Modulating neuroinflammation in COVID-19 patients with obsessive-compulsive disorder

V Nezgovorova, CJ Ferretti, S Pallanti, E Hollander. Modulating neuroinflammation in COVID-19 patients with obsessive-compulsive disorder. Journal of Psychiatric Research, 2021, DOI: 10.1016/j.jpsychires.2021.11.025.

Abstract: Exacerbation of symptoms of obsessive-compulsive disorder (OCD) during COVID-19 or new onset of the OCD symptoms resulting from COVID-19 infection is an understudied area of research. It is possible that increased proinflammatory immune status is associated with the onset of obsessive-compulsive symptoms in patients with COVID-19 and that targeted anti-inflammatory treatments for COVID-19 infection can mitigate the new onset of Obsessive-Compulsive (OC) spectrum symptoms. In this review, we cover OCD pathogenesis as related to COVID-19, summarize the impact of cytokines on behavior, and suggest that anti-cytokine treatments can help mitigate post-COVID-19 and new onset of the OC symptoms.



SARS-CoV-2 as a Trigger in the Development of Tourette’s-Like Symptoms: A Case Report

Sabine Hazan, MD, Sheldon Jordan, MD. SARS-CoV-2 as a Trigger in the Development of Tourette’s-Like Symptoms: A Case Report, 15 November 2021, PREPRINT (Version 1) available at Research Square DOI: 10.21203/  This case study has not been peer-reviewed.

  • Case report describe Tourette’s-like symptoms resulting from SARS-CoV-2 disrupting gut microbiota
  • SARS-CoV-2 could cause significant havoc in the enteric flora, damaging intestinal barrier, disrupting communication along the GMBA, imparing immune function, leading to neuropsychiatric symptoms
  • Several possible therapeutic approaches change the microbiome including prebiotics, postbiotics, synbiotics, and fecal transplantation
  • Using these therapies to modulate bacterial composition and enhance microbiota diversity is a pragmatic approach for enhanced protection against the acute morbidities associated with viral illnesses including COVID-19.


Treatment barriers in PANS/PANDAS: Observations from eleven health care provider families

Tang, A. W., Appel, H. J., Bennett, S. C., Forsyth, L. H., Glasser, S. K., Jarka, M. A., Kory, P. D., Malik, A. N., Martonoffy, A. I., Wahlin, L. K., Williams, T. T., Woodin, N. A., Woodin, L. C., Miller, I. K. T., & Miller, L. G. (2021). Treatment barriers in PANS/PANDAS: Observations from eleven health care provider families. Families, Systems, & Health. Advance online publication. DOI: 10.1037/fsh0000602

Despite published diagnostic and treatment guidelines for this condition, there are long delays in obtaining appropriate care. We sought to identify health care system barriers to timely treatment by examining cases of PANDAS/PANS occurring in children of health care professionals.

  • Parents included 11 physicians, 2 mental health professionals, 2 nurses, and a PharmD.
    Nine cases (82%) had “very delayed” diagnosis and treatment (>4 weeks after onset).
  • The most commonly encountered causes for treatment delay were clinician lack of awareness (82%), clinician skepticism (82%), overdependence on diagnostic testing (91%), and out-of-pocket expenses >$100 US (82%).
  • Other common challenges included difficulties finding a provider to spearhead care (64%), psychological misdiagnosis (55%), and children’s suppression of behaviors during assessments (55%).
Mycoplasma pneumoniae IgG positivity is associated with tic severity in chronic tic disorders

J Schnell, M Bond, N Moll, E Weidinger, B Burger, R Bond, A Dietrich, PJ. Hoekstra, A Schrag, D Martino, M Schwarz, U-X Meier, N Müller. Brain, Behavior, and Immunity. Vol 99, 2022. DOI: 10.1016/j.bbi.2021.10.012

  • M. pneumoniae IgG positivity was not associated with the presence of CTD.
  • M. pneumoniae IgG positivity was not associated with the first onset of tics.
  • M. pneumoniae IgG positivity was significantly associated with higher tic severity.

“It is possible that M. pneumoniae infection influences tic severity in CTD or, that having more severe tics, increases the risk of infection. However, it is more likely that the association observed in this study reflects a propensity toward enhanced immune responses in people with CTD and that, rather than a causal relationship, infection and greater tic severity are indirectly linked via shared underlying immune mechanisms.”

Clinical Manifestations of Patients with PANDAS in Patients Followed Up at Srebrnjak Children’s Hospital in 5-Year Period

Sizgoric MK, Kovac Sizgoric M, Miculinic A, et al. Clinical manifestations of patients with PANDAS in patients followed up at Srebrnjak children’s hospital in 5-year period. Archives of Disease in Childhood 2021;106:A169. Article

– 20 children, 16 (80%) male, 4 (20%) female, aged 3 to 11 years (median age 6.5)
-Elevated levels of antistreptolysin titers 19 of 20 (95%). Anti-DNAse-B levels were tested in 7 patients and was elevated in 4 (57%)
-Neuroimaging studies (N=12 or 60%) – no specific findings found
-Family history of tics and autoimmune disorders was positive in N=5

-All patients had OCD and tics with acute onset of symptoms
-Attention disorders N=17 (85%)
-Sleeping difficulties N=4 (20%)
-Speech difficulties N=5 (25%)
-Decline in school performance N=10 (71%)

-15 (75%) patients given first-line antibiotics. In 5 (25%) patients a full regression of symptoms was registered, 10 (50%) had partial improvement, 5 (25%) had no response.
-7 (35%) were given IVIG after initial antibiotic treatment with incomplete regression. Tics persisted in 11 patients and 4 had tics with behavioral difficulties. In 7 patients treated with IVIG we proceeded with parenteral antibiotics because of partial symptom regression and 2 were given corticosteroids (still followed).

Plasmapheresis, Rituximab, and Ceftriaxone Provided Lasting Improvement for a 27-Year-Old Adult Male with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)

A Krouse, H Li, JA Krenzer, WN Rose. Plasmapheresis, Rituximab, and Ceftriaxone Provided Lasting Improvement for a 27-Year-Old Adult Male with PANDAS. Dept of Pathology, University of Wisconsin Hospital. Article

  • At 17 – developed sudden psychosis and confusion after GAS infection. Had elevated anti-streptolysin O (ASO) titers. Did not present with typical symptoms of PANDAS – OCD and/or tic-like symptoms were not observed. A tentative diagnosis of PANDAS was given. Treated with antipsychotics, antibiotics, tonsillectomy, and IVIG which resulted in remissions and relapses of his neuropsychiatric symptoms.
  • At age 27 – received a trial of therapeutic plasma exchange (TPE), rituximab, and ceftriaxone. Eventually resulted in sustained benefit and minimal fluctuations of his clinical symptoms.
Brain areas involved with obsessive-compulsive disorder present different DNA methylation modulation

de Oliveira, K.C., Camilo, C., Gastaldi, V.D. et al. Brain areas involved with obsessive-compulsive disorder present different DNA methylation modulation. BMC Genom Data 22, 45 (2021). DOI:10.1186/s12863-021-00993-0

  • Confirms involvement of previously associated genes and biological processes in OCD as well as reports differences related to specific brain areas
  • Findings point to a role of cellular communication, inflammatory processes and behavior mediated by DNA methylation in OCD brain tissues.
  • Findings were related to the immune system, reaffirming the current literature findings about its involvement with OCD.
  • Changes in DNA methylation are involved with OCD and further studies are needed to characterize alterations in different paths in each brain area.
Disruptions and Adaptations in Family Functioning: A Study of Families’ Experiences with PANS/PANDAS

Dolce, J.L., LaRusso, M.D. & Abadia-Barrero, C. Disruptions and Adaptations in Family Functioning: A Study of Families’ Experiences with PANS/PANDAS. J Child Fam Stud (2021). DOI:10.1007/s10826-021-02101-3

  • Examined family functioning utilizing online parent forums and nine semi-structured interviews with PANS/PANDAS families.
  • Unpredictability & relapsing-remitting nature of neuropsychiatric symptoms cause significant disruptions to daily life.
  • Financial strain, social isolation, and lack of support from schools and medical institutions transform family functioning.
  • Parents’ frequent use of trauma metaphors to describe experience diverges from literature on other chronic illnesses.
Clinical Features in Patients With PANDAS/PANS and Therapeutic Approaches: A Retrospective Study

Rea I, Guido CA, Spalice A. Clinical Features in Patients With PANDAS/PANS and Therapeutic Approaches: A Retrospective Study. Frontiers in Neurology. Vol. 12, 2021. DOI=10.3389/fneur.2021.741176  

  • 62 patients with a clinical diagnosis of PANDAS/PANS.
    • 15 with PANS. 47 with PANDAS
  • Mean age at onset of PANDAS/PANS symptoms was 6.2 ± 1.2 years
    • 6.2 for PANDAS. 6.0 for PANS
  • Neurological and psychiatric symptoms were mostly evident in both groups with little difference
  • 93.5% had vocal tics
  • 79% had OCD
  • PANS kids had more irritability, aggressivity, and food restriction
  • PANDAS kids had 10 times higher levels of anti-streptolysin O and anti-DNAse B
  • PANS kid had a higher percentage of metabolic disorders
  • Psychotherapy significantly relieved OCD the most and reduced stress in patients and parents
  • Antibiotic prophylaxis was the most frequently used (90%) for acute neurological symptoms



Postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: Role of microglia and clinical implications

Manuel F. López-Aranda, Ishanu Chattopadhya, Gayle M. Boxx, Elizabeth R. Fraley, Tawnie K. Silva, Miou Zhou, Miranda Phan, Isaiah Herrera, Sunrae Talomam Rochelle Mandanas, Karen Bach and Michael Gandal and Daniel H. Geschwind, Genhong Cheng, Andrey Rzhetsky and Stephanie A. White, Alcino J. Silva. Postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: Role of microglia and clinical implications. Science Advances, vol 7. 38, 2021. DOI:10.1126/sciadv.abf2073

There is growing evidence that prenatal viral infections triggering immune activation contributes to neuropsychiatric disorders, including schizophrenia and autism spectrum disorders

Kids who had severe infections and are genetically predisposed to autism were more likely to develop the condition. So, the genetic factors don’t trigger autism but environmental factors play a significant role. One of the scientists said that childhood infections may be linked to higher instances of depression m, anxiety, schizophrenia.
  • Study links significant childhood infections to developing autism later.
  • In mouse models, mice that had an immune response later were no longer able to recognize familiar faces. This study was replicated with a focus on social interactions and the mice whose immune system was activated had increased difficulty communicating.
  • A different study reinforces the mouse model that tracked 3.6 million hospitalized children shoeing that hospitalizations due to infections during early childhood can predict a future diagnosis of ASD
Recent progress on Tourette syndrome

Ueda K, Black KJ. Recent progress on Tourette syndrome. Fac Rev. 2021;10:70. Published 2021 Sep 7. DOI:10.12703/r/10-70

“Recent years have seen increasing information about the relationship between tics and comorbidities and about new genetic findings. Inflammatory processes have also been a topic of continued interest.

“The prevalence and characteristics of tics in patients with encephalitis were reviewed in a systematic study, which found that sporadic cases of tics were associated with encephalitis, particularly during a post-encephalitis period, and with basal ganglia involvement. A case-control autopsy study (of nine individuals with TS) using basal ganglia transcriptome by RNA sequencing in the caudate and putamen found disrupted basal ganglia neuronal signaling. The study also found a significant increase in immune and inflammatory transcripts. These results suggest metabolic alterations and inflammatory involvement in TS pathophysiology.”

“Inflammation has been extensively discussed in tic pathophysiology. A recent review article on immunological mechanisms in the pathophysiology of tic disorders argues that innate and adaptive systemic immune pathways and neuroinflammatory mechanisms play an important role in the pathogenesis of at least some patients with TS.”

“Complementary and alternative medicines—including dietary or nutritional supplements (calcium, magnesium, coenzyme Q10, fish oil, gastrodin, and vitamins B, C, D, and E), chiropractic manipulations, meditation, acupuncture, hypnosis, homeopathy, and biofeedback—have been reported for the treatment of tics,; however, the evidence is limited because of a lack of randomized control studies. The efficacy and safety of a Chinese herbal medicine (5-Ling granule) in the treatment of TS were evaluated in a multicenter, double-blind randomized controlled trial, finding it as effective as tiapride in improving tic symptoms.”

GAPS Nutritional Protocol as a Treatment for PANDAS: A Case Study

Delaunay-Vagliasindi S, Seneff S, Coro S & Campbell-McBride N (2021) GAPS Nutritional Protocol as a treatment for PANDAS: A case study. J Orthomol Med. 36(3). 6 September 2021 

“Growing research is calling attention to the role of poor gut health in autoimmune conditions, psychological conditions, and neurological conditions – all of which are relevant to PANDAS. The gut microbiome is a perfect target for treatment as it is flexible and adapts quickly to changes. Currently, the first-line treatments for PANDAS are antibiotics and mood stabilizers. The GAPS Nutritional Protocol aims to heal the gut lining, and restore microbial balance in the gut flora. After 18 months, George saw all his PANDAS-related symptoms disappear – tics, anxiety, hypersensitivity to noise and odours, sleep issues, concentration issues, fine motor issues, digestive issues, restricted eating habits, and quality of eye-contact – to the point where his diagnosis was officially removed. In addition, the abnormal blood test results that were indicative of the PANDAS condition – EO, NEUT, LYMPH, NLR, MPV – were restored to normal ranges after the GAPS intervention.”