Research

Cytokine Effects on the Basal Ganglia and Dopamine Function: the Subcortical Source of Inflammatory Malaise

Felger JC, Miller AH. Cytokine effects on the basal ganglia and dopamine function: the subcortical source of inflammatory malaise. Front Neuroendocrinol. 2012 Aug;33(3):315-27. doi: 10.1016/j.yfrne.2012.09.003. Epub 2012 Sep 21. PMID: 23000204; PMCID: PMC3484236.

Cytokines released during inflammation target the basal ganglia and dopamine
Cytokines can disrupt dopamine function by effects on synthesis, packaging, release, and reuptake
Cytokine effects on basal ganglia dopamine may cause anhedonia, fatigue, and psychomotor slowing
Cytokines may contribute to behavioral disorders associated with chronic inflammation

Persistent SARS-CoV-2 Infection, EBV, HHV-6 and Other Factors May Contribute to Inflammation and Autoimmunity in Long COVID

Vojdani A, Vojdani E, Saidara E, Maes M. Persistent SARS-CoV-2 Infection, EBV, HHV-6 and Other Factors May Contribute to Inflammation and Autoimmunity in Long COVID. Viruses. 2023 Jan 31;15(2):400. doi: 10.3390/v15020400. PMID: 36851614; PMCID: PMC9967513.

“Based on our review of the literature, in both past and recent studies, we have found clues to these mechanisms that might drive this long COVID, with the goal of identifying host or virus factors that can be intervened upon to prevent or reverse this condition. A better understanding of these immunological mechanisms in patients with severe long COVID holds great promise for designing treatment strategies to minimize viral persistence, control the reactivation of latent viruses, and to modulate a dysregulated immune system and host microbiota, which together are involved in the virus-induced inflammation and autoimmunity that are observed in patients with long COVID.”

Neuropsychiatric Testing Provides Objective Insight into Beneficial Effects of IVIG in Patients with PANS

Dr. Daines and the team at the CPAE Center of Excellence (University of Arizona) recently conducted a poster presentation at the AAAAI. The study demonstrates the beneficial effects of IVIG treatments for PANS patients. 11 out of 12 PANS patients showed “significant” improvement following IVIG treatment.

The significant presence of baseline hypogammaglobulinemia in children with PANS emphasizes the presumed role of immune dysfunction in disease pathogenesis, especially given the known connection between immunodeficiency and autoimmunity (8,9). Thus, immunomodulatory interventions are presumed to have a crucial therapeutic role.

It did not assess the benefit of IVIG for OCD or Restricted Eating as the other psychiatric, and neuropsychological manifestations can sometimes overshadow OCD (1-3). Since objective post-treatment evaluations are scarce and challenging given disease complexity (5-7), the study used standardized neuropsychiatric testing to assess how (IVIG) treatment impacts cognitive function in children with PANS.

The research, as presented in the poster session, will be submitted as a journal article.

Risk of Major Mental Disorder after Severe Bacterial Infections in Children and Adolescents: A Nationwide Longitudinal Study

Hsu TW, Chu CS, Tsai SJ, Bai YM, Su TP, Chen TJ, Chen MH, Liang CS. Risk of Major Mental Disorder after Severe Bacterial Infections in Children and Adolescents: A Nationwide Longitudinal Study. Neuropsychobiology. 2022 Nov 18:1-11. doi: 10.1159/000526984.

11 investigated pathogens, namely, Streptococcus, Staphylococcus, Pseudomonas, Klebsiella, Hemophilus, Mycoplasma, Tuberculosis, Meningococcus, Escherichia, Chlamydia, and Scrub typhus.
The primary outcomes were the subsequent risk of seven MMDs: 1- autism spectrum disorder (ASD), 2- attention-deficiency hyperactivity disorder (ADHD), 3- obsessive-compulsive disorder (OCD), 4- tic disorder, -5 schizophrenia, 6- bipolar disorder, 7- depressive disorder.
The secondary outcomes were the subsequent risk of exposure to psychotropic medications.

Conclusions: After bacterial infection, the risk of MMDs increased in children and adolescents compared to controls, and such associations varied with different pathogens. Future studies are warranted to validate our study findings and investigate the potential mechanisms.

A Survey of Demographics, Symptom Course, Family History, and Barriers to Treatment in Children with Pediatric Acute-Onset Neuropsychiatric Disorders and Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections

SL O’Dor, S Homayoun, OM.Downer, MA Hamel, JS Zagaroli, KA Williams.A Survey of Demographics, Symptom Course, Family History, and Barriers to Treatment in Children with Pediatric Acute-Onset Neuropsychiatric Disorders and Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections.Journal of Child and Adolescent Psychopharmacology.Nov 2022.476-487.http://doi.org/10.1089/cap.2022.0063

At onset, OCD was the most common psychiatric symptom 83.06% reported in children, along with a high percentage of medical and psychiatric comorbidities.
Most psychiatric comorbidities began or worsened at the onset of PANS/PANDAS symptoms. However, major depressive disorder was the most frequently reported psychiatric disorder to develop after PANS/PANDAS onset (10%).
Family members report high frequency of autoimmune and inflammatory conditions, with 29.95% of mothers endorsing one or more autoimmune conditions.
Mean caregiver burden is above “burnout” level. Caregivers had mildly elevated levels of depression, anxiety, and stress.

Preexisting Neuropsychiatric Conditions and Associated Risk of Severe COVID-19 Infection and Other Acute Respiratory Infections

Ranger TA, Clift AK, Patone M, et al. Preexisting Neuropsychiatric Conditions and Associated Risk of Severe COVID-19 Infection and Other Acute Respiratory Infections. JAMA Psychiatry. Published online November 09, 2022. doi:10.1001/jamapsychiatry.2022.3614

Conclusions and Relevance In this longitudinal cohort study, UK patients with preexisting neuropsychiatric conditions and treatments were associated with similarly increased risks of severe outcome from COVID-19 infection and SARIs, except for dementia.

Roles of Th17 cytokines in microglial and neurovascular responses to recurrent intranasal Streptococcus pyogenes infections

Wayne, Charlotte Remy. Roles of Th17 cytokines in microglial and neurovascular responses to recurrent intranasal Streptococcus pyogenes infections. 2022 Theses Doctoral. Columbia Academic Commons. https://doi.org/10.7916/62va-6330

Academic Units: Cellular, Molecular and Biomedical Studies
Thesis Advisors: Agalliu, Dritan
Degree: Ph.D., Columbia University
Published: September 7, 2022

Obsessive-Compulsive Disorder With Inflammatory Cerebrospinal Fluid Changes and Intrathecal Antinuclear Antibody Staining

D Endres, MA Schiele, BC Frye, A Schlump, B Feige, k Nickel, B Berger, M Reisert, H Urbach, K Domschke, N Venhoff, H Prüss, L Tebartz van Elst. Obsessive-Compulsive Disorder With Inflammatory Cerebrospinal Fluid Changes and Intrathecal Antinuclear Antibody Staining. Biological Psychiatry. Elsevier. 3 September 2022. DOI:https://doi.org/10.1016/j.biopsych.2022.06.037

Autoimmune-mediated obsessive-compulsive disorder (OCD) during childhood has long been established in the context of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection. In adult psychiatry, the topic has increasingly gained interest in light of new developments regarding autoimmune encephalitis and autoimmune psychosis. Hence, diagnostic criteria for autoimmune OCD in adulthood have been proposed recently, and the first respective cases were reported. For the detection of neuroinflammatory processes, cerebrospinal fluid (CSF) analysis (besides the far more invasive brain biopsy) is considered the most sensitive diagnostic tool. Here, we present 2 paradigmatic OCD patients with inflammatory CSF signals including antinuclear antibody staining in CSF and magnetic resonance imaging (MRI)/electroencephalography (EEG) findings compatible with OCD.

Group A Beta-Hemolytic Streptococcus-Induced Tic-Like Movement Disorder in an Adult: A Case Report

Ilyas U, Umar Z, Lin D (August 26, 2022) Group A Beta-Hemolytic Streptococcus-Induced Tic-Like Movement Disorder in an Adult: A Case Report. Cureus 14(8): e28451. doi:10.7759/cureus.28451

“Our case report highlights the importance of a thorough history, including inquiring about past infections and investigations to look for autoimmune and infectious etiologies, including ASO and positive DNAse B titers, in adult patients with new onset movement disorders and no other identifiable etiology and risk factors. Further research is mandatory to investigate the incidence of movement disorders in the adult population after a streptococcal infection and the diagnostic approach and treatment modalities needed to manage such patients.”

An unusual case of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections(PANDAS) – diagnostic evaluation, treatment and the remarkable outcome

Divya Raj T, Santosh H, Chaturvedi S. 589 An unusual case of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections(PANDAS) – diagnostic evaluation, treatment and the remarkable outcome Archives of Disease in Childhood 2022;107:A224-A225.

“Conclusion Our observation in this case confirms the value of early diagnosis to reduce the risk of progression to disabling chronic neurologic sequelae in the PANDAS. Children with PANDAS derive a favourable response to IVIG. Our findings support its administration early in the course of the disease and continued until significant improvement or remission is achieved without side-effects.”

Sex and Aggression Characteristics in a Cohort of Patients with Pediatric Acute-Onset Neuropsychiatric Syndrome

Jaynelle Gao, Avis Chan, Theresa Willett, Bahare Farhadian, Melissa Silverman, Paula Tran, Sana Ahmed, Margo Thienemann, and Jennifer Frankovich.Sex and Aggression Characteristics in a Cohort of Patients with Pediatric Acute-Onset Neuropsychiatric Syndrome.Journal of Child and Adolescent Psychopharmacology.ahead of print http://doi.org/10.1089/cap.2021.0084

Males had a higher median Modified Overt Aggression Scale (MOAS) score in the first year of clinic when compared with females and a higher median subscore for physical aggression.
The median time from PANS symptom onset to first administration of immunotherapy, which did not include nonsteroidal anti-inflammatory drugs or short bursts of oral steroids, was 6.9 years for females and 3.7 years for males.
Although the physical aggression measured by the MOAS was significantly higher in males, caregivers of males and females reported similar levels of caregiver burden.
The two groups did not differ significantly in age of PANS onset, time from onset to clinic entry, other psychiatric symptom measures, or laboratory markers of inflammation.

Conclusion: Among patients with PANS, males exhibit more aggressive behavior when compared with females, which may advance the decision to treat with immunotherapy. Scores that capture a more global level of functioning show that despite there being a higher level of aggression in males, female patients with PANS have similar levels of overall impairment.

Back to the Future: The Role of Infections in Psychopathology. Focus on OCD

Della Vecchia A, Marazziti D. Back to the Future: The Role of Infections in Psychopathology. Focus on OCD. Clin Neuropsychiatry. 2022;19(4):248-263. doi:10.36131/cnfioritieditore20220407

“Several pathogens have been associated with an increased risk to develop a broad spectrum of neuropsychiatric conditions, such as schizophrenia, mood disorders, autism, attention-deficit/hyperactivity disorder, anorexia nervosa, and post-traumatic stress disorder. Some evidence supported a possible role of infections also in the pathophysiology of OCD. Infections from Herpes simplex virus 1, Borna disease virus, Group A-Beta Hemolytic Streptococcus, Borrelia spp., and Toxoplasma gondii were actually found in patients with OCD. Although different mechanisms have been hypothesized, all would converge to trigger functional/structural alterations of specific circuits or immune processes, with cascade dysfunctions of several other systems.”

Leah’s Story

In August of 2014 our daughter, Leah, was 6 years old. We had just returned home from a month-long trip to Illinois to visit family. When we arrived home in Arizona, she suddenly (overnight) developed a fear of vomit.