Research

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)
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. 2 Dec 2020 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.

The Jarisch-Herxheimer reaction associated with doxycycline in a patient with Lyme arthritis
Nykytyuk S, Boyarchuk O, Klymnyuk S, Levenets S. The Jarisch-Herxheimer reaction associated with doxycycline in a patient with Lyme arthritis. Reumatologia. 2020;58(5):335-338. doi: 10.5114/reum.2020.99143. Epub 2020 Oct 3. PMID: 33227092; PMCID: PMC7667941.
  • A 13-year-old boy developed Lyme arthritis and experienced a severe Jarisch-Herxheimer reaction on day 7 of doxycycline treatment.
  • Symptoms included low-grade fever, severe joint and muscle pain, and increased inflammatory markers.
  • Unlike the typical mild, short-lived reaction seen in adults, this case was prolonged and intense.
  • Raising awareness among healthcare professionals can help differentiate this reaction from allergies or other conditions, improving patient care.
Psychosocial Interventions and Immune System Function – A Systematic Review and Meta-analysis of Randomized Clinical Trials
Shields GS, Spahr CM, Slavich GM. Psychosocial Interventions and Immune System Function: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Psychiatry. 2020 Oct 1;77(10):1031-1043. doi: 10.1001/jamapsychiatry.2020.0431. PMID: 32492090; PMCID: PMC7272116.
  • Inflammation-linked diseases cause over 50% of global deaths. Psychosocial interventions may help, but it’s unclear which work best and for whom.
  • Study: Systematic review and meta-analysis of 56 RCTs (4,060 participants) across 8 psychosocial interventions and 7 immune markers.
  • Findings: Interventions led to a 14.7% improvement in beneficial immune function and 18% reduction in harmful immune activity.
  • Most effective: CBT and combined/multiple interventions, especially those targeting proinflammatory markers.
  • Lasting effects: Benefits persisted at least 6 months post-treatment and held across age, sex, and treatment duration.
  • Conclusion: Psychosocial interventions reliably improve immune function and may be a useful public health strategy.
Hypoferritinemia and iron deficiency in youth with pediatric acute-onset neuropsychiatric syndrome

Chan, A., Karpel, H., Spartz, E. et al. Hypoferritinemia and iron deficiency in youth with pediatric acute-onset neuropsychiatric syndrome. Pediatr Res 89, 1477–1484 (2021). https://doi.org/10.1038/s41390-020-1103-3

Conclusion: Hypoferritinemia and iron deficiency appear to be more common in PANS patients. More research is needed to confirm and understand this association.

  • 79 subjects (mean age of PANS onset of 8.7 years)
  • Hypoferritinemia was observed in 27% and three quarters occurred during a PANS flare
  • PANS patients with hypoferritinemia had worse global impairment, more comorbid inflammatory diseases, and exhibited a chronic course of PANS illness than those without
  • The estimated prevalence of iron deficiency was 3–8% in the PANS cohort, 1.4–2.0-fold higher than in the age- and sex-matched U.S. population.
  • Hypoferritinemia was commonly observed during a disease flare but not associated with dietary or demographic factors.
  • In patients with PANS and iron deficiency, clinicians should consider possibility of inflammation as the cause especially if iron deficiency cannot be explained by diet and blood loss.
Two-Tier Lyme Disease Serology Test Results Can Vary According to the Specific First-Tier Test Used

Alexandra B Maulden, Aris C Garro, Fran Balamuth, Michael N Levas, Jonathan E Bennett, Desiree N Neville, John A Branda, Lise E Nigrovic, for Pedi Lyme Net, Two-Tier Lyme Disease Serology Test Results Can Vary According to the Specific First-Tier Test Used, Journal of the Pediatric Infectious Diseases Society, Volume 9, Issue 2, June 2020, Pages 128–133, https://doi.org/10.1093/jpids/piy133

Significant variations in two-tier Lyme disease test results were observed in many children, depending on the specific first-tier test utilized. When dealing with children with a strong clinical suspicion of Lyme disease and an initially negative test result, clinicians should contemplate retesting for Lyme disease.

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

 

Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity

Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity Jian Xu, Rong-Jian Liu, Shaylyn Fahey, Luciana Frick, James Leckman, Flora Vaccarino, Ronald S. Duman, Kyle Williams, Susan Swedo, and Christopher Pittenger. Am Jrnl of Psychiatry 16 Jun 2020 https://doi.org/10.1176/appi.ajp.2020.19070698

See ASPIRE’s interview with Christopher Pittenger, MD, PhD, FAPA, FANA on this study.