Microglia Activation, Herpes Infection, and NMDA Receptor Inhibition: Common Pathways to Psychosis?

Klein, Hans; Doorduin, Janine; Witte, Lot de; Vries, Erik F. J. de

doi:10.1007/978-3-319-13602-8_12

Cited by 3 publications

(5 citation statements)

References 55 publications

(53 reference statements)

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“…The inhibition is caused by a cascade of events initiated by HSV glycoprotein on microglia/astroglia. The NMDA inhibition can also be through direct inhibition by HSV antibody [ 3 ]. Therefore, HSV psychosis is still plausible even in the absence of HSV antibody; in such situation, NMDA receptor becomes inhibited through the alternate route initiated by HSV glycoprotein on microglia/astroglia.…”

Section: Discussionmentioning

confidence: 99%

“…Herpes simplex encephalitis (HSE) remains a serious cause of morbidity and mortality despite advances in antiviral treatment [ 2 ]. Introduction of antiviral agent (acyclovir) reduced the mortality rate of herpes encephalitis to 6%–11% [ 3 ]; however, up to 44%–62% of survivors of herpes simplex encephalitis have neurological sequelae [ 4 ]. About a third of herpes encephalitis incidents occur in children.…”

Section: Introductionmentioning

confidence: 99%

“…Herpes encephalitis as a cause of psychosis is rare, affecting about 1 per 200,000 cases per year. It is suggested that herpes infection like other environmental stressors causes psychosis through inhibition of N-methyl-D-aspartate (NMDA) receptor and subsequent microglia activation in the hippocampus [ 3 ]. It typically presents as psychomotor agitation, fever, headache, visual hallucination, paranoia, seizures, and altered level of consciousness [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Psychosis in a 15-Year-Old Female with Herpes Simplex Encephalitis in a Background of Mannose-Binding Lecithin Deficiency

Asogwa

Buabeng

Kaur

2017

Case Reports in Psychiatry

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Historically, psychotic disorder has been associated with viral infection. Herpes simplex infections and Epstein-Barr virus (EBV) among other viral infections have been implicated in psychotic disorder. Of note in this case report is psychotic disorder that occurred following reactivation of herpes simplex infection in a background of mannose-binding lecithin (MBL) deficiency, childhood EBV infection, and severe psychosocial stress. Herpes simplex encephalitis (HSE) remains a significant cause of morbidity and mortality despite advancement in its treatment with intravenous acyclovir. Many studies have reported psychiatric and neurological manifestation of herpes simplex infection following primary or reactivated infection, while others suggest milder clinical course of herpes simplex encephalitis in a background of immunosuppression. Another contributory factor to psychotic disorder in this case is childhood EBV exposure which has been reported to increase the risk of psychosis in adolescence and adulthood. This case report describes a 15-year-old female with MBL deficiency who presented with psychosis caused by reactivated herpes simplex infection and had good clinical recovery. Based on childhood Epstein-Barr virus exposure and psychosis in adolescence (current case), she is at increased risk of psychotic disorder in adulthood, which underscores the importance of long-term monitoring.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Psychosis in a 15-Year-Old Female with Herpes Simplex Encephalitis in a Background of Mannose-Binding Lecithin Deficiency

Asogwa

Buabeng

Kaur

2017

Case Reports in Psychiatry

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“…Pathogens and microorganisms that invade the brain can directly affect organ function, causing delirium, psychosis, mania, and depression. 2–5…”

Section: Evidence For the Communicable Nature Of Psychiatric Disordersmentioning

confidence: 99%

Curtailing the communicability of psychiatric disorders

Wainberg

Helpman

Duarte

et al. 2018

The Lancet Psychiatry

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Although psychiatric disorders are classified as non-communicable diseases, we believe this classification is too rigid and limiting. We present evidence of the communicability of psychiatric disorders through three major pathways: infectious and ecological, familial, and sociocultural communicability. Successful strategies developed to control the spread of communicable infectious diseases are relevant to curtailing the communicability of psychiatric disorders, thereby reducing their burden. Current interventions and policies that conceptualise psychiatric illnesses as non-communicable mostly focus on the individual. By applying strategies from infectious disease and chronic illness prevention models within a socioecological framework, we posit a broad communicable chronic disease psychiatric illness control plan for effectively treating the patient with the psychiatric disorder (host) as early as possible, providing benefits to their family and the community, and preventing transmission to others.

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“…Mice mutants with reduced NMDAR levels develop symptoms resembling schizophrenia, which can be overcome by treatment with NMDAR agonists (107, 108). This suggests that NMDAR is a candidate pSAg involved in the striatal damage of schizophrenia patients (109). …”

Section: The Candidate Psags Of Npdsmentioning

confidence: 99%

Autoimmune Aspects of Neurodegenerative and Psychiatric Diseases: A Template for Innovative Therapy

Haan¹,

Klein

Hart

2017

Front. Psychiatry

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Neurodegenerative and psychiatric diseases (NPDs) are today’s most important group of diseases, surpassing both atherosclerotic cardiovascular disease and cancer in morbidity incidence. Although NPDs have a dramatic impact on our society because of their high incidence, mortality, and severe debilitating character, remarkably few effective interventions have become available. The current treatments, if available, comprise the lifelong intake of general immunosuppressants to delay disease progression or neurotransmitter antagonists/agonists to dampen undesired behaviors. The long-term usage of such medication, however, coincides with often severe adverse side effects. There is, therefore, an urgent need for safe and effective treatments for these diseases. Here, we discuss that many NPDs coincide with subtle chronic or flaring brain inflammation sometimes escalating with infiltrations of lymphocytes in the inflamed brain parts causing mild to severe or even lethal brain damage. Thus, NPDs show all features of autoimmune diseases. In this review, we postulate that NPDs resemble autoimmune-driven inflammatory diseases in many aspects and may belong to the same disease spectrum. Just like in autoimmune diseases, NPD symptoms basically are manifestations of a chronic self-sustaining inflammatory process with detrimental consequences for the patient. Specific inhibition of the destructive immune responses in the brain, leaving the patient’s immune system intact, would be the ultimate solution to cure patients from the disease. To reach this goal, the primary targets, e.g., the primary self-antigens (pSAgs) of the patient’s chronic (auto)immune response, need to be identified. For a few major NPDs, immunological studies led to the identification of the pSAgs involved in the autoimmune damage of specific brain parts. However, further research is needed to complete the list of pSAgs for all NPDs. Such immunological studies will not only provide crucial insights into NPD pathogenesis but also ultimately enable the development of a new generation of safe and effective immunotherapies for NPDs. Interventions that will dramatically improve the life expectancy and quality of life of individual patients and, moreover, will significantly reduce the health-care costs of the society in general.

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Microglia Activation, Herpes Infection, and NMDA Receptor Inhibition: Common Pathways to Psychosis?

Cited by 3 publications

References 55 publications

Psychosis in a 15-Year-Old Female with Herpes Simplex Encephalitis in a Background of Mannose-Binding Lecithin Deficiency

Psychosis in a 15-Year-Old Female with Herpes Simplex Encephalitis in a Background of Mannose-Binding Lecithin Deficiency

Curtailing the communicability of psychiatric disorders

Autoimmune Aspects of Neurodegenerative and Psychiatric Diseases: A Template for Innovative Therapy

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