Posts by:
Gabriella True

A systematic review and meta-analysis: Memantine augmentation in moderate to severe obsessive-compulsive disorder
Modarresi A, Chaibakhsh S, Koulaeinejad N, Koupaei SR. A systematic review and meta-analysis: Memantine augmentation in moderate to severe obsessive-compulsive disorder. Psychiatry Res. 2019 Dec;282:112602. doi: 10.1016/j.psychres.2019.112602. Epub 2019 Oct 4. PMID: 31630042.
  • Objective: Evaluate the efficacy of memantine as a glutamate modulator for moderate to severe OCD.
  • Methods: Systematic review of single, double-blinded, and open-label trials, using Y-BOCS scores as the primary measure.
  • Results:
    • 8 studies, 125 participants receiving memantine augmentation.
    • Significant reduction of 11.73 points in Y-BOCS scores.
    • Patients on memantine were 3.61 times more likely to respond than those on placebo.
    • 20 mg/day memantine for at least 8 weeks is safe and effective.
  • Conclusions: Memantine augmentation is a promising treatment option for moderate to severe OCD.
Brain-Immune Alterations and Mitochondrial Dysfunctions in a Mouse Model of Paediatric Autoimmune Disorder Associated with Streptococcus: Exacerbation by Chronic Psychosocial Stress

Ajmone-Cat MA, Spinello C, Valenti D, Franchi F, Macrì S, Vacca RA, Laviola G. Journal of Clinical Medicine. 2019; 8(10):1514. DOI: 10.3390/jcm8101514

  • Adverse psychosocial experiences have been shown to modulate individual responses to immune challenges and affect mitochondrial functions.
  • Results show chronic psychosocial stress altered the expression of neuroinflammatory markers in the hippocampal and hypothalamic regions, exacerbated the neuroinflammatory alterations induced by experimental GAS exposures in the same areas.
  • Psychosocial stress exacerbated individual response to GAS administrations whereby mice exposed to both treatments exhibited altered cytokine and immune-related enzyme expression in the hippocampus and hypothalamus.
  • Showed impaired mitochondrial respiratory chain complexes IV and V, and reduced adenosine triphosphate (ATP) production by mitochondria and ATP content.
  • These brain abnormalities, observed in GAS-Stress mice, were associated with blunted titers of plasma corticosterone.
  • Present data support the hypothesis that challenging environmental conditions, in terms of chronic psychosocial stress, may exacerbate the long-term consequences of exposure to GAS processes through the promotion of central immunomodulatory and oxidative stress.
The immune system and psychiatric disease: a basic science perspective
Bennett FC, Molofsky AV. The immune system and psychiatric disease: a basic science perspective. Clin Exp Immunol. 2019 Sep;197(3):294-307. doi: 10.1111/cei.13334. Epub 2019 Jun 9. PMID: 31125426; PMCID: PMC6693968.
“Mental illness exerts a major burden on human health, yet evidence-based treatments are rudimentary due to a limited understanding of the underlying pathologies. Clinical studies point to roles for the immune system in psychiatric diseases, while basic science has revealed that the brain has an active and multi-cellular resident immune system that interacts with peripheral immunity and impacts behavior. In this perspective, we highlight evidence of immune involvement in human psychiatric disease and review data from animal models that link immune signaling to neuronal function and behavior. We propose a conceptual framework for linking advances in basic neuroimmunology to their potential relevance for psychiatric diseases, based on the subtypes of immune responses defined in peripheral tissues. Our goal is to identify novel areas of focus for future basic and translational studies that may reveal the potential of the immune system for diagnosing and treating mental illnesses.”
Cellular Mechanisms of Neurovascular Breakdown and Neuronal Dysfunction Following Recurrent Group A Streptococcus Infections in Mice

Platt, Maryann P.
Columbia Academic Commons-2019 Theses Doctoral

Taken together, these data demonstrate the pivotal role of Th17 lymphocytes in brain pathology and olfactory processing deficits after recurrent GAS infections in our mouse model. Our intranasal inoculation model supports the conclusion that post-infectious BGE is autoimmune in nature, despite the absence of behavioral symptoms in this model. Using multiple mouse models of post-infectious BGE may allow us to study distinct facets of disease pathogenesis. Finally, this work underscores the ability of T cells to incite neuroinflammation, provides a useful clinical diagnostic test in olfactory functional assessments, and lends support to T cell immunotherapy strategies in patients with post-infectious BGEs.

Molecular Mimicry, Autoimmunity, and Infection: The Cross-Reactive Antigens of Group A Streptococci and their Sequelae

Madeleine W. Cunningham
Microbiology Spectrum-August 2019
Author manuscript – In advance of print

The studies suggest 1) that the antibodies against streptococci and brain in Sydenham chorea and related diseases produce CNS dysfunction through a neuronal signal transduction and subsequent excess dopamine release mechanism and 2) that the molecular targets of the chorea antibodies include lysoganglioside and the dopamine receptors in neuronal cell membranes. The anti-neuronal autoantibodies also target the group A streptococcal carbohydrate epitope N-acetyl beta-D-glucosamine present on the rhamnose backbone of the carbohydrate and present in the cell membrane and wall of the group A streptococci as well as the intracellular brain protein tubulin. The diagram in Figure 15 illustrates proposed events of how antineuronal autoantibodies against lysoganglioside and the dopamine receptors D1 and D2 may function in Sydenham chorea and PANDAS (3).

Obsessive-Compulsive Disorder: Autoimmunity and Neuroinflammation

Mona Gerentes, Antoine Pelissolo, Krishnamoorthy Rajagopal, Ryad Tamouza, Nora Hamdani,
Anxiety Disorders-August 2019

This review highlights that OCD is associated with low-grade inflammation, neural antibodies, and neuro-inflammatory and auto-immune disorders. In some subset of OCD patients, autoimmunity is likely triggered by specific bacterial, viral, or parasitic agents with overlapping surface epitopes in CNS. Hence, subset-profiling in OCD is warranted to benefit from distinct immune-targeted treatment modalities.