compulsive Disorder: Transcriptomic Data show Common Enriched Innate Immune Pathways

Hannah F. Jones, Velda X. Han, Shrujna Patel, Brian S. Gloss, Nicolette Soler, Alvin Ho, Suvasini Sharma, Kavitha Kothur, Margherita Nosadini, Louise Wienholt, Chris Hardwick, Elizabeth H. Barnes, Jacqueline R. Lim, Sarah Alshammery, Timothy C. Nielsen, Melanie Wong, Markus J. Hofer, Natasha Nassar, Wendy Gold, Fabienne Brilot, Shekeeb S. Mohammad, Russell C. Dale,
Maternal Autoimmunity and Inflammation are Associated with Childhood Tics and Obsessive-Compulsive Disorder: Transcriptomic Data show Common Enriched Innate Immune Pathways,
Brain, Behavior, and Immunity, 2021,ISSN 0889-1591 DOI: 10.1016/j.bbi.2020.12.035.

Highlights

  • Autoimmune disease is more frequent in mothers of children with tics/OCD.
  • Maternal inflammatory states are generally associated with childhood tics/OCD.
  • Maternal blood and Tourette brain transcriptomes show common innate immune pathways.
  • Inflammation may be an important environmental modifier in tic/OCD expression.
  • Targeting inflammation may mitigate risk and improve treatment of tics/OCD.

“Our findings demonstrate that maternal pro-inflammatory states, including autoimmune disease, are associated with tics/OCD in children, and support a possible role for maternal inflammation, in addition to immunogenetic and ‘neurogenic’ mechanisms in the aetiology of tic disorders and OCD. (Mataix-Cols et al., 2018) The breadth of immune conditions, including the heterogeneity of autoimmune diseases, and overlapping pathways in transcriptomic analysis of maternal blood and Tourette brain samples indicate that the innate immune response may be an important factor in disease expression. Inflammation is likely to be a more modifiable risk factor than susceptibility genes, and prospective studies which comprehensively assess pro-inflammatory states in mothers during pregnancy paired with detailed immunophenotyping, genomic and epigenomic testing, and careful evaluation of postnatal pro-inflammatory exposures in children, are needed to fully assess the role of inflammation as an environmental risk factor for neurodevelopmental disorders. Further understanding of the role of the immune system in neurodevelopment could unveil opportunities to mitigate risk to children by reducing exposure to inflammation and open new avenues for treatment.”

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Review: Investigational and Experimental Drugs to Treat Obsessive-Compulsive Disorder

Investigational and Experimental Drugs to Treat Obsessive-Compulsive Disorder

Grassi G, Cecchelli C, Vignozzi L, Pacini S. Investigational and Experimental Drugs to Treat Obsessive-Compulsive Disorder. J Exp Pharmacol. 2021;12:695-706. Published 2021 Jan 5. doi:10.2147/JEP.S255375

“Treatment-resistance is a frequent condition for obsessive-compulsive disorder (OCD). Over the past decades, a lot of effort has been made to address this issue, and several augmentation strategies of serotonergic drugs have been investigated. Antidopaminergic drugs are considered the first choice as augmentation strategy for treatment-resistant OCD patients, but they seem to work only for a subset of patients, and none of them have been officially approved for OCD. Recently, the role of glutamate and inflammation in OCD pathophysiology clearly emerged, and this has led to several investigations on glutamatergic and anti-inflammatory agents. Results seem promising but still inconclusive. Probiotic interventions (considered to modulate the immune systems and the brain activity) are gaining attention in several psychiatric fields but are still at their early stages in the OCD field. Research on new treatment approaches for OCD is moving forward, and more than one hundred interventional trials are ongoing around the world. While the vast majority of these trials involve neuromodulation and psychotherapeutic approaches, only a small proportion (around 20%) involve the investigation of new pharmacological approaches (tolcapone, nabilone, psilocybin, troriluzole, nitrous oxide, rituximab, naproxen, and immunoglobulins). Here, we provide a comprehensive review of investigational and experimental drugs to treat OCD.”

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Genes, Cells, and Neural Circuits Relevant to OCD and Autism Spectrum Disorder

Editor’s Note:
Genes, Cells, and Neural Circuits Relevant to OCD and Autism Spectrum Disorder
Ned H. Kalin, M.D.
Published Online:1 Jan 2021 DOI 10.1176/appi.ajp.2020.20111605

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“These cross-species translational data are potentially exciting and serve to focus the search for the pathophysiology of PANDAS toward a specific class of inter-neurons within the striatum that are known to fine tune and regulate striatal output via their influences on the abundant medium spiny GABAergic neurons that project to effector sites. Because of the similarities between PANDAS and bonafide OCD, these studies raise the possibility that striatal cholinergic interneurons are mechanistically involved in the pathophysiology of childhood OCD. In his editorial (9), Dr. Steve Hyman from Harvard University critically appraises this study and suggests that, in addition to the mechanism suggested by the findings in this article, other immune-related molecular pathways may also be important.”