Immuno-Psychiatry: When Your Body Makes Its Own Angel Dust
A new study in Biological Psychiatry reports structural brain damage from an autoimmune encephalitis that impairs behavior in ways that are somewhat similar to the effects of “angel dust”.
The body sometimes makes substances that have effects on the brain in ways that resemble the effects of illicit drugs. In their paper, the authors report findings on a syndrome called anti-NMDA receptor encephalitis that arises when the body makes antibodies that target one of the subunits of the N-methyl-D-aspartate (NMDA) subtype of receptor for the chemical messenger, glutamate.
The antibodies appear to mimic effects produced by the drug phencyclidine (PCP), also known as “angel dust”, which produces a schizophrenia-like syndrome by blocking the NMDA glutamate receptor. Schizophrenia itself is also associated with NMDA receptor dysfunction.
Senior author of the study, Dr. Carsten Finke, Professor at Charité–Universitätsmedizin Berlin, explains, “Anti-NMDA receptor encephalitis is a recently discovered autoimmune disorder of the brain, which causes a severe neuropsychiatric syndrome with behavioral changes, psychosis, memory loss, and decreased levels of consciousness. Although many patients recover well, the majority suffer from long-term cognitive impairment.”
In this issue of Biological Psychiatry, Finke and his colleagues analyzed multimodal magnetic resonance imaging data from 40 patients who were recovering from anti-NMDA receptor encephalitis.
They discovered that the patients had structural damage of the hippocampus and impaired hippocampal microstructural integrity, which strongly correlated with memory performance, disease severity, and disease duration. The hippocampus is a brain structure that plays an important role in memory.
“The results of the study therefore reveal a structural correlate of the persisting memory deficits - the chief complaint affecting daily life of patients after the acute disease stage,” said Finke. “Furthermore, these observations are also in line with evidence that dysfunction of hippocampal NMDA receptors causes severe amnesia.”
These findings suggest that the disease, which can be particularly difficult to quickly diagnose, is critical to treat promptly because the behavioral symptoms can be signs that the antibodies are actively damaging the brain.
“The atypical psychosis syndromes arising from the development of anti-NMDA receptor antibodies are extremely important to diagnosis and treat,” commented Dr. John Krystal, Editor of Biological Psychiatry. “They may be easily misdiagnosed as the psychiatric disorders that they superficially resemble. Nonetheless, these syndromes highlight the importance of NMDA receptor signaling for the genesis of symptoms associated with psychotic disorders.”
The article is “Structural Hippocampal Damage Following Anti-N-Methyl-D-Aspartate Receptor Encephalitis” by Carsten Finke, Ute A. Kopp, Anna Pajkert, Janina R. Behrens, Frank Leypoldt, Jens T. Wuerfel, Christoph J. Ploner, Harald Prüss, and Friedemann Paul (doi: 10.1016/j.biopsych.2015.02.024). The article appears in Biological Psychiatry, Volume 79, Issue 9 (May 1, 2016), published by Elsevier.
Notes for editors
Full text of the article is available to credentialed journalists upon request; contact Rhiannon Bugno at +1 214 648 0880 or Biol.Psych@utsouthwestern.edu. Journalists wishing to interview the authors may contact Dr. Carsten Finke at +49 30 2093 6124 or firstname.lastname@example.org.
The authors’ affiliations, and disclosures of financial and conflicts of interests are available in the article.
John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.
About Biological Psychiatry
Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.
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