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.”
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.”

Thank You to Our Generous Donors!
On behalf of ASPIRE, thank you for your ongoing support, and we hope you have a happy and healthy New...
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
“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.”
Catatonia in a 6-year-old Patient Following Disseminated Group A Streptococcus Infection
- Catatonia is a neuropsychiatric syndrome characterized by diverse features including mutism, posturing, negativism, staring, rigidity, and echophenomenon.
- The mechanism of catatonia is still being elucidated; in this case, catatonia triggered by GAS infection is one potential mechanism.
- Further systematic study of catatonia in the pediatric population is warranted to better understand pathogenesis and long-term neuropsychiatric outcomes.
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.

Announcing New Board Member – Michael McCartney
Michael McCartney serves as ASPIRE’s Vice President and focuses on organizational strategy, community engagement, communications, and...

2020 Year in Review
Despite the challenges of 2020, we are proud to report that the ASPIRE community continues to grow in size, support, and strength. We are grateful to all of you for your contributions: the...

Anu French, MD – Professional Advisory Board Highlight
"The goal of this project is to challenge the narrative about who in this country is on the front lines of the fight against COVID 19 by honoring women of color physicians with portraits reflecting...

COVID Patients with Psychotic Symptoms
“A small number of Covid patients who had never experienced mental health problems are developing severe psychotic symptoms weeks after contracting the...
Prevalence of PANS in Child Prevalence of pediatric acute-onset neuropsychiatric syndrome (PANS) in children and adolescents with eating disorders Adolescent Eating Disorders
- 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.”