Translational Medicine Friday

Parkinson's, Toxins AND Neuro-Developmental & Psychiatric Disorders

7/9/2026

Val's Take/Conjecture

One of the big messages of this video --- Parkinson's isn't just a brain disease.

Further, Parkinson's is greatly associated with Exposure to Toxins.

People with Parkinson's have psychiatric symptoms -- some of which are the result of the disease and some of the medication.

There are relationships, perhaps vulnerabilities, between Neuro-Developmental and Psychiatric Disorders.

Parkinson's is greatly associated with Lewy Body Dementia --- an Atypical Parkinson's Plus Disorder.
- Robin Williams had severe Lewy Body Dementia.

The associations among Neuro-Developmental and Psychiatric Disorders and Neuro-Degenerative Disorders such as Parkinson's and Alzheimer's are fairly well established.

Mark Hyman, M.D. with leading Parkinson's Neurologists
Dr. Ray Dorsey and Dr. Michael Okun
Why Parkinson's is Exploding and How to Protect Yourself

More and more we see associations with Neuro-Developmental Disorders, Psychiatric Disorders, Toxins and Auto-Immune Disease, Cancer and Obesity.

Historically, how we have come at these issues and questions: --- What is THE CAUSE of this problem or disorder?

The Research Evidence largely doesn't support --- a single cause --- but COMPLEX, MULTI-FACTORAL INTER-ACTIONS. Although for some disorders such as Parkinson's Disease, Toxins are greatly associated with the disease.

Toxins, both natural and synthetic, are significant factors in Neuro-Developmental and Psychiatric Disorders. The complexities of these relationships are great, AND missing the importance of Toxins as Triggers and Accelerants is a costly miss.

PD [Parkinson's Disease] is therefore best viewed not as an isolated movement disorder, but as part of a broader lifespan brain-disorder continuum that overlaps meaningfully, though incompletely, with neurodevelopmental and psychiatric disease.

Lifespan Links Across Brain Disorders

These relationships center on developmental timing, environmental exposures, and shared biology across mental, neurodevelopmental, and neurodegenerative disorders.

The literature connects neurodevelopmental and psychiatric disorders with Parkinson’s disease through a DOHaD-and-exposome model in which early-life and cumulative exposures shape later vulnerability.

Neurodevelopmental and psychiatric disorders, Parkinson’s disease, and toxins are linked through three facets: developmental programming, shared mechanisms, and lifelong cumulative exposure.

Research has progressed from early developmental programming to a lifespan exposome mode . . .

The arc moves from DOHaD [Developmental Origins of Health & Disease], which focused on early sensitive windows, to exposome frameworks that track interacting exposures from conception through aging.

More recent reviews explicitly connect neurodevelopment, psychiatric trajectories, and neurodegeneration within one life-course model

The key implication is that brain disorders form a lifespan continuum, not isolated childhood versus old-age diseases.

Across the 20 papers, the strongest synthesis is that cumulative and time-specific exposures within the exposome interact with genes and social context to shape risk for neurodevelopmental disorders, psychiatric illness, and Parkinson’s disease over decades.

In utero microglial dysregulation can durably alter brain wiring and immune set-points, increasing lifelong psychiatric risk.

7/6/2026

Val's Take/Conjecture

We're getting a clearer and clearer understanding of how Dysregulation of MICROGLIA --- the BRAIN'S INNATE IMMUNE CELLS ---- prenatally can lead to Lifelong Neurodevelopmental and Psychiatric Risk.
Further, IMMUNE SET POINTS are being re-set in ways we previously did not imagine.
- Which greatly affects so-called "SECOND HITS" [or more] throughout the Lifespan.

An "Over-reactive immune system" --- & Multiple, Cumulative, Diverse Triggers

6/18/2026

Val's Take/Conjecture

University of Michigan
The Study of Bipolar Disorder is the Study of Humanity (2017)

Cells that are DEVELOPMENTALLY MORE REACTIVE --- with a LIFE OF THIER OWN.

3 Big Take Aways from the Research

Crash Course World History
Disease! (2014)

What is the Exposome?

How does Maternal Immune Activation Prime Life-Long Immune-Brain Vulnerability?

Maternal immune activation reprograms the fetal brain and immune system, creating long‑term vulnerability to neurodevelopmental and psychiatric disorders.

Maternal immune activation (MIA) during pregnancy or early postnatal life acts as an early-life “hit” that reshapes fetal brain development, neuroimmune circuits, and epigenetic regulation, with effects lasting into adolescence and adulthood.

Thucydides

Ancient Greek Historian Thucydides is most famous for the History of the Peloponnesian War (431-404 B.C.)

As part of documenting the antecedents to the war, Thucydides includes the Plague of Athens in 430 B.C.

"The earliest known reference to immunity was during the plague of Athens in 430 BC. Thucydides noted that people who had recovered from a previous bout of the disease could nurse the sick without contracting the illness a second time" --- Wikipedia

That understanding of the Immune System is what a lot of us have today, but knowledge regarding the Immune System has exploded.

The Brain is NOT IMMUNE PRIVILEGED as once thought.
The Immune System is involved in "SOCIAL BEHAVIOR."
The Immune System is involved in Neuro-Developmental, Psychiatric & Addiction Disorders.
Aging of the Immune System is a strong predictor of longevity --- IMMUNOSENSCENCE --- "the gradual deterioration of the immune system."

Pathophysiological associations between maternal immune activation and neurodevelopmental disorders in offspring: a comprehensive review (2025)

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Summary

MIA primes lifelong immune–brain vulnerability by:

(1) altering placental signaling and fetal cytokine balance;

(2) reprogramming neural progenitors, microglia, and macrophages;

(3) inducing durable epigenetic and transcriptomic changes in neural circuits; and

(4) reshaping offspring immune responses to later challenges.

Together, these processes create a long‑lasting, system‑wide susceptibility to neurodevelopmental and psychiatric disorders.

Moving from short-term, acute Rehab to Long-Term Recovery and Support in Addiction care

6/6/2026

Val's Take/Conjecture:

Talking about Substance Use and Neuro-Diversity is fraught because Neuro-Diverse People often represent the EXTREMES and a wide range of unusual combinations.

Typically, people with ADHD are perceived to have more problems with Substance Use than people with Autism. It's a lot more complicated than that.

We have these broad categories --- BUT they often miss the CLINICAL COMPLEXITY.

Clinicians are presented with people with complex Developmental Issues and diverse and complex Neuro-Immune Trajectories over the LIFESPAN.

The public and policy makers and I often tell Clinicians -- like Zuzu to George Bailey, "Fix it Daddy (or Mommy)" ---- without a solid understanding of what we're talking about --- and that includes the Clinicians.

We're getting better understandings and that should help provide support for that Comprehensive Continuum of Care that can handle large numbers of "COMPLEX CASES" while at the same time providing the TRANSLATIONAL RESEARCH AND MEDICINE that we need to make the best use of limited resources.

"In summary: Clapton’s drug problems were severe and career‑damaging, but he never served time in prison for drug offenses. His recovery came through multiple rehab stays and personal resolve, not legal incarceration." --- Copilot.

BUT --- the Ethical and Policy Challenges of ADDICTION are REAL.

See Colorado community reels after police say driver with revoked license from a DUI hits 2 pedestrians, killing 1.

Can Maternal Immune Activation and Immune Priming predispose people to not only Neurodevelopmental and Psychiatric Disorders but also Addiction Disorders?

While maternal immune activation clearly increases risk for neurodevelopmental and psychiatric disorders, animal and review data also indicate it can heighten vulnerability to addictive behaviors, especially when combined with later “second hits” like adolescent stress or drug exposure.

Eric Clapton
Cocaine

Do Addiction Treatments need to be re-oriented from Short-Term Rehab to Long Term recovery?

Conclusion

Across quantitative, qualitative, and review studies, addiction is framed as a long-term condition, and longer, sustained, adaptive care outperforms brief, stand‑alone rehab.

The literature strongly supports re-orienting systems toward chronic-disease style, recovery-focused care that combines acute treatment with ongoing monitoring, supports, and community resources.

MAKING THE SUCCESSFUL HANDOFF FROM THE CRIMINAL JUSTICE SYSTEM TO Public Health, Housing, Etc.

PCOS/PMOS and relationships with neuro-Developmental and Psychiatric Disorders --- Challenging Organ-by-organ views of disease

6/5/2026

Dr. Melanie Cree is a Professor of Medicine
at the University of Colorado Anschutz

PBS NewsHour

How renaming PCOS [Polycystic Ovary Syndrome] to PMOS [Polyendocrine Metabolic Ovary Syndrome] could improve care for millions of women

Challenging Organ-by-organ views of disease, including Neuro-Developmental and
Psychiatric Disorders

Summary

Beyond PCOS and neurodevelopmental/psychiatric disorders, strong examples of conditions re‑framed as multi‑system include Parkinson’s disease, psychosis and bipolar disorder, periodontitis, NAFLD/MAFLD, obesity, and sarcopenia.

Across these, shared themes are chronic inflammation, metabolic–immune–endocrine crosstalk, and overlapping comorbidities, challenging organ‑by‑organ views of disease.

What is the relationship between Polycystic Ovary Syndrome and Psyciatric Disorders?

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)

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