The World Federation of Neurology (WFN) declared July 22 as World Brain Day (WBD 2025), with the theme: Brain Health for All Ages.
Anti-NMDA-Receptor Encephalitis
There is a new [July 21, 2025] spotlight in The New Yorker, Some psychiatric patients may actually have treatable autoimmune conditions. But what happens to the newly sane?, stating that:
“In 2020, in a paper in The Lancet Psychiatry, some two dozen researchers proposed a new category of illness called “autoimmune psychosis,” which may look like a milder or incomplete form of encephalitis, the illness never progressing beyond psychiatric symptoms. Their illness, which was named anti-NMDA-receptor encephalitis, usually began in their early twenties, just as schizophrenia often does. The discovery of the illness put pressure on the artificial division between psychiatry and neurology—the only two fields of medicine that focus on the same organ. Dalmau discovered that they had a form of encephalitis, inflammation of the brain.”
“Their immune systems had misidentified the NMDA receptor—a protein in the brain that affects mood and memory—as foreign and produced antibodies that attacked it. When these patients were treated with immunotherapy, the majority of them recovered completely, sometimes within a month. The S.N.F. Center is embarking on a project, beginning this fall, to screen all the patients hospitalized in the New York State mental-health system for autoimmune, metabolic, and genetic disorders, to see if there are people whose symptoms can be traced to a distinct biological mechanism. The S.N.F. Center will do blood work for everyone in the state’s psychiatric institutions, offering follow-up testing, such as lumbar punctures, to those with unusual results.”
The National Library of Medicine [in a December 11, 2022 update] wrote:
“N-methyl-D-aspartate (NMDA) receptor is a glutamate receptor, the human brain’s primary excitatory neurotransmitter. The NMDA receptor is ionotropic and controls a ligand-gated ion channel. It is particularly important because it is integral in long-term potentiation, synaptic plasticity, and memory formation. When a ligand binds to the NMDA receptor, the ligand-binding domain closes like a clamshell. This closure leads to an opening of the transmembrane ion channel. The transmembrane ion channel is nonspecific for positively charged ions.”
“However, due to the chemical properties of the channel and the concentrations of ions outside the cell, calcium ions often pass through the channel. Anti-NMDA receptor encephalitis is a rare, potentially lethal autoimmune encephalitis where autoantibodies are produced against the NMDA receptor. Patients present with psychiatric changes, epilepsy, motor, speech, or autonomic dysfunction, as well as decreased levels of consciousness. The diagnosis is made by collecting anti-NMDA receptor antibodies from the patient’s cerebrospinal fluid. This disease provides an excellent example of the ubiquity of NMDA receptors. When attacked by an autoimmune disease, dysfunction in numerous neurologic functions occurs. Treatment commonly involves steroids, intravenous immunoglobulin, and plasma exchange therapy. Anti-NMDA receptor encephalitis is often associated with ovarian teratomas.”
There is a [June 2015] paper in Trends in Biochemical Sciences, Emerging structural insights into the function of ionotropic glutamate receptors, stating that:
“Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate excitatory neurotransmission crucial for brain development and function, including learning and memory formation. Recently, a wealth of structural studies on iGluRs, including AMPA receptors (AMPARs), kainate receptors, and NMDA receptors (NMDARs), became available. These studies showed structures of non-NMDARs, including AMPAR and kainate receptors in various functional states, thereby providing the first visual sense of how non-NMDAR iGluRs may function in the context of homotetramers.”
Theoretical Neurology
There are two options to — conceptually — define how the human brain works: ions and molecules. How so? A summary of the above explanation is that if the passages [channels] of ions are affected or those of the molecules are [around neurons], there would be effects, negative or otherwise.
There are ions that pass through channels on neurons, correlating with what is called electrical signals. There are molecules that pass through synaptic channels, mostly called chemical signals. It is almost difficult to find any function in the brain [for human life and experiences] that does not involve mechanization by [those] ions and molecules.
There are several components within the brain. All of them are often active during functions. Any problem with anyone, somewhere, may result in some mild to serious problems. However, the question is the basis of functions. This means that if there is a memory of a chair, what is the build or basis of that memory in the brain? Oxygen? Genes? Blood? Glia? Neurons? Receptors? Synapses? Hormones? Ion channels? Lobes? Enzymes? Or what?
Contributions can be distributed, but what are the interpretations [or say sensations] of the external world based on, exactly? How about emotions of [say] delight or trauma? How about feelings of [say] thirst or pain? How about the regulation, or the limit and extent of which internal senses like circulation, respiration, and so forth?
This question can be likened to what is shelter? What must be present for anything to be a shelter from, say, the rain or the sun? There could be several components in shelter architectures: electrical wires, pipes, blinds, and so on. But what must be present [core components] to say this is a structured shield from cold, heat, and others?
What are the core components of functions in the nervous system? For example, many of the components in the brain are available [elsewhere or] outside the nervous system, so what makes the brain mostly responsible for major functions? Ions and molecules of neurons, specifically, are based on empirical evidence in neuroscience.
In the nervous system [central and peripheral], neurons are often in clusters [nuclei and ganglia, respectively]. It is theorized that electrical and chemical signals are often in sets or in loops, within clusters of neurons. Some of the clusters may have one set, others may have more, but all functions are based on the configurations of electrical and chemical signals in sets, in clusters of neurons. The collection of all sets of signals can be defined as the human mind.
In sets, electrical and chemical signals interact. This is by electrical signals striking at chemical signals. This interaction results in the completion of the configurations that are necessary for functions. So, say an emotion of anger or delight, chemical signals have an almost ready configuration, but it is when they are struck by electrical signals that the configuration is completed, resulting in the function, conceptually.
Also, a reason the brain is the headquarters of the nervous system is that several sets of signals that bear configurations are there. So, some electrical signals may start relaying from the PNS or elsewhere in the CNS; it is when they find a fit location in the brain that they terminate. This is why most sensations are interpreted in the brain, because the configurations are there. Interactions result in functions, but what measures or grades those interactions are the states of the signals at the time of the interactions.
Some electrical signals may split, with some going ahead. Some electrical signals may use a prior path [or an old sequence]. They may also use a new sequence. Electrical signals at one set may have the highest intensity. Volumes of chemical signals may vary from one end of the set to the other. There could be a set with the highest volume of chemical signals among others. There could also be a set with one chemical signal at a higher volume than other sets. Chemical signals may be displaced at an angle and so forth.
These attributes define labels like attention, subjectivity, and so on. Attributes also define intent and others. Why is an emotion different from a memory? It is theorized that sets [of signals] for emotions may have an angular displacement in some form or may have some bends that may be fixed, resulting in lingering stays. Feelings are sometimes similar. Basic interpretations of sensations [like relaying electrical signals] for memory may fit, but have residues that bounce off to a set for emotions or feelings.
The same applies to those for the regulation of internal senses. Such that the configuration for pain does not just specify the source [the set of a memory or location in the body] but goes to the set [of pain] that also defines the extent [with intensity of electrical signals, volume of chemical signals, angular displacements, and fix of the set as well]. Brain zap or shiver in fear is a relay of electrical signals with a lot of intensity that relays go to other sets, but without fits, resulting in a general buzz, seemingly across sets, conceptually.
NMDA: Conceptual Brain Science for Psychosis
The anti-NMDA-receptor encephalitis affects ion channels, which affects the configuration of electrical signals to convey functions or to contribute to configurations in sets. Since sets of electrical and chemical signals often consist of various ions and molecules, it presents the possibility to conceptually describe all the conditions in the DSM-5-TR by the interactions and attributes of signals.
This indicates that signals would not be assumed to be simply for the communication of neurons, but as the configurators for functions. While sources of psychiatric conditions are sought, it is possible to explain them directly by the [conceptual] actions of components within the brain. This would move away from the opacity in psychiatry, attempt [ahead] to map specific sets of molecules and ions to functions, including likely masses and volumes, as well as structure how to prospectively manage the conditions.
However, first, it is possible to use the interactions and attributes properties to conceptually explain everything in The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), moving knowledge forward, in psychiatry and neurology against all brain disorders.
This article was written for WHN by David Stephen, who currently does research in conceptual brain science with a focus on the electrical and chemical configurators for how they mechanize the human mind with implications for mental health, disorders, neurotechnology, consciousness, learning, artificial intelligence, and nurture. He was a visiting scholar in medical entomology at the University of Illinois at Urbana-Champaign, IL. He did computer vision research at Rovira i Virgili University, Tarragona.
As with anything you read on the internet, this article on NMDA should not be construed as medical advice; please talk to your doctor or primary care provider before changing your wellness routine. WHN neither agrees nor disagrees with any of the materials posted. This article is not intended to provide a medical diagnosis, recommendation, treatment, or endorsement.
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