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.”

Predictors and Prospective Course of PANS: A Pilot Study Using Electronic Platforms for Data Collection

Predictors and Prospective Course of PANS: A Pilot Study Using Electronic Platforms for Data Collection

Conclusion: Our study highlights the utility of electronic methods for tracking longitudinal symptoms in children with PANS and suggests that particular baseline characteristics (e.g., delay in identification and treatment of PANS, greater caregiver burden) may be indicative of a differential trajectory of PANS course, with more severe symptoms over the short term. clinicaltrials.gov NCT04382716.

Elizabeth C. Harris, Christine A. Conelea, Michael T. Shyne, and Gail A. Bernstein.Journal of Child and Adolescent Psychopharmacology. http://doi.org/10.1089/cap.2020.0124
Prevalence of PANS in Child and Adolescent Eating Disorders
Prevalence of PANS in Child and Adolescent Eating Disorders
Marya Aman, Jennifer Coelho, BoyeeLin, Cynthia Lu, Shannon Zaitsoff, John Best and S. Evelyn StewartBC Children’s Hospital Research Institute, University of British Columbia
“Conclusion
  •  The surprisingly high lifetime PANS rate of 52% within pediatric ED were higher than that previously reported for OCD populations. The large majority had abrupt onset of parent- reported OC symptoms as well as abrupt food restriction.
  • Those in the PANS group were more likely to be female, be prescribed an SSRI, and have parent reported abrupt OC symptom onset, abrupt food refusal, relapsing and remitting course, and concurrent anxiety, depression, irritability or aggression, behavioural regression, school deterioration, and sleep problems, enuresis, and/or frequent urination.
  • This appears to be a distinct subgroup that requires further characterization with respect to functional impacts and management approaches.”
Infections, inflammation, and risk of neuropsychiatric disorders: the neglected role of “co-infection”

Infections, inflammation, and risk of neuropsychiatric disorders: the neglected role of “co-infection

AmirAbdoli, AliTaghipour, MajidPirestani, Mirza AliMofazzal Jahromi, AbazarRoustazadeh, HamedMir, Hoda MirzaianArdakani, AzraKenarkoohi, ShahabFalahi, MahdiKarimi. Infections, inflammation, and risk of neuropsychiatric disorders: the neglected role of “co-infection. Heliyon Vol 6, Issue 12, Dec 2020, e05645. DOI: 10.1016/j.heliyon.2020.e05645

Abstract: Neuropsychiatric disorders (NPDs) have multiple etiological factors, mainly genetic background, environmental conditions and immunological factors. The host immune responses play a pivotal role in various physiological and pathophysiological process. In NPDs, inflammatory immune responses have shown to be involved in diseases severity and treatment outcome. Inflammatory cytokines and chemokines are involved in various neurobiological pathways, such as GABAergic signaling and neurotransmitter synthesis. Infectious agents are among the major amplifier of inflammatory reactions, hence, have an indirect role in the pathogenesis of NPDs. As such, some infections directly affect the central nervous system (CNS) and alter the genes that involved in neurobiological pathways and NPDs. Interestingly, the most of infectious agents that involved in NPDs (e.g., Toxoplasma gondii, cytomegalovirus and herpes simplex virus) is latent (asymptomatic) and co-or-multiple infection of them are common. Nonetheless, the role of co-or-multiple infection in the pathogenesis of NPDs has not deeply investigated. Evidences indicate that co-or-multiple infection synergically augment the level of inflammatory reactions and have more severe outcomes than single infection. Hence, it is plausible that co-or-multiple infections can increase the risk and/or pathogenesis of NPDs. Further understanding about the role of co-or-multiple infections can offer new insights about the etiology, treatment and prevention of NPDs. Likewise, therapy based on anti-infective and anti-inflammatory agents could be a promising therapeutic option as an adjuvant for treatment of NPDs.
Cognitive, Graphomotor, and Psychosocial Challenges in Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS)

Cognitive, Graphomotor, and Psychosocial Challenges in Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS)

Mary K. Colvin, Savannah Erwin, Priyanka R. Alluri, Alexandra Laffer, Kathryn Pasquariello, and Kyle A. Williams. Cognitive, Graphomotor, and Psychosocial Challenges in Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS). The Journal of Neuropsychiatry and Clinical Neuroscience. DOI: 10.1176/appi.neuropsych.20030065

Conclusions: These findings indicated relative difficulties with aspects of executive and motor functions. Although evaluations were performed following the resolution of acute symptoms, ongoing and significant academic difficulties and emotional, behavioral, and social concerns were targets for clinical intervention and support.

Anti-inflammatory Augmentation Therapy in Obsessive-compulsive Disorder: A Review
Hanie Ghasemi, Homa Nomani, Amirhossein Sahebkar* and Amir Hooshang Mohammadpour*, “Anti-inflammatory Augmentation Therapy in Obsessive-compulsive Disorder: A Review”, Letters in Drug Design & Discovery (2020) 17: 1198. DOI: 10.2174/1570180817999200520122910
Anti-inflammatory Augmentation Therapy in Obsessive-compulsive Disorder: A Review
“Results: Recent studies display that inflammation processes and the dysfunction of the immune system are likely to play a role in the pathophysiology of OCD, indicating that the disturbances in neurotransmitters such as serotonin and dopamine cannot be alone involved in the development of OCD. Therefore, it seems that medications with anti-inflammatory effects have the potential to be evaluated as a new therapeutic strategy for OCD. However, this issue can be studied closely if OCD etiological factors are thoroughly understood. The present review study aims at gathering all obtained results concerning new treatments targeting inflammation in OCD patients. Reviewing the conducted studies shows that the use of agents with anti-inflammatory properties, including some NSAIDs, Minocycline and Atorvastatin, could lead to promising and intriguing results in the treatment of OCD. Curcumin also showed good efficacy in the reduction of OCD-like behavior when it has been used in an animal model. However, there is still no definitive and conclusive evidence for any of the medications proposed.
Conclusion: More future studies are needed to investigate anti-inflammatory treatment strategies for OCD and its other subtypes such as Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS), and Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS)”
Borrelia miyamotoi Serology in a Clinical Population With Persistent Symptoms and Suspected Tick-Borne Illness

Borrelia miyamotoi Serology in a Clinical Population With Persistent Symptoms and Suspected Tick-Borne Illness

Delaney Shannon L., Murray Lilly A., Aasen Claire E., Bennett Clair E., Brown Ellen, Fallon Brian A. Borrelia miyamotoi Serology in a Clinical Population With Persistent Symptoms and Suspected Tick-Borne Illness. Front. Med., 27 October 2020 . DOI=10.3389/fmed.2020.567350

ABSTRACT=Eighty-two patients seeking consultation for long-term sequalae after suspected tick-borne illness were consecutively tested for Borrelia miyamotoi antibodies using a recombinant glycerophosphodiester phosphodiesterase (GlpQ) enzyme immunoassay. Twenty-one of the 82 patients (26%) tested positive on the GlpQ IgG ELISA. Nearly all of the patients (98%) had no prior B. miyamotoi testing, indicating that clinicians rarely test for this emerging tick-borne pathogen. Compared to patients who solely tested positive for Lyme disease antibodies, patients with B. miyamotoi antibodies presented with significantly more sleepiness and pain. A prospective study is needed to ascertain the relationship between the presence of B. miyamotoi antibodies and persistent symptoms.

Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections

Chain Jennifer L., Alvarez Kathy, Mascaro-Blanco Adita, Reim Sean, Bentley Rebecca, Hommer Rebecca, Grant Paul, Leckman James F., Kawikova Ivana, Williams Kyle, Stoner Julie A., Swedo Susan E., Cunningham Madeleine W. Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections. Jnl Frontiers in Psychiatry. Vol.11, 2020. DOI.10.3389/fpsyt.2020.00564   

See Dr. Susan Swedo on new research on Autoantibody Biomarkers for Basal Ganglia Encephalitis for PANDAS and SC