Mental Illness/ Immunology Research Timeline

Photo Credit: Timeline (World History Documentaries)

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2019

Autoimmunity in psychotic disorders. Where we stand, challenges and opportunities.
Autoimmunity Reviews (Sept. 2019)

Abstract

Psychotic disorders are debilitating mental illnesses associated with abnormalities in various neurotransmitter systems. The development of disease-modifing therapies has been hampered by the mostly unknown etiologies and pathophysiologies. Autoantibodies against several neuronal antigens are responsible for autoimmune encephalitis.

These autoantibodies disrupt neurotransmission within the brain, resulting in a wide range of psychiatric and neurologic manifestations, including psychosis. The overlap of symptoms of autoimmune encephalitis with psychotic disorders raised the question as to whether autoantibodies against a number of receptors, ion channel and associated proteins could ultimately be responsible for some forms of psychosis.

Here we review our current knowledge, on antibody mediated autoimmunity in psychotic disorders, the different diagnostic methods and their limitations, as well as on varying therapeutic approaches targeting the immune system.

Highlights
•Antibodies can alter receptor and channel functions leading to psychotic symptoms.

•Neurological signs can be subtle or misinterpreted in patients with prominent psychotic symptoms.

•The use of standardized assays and CSF [cerebriol spinal fluid] is essential to define autoimmunity in psychotic disorders.

•Specificity and sensitivity variations create controversial results in the field.

•Larger, homogeneous and systematically described cohorts need to be studied.

Excerpt

The idea that autoimmunity may play a role in neuropsychiatric disorders began to take root in the last decade. Dr. Dalmau was the first to describe a group of patients with encephalitis associated with ovarian teratoma.

After developing prodromal symptoms such as fever, headache and nausea, patients presented with a variety of severe psychotic and neurological manifestations, including anxiety, delusions, mania, short-term memory loss and seizures.

Extensive analysis showed that serum and cerebrospinal fluid (CSF) contained antibody reactivity towards neuronal tissue, which was also present in the tumor.

Autoantibodies reacted specifically against the NR1 subunits of the NMDAR.

After immunosuppressive treatment and tumor resection, most of the patients recovered completely, regaining their normal social behavior and cognitive abilities in the absence of any remaining neuropsychiatric manifestations.

This previously unassociated collection of symptoms was termed autoimmune encephaltitis [14].

School of Mental Health & Neuroscience, Maastricht University, Netherlands

An update on anti-NMDA receptor encephalitis for neurologists and psychiatrists: mechanisms and models
(July 2019)

Summary

The identification of anti-NMDA receptor (NMDAR) encephalitis about 12 years ago made it possible to recognise that some patients with rapidly progressive psychiatric symptoms or cognitive impairment, seizures, abnormal movements, or coma of unknown cause, had an autoimmune disease.

In this disease, auto-antibodies serve as a diagnostic marker and alter NMDAR-related synaptic transmission.

At symptom onset, distinguishing the disease from a primary psychiatric disorder is challenging.

The severity of symptoms often requires intensive care.

Other than clinical assessment, no specific prognostic biomarkers exist.

The disease is more prevalent in women (with a female to male ratio of around 8:2) and about 37% of patients are younger than 18 years at presentation of the disease.

Tumours, usually ovarian teratoma, and herpes simplex encephalitis are known triggers of NMDAR autoimmunity.

About 80% of patients improve with immunotherapy and, if needed, tumour removal, but the recovery is slow.

Animal models have started to reveal the complexity of the underlying pathogenic mechanisms and will lead to novel treatments beyond immunotherapy.

Future studies should aim at identifying prognostic biomarkers and treatments that accelerate recovery.

2018

Professor Edward Bullmore's book:

The Inflamed Mind-- A Radical New Approach to Depression (Dec. 2018)

Professor Bullmore is a neuropsychiatrist and neuroscientist who is a Cambridge Professor of Psychiatry.

PsychScene Hub (2018)

Immune Dysregulation in Bipolar Disorder and 3 Important Autoimmune Neuropsychiatric Disorders

Dr. Sanil Rege is a Consultant Psychiatrist and founder of Psych Scene (a platform to enhance psychiatry education) and Vita Healthcare, providing high-quality mental health care services to the public. He is a Fellow of the Royal Australian and New Zealand College of Psychiatrists and Member of the Royal College of Psychiatrists (UK).

Dr Sanil Rege begins with an overview of immune dysregulation in bipolar disorder and the role of cytokines in neuroinflammation.

Dr. Rege discusses neuropsychiatric systemic lupus erythematosus (NPSLE) and talks about the pathogenesis of the disease.

He covers the association of encephalopathy with synaptic antibodies and management of synaptic encephalitis.

The next autoimmune disease covered is autoimmune thyroiditis and he discusses treatment using steroids, concluding the presentation with a list of symptoms and signs that should raise suspicion for autoimmunity.

Neuroscience News (2018)

In one of the biggest breakthroughs in schizophrenia research in recent times, Professor Cynthia Shannon Weickert from Neuroscience Research Australia (NeuRA) and UNSW Sydney has identified immune cells in greater amounts in the brains of some people with schizophrenia.

https://neurosciencenews.com/schizophrenia-immune-cells-9867/

International Journal of Environmental Research & Public Health (2018)

seasonal allergies are a risk factor for Mental Illness

What Causes Schizophrenia?
Inflammatory Psychosis (2018)

This talk focuses on observations that excessive or misdirected inflammatory responses can cause symptoms of psychosis.

There are numerous examples of autoimmune illnesses causing symptoms that closely resemble schizophrenia.

It’s also clear that chronic inflammation is not only a risk factor for developing schizophrenia, but also can negatively impact the clinical course of people with schizophrenia.

An unresolved dilemma is whether inflammation is a contributing factor to schizophrenia – or whether “inflammatory psychosis” is a distinctly different illness that produces symptoms more or less identical to classically-defined schizophrenia.

Another unsettled question is the extent to which inflammation-reducing drugs are likely to help people with schizophrenia. If so, is this a benefit that can be expected by anyone with schizophrenia?

Or would the benefit only apply to those with blood tests that show an inflamed state.

These are important questions in light of numerous case reports of psychosis being caused by over-the-counter anti-inflammatory medications such as aspirin, indomethacin, ibuprofen, etc.

The lecture is part of Northeast Ohio University's education(+)consultation service, SZconsult. A powerpoint file for this lecture is available at http://szconsult.org/

2017

‘Drain Pipes’ in the Brain: Lymphatic Vessels Act As Pipeline Between Brain and Immune System (2017)

http://neurosciencenews.com/lymphatic-vessels-brain-7646/

Immune System linked to Alcohol Drinking Behavior (2017)
http://neurosciencenews.com/immune-system-alcohol-7494/

University of Adelaide, Australia

The Journal Intelligence (2017)

Hyper Brain, Hyper Body: The Trouble With High IQ

[Orchid: We think this probably applies to most people with different types of "giftedness" --probably not just High IQ -- because "overexcitabilities" are seen across the "giftedness" spectrum]

"A new study in the journal Intelligence reports that highly intelligent people have a significantly increased risk of suffering from a variety ofpsychological and physiological disorders.

"Lead author of the study, Ruth Karpinski, says the findings have implications both for the study of intelligence and for psychoneuroimmunology, which examines how stress responses to the environment influence communication between the brain and immune system.

“Our findings are relevant because a significant portion of these individuals are suffering on a daily basis as a result of their unique emotional and physical overexcitabilities.

"It is important for the scientific community to examine high IQ as being front and center within the system of mechanisms that may be at play in these dysregulations,” she says.

"Karpinski and her colleagues developed a hyper brain / hyper body theory of integration.

"It posits that individuals with high cognitive ability react with an overexcitable emotional and behavioral response to their environment.

"Due in part to this increased awareness of their surroundings, people with a high IQ then tend to experience an overexcitable, hyperreactive central nervous system."

https://neurosciencenews.com/iq-hyper-brain-body-7720/

Ruth Karpinski, Lead Author -- Also author of Independent Thesis: "High Cognitive Ability as a Risk Factor for Immune Dysregulation."

Pitzer College --- Claremont, California

What Does The Environment Have To Do With Diseases Affecting The Immune System
The rise in recent decades of diseases such as inflammatory bowel disease and rheumatoid arthritis suggests that factors in the environment are contributing. (2017)
https://ensia.com/features/environment-diseases-immune-system/

2016

Immune System Affects and Controls Social Behavior

 -----University of Virginia School of Medicine (July 2016)

Click Here

Lancet Psychiatry (April 2016)

A Clinical Approach to Diagnosis of Autoimmune Encephalitis

2015

Disorders Share Risk Gene Pathways for Immune, Epigenetic Regulation

Genome-wide findings add to evidence blurring traditional psychiatric categories

January 29, 2015

Genes that confer risk for schizophrenia, bipolar disorder, and depression most strongly work through pathways involved in the process of histone methylation, an epigenetic mechanism that regulates the switching on-or-off of genes in response to environment and experience.

Disruption in these pathways prenatally could adversely affect brain development, suggest the researchers.

https://www.nimh.nih.gov/news/science-news/2015/disorders-share-risk-gene-pathways-for-immune-epigenetic-regulation.shtml

2014

Elevated Risk for Autoimmune Disorders in Iraq and Afghanistan Veterans with Post-Traumatic Stress Disorder (2014)

http://www.biologicalpsychiatryjournal.com/article/S0006-3223(14)00457-0/fulltext

University of California @ San Francisco, Psychiatry Dept. & VA

Mind Body Scientists Identify Immune System Link to Mental Illness

University of Cambridge (2014)
https://www.cam.ac.uk/research/news/mind-and-body-scientists-identify-immune-system-link-to-mental-illness

2013

Journalist Susannah Cahalan's New York Times Bestseller "Brain On Fire" (Aug. 2013)

NOW A MAJOR MOTION PICTURE STARRING CHLOË GRACE MORETZ

An award-winning memoir and instant New York Times bestseller that goes far beyond its riveting medical mystery, Brain on Fire is the powerful account of one woman’s struggle to recapture her identity.

When twenty-four-year-old Susannah Cahalan woke up alone in a hospital room, strapped to her bed and unable to move or speak, she had no memory of how she’d gotten there. Days earlier, she had been on the threshold of a new, adult life: at the beginning of her first serious relationship and a promising career at a major New York newspaper. Now she was labeled violent, psychotic, a flight risk. What happened?

In a swift and breathtaking narrative, Susannah tells the astonishing true story of her descent into madness, her family’s inspiring faith in her, and the lifesaving diagnosis that nearly didn’t happen.

“A fascinating look at the disease that...could have cost this vibrant, vital young woman her life” (People), Brain on Fire is an unforgettable exploration of memory and identity, faith and love, and a profoundly compelling tale of survival and perseverance that is destined to become a classic.

The Brain-Immune -Gut Triangle: Innate Immunity in Psychiatric & Neurological Disorders

(Jan. 2013)
https://www.researchgate.net/publication/261994663_The_Brain-Immune-Gut_Triangle_Innate_Immunity_in_Psychiatric_and_Neurological_Disorders

Oslo University Hospital, Norway

2012

Childhood Trauma Can Result in Chronic Inflammation which can affect the Immune System (2012)

http://www.medicaldaily.com/childhood-trauma-can-result-chronic-inflammation-241114

University of California @ San Francisco, Psychiatry Dept. & VA

2011

Journal of Neuropsychiatry & Clinical Neuroscience (2011)

The Emerging Link Between Autoimmune Disorders and Neuropsychiatric Disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086677/

2007

Josep Dalmau, M.D., Ph.D. adjunct professor of neurology and founder and director of the Penn Center of Autoimmune Neurology in the Perelman School of Medicine at the University of Pennsylvania.

Anti-NMDA Receptor Encephalitis.

First described by Dr. Josep Dalmau in 2007

Wikipedia

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