Translational Medicine Friday

Oxford Professor Belinda Lennox, Auto-immune Psychosis and beyond --- Immune Involvement as a "common denominator" in Neurodevelopmental & Psychiatric Disorders

5/29/2026

Val's Take/Conjecture:

So there are currently RECOGNIZED TYPES of "AUTOIMMUNE PSYCHOSIS" --- see the Consensus AI Report below. This represents a small but significant percentage of cases that our public health systems are not set up to identify.
Additionally, there is MIA --- MATERNAL IMMUNE ACTIVATION --- while not the sole cause of Neurodevelopmental and Psychiatric Disorders --- it is broadly relevant and important in a large percentage of cases.
Further, there appears to be a general consensus that PATERNAL IMMUNE ACTIVATION --- is understudied and needs additional research.

When using a tool like Consensus AI that is SEMANTICALLY SENSITIVE --- it reveals inconsistencies in our understandings and conceptualizations from a LANGUAGE perspective.

Consensus AI is not prepared to say Neurodevelopmental and Psychiatric Disorders are generally Neuro-Immune Disorders, or even consistently have Neuro-Immune Mechanisms, but Consensus AI will say that the Immune Involvement is the COMMON DENOMINATOR.

Val's REAL INTELLIGENCE --- these inconsistencies are negatively affecting patient access to appropriate treatment and better outcomes.

The British Neuropsychiatry Association
Oxford Professor Belinda Lennox

Autoimmune Psychosis and the Challenge for Psychiatry

Cont.

Further, I think concepts like the "EXPOSOME" --- the totality of exposures of all types --- and unique combinations --- helps to explain both the diversity and transdiagnostic character of Neurodevelopmental and Psychiatric Disorders.

What are examples of Autoimmune Psychosis?

Does Maternal Immune Activation have Broad Relevance Across Neurodevelopmental and Psychiatric Disorders?

Is Paternal Immune Activation a newly emerging pathway with respect to Neurodevelopmental and Psychiatric Disorders that needs additional research?

Is Immune Involvement a common denominator in Neurodevelopmental, Psychiatric and Neurodegenerative Disorders?

MIA and Energy Demanding Hyper-connected brain Networks, a Compromised metabolic Foundation and Greater Risk for PsYchiatric problems

5/16/2026

Val's Take/Conjecture

We need a Neuro-Immune Informed Understanding of Brain Development and how that impacts the LIFESPAN and MULTIPLE DOMAINS of the SOCIETY.
We often seem to have leaders across multiple domains with big strengths and big deficits.

Hyperconnected or hub‑heavy network organization, even when compensatory, raises local energy demands and metabolic stress in precisely the regions critical for integration (Hillary & Grafman, 2017; Roy et al., 2017; Gasser et al., 2024; Deery et al., 2024; Palombit et al., 2022). •

Conclusion

Research indicates that maternal immune activation programs long‑lasting mitochondrial dysfunction, oxidative stress, and glucose and lipid abnormalities in offspring.

Separately, compensatory hyperconnectivity and hub‑centered network organization are metabolically costly, concentrating glucose use and stress in key brain regions.

The convergence of these processes implies that brains shaped by MIA may be forced to operate demanding, hyperconnected networks on an already compromised metabolic foundation, heightening risk for cognitive and psychiatric difficulties across the lifespan.

A LIFESTYLE APPROACH WITHOUT AN UNDERSTANDING OF DOHaD CAN BE ABUSE

5/16/2026

Val's Take/Conjecture

I just don't think we can say DIET and EXERCISE don't matter. THEY MATTER A LOT.
BUT if we don't appreciate the DEVELOPMENTAL ORIGINS OF HEALTH and DISEASE, especially in DEVELOPMENTAL DISORDERS ---
- a lot of HARM is going to be done.

Resolving the Tension Between Traditional Diet and Exercise Recommendations and the Developmental Origins of Multiple Dysregulations in Neurodevelopmental and Psychiatric Disorders

International DOHaD Talks
Developmental Origins of Health and Disease

Electronic Medical Records --- DNA Methylation records --- cheaper than full multi-omics -- but may not be sufficient

5/14/2026

Val's Take Conjecture: One of the things that happened in our quest to understand many chronic diseases and certainly Neurodevelopmental and Psychiatric Disorders --- the number of puzzle pieces increased exponentially and researchers found they need a "SYSTEMS BIOLOGY" approach to understand what's going on.

Summary

DNA methylation is emerging as a clinically useful biomarker and mechanistic window in neurodevelopmental and psychiatric disorders, and scores based on CpG panels can proxy some exposures, pathways, and risks.

However, current data show that methylation does not replace full multi‑omics; instead, it works best as one complementary layer integrated with genetics, transcriptomics, proteomics, metabolomics, and imaging.

Using DNA Methylation Substitutes for the full range of Multi-omics for Neuro-Developmental and Psychiatric Disorders

Stanford Innovation Lab
Dr. Jessica Lasky-Su, DSc, MS (Harvard)
Realizing Precision Medicine through multi-omics with EMRs

Lasky-Su argues we want everything --- we may not be able to afford it.

Dr. Lasky-Su is an Associate Professor of Medicine and an Associate Statistician at Harvard Medical School and Brigham and Women’s Hospital (BWH).

With over two decades of experience, her research has concentrated on the analysis of genetics, genomics, and metabolomics data, particularly in relation to complex diseases such as asthma, allergies, and lung disease. A significant portion of Dr. Lasky-Su’s work has been dedicated to “integrative metabolomics,” which involves the integration of various omics disciplines with a metabolomics-centric perspective.

Her research encompasses a broad spectrum of disease outcomes, including cancers, respiratory and ocular conditions, infections, metabolic disorders, and neurodevelopmental/mental health issues.

She has also studied diverse exposures, such as air pollutants, PFAS, nutrition, and exercise. Dr. Lasky-Su has held several prominent leadership positions.

She is the immediate past president of the Metabolomics Society, the largest society of its kind globally, and the chairperson of the NIH’s Consortium of Metabolomics Studies (COMETS), the largest international consortium of prospective metabolomics cohorts.

Currently, she leads the RECOVER systems biology initiative through NHLBI, which utilizes multi-omic data to characterize Post-Acute Sequelae of SARS-CoV-2 (PASC).

Throughout her career, Dr. Lasky-Su has trained over 25 postdoctoral fellows, many of whom have achieved successful academic careers, reaching ranks as high as Full Professor.

Her academic achievements are evidenced by her authorship of over 250 peer-reviewed publications and her delivery of more than 60 national and international talks.

Dr. Lasky-Su is an Associate Professor of Medicine and an Associate Statistician at Harvard Medical School and Brigham and Women’s Hospital (BWH). With over two decades of experience, her research has concentrated on the analysis of genetics, genomics, and metabolomics data, particularly in relation to complex diseases such as asthma, allergies, and lung disease.

A significant portion of Dr. Lasky-Su’s work has been dedicated to “integrative metabolomics,” which involves the integration of various omics disciplines with a metabolomics-centric perspective.

Her research encompasses a broad spectrum of disease outcomes, including cancers, respiratory and ocular conditions, infections, metabolic disorders, and neurodevelopmental/mental health issues.

She has also studied diverse exposures, such as air pollutants, PFAS, nutrition, and exercise. Dr. Lasky-Su has held several prominent leadership positions.

She is the immediate past president of the Metabolomics Society, the largest society of its kind globally, and the chairperson of the NIH’s Consortium of Metabolomics Studies (COMETS), the largest international consortium of prospective metabolomics cohorts.

Currently, she leads the RECOVER systems biology initiative through NHLBI, which utilizes multi-omic data to characterize Post-Acute Sequelae of SARS-CoV-2 (PASC).

Throughout her career, Dr. Lasky-Su has trained over 25 postdoctoral fellows, many of whom have achieved successful academic careers, reaching ranks as high as Full Professor.

Her academic achievements are evidenced by her authorship of over 250 peer-reviewed publications and her delivery of more than 60 national and international talks.

Neuro-Immune Circuits and Neuro-Developmental and Psychiatric Disorders

5/14/2026

Conclusion

Neuro-immune circuits are not peripheral to brain disorders—they are deeply embedded in how neural networks develop, function, and fail.

Dysregulated immune signaling (especially microglial activity, cytokines, complement, and maternal or gut-driven inflammation) is a common pathway that links diverse neurodevelopmental and psychiatric conditions and is a major target for future diagnostics and therapies.

What is the relationship between Neuro-Immune Circuits and Neurodevelopmental and Psychiatric Disorders

MGH Martinos Center
BrainMap: Psychedelic rewiring of neuroimmune circuits in psychiatric disorders- Dr. Michael Wheeler (Harvard Medical School & Brigham & Women's Hospital)

What is transdiagnostic, immune-stratified precision psychiatry?

5/11/2026

Val's Take/Conjecture

Transdiagnostic, Immune-Stratified Precision Psychiatry is rejecting the Diagnostic Manual of the American Psychiatric Association.
It is once again underlining the importance of a transdiagnostic perspective and the integral role of the IMMUNE SYSTEM in multiple psychiatric disorders.
It's also recognizing the importance of PRECISION MEDICINE --- ONE SIZE DOES NOT FIT ALL.

Systems Biology, Neurodevelopment, and Psychiatry Beyond the Brain

5/7/2026

Val's Take/Conjecture: This is the 2nd video I've posted from the Institute for Systems Biology.

One of the things that has happened with respect to Neuro-Developmental and Psychiatric Disorders is that we're understanding them beyond the BRAIN and the CENTRAL NERVOUS SYSTEM.

Relationships Among Systems Biology and Neurodevelopmental & Psychiatric Disorders Beyond the Brain & Central Nervous System

Institute for Systems Biology
Microbiota-Regulated Immune Pathways in Early Life and Pregnancy -- Dr. Melody Zeng (Weill Cornell Medicine)

It's not that the BRAIN and CENTRAL NERVOUS SYSTEM aren't involved but they may be involved in ways we didn't appreciate ---AND it's that many other systems of the body are involved as well, including:

The Immune System
The Microbiome
The Endocrine System
The Metabolism
And for some of us other systems such as the SKELETAL SYSTEM and BONE DISORDERS, or more of the NERVOUS SYSTEM such as the EYES, or HYPER-MOBILITY and the AUTONOMIC NERVOUS SYSTEM.

For a lot of complex Chronic Conditions such as Neuro-Developmental and Psychiatric Disorders, Auto-Immune Disorders, Cancer, etc. ---- A SYSTEMS BIOLOGY APPROACH IS NEEDED TO UNRAVEL THEIR COMPLEXITY.

Paradigm shifts ad infinitum

5/7/2026

And so the Cycle goes on Ad Infinitum

Val's Take/Conjecture: Even before Kuhn, there were Historians in the 1950s and probably before who would say the key to NEW IDEAS gaining ascendancy is the OLD GUARD dies out.

In a medical context, the problem is often that you and the people you are concerned about are DYING OUT at a faster pace than the "OLD GUARD."

BUT as Ma Joad said in "The Grapes of Wrath": "THOSE PEOPLE KEEP COMING."

AI is imperfect and concerning and amazing all at the same time. I'm not going to review 117 million papers this afternoon for one report or multiply that several times for several reports.

Most of AI with regard to medical matters is fairly measured --- but still not perfect. We can't check our CRITICAL THINKING at the door.

The Living Philosophy
Paul Cossens --- Irish Youtuber & Philosopher

The Structure of Scientific Revolutions - Thomas Kuhn

When it comes to Neuro-Developmental and Psychiatric Disorders, there is a overwhelming evidence of NEURO-IMMUNE MECHANISMS and the benefit of more thoroughly integrating NEUROLOGY and PSYCHIATRY.

Profound Neuro-immune Paradigm Shifts ---Beyond KetO ---Microglial Replacement

5/2/2026

Val's Take/Conjecture
One of the ways to think of MICROGLIA and Maternal Immune Activation ------

A lot of MILEAGE can be put on that MICROGLIA before it's ever left the lot.

This is one of the reasons that neuro-developmental and psychiatric disorders can be a form of premature aging.

Now, is microglia replacement ready for PRIME TIME --- not really.
BUT research in NEURO-IMMUNOLOGY is exploding around the world.

Providing some kind of Certification in Neuro-Immunology for working professionals might be helpful.
- Especially with respect to known AUTO-IMMUNE DISEASES with psychiatric symptoms.

See also:

Primary Microglia Dysfunction or Microgliopathy: A Cause of Dementias and Other Neurological or Psychiatric Disorders (2022)

What is the research on Microglial Replacement for Neurodevelopmental and Psychiatric Disorders?

Microglia replacement halts the progression of microgliopathy in mice and humans (2025)

*Chinese Researchers

Replacing microglia to treat a brain disease (2025)

Affiliations
1Brain Immunology and Glia Center, School of Medicine, Washington University in St Louis, St Louis, MO, USA.
2Department of Pathology and Immunology, School of Medicine, Washington University in St Louis, St Louis, MO, USA.

Mitochondrial transplantation to address psychiatric Disorders

4/26/2026

Val's Take/Conjecture

For a simplied version of what seems to be going on in many cases of Neuro-Developmental and Psychiatric Disorders.
- Maternal Immune Activation dysregulates Microglia
- Which in turn leads to Mitochondrial Dysfunction.

Microglial dysregulation and Mitochondrial Dysfunction are associated with a wide range of disorders and illnesses, some of which do have psychiatric symptoms.

There is more and more a "MECHANISTIC" paradigm that the body is unable to sufficiently fuel the brain due to metabolic abnormalities.

Further due to microglial dysregulation and lack of pruning, neuro-diverse people often start out with more Synapses.
Those additional Synapses are placing a higher energy burden on already dysfunctional mitochondria.
As adults, neuro-diverse people often have fewer Synapses.

Mitochondrial Transplantation in Animal Models of Psychiatric Disorders: A Novel Approach to Psychiatric Treatment (2025)

*Japanese Researchers

Mitochondrial transplantation in brain disorders: Achievements, methods, and challenges (2025)

*Swiss Researchers

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