When "invisible disabilities" remain "invisible"  . . .

Val's Take/Conjecture
  • Both Denver Mayor Mike Johnston and Aurora Mayor Mike Coffman are trying to provide solutions to homelessness---
    • Help people get back on their feet​
    • ​Get their lives together
  • One of the things that I find fascinating is that our classic definition of "immaturity" may in fact point to premature biological aging.
    • ​Especially, premature aging of the IMMUNE SYSTEM.
  • Many states including Colorado amended their Civil Commitment Statutes to include not only danger to self or others but also "GRAVELY DISABLED."
    • There's been a lot of "word-smithing" of the Civil Commitment Statutes.
    • And many states, including Colorado, have some version of OUTPATIENT CERTIFICATION.
  • While RESOURCES are a big issue, it is hard to overstate how challenging the situation is made by PRIMITIVE MENTAL HEALTH UNDERSTANDINGS and TREATMENTS.
    • ​Who said that --- the US National Institute of Mental Health.
Next with Kyle Clark

​Housing voucher program leaves Denver landlords managing formerly homeless tenants (Dec. 2025)
Current Mental Health Treatment has had some spectacular successes.  It has also had some spectacular failures.
  • Further, our current understandings are NOT SUFFICIENT to solve the ubiquity of mental health problems in the US and around the world.
Are Neuro-Immunologists our Saviors?
  • I'm sure we would find Neuro-Immunologists wanting too ---
    • But these new understandings do seem to be a significant step up
    • And we ignore at our peril.
Ten years before Rob and Michele Reiner were killed in their home, Rob made a movie about the family's tensions, including with son Nick  (Dec. 2025)
"When Nick would tell us that it wasn't working for him, we wouldn't listen.

We were desperate and because the people had diplomas on their wall, we listened to them when we should have been listening to our son," the Princess Bride director told the L.A. Times at a dinner at the festival with a reporter and his family, including Nick, who had by then achieved sobriety.
  • My brilliant nephew killed himself earlier this year.
    • ​Ironically, his name was Nick, too.
    • He had been through all kinds of treatment programs, had been in jail, homeless, etc.  ---
      • ​including harmful behavior.
    • In his suicide  note, he acknowledged that some people had actually tried to help him ---
      • ​​BUT IT DIDN'T HELP.

Medical research and the creation of clinicians of gross incompetence

Val's Take/Conjecture
  • The first reaction to the "COMPETENCE PROBLEM" in Mental Health is:
    • to admonish clinicians to stay on top of the research --
      • ​I've done that a lot --- I don't know that it's done a lot of good.
      • ​Additionally, more and more you'll see mental health professional articles advising clinicians to stay on top of the research.
  • I think most people who have had to grapple seriously with this issue of Information Overload know that we are needing some new solutions.​
  • For some clinicians practicing now, they will likely never be on top of the current research of 2025. 
    • ​Now if this were just "VARIATIONS ON A THEME" ---
      • ​there might be harms, but not the level of harm by ignorance of major paradigm shifts.
  • Now we could play musical chairs with clinicians, BUT if we don't change this system and improve and increase our TRANSLATIONAL MEDICINE & RESEARCH efforts    ----
    • ​I don't see patients and the community benefitting from improved INTEGRATED UNDERSTANDINGS in a timely manner.​​

​Mycobacterium vaccae ATCC 15483T administered to nulliparous C57BL/6N mice prior to mating

protects their male offspring against the negative consequences of prenatal stress  (2026)

*Research institutions in Germany
*Department of Integrative Physiology, Department of Psychology and Neuroscience, Center for Neuroscience and Center for Microbial Exploration, University of Colorado Boulder;
*Department of Physical Medicine and Rehabilitation and Center for Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO;
*Military and Veteran Microbiome: Consortium for Research and Education (MVM-CoRE), Aurora, CO 

The prenatal period is a vulnerable phase for the offspring's development in utero and ex utero.   Accordingly, negative environmental influences such as chronic maternal stress pose a major risk factor for the offspring to develop a variety of mental and physical disorders later in life.

Many of these pathologies are accompanied by an over-reactive immune system and chronic low-grade inflammation, and prospective human and mechanistic animal studies strengthen the idea that an exaggerated immune (re)activity plays a causal role in their pathogenesis.

In line with the latter, we have shown in mice that repeated administrations with heat-inactivated preparations of different immunoregulatory nontuberculous mycobacteria (NTM), such as M. vaccae NCTC 11659 and the closely related strain M. vaccae ATCC 15483T promote immunoregulation and stress protection

.  .  .

​
The protective effects of M. vaccae ATCC 15483T on female offspring are harder to interpret, as the latter were not as reliably affected by PS.

Collectively, our findings indicate that repeated i.g. administration of M. vaccae ATCC 15483T in an intergenerational manner is protective against the negative consequences of PS  [PRENATAL STRESS] on the immune and musculoskeletal system.
Val's Take/Conjecture:  The point is not that this "vaccae" is ready for prime time --- but rather researchers around the world are by and large not basing their research on the DSM --- they left that behind over a decade ago.

The big focus in the 21st Century is MATERNAL IMMUNE ACTIVATION and even more generally PRENATAL STRESS. 

In Utero immune dysregulations And Multi-system repercussions

FENS --- Federation of European Neuroscience Societies

FENS Friday: “The microbiome, immunity, and neurodevelopment trialogue: from womb to adulthood”  (2022)
Chasing Consiousness Podcast
Interview with King's College London
Professor of Clinical Microbiology Graham Rook

The Microbiome, Mental Health + Re-Thinking Hygiene Theory  (2023)
Val's Take/Conjecture:  The Mental Health Profession is more and more obviously ill-prepared to handle Neuro-Developmental and Psychiatric Disorders with a LARGE IMMUNE COMPONENT.

On the other hand, most Medical Disciplines dealing with Chronic Disease whether Neurology, Oncology, etc. --- might be a little more ahead of Psychiatry in identifying BIO-MARKERS ---- BUT aren't achieving the SUCCESS they might with a thoroughly integrated DEVELOPMENTAL, PHYSICAL & MENTAL HEALTH CARE SYSTEM.

One of the great insights of Psychiatry was that early life experiences and ADVERSE CHILDHOOD EXPERIENCES (ACES) could affect people's later mental health.

The insights of MICROBIOLOGISTS around the World are pushing that back to IN UTERO DYSREGULATIONS of the INNATE IMMUNE SYSTEM leading to Neuro-Developmental and Psychiatric Disorders.

TIMING MATTERS: 
  • Maternal Immune Activation occurring IN UTERO can lead to DYSREGULATION OF MICROGLIA (the brain's innate immune cells),
  • Dysregulation of Multiple Systems of the Body through IMMUNOLOGICAL "CROSSTALK" --- including not only the Central Nervous System, but also the Microbiome, Metabolism and the Endocrine System
  • Mitochondrial Dysfunction----
  • AND ACCELERATED EPIGENETIC AGING 

While DIET and EXERCISE are exceedingly important --- that "TRUISM" is often IGNORANT AND ABUSIVE when applied to some to many Neuro-Diverse Folks.

Further, the Holy Grail of MEDICATION ADHERENCE is much more complicated than advertised.
Do immune system and microbiome-gut-brain axis interactions

associate with major depressive disorder?  (2025)

*China
Increasing evidence highlights the complex interplay between the immune system, gut microbiota, and their bidirectional crosstalk with the central nervous system.

Gut microbiota dysbiosis affects neuroimmune and intestinal immune homeostasis, driving bidirectional peripheral-central immune responses through immune-to-brain and gut-to-brain communication.

​This process involves impaired intestinal barrier integrity (bacterial translocation), systemic low-grade inflammation, activation of innate immune signaling pathways (e.g., TLR4 and NLRP3 inflammasomes), glial cell activation, neuroinflammation, and blood-brain barrier (BBB) dysfunction, ultimately leading to neuronal injury and disturbances in mood, cognition, and behavior. 
Peripheral cytokine dysregulation, microglial dysfunction in adolescent major depressive disorder: Neuroimmune crosstalk implications

*China and the US
*to be published in 2026, epublished in 2025
Background: Major depressive disorder (MDD) exhibits a high prevalence among adolescents; however, its pathogenesis remains unclear. This study aimed to investigate the relationship between cytokine dysregulation and microglial dysfunction in adolescents with MDD (regardless of disease onset or duration) during the course of the disorder.
. . .
Conclusion: 

Dysregulation of cytokines may lead to excessive activation of microglia, resulting in increased release of the neurotoxic KP metabolite 3-HK.

This suppresses microglial proliferation and induces microglial cell death, including pyroptosis, accompanied by the release of pro-inflammatory cytokines.

Pyroptosis:  "Highly inflammatory form of programmed cell death"
Highlights

  • Pyroptosis is an inflammatory form of cell death distinct from the immunologically silent apoptosis.

  • Coined in 2001, pyroptosis involves caspases and promotes innate immunity.

  • Neuropsychiatric disorders often lack clear biological markers for diagnosis.

  • NOD-like receptors induce inflammation by activating pro-inflammatory cytokines.

  • Understanding pyroptosis may reveal potential therapeutic pathways for neuropsychiatric disorders
Microglia as critical mediators linking perinatal immune stress to mental health trajectories
*to be published in 2026, epublished in 2025
​*The US Big Leagues:  Harvard, MIT & Boston College
Abstract

Neurodevelopmental and neuropsychiatric disorders that emerge in childhood (such as autism) and adolescence (such as depression and schizophrenia) currently lack broadly effective therapies, underlying an urgent need to better understand their etiology.

While each disorder has its own set of complex genetic and environmental risk factors, perinatal exposure to intense immune activation and/or stress has been linked to increased disease risk.

Microglia, the resident immune cells of the brain, are impacted in each disorder and exquisitely sensitive to early life experience.

Here, we review the literature suggesting microglia-specific changes in response to early life immune activation and/or stress with an emphasis on microglial interactions with neural synapses and circuits.

We also review the existing literature linking these findings to microglia-specific changes in the brain in autism, depression, and schizophrenia.

Our goal is to bridge the gap between developmental insults and the subsequent pathogenesis of these disorders, highlighting key areas for future mechanistic work.
Autoantibodies and psychiatric diseases 

*Scheduled for publication in 2026
​*Germany
It is important to identify neuropsychiatric conditions presenting with psychotic symptoms to ensure appropriate treatment is initiated, which should provide

both immunotherapy and antipsychotic treatment.
​Risk of Parkinson Disease Higher in Individuals With Autism Spectrum Disorder

(2025)

*Sweden, US and Israel
Val's Take/Conjecture

  • Neuro-Developmental Disorders are not necessarily a "DISEASE," but they often are forms of PREMATURE AGING that will lead to "DISEASE."
People who are very intelligent in their 20s --- have a greater risk for Parkinson's.
Picture
Val Corzine
PANDAS Physicians Network 

Early Recognition & Treatment of Neuroimmune Psychiatric Conditions:  A Paradigm Shift in Neuropsychiatry - PANS/PANDAS (Nov. 2025)

Icahn School of Medicine at Mount Sinai

Fighting Neuroimmune Disorders (2019)​

Working to Eliminate Homelessness & Criminal Justice Involvement of People with Cognitive Disabilities


  • Current Scientific Research
  • Legal Analysis, and
  • Authenticity & Lived Experience
PREVIEW:  Neuro-Diversity Wednesday

Neuro-Diversity and Auditory Differences
Val's Take/Conjecture
  • I'm going to reference the videos below featuring David Flink with Neurodiversity Alliance and Lyric Riviera, the Neurodivergent Rebel as well as my own experience.
  • David Flink was diagnosed with ADHD and Dyslexia and Lyric Riviera has said she is Hyperlexic with Autism.
    • ​David needed a Phonetic Strategy to learn to read.
    • Lyric advises that you might want to do a writing exercise to figure out what you need in accommodations.
  • Now both David and Lyric are quite sophisticated when it comes to Neuro-Diversity
    • So I think they would be the first to say ---- "My strategy isn't necessarily going to work for you."
  • My own experience in Elementary School was that Phonics was extremely taxing ----
    • Trying to distinguish different vowel sounds with the same letter --- OMG! Will this torture never --- I think we only have 5 more minutes that we have to do this.
  • I was in Speech Therapy in Elementary School in which we had to sound out everything.
    • It took a lot of energy for me do that and I was embarrassed about being pulled out for the Speech Therapy Group.
    • At one point --- I graduated only to be put back in the next year.
  • In Middle School, I was asked to consider being part of the BAND because I was "Smart."
    • I turned that down because distinguishing between sounds is not what I'm smart at.
  • But I've always loved songs.
A big part of why music can be helpful for mental health --- it uses many parts of the brain.
  • My husband's special interest was "Guitar Playing,"  the Beatles,  musical chords and all the great guitar players
    • ​He wasn't as interested in lyrics.
  • I didn't even really know what a chord was until this last year, although I knew the word.
  • After my husband died, I got involved with Swallow Hill Music in Denver and the Neuro-Tribes there:​
    • for a lot of people they love music and this is a big social outlet.​
    • for others --- this isn't their first Rodeo or personal performance Mixed Tape.
  • At Swallow HIll, they might very well ask students to practice, but they are even more likely to advise budding musicians to RELAX.
  • I think a big part of TRYING or RELAXING is understanding that Neuro-Diversity is REAL.
Picture
Therabeat:  Mental Health and Community Music Therapy

Preview:  Neuro-Diversity Wednesday

Dealing with Executive Functioning At the get go in Treatment

Beyond "Authenticity," to Effective use of "EnergY"

Val's Take/Conjecture
  • When we talk about "TRANS-DIAGNOSTIC PHENOTYPES" of Neuro-Developmental & Psychiatric Disorders, we're often talking about different:
    • ​Sensory Processing 
    • Executive Functioning
    • Regulation of Microglia -- the Brain's Innate Immune Cells, and
    • Mitochondrial Dysfunction --- dysfunction of CELLULAR ENERGY
  • Even as it is costing NEURO-DIVERSE folks a lot of ENERGY to MASK --- 
    • It is costing the Society a lot of ENERGY & MONEY to understand Neuro-Developmental and Psychiatric Disorders.
    • Further, Neuro-Diverse Folks are DIVERSE and they need PRECISION MEDICINE and PSYCHIATRY ---
      • ​That is a lot different than just handing out that Large T-Shirt or a prescription of pills.
        • ​There may be a complicated social history;
        • There may be a complicated family medical history that goes beyond mental health diagnoses, and includes immune disorders and other illnesses.
        • Etc., Etc., Etc.
SYSTEMATICALLY ADDRESSING EXECUTIVE FUNCTIONING in:
  • Education
  • Treatment, and
  • Employment
  • Generally, Education and Employment are looking to the Mental Health Profession to address Executive Functioning.
    • ​Most mental health professionals have plenty on their plates without that.
    • The Job Accommodation Network tries to SYSTEMITIZE accommodations for people with disabilities and at least give people a starting point.
A FUNCTIONAL ASSESSMENT FOR EXECUTIVE FUNCTIONING
  • Colorado currently has a functional assessment tool for Medicaid Long Term Care.
    • ​That was a collaborative effort among Stakeholders.
  • We need FUNCTIONAL, INEXPENSIVE, PRACTICAL assessments for Executive Functioning.​
FREE EXECUTIVE FUNCTIONING ASSESSMENT
For those seeking functional and inexpensive executive functioning assessments, the Free Executive Functioning Assessment stands out as a practical and cost-effective option.

It covers 11 key executive function skills and includes a dynamic scoring spreadsheet for tracking progress. The assessment is available in both English and Spanish, with expert human translation to ensure clarity and accessibility.

​It is designed for everyday use, making it easy to complete, interpret, and apply, and it has been scientifically validated based on real-world experiences and practical application.
The Health Foundation --- UK
Shared Decision Making Can Improve the Experience of Care
Understood --- 
David Flink --- Co-Founder & CEO of The Neurodiversity Alliance
ADHD, Dyslexia --- Advice for Kids

Try Smarter Not Harder
“Can you try a little harder to just focus here?”

​Kids with learning and thinking differences hear that bit of advice often.

But many kids with dyslexia, ADHD, and other learning and thinking differences are already trying their hardest.

The better advice is to “try smarter.”
Neuro-Divergent Rebel --- Lyric Riviera
Boundaries

When I first discovered I was Autistic at the age of 29:

* it was because I was going through Autistic burnout and

* that's because I was in a perpetual state of burning myself out
​
*because I didn't know I was Autistic and

​* I didn't know how to establish healthy boundaries with the neurotypical people around me that kept insisting I didn't really need the things I was saying I needed.

All of that dismissal of my own thoughts and needs for so many years, 29 years, not knowing - led me to being someone who really, really struggled with boundaries and I found that reflecting on my life, a lot of the things I did were things I was doing, not because I even wanted to do them.

Dr. Gail Saltz is a prominent psychiatrist and author of The Power of Different.

Two of the big messages from The Power of Different:
  • Rough rule of thumb --- 80% of time on Strengths Development, 20% on "work-arounds" for weaknesses.
  • If we're spending 100% of time on Executive Functioning Issues that probably is a recipe for worsening mental health.
Workarounds are a BY-PASS of a recognized problem or limitation --- and it is a lot easier to do if that limitation is identified and accurate.

Preview

Eye Disorders and Co-Morbid Psychiatric Disorders

Beyond Differential Diagnosis to co-morbidity

Val's Take/Conjecture
  • MANY Disorders and Diseases may contain a PSYCHIATRIC COMPONENT.
  • There are a number of papers that recently came out with regard to co-morbidity of eye disorders and psychiatric disorders.
  • Not everyone with a psychiatric disorder has an eye disorder.
  • ​That complexity is driving PRECISION MEDICINE.
Major sight-threatening eye disorders and mental disorders  (2025)

*China, US, United Arab Emirates, Portugal & Poland
Causal Relationships Between Retinal Diseases and Psychiatric Disorders Have Implications for Precision Psychiatry (2025)

*China
Abstract

​Observational studies and clinical trials have reported potential associations between retinal diseases and psychiatric disorders.

However, the causal associations between them have remained elusive.

In this study, we used bi-directional two-sample Mendelian randomization (MR) analysis to explore unconfounded causal relationships between retinal diseases and psychiatric disorders using large-scale genome-wide association study (GWAS) summary statistics of over 500,000 participants of European ancestry from the FinnGen project, the Psychiatric Genomics Consortium, the European Bioinformatics Institute, and the UK Biobank.

Our MR analysis revealed significant causal relationships between major retinal diseases and specific psychiatric disorders.

Specifically, susceptibility to dry age-related macular degeneration was associated with a reduced risk of anorexia nervosa (OR = 0.970; 95% CI = 0.930 ~ 0.994; P = 0.025).

Furthermore, we found some evidence that exposure to diabetic retinopathy was associated with an increased risk of schizophrenia (OR = 1.021; 95% CI 1.012 ~ 1.049; P = 0.001), and exposure to retinal detachments and breaks was associated with an increased risk of attention deficit hyperactivity disorder (OR = 1.190; 95% CI 1.063 ~ 1.333; P = 0.003).

These causal relationships were not confounded by biases of pleiotropy and reverse causation.

Our study highlights the importance of preventing and managing retinal disease as a potential avenue for improving the prevention, management and treatment of major psychiatric disorders.
Dry Eye Disease and Psychiatric Disorders: Neuroimmune Mechanisms and Therapeutic Perspectives  (2025)

*Croatia
Study Underscores Need for Eye Exam in Psych Disorders  (2025)
Neurovascular dysfunction in psychiatric disorders: Underlying mechanisms and therapeutic approaches (2025)

*Portugal
Background: Neurovascular interfaces, specifically the blood-brain barrier (BBB) and blood-retinal barrier (BRB), play pivotal roles in maintaining the homeostasis of the central nervous system (CNS).

For a long time, these structures were seen only as a way of protection, but we currently know that they have a critical role in CNS (dys)function.

Several studies have identified neurovascular alterations in early stages of brain and eye diseases, contributing to the pathophysiology of such conditions.

​More recently, interesting data have also highlighted the importance of neurovasculature in psychiatric disorders.

Preview:  Neuro-Diversity Wednesday

"I am too smart!"

But what's up with those executive functioning issues?

Val's Take/Conjecture
  • There are many aspects to the ENERGY/Mitochondria/ATP issues that people with Neuro-Developmental and Psychiatric Disorders tend to have.​
  • One of the things that I shared on "Val's Slow Processing" was that my psychiatrist of many years was really the first to point that out.
  • What l didn't say was the full line was along the lines of:
    •  "Your processing is slow --- you seem cognitively impaired."
The SLOW PROCESSING I think in many cases is related to SENSORY PROCESSING and ATYPICAL SYNAPSES that are in many cases:
  • processing more information, and
  • requiring more ATP.
One of the things that YOUNGER NEURO-DIVERSE PEOPLE are doing is getting those EXECUTIVE FUNCTIONING ISSUES out on the table.
  • As any good trial  attorney will tell you, get those weaknesses in your case out on the table in OPENING STATEMENT.
BUT for OLDER NEURO-DIVERSE PEOPLE we conflated "TRADITIONAL INTELLIGENCE" with "EXECUTIVE FUNCTIONING" as everyone else---
  • "Executive Functioning" as a term didn't come about until the 1970s ---
    • ​Believe it or not  some of us were born before then.
  • Further, "Executive Functioning" didn't really become a BUZZ WORD until the 2000s.
The CRITICAL PIECE that hadn't been fully articulated until Dr. Chris Palmer's book Brain Energy is none other than the role of ENERGY DYSREGULATIONS in Neuro-Developmental and Psychiatric Disorders.
  • I think the "KETO DIET" needs to be subject to PRECISION MEDICINE, but
  • It's not an exaggeration to say these insights are REVOLUTIONARY.
Antoine Giraud
Perinatal inflammation exposure and developmental outcomes after neonatal stroke.

Val's Note:  Results of IQ Scores of children with perinatal inflammation exposure were actually higher than that of "normal" children.
Transdiagnostic features of inflammatory markers and executive function across psychiatric disorders  (2025)​

*Taiwan, US and China

Orchid and Looking to 2026

Val's Take
  • People who followed Orchid in the early days may have known that at one point I had another website Orchid Global.
  • Basically, my deceased husband, who was not deceased at the time said:  "We're  not having 2 websites that don't make any money [or not self-sustaining]."
  • At least in 2026, I don't anticipate resurrecting Orchid Global.
  • I will be exploring expanding the mission of Orchid beyond Colorado with more of a focus on short science pieces as well as citizen journalism.
  • There's not going to be much money to pay journalists, but I do anticipate we might pay something in the range of $25 per piece and it won't be limited to people in Colorado or the United States.

Preview

Mayors Johnston & Coffman's impressive homeless initiatives

We're slowly moving up the continuum of care --- but recognizing the needs of those at the highest end often eludes us

Val's Take
  • ​​One of the things the Johnston Administration learned was that  addressing "HOMELESSNESS" was more than providing housing and helping people get back on their feet.
    • ​They had major security problems early on.
    • They learned they needed to be providing significant case management, and
    • Provide targeted efforts for those with the most serious mental health and addiction issues.
  • Aurora Mayor Mike Coffman's big innovation is EMPLOYMENT.
    • ​This is important even ESSENTIAL.
    • ​BUT like Johnston, if one doesn't appreciate the complexity of requiring employment of people with:
      •  demonstrable executive functioning issues  ---
      • and serious Neuro-Immune Disorders affecting multiple systems of the body, including "BRAIN ENERGY,"
    • ​​​​this could be a rough ride.
Next:  9 News
City of Denver Reports Unsheltered Homelessness is Down in an Historic Way

Kyle Clark:  "It's not magic it's money --- and Johnston spent a ton of it."
All In Mile High
Aurora's Regional Navigation Campus
Accelerated Aging in Serious Mental Disorders  (2020)
Serious mental disorders (SMD’s) are associated with an increased risk of medical illnesses and premature mortality from natural causes, with lifespans up to 25 years shorter than the general population .

Although lifestyle and socioeconomic factors play a role, the psychiatric condition itself may be an independent risk factor, even after excluding death by suicide.

The particular medical illnesses that are more frequent in SMD’s are those that are more commonly seen with advanced age, such as cardiovascular disease and others.

This has raised the possibility that SMD’s are associated with accelerated biological aging.

Whereas chronological age is measured by the passage of time, biological age is defined physiologically and functionally and is more closely associated with disease processes and mortality.
Nevada:  Brain Injury and Homelessness

Preview

Neanderthals, Precision Medicine, Quantum Medicine & Psychiatry

Val's Take/Conjecture
  • When it comes to factors or variables influencing mental health, this does seem to be more addition than subtraction and perhaps multiplication.
Janus:  The Roman God who Looks Forward & Back
Quantum Medicine with its focus on "ENERGY" has great potential to address the ENERGY DYSREGULATIONS in Neuro-Developmental and Psychiatric Disorders.

​On the other hand, it doesn't mean there aren't scams out there.
8:20:  Counseling Psychologist Stephen Munt discusses "MILLIONS OF SPECTRA."

The number of variables and cross-interactions is mind-boggling.  Psychiatrist and author Dr. Chris Palmer says we need a Super Computer to sort it out.

This complexity is driving the need for PRECISION MEDICINE.
​A Brief Quantum Medicine Policy Guide
(2024)
The concept of biophotonic signaling in the human body and brain: rationale, problems and directions (2025)

Immunology, Endocrinology & Neuro-Psychiatric Disorders

Reverse T3 in Hypothyroidism & Neuro-Psychiatric Disorders

​ --- not as passive as we thought​

Val's Take/Conjecture
  • More and more there is evidence that PSYCHIATRIC DISORDERS are BLURRED.
  • Additionally, evidence is accumulating that other DISEASES and DISORDERS not traditionally thought of as PSYCHIATRIC are also blurred with NEURO-PSYCHIATRIC DISORDERS.
  • Auto-Immune Disorders definitely seem to have an "overlap" with Neuro-Developmental & Psychiatric Disorders, especially in females -- and males can have auto-immune disorders, too.
AUTOIMMUNITY, AUTOANTIBODIES, AND AUTISM SPECTRUM DISORDERS (ASD) (2016)
Further, it is becoming more and more apparent to Doctors who specialize in Thyroid Disorders that current tests seem inadequate in a significant percentage of cases.

​That is driving among other things a diagnosis of "Functional Hypo-Thyroidism."

Thyroid Disorders are not like Multiple Sclerosis or Lupus --- Thyroid Disorders are very common.

Thyroid Disorders have been referred to as "The Tallest Tree in the Forest of Poly-Auto-Immunity."
In some respects, Mental Health is the "Tallest Tree" in the need for Integrated Developmental, Mental and Physical Health.
  • Ironically, that has been driven by the paucity of "BIOMARKERS."
  • Researchers had to question their assumptions in a way other Medical Disciplines have delayed.
  • Those Biomarkers are starting to come --- but those Biomarkers are often implicating other systems of the body beyond the Brain and the Central Nervous System.
The Influence of Reverse Triiodothyronine on Neuropsychiatric Disorders: A Narrative Review (Oct. 2025)
Conclusions: Reverse T3, long viewed as a passive by-product, may play an active regulatory role in neuropsychiatric disorders by interfering with T3 signaling at the cellular level.

Functional hypothyroidism driven by excess rT3 represents a distinct biochemical phenotype contributing to mood, cognition, and behavioral dysfunction.

Recognition of this mechanism underscores the need for expanded thyroid assessment beyond standard TSH and T4 testing in psychiatric populations.

​Future research should focus on the therapeutic implications of correcting rT3 dominance and restoring optimal intracellular thyroid hormone activity.
What is "Functional Hypothyroidism"  ---???
​Functional hypothyroidism refers to a
condition where the thyroid produces 
normal levels of hormones, but other
hormonal imbalances prevent these
hormones from functioning effectively in
the body.

​Definition and Mechanism

Functional hypothyroidism occurs when the thyroid gland produces adequate amounts of thyroid hormones (primarily T4 and T3), but factors such as stress or other hormonal imbalances hinder the proper utilization of these hormones at the cellular level. For instance, elevated cortisol levels due to chronic stress can block thyroid hormone action, leading to symptoms similar to those of traditional hypothyroidism, despite normal lab results. 

Dr. Tina Marcantel, RN, ND
​SymptomsIndividuals with functional hypothyroidism may experience symptoms commonly associated with hypothyroidism, such as:
Fatigue
Weight gain
Cold intolerance
Hair thinning
Mood changes (e.g., depression or anxiety). 
​
Functional Medicine Approach
The functional medicine approach to managing functional hypothyroidism emphasizes identifying and addressing
the root causes of the condition rather than merely replacing thyroid hormones. 

This may include:

Stress Management: Reducing stress through lifestyle changes, mindfulness, and relaxation techniques to lower cortisol levels.

Dietary Adjustments: Implementing an anti-inflammatory diet that may include nutrient-rich foods to support thyroid health, such as those high in iodine and selenium. 

Holistic Assessment: Conducting thorough evaluations to understand the interplay between various hormones and the thyroid, allowing for personalized treatment plan

Conclusion
Functional hypothyroidism highlights the complexity of thyroid health, where normal hormone production does not guarantee effective hormone action. A comprehensive approach that includes lifestyle modifications, dietary changes, and stress management can help restore balance and improve overall thyroid function. For individuals experiencing symptoms of hypothyroidism despite normal lab results, consulting a healthcare provider familiar with functional medicine may be beneficial. 


​Transcriptional imprints of prenatal stress:

sex- and time-specific signatures in early neurodevelopment

(Nov. 2025)

*Italy
Val's Take/Conjecture
  • If Clinicians need someone to perform with, Prosecutors and Criminal Defense Attorneys definitely do.
  • One of the huge issues I have seen is that Clinicians weren't knowledgeable when it came to these Developmental Neuro-Immune Issues.
  • That is probably less and less the case.
  • But also, there seems to be much more of a Critical Mass of Researchers who are familiar with these issues.
Prenatal maternal stress and long-term neurodevelopmental outcomes: a narrative review (2025)
Summary: 

Current literature supports a robust association between maternal stress during pregnancy and a heightened risk of neurodevelopmental challenges in children.

These include deficits in executive function, increased anxiety and depressive symptoms, emotional dysregulation, and susceptibility to psychiatric disorders.

The effects appear to be moderated by timing of exposure, genetic predispositions, and the postnatal environment.


Outlook: While the evidence base is growing, methodological limitations such as variability in stress assessment and inconsistent follow-up durations persist.

Future research should emphasize longitudinal, biomarker-informed designs and evaluate interventions aimed at reducing prenatal stress.

Integrating maternal mental health support into routine prenatal care may offer a promising pathway to improving both maternal and child outcomes.
Prenatal stress (PNS) is a well-established animal model of foetal exposure to maternal stress and related psychiatric disorders . . .

​The collected findings suggest a sex- and time-dependent different modulation of multiple biological processes, with mitochondrial dysfunction emerging as a central mechanism underlying developmental programming that may predispose to future behavioural impairments.​
​

​"$2 Saliva Test Could Help Detect Depression and Schizophrenia"

Val's Take/Conjecture
  • Is the Saliva Test for Depression and Schizophrenia going to work?
  • ​Is  Withania somnifera root extract the answer to Mitochondrial Dysfunction?
  • I don't know, but there are as the Researchers from India point out "converging lines of evidence." 
  • Further, there are Researchers all over the world making incredible progress in understanding the nature of Neuro-Developmental and Psychiatric Disorders.
The Role of Brain-Derived Neurotrophic Factor in Immune-Related Diseases: A Narrative Review (2022)

​*Poland
The Role of Brain-Derived Neurotrophic Factor as an Essential Mediator in Neuronal Functions and the Therapeutic Potential of Its Mimetics for Neuroprotection in Neurologic and Psychiatric Disorders (2025)

*Japan
BDNF is a prognostic biomarker involved in the immune infiltration of lung adenocarcinoma and associated with programmed cell death (2025)

​*China
Hypothyroidism Promotes Microglia M1 Polarization by Inhibiting BDNF-Promoted PI3K-Akt Signaling Pathway (2024)

*China
Neuroscience News:  October 29, 2025
*Brazil
Summary: 

Scientists have developed a portable biosensor that can detect levels of BDNF, a protein linked to mental health conditions such as depression, schizophrenia, and bipolar disorder.

The flexible, low-cost device analyzes a drop of saliva in under three minutes, offering a fast, affordable, and noninvasive diagnostic tool.

Because low BDNF levels are associated with depression and cognitive decline, the test could help clinicians detect and monitor disorders earlier.

With an estimated cost of just $2.19 per unit, the biosensor could transform mental health screening, especially in low-resource settings.


Key Facts


  • Rapid Results: The saliva-based biosensor measures BDNF levels in less than three minutes.

  • Affordable Innovation: Each unit costs around $2.19, making it accessible for widespread use.

  • Clinical Relevance: Low BDNF levels are linked to depression, while increases can track recovery
From Synaptic Plasticity to Neurodegeneration: BDNF as a Transformative Target in Medicine (2025)

*Romania
Withania somnifera Regulates Mitochondrial Biogenesis and Energetics in Rat Cortical Neurons: Role of BDNF and SIRT1 (2025)

*India
Given converging evidence suggests a critical role for mitochondrial dysfunction in the pathophysiology of neuropsychiatric and neurodegenerative diseases, we hypothesized that Withania somnifera may exert pleiotropic effects via targeting mitochondria.

. . .



​
Collectively, these results indicate that Withania somnifera root extract and specific phytochemical constituents robustly influence mitochondria in cortical neurons, contributing to stress adaptation and neuroprotection via BDNF and SIRT1 signaling.

Preview

Programs in Translational Medicine and Applied Research

Val's Take/Conjecture
  • I come at this from the perspectives of a lawyer and a patient.
  • What I saw 20 years ago were clinicians who were meeting the STANDARD OF CARE, but the STANDARD OF CARE was INSUFFICIENT.
  • When one says like I do all the time, "Hey, there are these great new understandings in the RESEARCH that Neuro-Developmental and Psychiatric Disorders are NEURO-IMMUNE DISORDERS affecting Multiple Systems of the Body ---
  • From a practical standpoint --- what's a Clinician supposed to do with that?
​Master of Translational Medicine

A Big Idea is Just the Beginning

M-Tram

The one-year Master of Science in Translational Research and Applied Medicine (M-TRAM) trains the next generation of academic and industry leaders to successfully translate scientific discoveries and clinical applications into practical solutions that improve and save lives. 

​Drawing on Stanford Medicine’s exceptional expertise in medicine, technology, and business, M-TRAM is the only early translational program of its kind on the West Coast and one of only a few such one-year programs offered by a top-ranked U.S. university.
Master in Translational Medicine

The many ironies of Divide & Conquer ----

individualized precision medicine

Val's Take/Conjecture
  • I think for some time there was the reasoning that --- "I knew somebody with Schizophrenia, Bipolar Disorder, etc. --- they didn't commit a horrible crime, therefore, any claim of illness or biological explanation for bad behavior is FALSE."​
    • ​Further, these arguments were often made from a place of MORAL SUPERIORITY and solidarity with a PARTICULAR SEGMENT of the MENTAL HEALH COMMUNITY.
  • Really beginning in the earlier part of the 20th Century --- which was a pretty wild century ---
    • ​There was both Freud, and
    • Monez  --- the doctor who performed the 1st lobotomy in 1935.
  • Later --- MID-CENTURY MODERN --- we get the first psychotropic drugs in the 1950s.
  • Psychiatric Medication was viewed as a great miracle and for some people it was.
    • ​It was always more complicated than advertised and that was not only problematic for clinicians and the society --- it could be incredibly problematic for the person.
  • By 1975, there is the reference to psychoneuroimmunology -- and attempts to integrate MIND & BODY.
    • ​But those attempts were still relatively primitive, largely out of necessity   ---
      • ​​The technology didn't exist to integrate those concepts in the way we're doing today.
  • When we think about Human Individuality and Uniqueness --- in Modern Times we're often thinking about the BRAIN, not the IMMUNE SYSTEM.
  • Further, when we think about BIOLOGICAL EXPLANATIONS for behavior we've often thought GENETICS ---- not PRE-NATAL INFLAMMATION and AUTO-IMMUNE DISEASE.
  • For a celebrity or politician we might talk about a BREAK-OUT album or movie or speech.
  • Is 2025, is this the break out year for NEURO-IMMUNOLOGY?
Reverend Paul Jones
I Won't Complain
That's My Boy (1951)

This is one of Dean Martin & Jerry Lewis' funniest movies --- it's about 2 middle aged men and their sons who are now college age --- who turned out very different from their fathers.
Benjamin Clementine
I Won't Complain
I love this music video --- it's sophisticated --- very "psychological" --- has a SURREAL quality and references SURREAL ART and MENTAL HEALTH.
I'm referencing the quote below, really to highlight how much ENERGY we can get from the OPPOSITION.

And at the end of the day, a lot of Mental Health  problems are about MITOCHONDRIAL "BIOENERGETICS."
​And for those who hate me, the more you hate me
The more you help me
And for those who love me, the more you love me
The more you hurt me
Professor of Immunology Dan Davis
University of Manchester

---the Immune System is the SOURCE of the GREATEST DIVERSITY
René Magritte. La Reproduction Interdite (Not to Be Reproduced). Brussels  (1937)

Benjamin Clementine:  "My Mind is a Mirror Known Only to Me."
Val's Take:  I love Art, Symbolism, Myth and Metaphor.

But sometimes, one needs HARD SCIENCE -- getting to the Cellular and Molecular Levels of understanding.

It's amazing that the World's Scientists are largely on the same page with regard to Neuro-Developmental and Psychiatric Disorders --- it is concerning that we don't have the systems for the CLINICIANS who ACTUALLY TREAT THE PATIENTS.
That's not really the fault of Mental Health Professionals -- BUT they're not dealing competently with Neuro-Immune Multi-System Disorders by themselves.

Nasal administration of mitochondria

Is it the elexir of Youth? It seems to be able to improve a wide range of cognitive issues

Val's Take/Conjecture
  • This is an amazing story of some of the researchers and doctors addressing "rare, orphan" Mitochondrial Disorders.
  • What they did was point out that Diseases and Disorders that affected MILLIONS OF PEOPLE also involved MITOCHONDRIAL DYSFUNCTION.
  • People with Neuro-Developmental & Psychiatric Disorders owe them a great debt of GRATITUDE as do those with many other common Diseases and Disorders.
Mitochondrial dysfunction linked to Alzheimer’s onset and treatment response  (2024)
​
Nasal administration of mitochondria reverses chemotherapy-induced cognitive deficits (2021)

*University of Texas, Germany
Intranasal delivery of mitochondria for treatment of Parkinson's Disease model rats lesioned with 6-hydroxydopamine (2021)

*Taiwan
Nasal administration of mitochondria relieves depressive- and anxiety-like behaviors in male mice exposed to restraint stress through the suppression ROS/NLRP3/caspase-1/IL-1β signaling pathway (2025)

*Iran
​
[Iran is another country outside of the West that is doing important mental health research. 

They may not be as prolific as China --- BUT they are strategic and impactful in their research]
Intranasal delivery of mitochondria targeted neuroprotective compounds for traumatic brain injury: screening based on pharmacological and physiological properties (2024)

Affiliations
1TBI Bioenergetics, Metabolism and Neurotherapeutics Program, Brain Trauma Neuroprotection (BTN) Branch, Center for Military Psychiatry and Neuroscience (CMPN), Walter Reed Army Institute of Research (WRAIR), 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA. 
2TBI Bioenergetics, Metabolism and Neurotherapeutics Program, Brain Trauma Neuroprotection (BTN) Branch, Center for Military Psychiatry and Neuroscience (CMPN), Walter Reed Army Institute of Research (WRAIR), 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA.
The New Paradigms of Cognitive Disability are not throwing out all the older paradigms of Neuro-Developmental and Psychiatric Disorders --- although they are throwing out some and the New Paradigms are making clear:
  • We need PRECISION MEDICINE & PSYCHIATRY
  • Pre-Natal Inflammation is playing a big role,
  • Dysregulation of Microglia --- the Brain's Innate Immune Cells --- is playing a big role, and
  • The "BIOENERGETICS" of Mitochondrial Dysfunction are playing a big role.

psychiatric disorders as auto-inflammatory innate immune disorders

Mediated by MICROGLIA

Val's Take/Conjecture
  • Differential Diagnosis between Auto-Immune Diseases and Auto-Inflammatory Psychiatric Disorders is complicated.
  • Some people with diagnosed Psychiatric Disorders actually have Auto-Immune Diseases such as Auto-Immune Encephalitis.
  • Auto-Immune Thyroid Disorders are common among people with Psychiatric Diagnoses.
    • For some people, addressing the Thyroid Disorder may be sufficient.
    • For many people, they may have both the Auto-Immune Thyroid Disorder and Psychiatric Disorder.
One of my pet peeves is "Life Style Choices" in the context of Neuro-Developmental and Psychiatric Disorders.

It is not that I don't think Life Style Choices are important.  But Pre-Natal Dysregulations make those "choices" a lot harder for some people than others and they don't always get the same benefit.

On the other hand, the Life Style Choices needed by people with Neuro-Developmental and Psychiatric Disorders and the Society may be much more significant than currently contemplated.
The Role of Prenatal Microglial Activation and Its Sex Differences in the Development of Neuropsychiatric Disorders and Neurodegenerative Diseases  (2025)

*Russia
Microglia: the brain’s ‘immune cells’ protect against diseases – but they can also cause them (2020)
Examining the genetic links between clusters of immune-mediated diseases and psychiatric disorders (2025)
Author information

1Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO USA
2Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO USA
3Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA USA
4Department of Psychiatry, Harvard Medical School, Boston, MA USA
5Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA USA
6Massachusetts General Hospital Brigham, Boston, MA USA
7Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA USA
8Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO USA
Autoimmune diseases result from abnormal adaptive immune responses, whereas autoinflammatory diseases arise from a malfunctioning innate immune system 

What is "Disability" under the ADA?

​Clinicians aren't lawyers & it shows

Val's Take
  • Clinicians struggle with Definitions in the Civil Commitment Statutes --- but I think they are more aware of the issues.
  • When it comes to "DISABILITY" --- there is more than one Statute or Regulation out there -- is this Social Security Disability, Medicaid, Education or Employment.
  • For purposes of Employment, most people are going to be concerned about the  definition of "Disability" under the AMERICANS WITH DISABILITIES ACT.
  • We're piling too much on Mental Health practitioners, and we're really piling too much on Teachers.​
  • Maybe not everyone with a Neuro-Developmental or Psychiatric Diagnosis needs ACCOMMODATIONS, but many people do and those ACCOMMODATIONS often relate to BRAIN ENERGY and EXECUTIVE FUNCTIONING.
    • Even when the person has an IQ over 70 and even is highly educated.
      • ​Appreciating the role of the IMMUNE SYSTEM, Microglia Dysregulation and Mitochondria Dysfunction makes this more understandable.
  • Theoretically, Occupational Therapists could be a good fit for this, but it may not be PRACTICAL
  • Further, does everyone need a NEURO-PSYCH to request accommodations for a Neuro-Developmental or Psychiatric Disorder ---
    • ​​I don't think so --- and it's not necessarily a good use of resources.
  • It seems to me that professionals receiving some kind of certification or equivalent specialized knowledge could make Accommodation Recommendations.
  • These ACCOMMODATIONS under the Americans With Disabilities Act (ACT) are critical for Employment and most clinicians are NOT COMPETENT to make recommendations.
Social Security Disabilty
DI 00115.015 Definitions of Disability

​CITATIONS:

Social Security Act, Section 216(i) , Section 223(d)(1) , and Section 1614(a)(3)(C)
20 CFR 404.1505 , 416.905 , 416.906
For all persons applying for disability benefits under title II, and for adults applying under title XVI, the definition of disability is the same.

​A. Definition of disability for adultsUnder title II and title XVI, we consider a person disabled under Social Security rules if he or she has a medically determinable physical or mental impairment (or combination of impairments):
  • •that prevents him or her from doing any substantial gainful activity (SGA), and
  • •has lasted or is expected to last for a continuous period of at least 12 months, or is expected to result in death.
IDEA (Individual with Disabilities Education Act)
(3) Child with a disability
(A)In generalThe term “child with a disability” means a child--
(i)
with intellectual disabilities, hearing impairments (including deafness), speech or language impairments, visual impairments (including blindness), serious emotional disturbance (referred to in this chapter as “emotional disturbance”), orthopedic impairments, autism, traumatic brain injury, other health impairments, or specific learning disabilities; and
(ii)
who, by reason thereof, needs special education and related services.
(B)Child aged 3 through 9The term “child with a disability” for a child aged 3 through 9 (or any subset of that age range, including ages 3 through 5), may, at the discretion of the State and the local educational agency, include a child--
(i)
experiencing developmental delays, as defined by the State and as measured by appropriate diagnostic instruments and procedures, in 1 or more of the following areas: physical development; cognitive development; communication development; social or emotional development; or adaptive development; and
(ii)
who, by reason thereof, needs special education and related services.
Americans with Disabilities Act
42 U.S. Code § 12102 - Definition of disability

As used in this chapter:
(1)DisabilityThe term “disability” means, with respect to an individual--
(A)
a physical or mental impairment that substantially limits one or more major life activities of such individual;
(B)
a record of such an impairment; or
(C)
being regarded as having such an impairment (as described in paragraph (3)).
(2)Major life activities
(A)In general
For purposes of paragraph (1), major life activities include, but are not limited to, caring for oneself, performing manual tasks, seeing, hearing, eating, sleeping, walking, standing, lifting, bending, speaking, breathing, learning, reading, concentrating, thinking, communicating, and working.

(B)Major bodily functions
For purposes of paragraph (1), a major life activity also includes the operation of a major bodily function, including but not limited to, functions of the immune system, normal cell growth, digestive, bowel, bladder, neurological, brain, respiratory, circulatory, endocrine, and reproductive functions.

(3)Regarded as having such an impairmentFor purposes of paragraph (1)(C):
(A)
An individual meets the requirement of “being regarded as having such an impairment” if the individual establishes that he or she has been subjected to an action prohibited under this chapter because of an actual or perceived physical or mental impairment whether or not the impairment limits or is perceived to limit a major life activity.
(B)
Paragraph (1)(C) shall not apply to impairments that are transitory and minor. A transitory impairment is an impairment with an actual or expected duration of 6 months or less.
(4)Rules of construction regarding the definition of disabilityThe definition of “disability” in paragraph (1) shall be construed in accordance with the following:
(A)
The definition of disability in this chapter shall be construed in favor of broad coverage of individuals under this chapter, to the maximum extent permitted by the terms of this chapter.
(B)
The term “substantially limits” shall be interpreted consistently with the findings and purposes of the ADA Amendments Act of 2008.
(C)
An impairment that substantially limits one major life activity need not limit other major life activities in order to be considered a disability.
(D)
An impairment that is episodic or in remission is a disability if it would substantially limit a major life activity when active.
(E)
(i)The determination of whether an impairment substantially limits a major life activity shall be made without regard to the ameliorative effects of mitigating measures such as--
(I)
medication, medical supplies, equipment, or appliances, low-vision devices (which do not include ordinary eyeglasses or contact lenses), prosthetics including limbs and devices, hearing aids and cochlear implants or other implantable hearing devices, mobility devices, or oxygen therapy equipment and supplies;
(II)
use of assistive technology;
(III)
reasonable accommodations or auxiliary aids or services; or
(IV)
learned behavioral or adaptive neurological modifications.
(ii)
The ameliorative effects of the mitigating measures of ordinary eyeglasses or contact lenses shall be considered in determining whether an impairment substantially limits a major life activity.
(iii)As used in this subparagraph--
(I)
the term “ordinary eyeglasses or contact lenses” means lenses that are intended to fully correct visual acuity or eliminate refractive error; and
(II)
the term “low-vision devices” means devices that magnify, enhance, or otherwise augment a visual image.

Is the gap between researchers & Clinicians Narrowing?

ACCELERATED TMS Approved by the FDA

Among other things, Transcranial magnetic Stimulation (tmS) appears to have beneficial effects on Glial cells --- Microglia (the brain's immune cells) & AstrocyTes

Val's Take/Conjecture
  • TMS is something that many mental health practitioners already provide or they are able to make referrals.
  • TMS and Accelerated TMS are not necessarily panaceas, but these treatments can help some people.
  • TMS also seems to be a great bridge between traditional mental health treatment and an approach recognizing the importance of the IMMUNE SYSTEM.
Alcohol-Induced Changes in Brain Microstructure: Uncovering Novel Pathophysiological Mechanisms of AUD Using Translational DTI in Humans and Rodents (2025)

*Germany & Spain
Our studies demonstrate that increased mean diffusivity (MD) in gray matter reflects microglial reactivity and reduced extracellular space tortuosity, leading to enhanced volume neurotransmission.

In white matter, fractional anisotropy (FA) reductions indicate progressive deterioration of key tracts, particularly the fimbria/fornix, linked to impaired cognitive flexibility.

Importantly, longitudinal analyses reveal that white matter degeneration continues during early abstinence, suggesting that neuroinflammation and demyelination persist beyond alcohol cessation.

Finally, we discuss how neuromodulatory interventions, such as transcranial magnetic stimulation (TMS), may promote recovery by enhancing myelin plasticity.

​These findings provide crucial insights into AUD’s neurobiological underpinnings and highlight potential therapeutic targets for improving treatment outcomes.
An accelerated course of TMS using intermittent theta burst for veterans with major depressive disorder: A case series (2023)

*Florida
Conclusions: This case series details the safety and efficacy of an accelerated iTBS TMS protocol consisting of 25 treatments over 5 days.

Improved depressive symptoms were observed, with remission and response rates similar to standard TMS protocols of daily TMS for ≥6 weeks.
Microglia and Astrocytes Responses Contribute to Alleviating Inflammatory Damage by Repetitive Transcranial Magnetic Stimulation in Rats with Traumatic Brain Injury  (2024)

*China

Mind the gap

The gap between researchers and clinicians

Val's Take/Conjecture
  • Acclaimed Oxford Psychiatry Professor Belinda Lennox attributes the lack of Mental Health Professional interest in the new immunological paradigms to being "down on their knees."
  • Mental Health Professionals are generally good to excellent at titrating approved medications and providing therapy.
    • ​​THAT'S A LOT!
  • On the other hand, the KNOWLEDGE regarding Neuro-Developmental and Psychiatric Disorders has moved far ahead of the clinicians.

A public health approach to criminal Justice 
​
"Immunity finely regulates brain function"

Val's Take/Conjecture
Neuroimmune modulators as novel pharmacotherapies for substance use disorders (2024)
  • But not every neuro-immune modulator is found effective.
Immunity in neuromodulation: probing neural and immune pathways in brain disorders (2025)
​
*France
Abstract

Immunity finely regulates brain function.

​It [Immunity] is directly involved in the pathological processes of neurodegenerative diseases such as
*Parkinson’s and Alzheimer’s disease,
*post-stroke conditions,
*multiple sclerosis,
*traumatic brain injury, and
*psychiatric disorders
        *mood disorders,
        *major depressive disorder (MDD),
        *anxiety disorders,
        *psychosis disorders and
        *schizophrenia, and
*neurodevelopmental disorders (NDD)).

Neuromodulation is currently a leading therapeutic strategy for the treatment of these disorders, but little is yet known about its immune impact on neuronal function and its precise beneficial or harmful consequences.

We review relevant clinical and preclinical studies and identify several specific immune modifications.

These data not only provide insights into how neuromodulation acts to optimize immune-brain interactions, but also pave the way for a better understanding of these interactions in pathological processes.
Bullets added.

where are those mental health centers of excellence?

Val's Take
  • It is AWKWARD questioning the COMPETENCE of the Mental Health Profession as a Mental Health Patient.
  • In the past, Mental Health Advocates have railed against the MEDICAL MODEL.
  • Well, it wasn't a very good MEDICAL MODEL and it was called into questions by the US National Institute of Mental Health and Researchers around the world.​
  • The new "MEDICAL MODEL" that has emerged in the last 10 to 15 years is:
    • ​Neuro-Immune
    • Multi-System
    • ​Developmental
  • Ultimately, much of this may be handled by obstetrics and pediatrics.
Annie Hall --- Diane Keaton, Woody Allen
There needs to be a recognition how fast the research is moving and that current systems are not well designed to address that.
CANCER CENTERS OF EXCELLENCE are a good model.

Preview

bodily systems and social media bi-Directional Cross-talk

Val's Take/Conjecture
  • A lot of us grew up with  understandings that Psychiatric Disorders are:
    • ​About the Brain, and
    • Chemical Imbalances, specifically:
      • ​Dopamine , and 
      • Serotonin
  • ​Is that wrong?  Probably not, but It can be grossly partial and misleading --- and it is not really where the research is today with a focus on:
    • ​Glial Cells
    • Mitochondrial Dysfunction
    • the Immune System
    • the Microbiome
    • the Endocrine System
    • the Metabolism, and
    • ​Maternal Immune Activation

  • Discoveries'
    • Thyroid --- 1656 was the first time the term "thyroid" was used.
    • Mitochondria were discovered in 1857
    • Astrocytes were discovered in the late 1880s
    • ​Microglia were discovered in 1919
    • Serotonin was discovered in 1935
    • Cortisol was discovered in 1936
    • Dopamine was discovered in 1958
    • ​Focus on Maternal Immune Activation in the 21st Century.
Bidirectional crosstalk between the gut microbiota and cellular compartments of brain: Implications for neurodevelopmental and neuropsychiatric disorders (2025)

*Sweden & Denmark
Major Systems 
  • Immune System
  • Microbiome
  • Endocrine System
  • Metabolism
  • ​Central Nervous System
Immune cells mediated the causal relationship between the gut microbiota and anxiety disorders: A Mendelian randomization study  (2025)

*China
Crosstalk Between Mitochondrial DNA and Immune Response: Focus on Autism Spectrum Disorder  (2025)

​*China

Precision Psychiatry and PsycGM
​

Val's Take/Conjecture
  • Countries like people can be complicated MIXED BAGS.
  • Authoritarian Regimes have often had an UNHEALTHY RELATIONSHIP with Psychiatry.
  • So when one first hears about Psychiatric Research and China  --- OMG they're not experimenting on the  Uyghurs, are they?
  • I don't know all that China is doing from a research perspective.
  • What I do know is that a large number of serious research papers are coming out of China addressing the biology of psychiatric disorders from a traditional medical perspective.
PsycGM: a comprehensive database for associations between gut microbiota and psychiatric disorders (2025)

​*China
In total, PsycGM incorporated 559 studies from 31 countries worldwide, encompassing research involving humans, rats, mice, and non-human primates.

PsycGM documented 8907 curated associations between 1514 gut microbial taxa and 11 psychiatric disorders, as well as 4050 associations between 869 taxa and 232 microbiota-based and non-microbiota-based interventions.

Moreover, PsycGM provided a user-friendly web interface with comprehensive information, enabling browsing, retrieving and downloading of all entries.

In the application of PsycGM, we panoramically depicted the intestinal microecological imbalance in depression.

Additionally, we identified 9 microbial taxa consistently altered in patients with depression, with the most common dysregulations observed for Parabacteroides, Alistipes, and Faecalibacterium; in animal models of depression, consistent changes were observed in 21 microbial taxa, most frequently reported as Helicobacter, Lactobacillus, Roseburia, and the ratio of Firmicutes/Bacteroidetes.

​PsycGM is a comprehensive resource for future investigations on the role of gut microbiota in mental and brain health, and for therapeutic target innovations based on modifications of gut microbiota. PsycGM is freely accessed at http://psycgmomics.info.

Why are neuro-developmental and Psychiatric Disorders ---
Neuro-Immune and Multi-system?

Microglia

Val's Take/Conjecture
  • Microglia are the Brain and Central Nervous System's --- IMMUNE CELLS.
  • During Embryonic Development, Microglia begin in the "yolk sac."
  • Maternal Immune Activation --- "DYSREGULATES" the Microglia.
  • ​This "DYSREGULATES" normal brain development.
  • The DYSREGULATION of Synapse Formation & Pruning is especially relevant to Neuro-Developmental and Psychiatric Disorders.
  • Dysregulation of Microglia can also lead to "ATYPICAL RESPONSES" to Viruses.
This rendition is SIMPLISTIC, but it provides a rough Narrative of why Neuro-Developmental & Psychiatric Disorders are Neuro-Immune and Multi-System.
Role of microglia in brain development after viral infection (2024)
University of Texas
Why MULTI-SYSTEM?  ---
Microglial Cross-Talk
  • So the IMMUNE SYSTEM is a big player in the brain and the central nervous system.
  • But it doesn't stop there.
  • DYSREGULATED Microglia can dysregulate:
    • ​The Microbiome
    • The Endocrine System
    • Mitochondrial Function and Promote Cell Death.

scientists linked 29 immune-related proteins to seven neuropsychiatric disorders

suggesting the brain is not the only organ involved in mental health (2025)

Val's Take/Conjecture
  • Immunopsychiatry, especially at the Research Level, is not new.
  • ​What is new in 2025 is the degree to which Researchers are drilling down with amazing specificity.
  • This is considerably different than current treatments and current assumptions in the society and criminal justice.
  • ​We need a "BRIDGE" from where we are to where we need to go.
Royal Gorge Bridge

A big jump in our understanding --

Mitochondrial energetics and synapses​

Val's Take/Conjecture
  • ​Mitochondrial Dysfunction is an aspect of many illnesses and diseases.
  • It is probably most profoundly seen in Neuro-Degenerative Diseases such as Parkinson's and Alzheimer's.
  • Neuro-Developmental and Psychiatric Disorders often come with Microglial Dysregulation and various levels of Mitochondrial Dysfunction.
  • The book chapter to the right not only references Schizophrenia and Bipolar Disorder, but also Diabetes and Obesity.​
    • If you look at the widespread nature of weight issues in the society, one could certainly conclude we need to eat better and exercise more --- and we do.
    • But some people may need a KETO DIET high in fat --- at least according to the Metabolic Mind folks.
    • Further, DEVELOPMENTAL ISSUES IN UTERO appear to play a role in a large number of issues and diseases experienced later in the lifespan.
      • ​Further, Researchers are identifying  these DEVELOPMENTAL ISSUES as the "PROXIMATE CAUSE" of issues and disease later in the lifespan.
The Developmental Origins of Health & Disease, Mitochondrial Bioenergetics, and Executive Functioning Issues have so many ramifications for Treatment and Public Policy.
When it comes to people who are Justice-Involved with Neuro-Developmental and/or Psychiatric Disorders, treatment and programs need to address Mitochondrial Bioenergetics and Executive Functioning Issues.
Neuronal Synaptic Communication and Mitochondrial Energetics in Human Health and Disease (2025)
Abstract

​The human brain is an energetically costly organ, consuming 20-25% of all biochemical energy produced in the body, despite comprising only 2-3% of total body mass.

Most energy in the brain is consumed to support synaptic neurotransmission, which is the primary means of neuron-to-neuron communication between.

This energy is in the form of adenosine triphosphate (ATP), and within neural cells, nearly all ATP is produced by mitochondria via the process of oxidative phosphorylation (OXPHOS).

To ensure that ATP is readily available, mitochondria are trafficked to areas of greater energy use, such as neuronal synapses.

The balance between energetic supply and synaptic communication is essential for proper brain functioning.

This chapter begins with a brief introduction to key features of neuronal synapses and mitochondrial energy production in the cerebral cortex.

Next, the tight and bidirectional coupling of neuronal synaptic activity and mitochondrial OXPHOS is examined from functional, ultrastructural, and molecular perspectives.

​The effects of brain and non-brain organ system perturbations on synaptic-mitochondrial coupling are then examined within the context of (1) primary brain disorders, such as schizophrenia and bipolar disorder, and (2) primary peripheral disorders, such as diabetes and obesity.

​Finally, a discussion of potential intervention strategies that may restore neural communication and mitochondrial bioenergetics, within the framework of the brain-body connection, is provided.

PRENATAL INFLAMMATION

synapses, ATP & Executive Functioning Challenges

Val's Take/Conjecture
  • One of the things that some Psychiatrists have pointed out about ADHD ---
    • ​It's actually an EXCESS OF ATTENTION, not a deficit of attention.
  • What is causing this "EXCESS OF ATTENTION"?
  • Maybe poorly pruned SYNAPSES.  
  • ​DYSREGULATED MICROGLIA are implicated in that.
  • This brings in the NEW PARADIGM regarding NEURO-DEVELOPMENTAL and PSYCHIATRIC DISORDERS as ----
    • ENERGY DISORDERS involving ATP.
    • There's not enough ATP to run all those SYNAPSES.
  • For many people, EXECUTIVE FUNCTIONING CHALLENGES may be tied to ATP CHALLENGES.
LINKING PRENATAL INFLAMMATION TO SYNAPTIC DYSFUNCTION IN PSYCHIATRIC DISORDERS (2025)

What's trending on Orchid?

  • As much stigma as Mental Health has had, it has also had a certain cachet --- because it was about the BRAIN -- the most complicated thing in the universe -- or so we've thought.
  • AND now we're talking about Maternal Immune Activation, T-Cell Exhaustion, Mitochondrial Dysfunction, the Microbiome, etc. when it comes to the "Neuro-Developmental - Psychiatric Continuum."
  • Further, Trauma can damage the immune system.
  • On the one hand, INFLAMMATION is an efficient, universal biological language.
    • But it can be addressing a staggering variety of things over the course of the Lifespan and even Trans-Generationally.
    • This complexity to such an elegant mechanism is one of the things driving the need for PRECISION MEDICINE and PRECISION PSYCHIATRY --- one size does not fit all.
PBS NewsHour
Fauci Remembers AIDS Activist Larry Kramer
60 Minutes
Cook County Sheriff Tom Dart --- Jails are the New Asylums (2013)

Right around the time the National Institute of Mental Health said the DSM was not a "valid" diagnostic manual because it was not based on the underlying biology but vague symptom clusters.

Mixed bags

ThE link between bipolar disorder,

intelligence and mitochondrial dysfunction

Val's Take/Conjecture
  • ​Intelligence and Creativity and Mental Illness have been such subjects of CONTENTION.
    • ​There has been great concern not to ROMANTICIZE any connection.
  • Further,  there has been a lot of confused reasoning on a lot of different sides, because we're often equating "INTELLIGENCE" with Emotional Stability.
    • ​"Hey, if I'm smart or talented --- I must not have a mental illness."
    • Unfortunately, that is not necessarily the case.
  • Additionally, researchers and others have often honestly not appreciated the "intelligence" because the person had slower processing which came off as and maybe is cognitive impairment.
    • ​But that cognitive impairment is often the result of MITOCHONDRIAL DYSFUNCTION not lack of intelligence.
  • One of the big breakthroughs that has come out in recent years is the connection of MITOCHONDRIAL DYSFUNCTION to Neuro-Developmental and Psychiatric Disorders.
    • ​​THESE ARE ENERGY ISSUES.
Bidirectional genetic overlap between bipolar disorder and intelligence (2022)

*China
How to Solve Wicked Problems Using Integrative Thinking (2010)
Val's Take:  To talk about "UNPLEASANT TRADE-OFFS" does not capture the HORROR SHOW that some people experience with Neuro-Developmental, Psychiatric and sometimes surprisingly related conditions such as Auto-Immune Disease and Cancer.

​THIS IS A WICKED PROBLEM.
Mitochondria, Oxidative Stress and Psychiatric Disorders:  An Integrative Perspective on Brain Bioenergetics (2025)

*Brazil
​These insights underscore the centrality of mitochondrial health in psychiatric disease and support the development of precision psychiatry grounded in metabolic phenotyping.

Maternal Mitochondrial dna and dna copy number variation

Val's Take/Conjecture
  • As the biology of Neuro-Developmental and Psychiatric Disorders is understood with greater and greater specificity, additional treatment targets are identified. and with them additional ethical issues.
Crosstalk Between Mitochondrial DNA and Immune Response: Focus on Autism Spectrum Disorder (2025)

*China
Correction of pathogenic mitochondrial DNA in patient-derived disease models using mitochondrial base editors (2025)

*The Netherlands
​Mutations in the mitochondrial genome can cause maternally inherited diseases, cancer, and aging-related conditions.

Our study thus demonstrates the potential of mitochondrial base editing to not only generate unique in vitro models to study these diseases, but also to functionally correct mitochondrial mutations in patient-derived cells for future therapeutic purposes.
More and more Neuro-Developmental and Psychiatric Disorders are described as a form of PREMATURE AGING.
Mitochondrial DNA copy number and neurocognitive outcomes in children (2024)

*Columbia University
Conclusions: Our study provides novel evidence that mtDNAcn measured in childhood is associated with children's neurocognitive performance. mtDNAcn may be a marker of healthy child development.

​Impact: 

Mitochondrial DNA copy number (mtDNAcn) may serve as a biomarker for early-life neurocognitive performances in the children's population.

Both low and high mtDNAcn may contribute to poorer neurocognition, reflected through learning and memory abilities.

This research elucidated the importance of investigating mitochondrial biomarkers in healthy populations and facilitated advancements of future studies to better understand the associations between mitochondrial markers and adverse children's health outcomes.

Talking about mental Health

Where we've been, where we appear to be going

Developmental disorders, dysregulation of the Immune System, Mitochondrial Dysfunction and Genetic Copy Number Variations

Val's Take/Conjecture
  • How many people know that Schizophrenia and Bipolar Disorder are now considered Neuro-Developmental Disorders?
  • Further, the complex mechanisms are not only driving the need for Precision Psychiatry, the complexity is driving the need for Precision Medicine more broadly.

  • There are ethical issues involving genetic counseling of parents.
  • There are ethical issues regarding how we handle Neuro-Developmental Disorders in:
    • the Criminal Justice System,
    • Homelessness, and
    • the Society generally.
  • Further, these Neuro-Developmental Disorders are throughout our Society  ---
    • Some people are paying a big price, and
    • Others with "similar symptoms" are in one sense getting away with these challenges.
      • On the other hand, they may not appreciate that they have underlying challenges and that those challenges can be significant.
    • I'm not for mass punishment, AND we need to get more realistic and accurate about who we really are.
    • Ironically, that is especially true for people with an IQ over 70 and people with an Above-Average IQ and a Neuro-Developmental Disorder or Disorders.
Copy Number Variants: Deletion and Duplication Syndromes (2025)

Abstract

​Rare genetic variants have illuminated mechanisms of common diseases and have even led to novel treatment approaches.

Some copy number variants (CNVs) have been associated with extraordinary risk for complex neuropsychiatric phenotypes and thus offer a valuable entry point for investigating the biological mechanisms and pathways underlying autism, intellectual disability, and schizophrenia, among other neuropsychiatric disorders.

For example, cellular and animal models of multiple CNVs have identified mitochondrial dysregulation as a key pathway underlying these disorders.

In the clinic, there is a growing potential for improving the quality of life of individuals affected by these rare variants.

Early targeted intervention leveraging data from robust clinical studies will be critical for providing patients and their families with the best possible outcomes.

In this review, we highlight the current challenges and opportunities in the field of neurodevelopmental CNV research in both the lab and the clinic.
Penetrance of Neurodevelopmental Copy Number Variants Is Associated With Variations in Cortical Morphology (2025)

Authors:  long list of Global Leaders
Results: For both schizophrenia and developmental disorders, increased penetrance scores were associated with lower surface area in the cerebral cortex and lower intracranial volume.

​For both conditions, associations between CNV-penetrance scores and cortical surface area were strongest in regions of the occipital lobes, specifically in the cuneus and lingual gyrus.

Conclusions: Our findings link global and regional cortical morphometric features with CNV penetrance, providing new insights into neurobiological mechanisms of genetic risk for schizophrenia and other developmental disorders.
The contribution of copy number variants to psychiatric symptoms and cognitive ability (2023)
Copy number variants (CNVs) are deletions and duplications of DNA sequence.

The most frequently studied CNVs, which are described in this review, are recurrent CNVs that occur in the same locations on the genome.

These CNVs have been strongly implicated in neurodevelopmental disorders, namely autism spectrum disorder (ASD), intellectual disability (ID), and developmental delay (DD), but also in schizophrenia.

More recent work has also shown that CNVs increase risk for other psychiatric disorders, namely, depression, bipolar disorder, and post-traumatic stress disorder.

Many of the same CNVs are implicated across all of these disorders, and these neuropsychiatric CNVs are also associated with cognitive ability in the general population, as well as with structural and functional brain alterations.

Neuropsychiatric CNVs also show incomplete penetrance, such that carriers do not always develop any psychiatric disorder, and may show only mild symptoms, if any.

​Variable expressivity, whereby the same CNVs are associated with many different phenotypes of varied severity, also points to highly complex mechanisms underlying disease risk in CNV carriers.

The crux of it

Precision Psychiatry and Neuro-Developmental Disorders

​

Val's Take/Conjecture
  • When we think of Neuro-Developmental Disorders we often think of ADHD and Autism.
  • But Schizophrenia, Bipolar Disorder and even Depression may be considered Neuro-Developmental.
What many Canadian researchers did was start to link the Mental Health Crisis with Population Genetic Copy Number Variation.
One of the bromides of Modern Society is that ADHD is over-diagnosed.  That probably does sometimes happen, but if you look at the biological drivers of ADHD and Autism, it is not surprising we've seen large increases.
Trying to effectively deal with conditions that often come with big strengths and big weaknesses is complicated.
  • ​Further, the need for individual tailoring is great.
Exploring Copy Number Variants in a Cohort of Children Affected by ADHD: Clinical Investigation and Translational Insights (2025)

*Italy
ADHD symptoms were pronounced across all groups, but PC-CNVs [Potentially Causative-Copy Number Variations] showed a higher burden of comorbidities, suggesting a stronger genetic contribution to ADHD complexity.

Significant differences were observed in oppositional behavior, inattentive symptoms, brain MRI findings, and developmental language anomalies.

Several CNVs involved genes previously implicated in neurodevelopmental disorders, supporting a potential genetic contribution to the clinical complexity of ADHD. 

​Conclusions:

This exploratory study supports the role of CNVs [Copy Number Variations] in ADHD susceptibility and highlights the value of genetic screening for understanding clinical variability.

Larger studies are needed to clarify genotype-phenotype correlations in ADHD and to guide personalized clinical management.
Gene copy number variation and pediatric mental health/neurodevelopment in a general population (2023)
​
*Canada
Abstract

​We assessed the relationship of gene copy number variation (CNV) in mental health/neurodevelopmental traits and diagnoses, physical health and cognition in a community sample of 7100 unrelated children and youth of European or East Asian ancestry (Spit for Science).

Clinically significant or susceptibility CNVs were present in 3.9% of participants and were associated with elevated scores on a continuous measure of attention-deficit/hyperactivity disorder (ADHD) traits (P = 5.0 × 10-3), longer response inhibition (a cognitive deficit found in several mental health and neurodevelopmental disorders; P = 1.0 × 10-2) and increased prevalence of mental health diagnoses (P = 1.9 × 10-6, odds ratio: 3.09), specifically ADHD, autism spectrum disorder anxiety and learning problems/learning disorder (P's < 0.01).

There was an increased burden of rare deletions in gene-sets related to brain function or expression in brain associated with more ADHD traits.

With the current mental health crisis, our data established a baseline for delineating genetic contributors in pediatric-onset conditions.

Japanese Researchers On Copy Number variations and a

​Prescription to move forward

Val's Take/Conjecture
  • We're here at the need for Eternal Vigilance and concerns about Eugenics, even as this is hugely promising avenue of research.
  • DNA Copy Number Variations in one sense are less dramatic than saying there is one or several genes that are being targeted.
    • ​It is more about copy number variations that are leading to health concerns.
    • Further, aging also often leads to copy number variations.
Japanese researchers propose the following key priorities for Clinical Implementation:
  • the need for longitudinal studies,
  • standardized guidelines for CNV (Copy Number Variation) result reporting and genetic counseling, and
  • integrated care networks to provide a foundation for advancing the field of precision psychiatry.
Genetic insights into neurodevelopment: the critical role of copy number variations in neurodevelopmental disorders (2025)

*India
Intelligence, Hyper-Connected Brains, Sensory Processing & Energy
  • Psychiatric Disorders are not just affecting people with Intellectual Disabilities.
  • This has confused the person, clinicians and the society.​
  • Many Neuro-Diverse people are more and more aware of their own individual challenges.
  • ​It is equally important to be aware of the gifts.
  • The gifts are often tied to idiosyncratic Sensory Processing --- the intellectual and other talent gifts are real ---
    • And the dysregulations and energy problems are also real.
  • Some people who went through Maternal Immune Activation came out with both Above Average Intelligence and various energy and health issues.
    • ​Many Neuro-Diverse YouTubers and other have gone to great lengths to detail Executive Functioning Issues, Burnout Issues, Meltdown Issues, etc.
    • On the other hand, part of all this authenticity is being able to acknowledge their real intelligence and/or talent.
      • ​Even if it is coming in a package people aren't expecting.
Mitochondrial DNA oxidation, methylation, and copy number alterations in major and bipolar depression (2023)

*Turkey
Copy Number Variations and Human Well-Being: Integrating Psychiatric, Physical, and Socioeconomic Perspectives (2025)

​*Japan
Abstract

​Copy number variations (CNVs) have emerged as crucial genetic factors that influence a wide spectrum of human health outcomes, with particularly strong associations to psychiatric disorders.

In this review, we present a synthesis of diverse impacts of psychiatric disorder-associated CNVs on neurodevelopment, brain function, and physical health across the lifespan.

Large-scale studies have revealed that CNV carriers exhibit an increased risk for psychiatric disorders, cognitive deficits, sleep disturbances, neurological disorders, and other physical conditions, including cardiovascular diseases, diabetes, and renal disease, highlighting the wide-ranging impact of CNVs beyond the brain.

​Neuroimaging studies have revealed substantial CNV effects on brain structure, from cortical and subcortical alterations to white matter microstructure, with effect sizes often exceeding those observed in idiopathic psychiatric disorders.

Cellular and animal models have begun to elucidate dynamic CNV effects on neurodevelopment, neuronal function, and cellular energy metabolism, while revealing complex CNV-environment interactions and cell type-specific responses, particularly in studies of 22q11.2 deletion syndrome.

This review also explores the complex interplay between psychiatric and physical health conditions in CNV carriers and how these interactions contribute to adverse socioeconomic outcomes, including reduced educational attainment and income levels, creating a feedback loop that further impacts health outcomes.

Finally, in this review, we also highlight research limitations and propose key priorities for clinical implementation, including the need for longitudinal studies, standardized guidelines for CNV result reporting and genetic counseling, and integrated care networks to provide a foundation for advancing the field of precision psychiatry.
Maternal immune activation and its multifaceted effects on learning and memory in rodent offspring: A systematic review (2024)
​Highlights

•  Maternal immune activation (MIA) can impair offspring learning and memory.

•  MIA negatively impacts cognition in rodents.

•  Males are more susceptible to cognitive deficits.

•  Some studies show improved cognition after MIA.

•  Sex differences in immune responses may explain cognitive outcomes.

The psychological Lens or -- and ---- the biological lens

Working with different levels of analysis

Val's Take/Conjecture
  • ​DIFFERENT LEVELS OF ANALYSIS are important to UNDERSTANDING.
  • Additionally, there are many, many levels of analysis.
  • One of the things that happened in Mental Health --- PSYCHOLOGICAL ANALYSIS  got top heavy and out of balance.
  • An earlier criticism was against "The Medical Model" saying the individuals needed access to more alternative therapies.
    • ​There's truth to the Medical Model criticism, even as the DSM has been found to be scientifically invalid.  Really not much of Medical Model.
    • ​Further, Alternative Therapies can be helpful.
That being said, Research is Exploding around the Globe --- we're starting to get answers and surprising therapeutic targets.
Billy Joel
Shades of Grey
We need these DIFFERENT LEVELS of ANALYSIS as CROSS-CHECKS against each other.

As we first start to consider another perspective --- it can feel grey and maybe a sense of guilt that we weren't totally right.

BUT ultimately, either for ourselves or someone down the road --- we have a more complete and colorful view.

The biological basis of neuro-developmental & Psychiatric disorders 

may be more routine nuts, bolts and fuel than we expected

Val's Take/Conjecture
  • Additionally, dysregulation of Glial Cells, including Micorglia -- the brain's innate immune cells ---
    • ​Is involved in Neuro-Developmental and Psychiatric Disorders.
​
Susceptibility and resilience to maternal immune activation are associated with differential expression of endogenous retroviral elements (2023)

*Swiss Researchers

​Genetic insights into the role of mitochondria-related genes in mental disorders: An integrative multi-omics analysis (2025)
Conclusions: These findings suggested that dysfunction in mitochondria-related genes may underlie the molecular mechanisms of ADHD and SCZ [Schizophrenia], providing novel biomarkers for diagnosis and therapeutic interventions.
So people with Neuro-Developmental and Psychiatric Disorders have often been considered EXOTIC WEIRDOS.

I don't want to take away the cachet of that --- BUT it appears we're still talking about INFLAMMATION or Dysregulated Cytokines --- which we're often talking about in illness of many types.
Epstein-Barr Virus (EBV) and Human Endogenous Retroviruses (HERV-E) 

&

Maternal Immune Activation

Medical School Programs combining Psychiatry and Immunology

Val's Take
  • The level of support for these programs varies wildly.
  • On the HIGH END ---- is Washington University in St. Louis School of Medicine and the Brain, Immunology and Glia (BIG) Center 
    • ​WashU apparently wooed Global Superstar Researcher Jonathan Kipnis away from the University of Virginia School of Medicine.
    • The BIG Center has 30 Labs.
  • In many of these academic programs, it is not limited to psychiatry and immunology.  They are looking more broadly at the Brain, Immunology and Glial Cells for insights that could benefit a wide range of disease categories.
    • ​This includes Neuro-Developmental and Psychiatric Disorders.
    • ​It also includes autoimmune diseases, cancer, neuro-degenerative disorders, etc.

  • The University of Texas is all about "MOLECULAR MEDICINE," and the University of Bristol is clear it wants the current DSM symptom clusters replaced with biological categories.
 
  • Forty, fifty years ago --- criminal defense attorneys went to psychiatrists and psychologists and said --
    • Would you please, please, please evaluate my client and testify in court.
  • The "CLUSTER" of ancient legal concepts and certainly now out-dated mental health concepts is a dangerous combination.
  • If we could just provide for safety and get out of punishment ---- I don't think we would be as MORALLY FRIED as we are right now.
​Such research could lead to new insight into neurological illnesses – ranging from Alzheimer’s and Parkinson’s disease to schizophrenia and autism – that are linked to an immune system gone awry, and lay the groundwork for developing promising immune-based therapies to treat such illnesses.
Behavioral Immunology Lab of Tulsa
We study interactions between the brain and the immune system, especially as they relate to the effects of inflammation on the development of psychiatric disorders including depression, anxiety disorders and schizophrenia.

We also study the impact of inflammation on the brain in medically ill patients including patients with cancer.

Special emphasis in our studies is placed on the effects of inflammation on neurotransmitter systems involving dopamine and glutamate, as well as the integrity of local and regional brain networks.

Finally, we are exploring a variety of treatment strategies that target the immune system to treat psychiatric disorders.

​By combining multiple frames of reference, we believe novel approaches to human suffering can be achieved through strategies that address both brain and immune aspects of health and illness

​Behavioral Immunology &
Endocrinology Lab
The Brown Foundation Institute of Molecular Medicine
Center for Neuroimmunology and Glial Biology

Free Speech as a luxury for Working Stiffs

Val's Take
  • ​From a PRACTICAL STAND-POINT, most people's FREE SPEECH rights are greatly limited by EMPLOYMENT.
  • For many people, FREE SPEECH is not necessarily the biggest issue out there.
  • For people who have a lot to say and are dealing in words, ideas and art ---- FREE SPEECH is what it is all about.
  •  FREE SPEECH is a safety valve in society.  But it is not necessarily a panacea.
Channel 9 News -- Legal Analyst Whitney Traylor
Employee Free Speech Rights
MUSICAL SCAPEGOATS
  • The challenge of managing individual and group aggression in a society is huge.​
  • What we often use are scapegoats.
  • Nobody can agree to be a Scapegoat. ​
GROUPS, OUT GROUPS and BROADENING THE CIRCLE

Crafting public policy responses to the new paradigms in mental health & Beyond

Val's Take/Conjecture
  • Integration of Mental, Physical and Developmental Health is critical to address Neuro-Developmental and Psychiatric Disorders.
  • Researchers around the world have rejected the OLD MEDICAL MODEL as contained in the DSM.
  • The emerging NEW MEDICAL MODEL is largely of Neuro-Immune Disorders originating IN UTERO that affect multiple systems of the body.
  • If psychiatric disorders tend to be blurred, psychiatric disorders and other illness categories appear "blurred" as well.
  • IMMUNOLOGY needs to take a large role in the treatment of Neuro-Developmental and Psychiatric Disorders.
    • ​There are many different ways of doing this.
    • It needs to be done sooner rather than later.
  • On the other hand, psychiatry needs to be a more integrated component in the treatment of illness and disease.
  • Policy makers need to address the implications of the emerging NEW MEDICAL MODEL with regard to:
    • Healthcare Funding, and
    • Criminal Justice

Peripheral Inflammatory Parameters in Patients with Antisocial Personality Disorder (2021)

*Turkish Researchers
Conclusion:  The results of our study suggested that inflammation might play a role in the etiopathogenesis of APD.

Furthermore, a significant relationship was found between the severity of symptoms and some inflammatory parameter levels such as RDW and basophil in APD patients.
Disease severity across psychiatric disorders is linked to pro-inflammatory cytokines
​(Oct. 2025)

​*French, German, Iranian, Australian, Austrian, and US Researchers
Importance: Numerous studies indicate that the traditional categorical classification of severe mental disorders (SMD), such as schizophrenia, bipolar disorders, and major depressive disorders, does not align with the underlying biology of those disorders as they frequently overlap in terms of symptoms and risk factors.
​
Conclusion: The observed differences in serum protein expression suggest that disease severity is associated with the convergence of immune system dysregulation and neurodevelopmental alterations, particularly involving pathways related to inflammation and brain plasticity.

The identification of pro-inflammatory proteins among the differentially expressed markers underscores the potential role of systemic inflammation in the pathophysiology of SMD.

​These results highlight the importance of considering illness severity as a core dimension in psychiatric research and clinical practice and suggest that targeting immune-related mechanisms may offer promising new therapeutic avenues for patients with SMD.

Hypo-thyroidism and Psychiatric & Neuro-Developmental Disorders

hypothalamic-pituitary-thyroid (HPT) axis ---
ENDOCRINE DYSREGULATION

Val's Take/Conjecture
  • In one sense, Neuro-Developmental and Psychiatric Disorders can be like Covid-19:
    • One person may be technically infected with the virus but be asymptomatic, while another is deathly ill --- and everything in between.
  • When it comes to Thyroid Disorders, not everyone has Thyroid Cancer.
    • On the other hand, many, many people with psychiatric disorders also have thyroid disorders. 
      • That does not appear to be a coincidence.
Association of major depression, schizophrenia and bipolar disorder with thyroid cancer: a bidirectional two-sample mendelian randomized study  (2024)
Possible role of glial cells in the relationship between thyroid dysfunction and mental disorders (2015)
Thyroid Dysfunction and Bipolar Disorder: A Literature Review Integrating Neurochemical, Endocrine, and Genetic Perspectives  (2024)
Recent advances in understanding autoimmune thyroid disease: the tallest tree in the forest of polyautoimmunity   (2017)

KETO Research

On Sale --- FREE

Val's Take/Conjecture
  • We need to include Dietitians in Mental Health Care.
  • ​Medical Keto is more specialized than other diets.

Why aren't we using civil commitment More??? ---

No Adequate Continuum of care

Val's Take/Conjecture
  • I'm not a big fan of civil commitment.
  • My experience is that most people want help --- even if it's not the help that is being offered.​
  • Even Colorado Judges will say --- they need "RESOURCES, RESOURCES, RESOURCES" and options for people facing civil commitment.
  • Which brings up the need for BETTER UNDERSTANDINGS and TREATMENTS as an Economic Issue.
Forbes Breaking News
Fox News Host Apologizes For Suggesting ‘Involuntary Lethal Injection’ For Homeless Refusing Help

PV inter-neuron metabolic dysfunction

In Neuro-Developmental Disorders, Psychiatric Disorders, TBI, etc.

Val's Take/Conjecture
  • ​Neuro-Developmental and Psychiatric Disorders are more and more referred to as NEURO-IMMUNE DISORDERS
    • ​that affect MULTIPLE SYSTEMS OF THE BODY.
  • METABOLISM is a part of this --- and it is often affecting people in unexpected ways.
Cortical inhibitory parvalbumin interneurons exhibit metabolic specializations coordinated by PGC-1α that are lost in rodents and humans after traumatic brain injury (2024)

*US Researchers
Parvalbumin-positive interneurons (PV-INs) regulate neuronal and circuit activity, and their dysfunction is observed across neurological conditions, including traumatic brain injury (TBI), epilepsy, Alzheimer’s disease, and schizophrenia.

PV-INs are particularly vulnerable to cell loss, potentially due to their increased metabolic demands arising from their uniquely high level of electrical activity, which render them susceptible to metabolic pressure. 
Parvalbumin interneuron deficits in schizophrenia (2024)

*UK
The Role of Parvalbumin Interneurons in Autism Spectrum Disorder (2024)

*China
The role of neuroinflammation in PV interneuron impairments in brain networks; implications for cognitive disorders (2025)

*Iranian Researchers
Abstract

​Fast spiking parvalbumin (PV) interneuron is an inhibitory gamma-aminobutyric acid (GABA)ergic interneuron diffused in different brain networks, including the cortex and hippocampus.

As a key component of brain networks, PV interneurons collaborate in fundamental brain functions such as learning and memory by regulating excitation and inhibition (E/I) balance and generating gamma oscillations.

The unique characteristics of PV interneurons, like their high metabolic demands and long branching axons, make them too vulnerable to stressors.

Neuroinflammation is one of the most significant stressors that have an adverse, long-lasting impact on PV interneurons.

Neuroinflammation affects PV interneurons through specialized inflammatory pathways triggered by cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6).

The crucial cells in neuroinflammation, microglia, also play a significant role.

The destructive effect of inflammation on PV interneurons can have comprehensive effects and cause neurological disorders such as schizophrenia, Alzheimer’s disease (AD), autism spectrum disorder (ASD), and bipolar disorder.

In this article, we provide a comprehensive review of mechanisms in which neuroinflammation leads to PV interneuron hypofunction in these diseases.

The integrated knowledge about the role of PV interneurons in cognitive networks of the brain and mechanisms involved in PV interneuron impairment in the pathology of these diseases can help us with better therapeutic interventions.
Neuro-Developmental, Psychiatric, Neuro-Degenerative Disorders and Normal Aging

  • It's interesting because we're often not necessarily talking about a BRAIN REGION or REGIONS (although that is not irrelevant)---
    • ​We're often talking about supporting cells, specialized neurons, mitochondria, etc. that are dysregulated or dysfunctional.
    • If that can be turned around with a Special Diet and Exercise --- great.
    • For some people, more direct REPAIR may be needed.
    • For others, REPLACEMENT may be necessary.
    • This isn't to the ubiquity of the HIP or KNEE REPLACEMENT --- but it's getting there.
    • What may start out as a treatment for Neuro-Degenerative, Psychiatric, and Neuro-Developmental Disorders, may become a standard option in Aging.

Polis champions personal responsibility on ABC's This Week

Val's Take
  • Mental Illness (or Brain Injury, Neuro-Developmental Disorders, etc.) are controversial in the Criminal Justice System.
    • ​Especially, when such considerations are just viewed as a means of getting someone off and are not connected to Safety or not sufficiently connected to Safety.
  • On the other hand, mental illness deniers in the name of "STIGMA PREVENTION" are often in a fight with reality.
    • ​Many of these shooters have had serious mental health problems.
    • ​It's gotten harder and harder to deny that.
  • Of course, what people really want is prevention.  Our systems are able to PREVENT many bad acts.

  • We could prevent many more with precision medicine and biomarkers.
  • Further, we need those BIOMARKERS to address widespread skepticism among the public.

Precision psychiatry: 
Immuno-therapy and more

The need for an inter-disciplinary clinical practice to address the gut microbiota-immune-brain axis

Val's Take/Conjecture
  • A lot has been done to integrate Physical and Mental Health.
  • When it comes to the gut microbiota-immune-brain axis --- we need not only Interdisciplinary Research --- We need Interdisciplinary Practice.
The gut microbiota-immune-brain axis: Therapeutic implications (2025)

*Irish Researchers
Abstract

The microbiota-gut-brain axis has major implications for human health including gastrointestinal physiology, brain function, and behavior.

The immune system represents a key pathway of communication along this axis with the microbiome implicated in neuroinflammation in health and disease.

In this review, we discuss the mechanisms as to how the gut microbiota interacts with the brain, focusing on innate and adaptive immunity that are often disrupted in gut-brain axis disorders.

We also consider the implications of these observations and how they can be advanced by interdisciplinary research.

Leveraging an increased understanding of how these interactions regulate immunity has the potential to usher in a new era of precision neuropsychiatric clinical interventions for psychiatric, neurodevelopmental, and neurological disorders.

A Case Series of Young People Receiving Adjunctive Immunotherapy for Neuroimmune-Mediated Major Mood or Psychotic Syndromes (2025)

*Australian & German Researchers

Lead author Dr. Elizabeth Scott at the Brain Mind Centre at the University of Sydney is a global leader in this area.

Maternal immune activation and above average intelligence

BUT Microglia dysregulation and mitochondria dysfunction

Dr. Dan Peters
Summit Center
What is Twice-Exceptional & Gifted?
Tonic On Demand
Bipolar Disorder
A systematic review on the role of mitochondrial dysfunction/disorders in neurodevelopmental disorders and psychiatric/behavioral disorders (2024)
Maternal immune activation and its multifaceted effects on learning and memory in rodent offspring: A systematic review (2024)
​Highlights

•  Maternal immune activation (MIA) can impair offspring learning and memory.

•  MIA negatively impacts cognition in rodents.

•  Males are more susceptible to cognitive deficits.

•  Some studies show improved cognition after MIA.

•  Sex differences in immune responses may explain cognitive outcomes.
Microglia as Dynamic Cellular Mediators of Brain Function (2019)
Abstract

​Originally hypothesized to function solely as immunologic responders within the central nervous system (CNS), emerging evidence has revealed that microglia have more complex roles in normal brain development and in the context of disease.

In health, microglia influence neural progenitor fate decisions, astrocyte activation, neuronal homeostasis, and synaptogenesis.

In the setting of brain disease, including autism, brain tumors, and neurodegenerative disorders, microglia undergo substantial morphological, molecular, and functional changes, which establish new biological states relevant to disease pathogenesis and progression.

​In this review, we discuss the function of microglia in health and disease and outline a conceptual framework for elucidating their specific contributions to nervous system pathobiology.

Preview

Research:  Potential treatments for maternal immune activation

Val's Take/Conjecture
  • ​Maternal Immune Activation is a different way of looking at Neuro-Developmental and Psychiatric Disorders.
  • At this point, it is not as new as it was, and it is being refined.
  • Infection is not the only source of MIA.
  • Further, Paternal Immune Activation is also a significant factor.
  • Some of these alterations do not require "Neuro-Inflammation," but may result from "transient" developmental increases of Interleukin-6.

  • This is complicated.
  • Amantadine is often used for Parkinson's and is currently being used in psychiatry as a treatment.
  • It appears here the Chinese researchers are concluding that Amantadine can "prevent the development of neuropsychiatric disorders" as a result of MIA.
  • They are not necessarily claiming that Amantadine can "cure" existing psychiatric disorders. 
Mesenchymal stem cell-derived extracellular vesicles alleviate autism by regulating microglial glucose metabolism reprogramming and neuroinflammation through PD-1/PD-L1 interaction (2025)
​
*Chinese Researchers
After first detecting elevated glycolysis and neuroinflammation in prefrontal cortex (PFC) tissue from the maternal immune activation (MIA) mice, we also demonstrated that PD-1 expression level was upregulated in microglia.

. . .

Our research indicated the significant immunomodulatory capabilities of MSC-EVs, which play an important role in reprogramming microglial glucose metabolism and suppressing neuroinflammation in ASD.

​By activating the PD-L1/PD-1 axis and inhibiting the downstream ERK/HIF-1α pathway, MSC-EVs were found to alleviate autism-like behaviors, which revealing a novel pathological mechanism and offering promising therapeutic insights into ASD
Maternal Inflammatory Proteins in Pregnancy and Neurodevelopmental Disorders at Age 10 Years (2025)

*Danish Researchers
CONCLUSIONS AND RELEVANCE

The maternal inflammatory proteome during pregnancy was associated with NDDs [Neuro-Developmental Disorders] risks in offspring at age 10 years.

Further research is warranted to elucidate the specific pathways involving these proteins during pregnancy that could be targeted with prevention strategies to reduce risk of NDDs in children.

​Val's Take:  Neuro-Developmental and Psychiatric Disorders may be largely prevented by the end of the century if not before.
Maternal natural killer cells drive neuroimmune disorders in offspring through aberrant secretion of extracellular granzyme B (2025)
Targeting extracellular GzmB through the systemic administration of the serine protease inhibitor Serpina3n or genetic ablation of Gzmb in maternal NK cells mitigated neuroimmune disorders in the fetal brain. ​
A potential strategy for improving offspring behavior in maternal immune activation: Amantadine-mediated suppression of neuroinflammation (2025)

*Chinese Researchers
Conclusion: 

AMA [Amantadine] can prevent the development of neuropsychiatric disorders in MIA offspring.

This effect may be related to its ability to attenuate neuronal damage, reduce neuronal apoptosis, and inhibit neuroinflammation, indicating that the antiviral drug AMA may be a potential treatment for MIA.
Interleukin-6 produces behavioral deficits in pre-pubescent mice independent of neuroinflammation (2025)

*Rutgers University, New Jersey
Maternal inflammation during pregnancy increases the offspring’s risk of developing autism, ADHD, schizophrenia, and depression.

Epidemiologic studies have demonstrated that maternal infections stimulate the production of interleukin-6 (IL-6), which can cross the placenta and fetal blood–brain barrier to alter brain development with functional and behavioral consequences.

. . .

Altogether, these studies show that changes in the three core behavioral domains associated with several psychiatric disorders can be detected early in pre-pubescent mice following a transient developmental increase in IL-6.

Yet, these behavioral alterations do not require neuroinflammation.
Resveratrol prevents offspring's behavioral impairment associated with immunogenic stress during pregnancy (2025)

*Brazilian Researchers

PREVIEW

Inflammation acquired in Utero

and the developmental origins of health & disease

Val's Take/Conjecture
  • ​A number of papers refer to the "TRANSGENERATIONAL EFFECTS" of Maternal & Paternal Immune Activation.
  • Now we refer to the Neuro-Developmental/Psychiatric Continuum  --- but that is relatively recent.
  • Further, people with Neuro-Developmental/Psychiatric Disorders are more likely to have:
    • ​An atypical response to common viruses,
    • An atypical response to toxins.
  • Additionally, people with Neuro-Developmental/Psychiatric Disorders are more subject to:
    • ​Addiction Disorders
    • Autoimmune Disorders
    • Type 1 Diabetes
    • Type 2 Diabetes
    • Cancer
    • Neuro-Degenerative Disorders
  • If we start to consider the "fetal programming effect of maternal immune activation" on the immune system ----
    • ​maybe the long list of subsequent health challenges is not that surprising.
  • So one of the challenges is appreciating that DIET and EXERCISE are important.
    • ​But traditional DIET and EXERCISE approaches are NOT SUFFICIENT to address fetal immune dysregulation.
      • ​This isn't just calories in, calories out.
    • Would a more STRICT KETO DIET help --- it seems that it helps some people.​
  • Further, researchers are pursuing microglia and mitochondria repair and replacement.

Influence of Immune System Abnormalities Caused by Maternal Immune Activation in the Postnatal Period  (2023)

*Japanese Researchers
​Abstract

​The developmental origins of health and disease (DOHaD) indicate that fetal tissues and organs in critical and sensitive periods of development are susceptible to structural and functional changes due to the adverse environment in utero.

Maternal immune activation (MIA) is one of the phenomena in DOHaD [Developmental Origins of Health and Disease].

​Exposure to maternal immune activation is a risk factor for neurodevelopmental disorders, psychosis, cardiovascular diseases, metabolic diseases, and human immune disorders.

It has been associated with increased levels of proinflammatory cytokines transferred from mother to fetus in the prenatal period.

Abnormal immunity induced by MIA includes immune overreaction or immune response failure in offspring. Immune overreaction is a hypersensitivity response of the immune system to pathogens or allergic factor.

Immune response failure could not properly fight off various pathogens.

The clinical features in offspring depend on the gestation period, inflammatory magnitude, inflammatory type of MIA in the prenatal period, and exposure to prenatal inflammatory stimulation, which might induce epigenetic modifications in the immune system.

​An analysis of epigenetic modifications caused by adverse intrauterine environments might allow clinicians to predict the onset of diseases and disorders before or after birth.
The fetal programming effect of maternal immune activation (MIA) on the offspring’s immune system  (2024)
​Paternal immune activation by Poly I:C modulates sperm noncoding RNA profiles and causes transgenerational changes in offspring behavior (2024)
Neuroimmune and behavioral changes elicited by maternal immune activation in mice are ameliorated by early postnatal immune stimulation (2025)

*University of Texas Researchers
Highlights

•Maternal immune activation (MIA) may act as a disease primer for neurodevelopmental pathology.
​
•Here we investigated if MIA synergized with postnatal inflammation to exacerbate pathology.

•MIA decreases sociability and increases repetitive-like behaviors in males.

•CD8 + T cells are impacted by MIA in a sex-dependent manner.

•Postnatal immune inflammation did not exacerbate ASD-like pathology in either sex.
  • One of the problems with the traditional DIET and EXERCISE approach is that it is MISSING the HUGE SIGNIFICANCE and CHALLENGE of FETAL IMMUNE DYSREGULATION.

Preview

Moving from a Uniform treatment model to Precision Psychiatry

Val's Take/Conjecture
  • The wording in the study to the right is significant:  "precision neuropsychiatric clinical interventions."
  • It's hard to miss that the Researchers and the Clinicians are by and large not quite in the same Neuro-Tribe.
  • Further, the Researchers in study after study, involving Researchers around the world, are in their own way BASHING THE STATUS QUO.
  • If one size doesn't fit all --- what does mean for current diagnostics and for applications in the Criminal Justice System?
The gut microbiota-immune-brain axis: Therapeutic implications (2025)

*Irish Researchers
Leveraging an increased understanding of how these interactions regulate immunity has the potential to usher in a new era of precision neuropsychiatric clinical interventions for psychiatric, neurodevelopmental, and neurological disorders.

Neuro-Developmental & Psychiatric Disorders, Immune cell types and

BUDGETS

Val's Take/Conjecture
  • What researchers found and continue to corroborate with greater and greater specificity --
    • A ROOT CAUSE ANALYSIS of Neuro-Developmental and Psychiatric Disorders must include the IMMUNE SYSTEM.​
Neonatal inflammation impairs developmentally-associated microglia and promotes a highly reactive microglial subset (2025)

[Microglia are the brain's resident immune cells.]
Role of the T-cell network in psychiatric disorders.  (2021)

[T-cells are immune cells that play a significant role in adaptive immunity]
Maternal natural killer cells drive neuroimmune disorders in offspring through aberrant secretion of extracellular granzyme B (2025)

[Natural Killer (NK) cells are a type of immune cell]
These findings suggest that exposure to a perturbed maternal milieu reprograms decidual NK cell immunity, disrupting fetal neuroimmune homeostasis and increasing offspring susceptibility to neurodevelopmental disorders later in life.
What Do ADHD, Long Covid And Ehler’s Danlos Have In Common? Meet The Mast Cell. (2022)

[Mast cells are tissue-resident immune cells.]
The future of immunopsychiatry: Three milestones to clinical innovation  (2021)
One of the Top Strategic Priorities for Clinical Translation of Immunopsychiatry Research:

​"Set up expert clinical facilities with psychiatric, immunological and other relevant expertise"

Mast Cell Activation Syndrome and Neuro-Psychiatric Disorders

Prevalence and treatment response of neuropsychiatric disorders in mast cell activation syndrome (2025)
Affiliations
  • 1Gastroenterology Department, Gastrointestinal Alliance, 11525 Olde Cabin Road, St. Louis, MO, 63141, USA.
  • 2AIM Center for Personalized Medicine, Senior Consultant in Hematology/Oncology, Department of Mast Cell Studies, 3010 Westchester Avenue, Suite 404, Armonk, NY, 10577, USA.
  • 3Washington University in St. Louis School of Medicine, Department of Psychiatry Box 8134, 660 S Euclid Ave, St. Louis MO, 63110, USA.
  • 4PatientsCount.org, 13285 Roundhill Drive, Truckee, CA, 96161, USA.
  • 5Clinical Associate Professor of Neurology, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY 14203, USA.
  • 6Neuroveda Health, 1700 Westlake Ave N, Suite 100, Seattle, WA, 98109, USA.
  • 7University of Colorado Anschutz School of Medicine, 13001 E 17th Pl, Aurora, CO, 80045, USA.
  • 8SSM Health St Clare Neuroscience Institute, Adjunct Professor in Neurology, Saint Louis University, Fenton, MO, 63390, USA.
  • 9Center for Complex Diseases, 2206 Queen Anne Ave. N, #303, Seattle, WA, 98109, USA.
  • 10AIM Center for Personalized Medicine, Department of Integrative Medicine, 3010 Westchester Avenue, Suite 404, Armonk, NY, 10577, USA.
  • 11University Hospital of Bonn, Institute of Human Genetics, Venusberg-Campus 1, D-53127 Bonn, Germany.
​Abstract

Background: Neuropsychiatric disorders have been observed in mast cell activation syndrome (MCAS). MCAS is a common, yet rarely diagnosed, inflammatory, and immunologic disease characterized by mast cell dysregulation.

Methods: Questionnaires from 553 MCAS and 558 control subjects determined the prevalence and odds ratio of neurologic disorders (fatigue, cognitive dysfunction, fainting/near fainting, migraine-like headaches, muscle pain/tenderness/weakness, pain/numbness/tingling in extremities, restless legs syndrome, seizure-like activity, insomnia, sleep attacks, tinnitus, acoustic startle, Tourette's syndrome, resting tremor, and light/sun/pain/odors/scents/noise hypersensitivity) and psychiatric disorders (anxiety, agoraphobia, panic attacks, depression, bipolar depression, mania/hypomania, psychosis/schizophrenia, hallucinations, obsessive compulsive disorder, attention-deficit/hyperactivity disorder, anger management problems, post-traumatic stress disorder, suicidal thoughts, and eating disorders).

Results: Among 19 neurologic disorders, female MCAS patients reported higher rates in all but 1 disorder and male MCAS patients reported higher rates in all but 2 disorders. Among 14 psychiatric disorders, female MCAS patients reported higher rates in all and male MCAS patients reported higher rates in 8 disorders.

Many of the disorders with increased prevalences were statistically greater compared to corresponding controls.In self-reported ratings for effects on health status (0 = no benefit, 10 = maximum benefit), mean (SD) response was 6.3 (2.5) for antihistamines, 5.6 (3.2) for low-dose naltrexone, and 5.6 (3.1) for benzodiazepines.

​Conclusion: MCAS subjects have significantly elevated odds ratios for many neuropsychiatric disorders and may see improvement of symptoms using MCAS-targeted therapies, suggesting that mast cell dysregulation affects the brain and peripheral nervous systems and contributes to neuropsychiatric symptoms.

Certain mast cell mediators, specific genetic predisposition, and life experiences could determine which disorder is apt to develop or worsen.
Yes, mast cells are an integral part of the immune system, playing crucial roles in allergic reactions and immune regulation.
2019 Article below discusses among other things Mast Cell issues.
​PHYSIOLOGICAL CORRELATIONS WITH GIFTEDNESS -- Gro-gifted.org

Jama Psychiatry is driving another stake into DSM DIAGNOSTIC CATEGORIES

with some practical alternatives --- BIO-MARKERS

Treatment For Psychosis May Be 'Fundamentally Flawed',
​Study Finds
Science Alert
August 31, 2025

"This discovery challenges some aspects of modern psychiatric practice. Currently, treatment decisions rely heavily on diagnostic categories that may not reflect what is actually happening in people's brains."

. . .

"As our understanding of the brain advances, the rigid categories that have dominated psychiatry for decades are beginning to blur. If the brain (and mother nature) does not respect diagnostic boundaries, neither should our treatments."
Val's Take/Conjecture
  • Lead author of the Study and the article in Science Direct is Sameer Jauhar, PhD with Imperial College London.
  • There were also several other authors of the Study from the UK including others from Imperial College London, Oxford and King's College London, and also Italy -- the University of Padua.
  • DSM Categories have been under fire from the highest tops of the Scientific Establishment for over a decade.
  • Slowly biomarkers are being identified.
  • In the meantime, there are plenty of questions about how we should be handling imperfect and incomplete psychiatric knowledge in the Criminal Justice System.
Dopamine and Mood in Psychotic Disorders: An 18F-DOPA PET Study (2025)

 Use of PET Scan to determine Striatal dopamine synthesis capacity (Kicer).
Metabolomic Biomarker Signatures for Bipolar and Unipolar Depression (2024)

Keto diet & Microglial repair

Val's Take/Conjecture
  • ​It appears the research is supporting a KETO DIET for Neuro-Developmental and Psychiatric Disorders.
  • The proponents generally do make the point that a KETO DIET is not a cure-all.
  • There is the danger that MEDICATION ADHERENCE is replaced with KETO ADHERENCE.
    • ​I'm not against medication, I take medication --- as do millions of people in this country.
      • ​The problem with neuro-diverse folks is that they are neuro-diverse --- and a medication that works for one person will not necessarily work for someone else.
    • With respect to KETO, it is a fairly strict regimen for people who may have a hard time following a strict regimen --- which is most Americans.​
Ketogenic diet and metabolic regulation of brain microglia (2019)

(Cancer)
MKP ---
The Mitochondrial Ketogenic Pathway

​The ketone body β-hydroxybutyrate shifts microglial metabolism and suppresses amyloid-β oligomer-induced inflammation in human microglia (2023)
These results indicate that:
​
* microglia MKP [Mitochondrial Ketogenic Pathway] can be induced to modulate microglia immunometabolism, and
*that BHB can remedy "keto-deficiency" resulting from MKP suppression and
           *shift microglia away from proinflammatory     
             mitochondrial metabolism.

Bullets added.
A ketogenic diet regulates microglial activation to treat drug addiction (2025)

*Chinese Researchers
Measuring the effects of ketogenic diet on neuropsychiatric disorder: A scoping review (2025)
Conclusion: The KD may serve as a promising therapeutic intervention for various neuropsychiatric disorders.

However, the evidence is heterogeneous, and further rigorous research is needed to establish the KD as a standard treatment for these disorders and to understand the underlying mechanisms of its effects.

Implications for practice:  This review underscores the need for healthcare professionals to consider the potential benefits and limitations of the KD when managing patients with neuropsychiatric disorders.

It also highlights the importance of individualized treatment plans based on the specific needs and responses of each patient.

"Psychiatric Symptoms" across Disease & Disorder Categories

​The Bias that comes with that primary psychiatric diagnosis

Val's Take/Conjecture
  • This is building on the work of Neuro-Scientist David Eagleman and his observations that a ONE WORD LABEL could change how much we care about someone.
  • One of the things that has been interesting to me in my research as well as my professional and personal experience:  
    • ​People with other illnesses and disorders such as:
      • CANCER,
      • MULTIPLE SCLEROSIS,
      • DIABETES,
      • NEURO-DEGENERATIVE DISORDERS,
      • etc.
                     often experience PSYCHIATRIC SYMPTOMS, 
​                     too.
  • When we say someone has a "PSYCHIATRIC DISORDER" ---- what does that really mean?
    • It often means they have a complex developmental Neuro-Immune Disorder
    • Including dysregulated Microglia -- the brain's innate immune cells, and
    • Dysfunctional Mitochondria
    • ​Further, those challenges often track with other diseases and disorders.
  • On the other hand, people with a primary psychiatric diagnosis are often:
    • younger
    • mobile  
    • experience significant emotional dysregulation
    • executive functioning challenges and
    • some unusual fatigue
    • sometimes some speech issues
  • The lack of biomarkers,  BROAD SPECTRUMS and the existence of genuine dangerous behavior among a small minority of people with psychiatric disorders, leads to chronic stress---
    • ​not only for individuals,
    • ​but also the society at large.
Evaluating metabolome-wide causal effects on risk for psychiatric and neurodegenerative disorders (2025)
Elevated mortality risks associated with late diagnosis of cancer in individuals with psychiatric disorders?  (2025)

​Mental Illness Might Be Early Feature of Multiple Sclerosis (2023)
Unraveling the genetic links between depression and type 2 diabetes (2025)
Demyelination in psychiatric and neurological disorders: Mechanisms, clinical impact, and novel therapeutic strategies (2025)

Preview

​An age of Discovery
The importance of Glial Cells in:

Neuro-Developmental Disorders, Psychiatic Disorders, Neuro-Degenerative Disorders, Cancer and Auto-immune Disease

Val's Take/Conjecture
  • Over a decade ago, former Director of the National Institute of Mental Health said ----
    • WE'RE IN AN "AGE OF DISCOVERY"
    • Wherever we are in a decade will likely be more extraordinary than anything we can imagine, and
    • "WE WANT TO BE OPEN TO THAT." ​
The real point of this little exercise regarding GLIAL CELLS and Microglia and Mitochondria Transplantation (below) is that:
  • Neuro-developmental and psychiatric disorders are much more complicated than we are treating them, and
  • Certainly more complicated than we are treating them in Criminal Justice.
Glia Cells in general
Microglia -- Immune Cells of the Brain and Central Nervous System (CNS)
Astrocytes
Oligodendrocytes (OLs) -- are the Myelin forming cells of the CNS.
Ependymal Cells
In College, I was not particularly interested in EPISTEMOLOGY in philosophy class --- OMG this is SO BORING!!!!!

But I find, I have become very interested in Epistemology as it relates to OUT-DATED DIAGNOSTIC MANUALS and ANCIENT LEGAL CONCEPTS.

Mitochondrial transplantation to address psychiatric Disorders

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 have more Synapses.  Those additional synapses are placing a higher energy burden on already dysfunctional mitochondria.
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

Profound Neuro-immune Paradigm Shifts

Beyond KetO ---
Microglial Replacement

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)
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.

Preview:  Olmstead Law & order Thursday

Individualized Keto & Reducing Institutionalization

Val's Take/Conjecture
  • ​How many times have we been told that the PERFECT DIET will lead to HEALTH & HAPPINESS?
  • This goes back to Ancient Times and even Modern Times.
  • Remember Olestra --- the fat substitute that was going to make us all thin.
  • Keto is on the opposite end of that.  If you have epilepsy, obesity, neuro-developmental and/or psychiatric disorders --- you need a lot of fat.
  • Globally, there is enormous interest in utilizing KETO to address psychiatric disorders.
  • Texas Tech University has recognized the potential, and cautioned this needs to occur within an "INDIVIDUALIZED TREATMENT PLAN."
Stanford Medicine
2025 Keto Research for $2.50

A non-exhaustive look at research relating to Ketogenic Diets and Mental Health over the current year.

2025 Ketogenic Diet for Mental Health --- Selected Research

$2.50
Buy Now

Selected non-exhaustive research that includes traditional psychiatric disorders, neuro-developmental disorders and addiction disorder with regard to Ketogenic Diets

[There's nothing on this research table that isn't free and publicly available on PubMed and to a lesser extent AI.  

This table compiles that information and puts it in a convenient format to save time for those who want access to this more detailed information on specific studies.]

Keto Diets and Regulating Microglial activation

Val's Take/Conjecture
  • The Keto Diet isn't a CURE-ALL, but much of the research is showing it can help some people across a range of disorders and illnesses.
  • One of the things a Keto Diet appears to do is regulate microglial activation.
    • ​Microglia are the brain's innate immune cells.
    • Dysregulation of microglial result in a negative cascade of chain reactions throughout:
      • ​The Central Nervous System
      • The Immune System
      • The Endocrine System, and
      • The Gut Microbiome
  • Maternal Immune Activation can dysregulate microglia in utero. 
A ketogenic diet regulates microglial activation to treat drug addiction (2025)
When we think about that care team for people with Neuro-Developmental, Psychiatric and/or Addiction Disorders --- including a Dietician may be an effective and efficient use of resources.

The Current direction of psychiatric research --- 

"Frontiers in Immunology"

Val's Take/Conjecture
  • Some researchers do appreciate that Clinicians need considerably more SUPPORT than they are getting to stay on top of the research.
​Global medical research is going at a very fast pace --- which continues to increase in speed.
  • Clinicians earn a living by seeing patients --- theoretically it's important to stay on top of the research ----
    • But where does that time come from --
    • Especially, when the quantity (and quality) of research is increasing.
  • More and more maybe this will be updated by AI or some professionally approved version.
  • Major paradigm shifts are occurring at the global research level regarding Neuro-Developmental and Psychiatric Disorders.
  • Those paradigm shifts have significant medical and policy implications.
  • These new understandings are most crucial for patients who are a danger to themselves, others or gravely disabled regardless of whether they have been "certified."

​Extracellular vesicles as precision therapeutics for psychiatric conditions: targeting interactions among neuronal, glial, and immune networks (2025)

A bi-directional feedback loop between the pancreas and the hippocampus

Val's Take/Conjecture
  • These studies are more support for Psychiatric Disorders as MULTI-SYSTEM DISORDERS.
  • While Neuro-Developmental and Psychiatric Disorders are more and more referred to as NEURO-IMMUNE DISORDERS --- other systems of the body are involved as well --- significantly the ENDOCRINE SYSTEM.
  • ​​The Endocrine System is a crucial player in METABOLISM.
  • As noted in the paper to the right, people with NEURO-PSYCHIATRIC DISORDERS often have "metabolic symptoms."
Microglia-Derived Interleukin-6 Triggers Astrocyte Apoptosis in the Hippocampus and Mediates Depression-Like Behavior (2025)
  • Some of the KEY DOMINOES that are disrupted/dysregulated during MATERNAL IMMUNE ACTIVATION are MICROGLIA -- the brain's INNATE IMMUNE CELLS.
  • These microglial dysregulations have many complex cellular and molecular chain reactions throughout systems of the body and across the lifespan, and even across generations.​​
Transgenerational consequences of maternal immune activation (2020)
Abstract
​
Prenatal exposure to infectious or inflammatory insults is increasingly recognized in the etiology of neuropsychiatric diseases, including schizophrenia, autism, depression and bipolar disorder.

New discoveries highlight that maternal immune activation can lead to pathological effects on brain and behavior in multiple generations.

This review describes the transgenerational consequences of maternal immune activation in shaping brain and behavior anomalies and disease risk across generations.

We discuss potential underlying mechanisms of transmission, by which prenatal immune activation can mediate generation-spanning changes in brain development and functions and how external influences could further determine the specificity of the phenotype across generations.

The identification of the underlying mechanisms appears relevant to infection-related neuropsychiatric illnesses independently of existing diagnostic classifications and may help identifying complex patterns of generation-spanning transmission beyond genetic inheritance.

The herein described principles emphasize the importance of considering ancestral infectious histories in clinical research aiming at developing new preventive treatment strategies against infection-related neurodevelopmental disorders and mental illnesses.
A pancreas–hippocampus feedback mechanism regulates circadian changes in depression-related behaviors (2025)
[The pancreas is part of the endocrine system.]
Abstract

Individuals with neuropsychiatric disorders often show metabolic symptoms.

However, the mechanisms underlying this co-occurrence remain unclear.

Here we show that induced pluripotent stem cell-derived pancreatic islets from individuals with bipolar disorder have insulin secretion deficits caused by increased expression of RORβ, a susceptibility gene for bipolar disorder.

Enhancing RORβ expression in mouse pancreatic β cells induced depression-related behaviors in the light phase and mania-like behaviors in the dark phase.

Pancreatic RORβ overexpression in the light phase reduced insulin release from islets, inducing hippocampal hyperactivity and depression-like behaviors.

Furthermore, this hippocampal hyperactivity in the light phase had the delayed effect of promoting insulin release in the dark phase, resulting in mania-like behaviors and hippocampal neuronal hypoactivity.

​Our results in mice point to a pancreas–hippocampus feedback mechanism by which metabolic and circadian factors cooperate to generate behavioral fluctuations and which may play a role in bipolar disorder.

Getting it to ClinIcians: 

The imPortance of Maternal Immune Activation

Val's Take/Conjecture
  • It's in the 21st Century that researchers have identified and corroborated a link between Maternal Immune Activation and Neuro-Developmental/Psychiatric Disorders such as:
    • ​ADHD
    • Autism
    • Bipolar Disorder
    • Depression, and
    • Schizophrenia
  • This information is more and more put in handbooks and textbooks as opposed to mainly being found in scattered academic and professional journals.
  • This is also supporting the idea of the Developmental Origins of Health and Disease.
  • A couple of things with regard to the "Snippets" to the right:
    • Infection is not the only source of Maternal Immune Activation.
    • Paternal Immune Activation is a "thing" and has a relationship to Neuro-Developmental and Psychiatric Disorders as well.
From womb to world: The interplay between maternal immune activation, neuroglia, and neurodevelopment (2025)
Affiliations
1Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, Friedman Brain Institute, New York, NY, United States.
2Department of Neurobiology, Harvard Medical School, Boston, MA, United States.
3Department of Psychoneuroimmunology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
4Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Section snippets

The Dynamic Role of Neuroglia in Brain Development and Adulthood

Neuroglia have recently been recognized as indispensable players throughout brain development and adulthood, with growing evidence highlighting their involvement in disease progression (Rahman et al., 2022).

There are four types of neuroglia—astroglia, oligodendroglia, microglia, and radial glial cells (RGCs) (the latter only present in prenatal brain)—each performing diverse functions from supporting and guiding neuronal networks, to maintaining synapse plasticity and the innate immune
​
Maternal Immune Activation

​Maternal immune activation (MIA) refers to the activation of a mother's immune system during pregnancy, often due to infection, inflammation, or other triggers (Fig. 15.1).

This immune response can potentially affect the fetal brain development and increase the risk for neurologic disorders (PrabhuDas et al., 2021).

The link between MIA and NDDs was first recognized and proposed in epidemiological studies of influenza A infection.

​Various neuropsychiatric symptoms were observed after the 1385 . . .

Inflammation and Cytokines Associated With MIA

At present, MIA is rather represented by fluctuations in specific cytokine levels in the maternal serum and how they affect neurodevelopment and predisposition to psychiatric disorders.

All epidemiological human studies dispose of maternal and neonatal plasma that can be tested for cytokine amount along with behavioral and cognitive studies performed on the progeny (for schematic illustration, see Fig. 15.2).

Increased concentrations of proinflammatory cytokines in the maternal serum have been . .  .

Temporal Stage of Infection and Cytokine Exposure

​The gestational timing at which the infection and immune response occurs is believed to be a regulator of the MIA impact on neurodevelopment.

While Zika virus and Cytomegalovirus infections provide a risk of developing NDDs regardless of the gestational time window, other viral infections have been shown to have a greater risk at specific stages of pregnancy.

Rubella infection poses a higher risk during the first trimester, while Parvovirus and Treponema pallidum poses a higher risk during the

​Modeling MIA: Animal and Human

Human epidemiological studies along with preclinical models indicate that MIA may prime for altered neurodevelopment in susceptible individuals, with possible neuropsychiatric manifestations later in life.

In this section, we will review the most prominent preclinical in vivo and in vitro MIA models (also listed in Table 15.1 with additional studies), summarizing their translational utility in understanding the role of MIA as a potential risk factor for neuropsychiatric conditions of

Maternal Immune Activation Effect on Neuroglia

As mentioned above, preclinical models revealed that MIA is able to induce fetal brain changes via inflammatory mediators such as cytokines (Smith et al., 2007; Pratt et al., 2013; Schaafsma et al., 2017).

Preclinical MIA models further implicated IL-6 as a potential propagator of the maternal-to-fetal brain inflammatory response (Smith et al., 2007).

Alteration in fetal brain immune functions can have profound consequences for neurodevelopment, as the brain immune system is directly involved

The COVID-19 Pandemic

Since November 2019, a novel viral pandemic, called coronavirus disease 2019 (COVID-19) and caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), placed pregnant women in a high-risk group.

Meta-analysis studies reported that pregnant women show a more severe COVID-19, manifesting less of the common symptoms such as fever, cough, and dyspnea, but are at higher risk of admission to the intensive care unit, preterm birth, and subsequent admittance into neonatal unit (Allotey et

Conclusions, Speculations, and Future Directions

The susceptibility to infections is strongly linked to MIA, but a genetic component and secondary stressors also play a role, especially in neuropsychiatric disorders with late onset like SCZ (Nudel et al., 2019). It was mentioned above that some studies are focusing on modeling MIA via double-hit models.

Future research should be focusing more on those studies, in which the MIA hit is later on accompanied by a secondary stressor model. The recently introduced use of iPSC-derived human models

We need a frank discussion about "Competency"

Val's Take
  • These discussions are often couched in terms of "holding people accountable."
  • ​To me, the stronger argument is centered around SAFETY.
2 Issues that Need to be Addressed
  1. A Need for an Adequate Continuum of Care that includes sufficient Secure Placements, and
  2. A Need for Objective Biomarkers in both Suicidality and Homicidality, etc.

We're on the cusp of actually getting biomarkers with respect to Suicidality.
Who bears the burden if we don't have adequate Biomarkers, Understandings and Treatments?

What does that "BURDEN" look like?
Colorado parents group calls on lawmakers to amend or repeal criminal competency laws

​August 12, 2025
When we know too much to go back, and we don't have all the answers.

Preview:  Neuro-Diversity Wednesday

Mitochondrial Energy, Sensory Processing and Emotional Regulation

Mitochondrial Energy Transformation Capacity Influences Brain Activation During Sensory, Affective, and Cognitive Tasks (2025)
Therapy In A Nutshell
Exploring a Sensory Diet for Emotional Regulation

"She died because the people around her were ignorant.” 

Val's Take/Conjecture
  • I'm adding another theme to Orchid:  Knowledge and Ignorance.
  • In modern times, we know all too well that the illnesses our loved ones suffer and die from will likely have better treatments and even cures in the future.
  • There is plenty of ignorance to go around.  There always is when the more you know --- the more you realize you don't know.
  • The mother in the Guardian article is interested in more public education surrounding Mental Health issues.
  • ​That's a critical piece.
  • Another critical piece is understanding the importance of better understandings and treatments.
‘I had her right in front of me. And now she’s gone’: how one mother lost her daughter to mental illness

​ (Aug. 9, 2025)

A public Health approach to criminal justice can include Custodial Care

It can and should be every bit as individualized and sophisticated as cancer care with up-to-date precision medicine.
​
The US should be included in Google AI's List of Countries that try various "Public Health ApproachES to Criminal Justice"

Val's Take/Conjecture
  • When people are invoking a Public Health Approach to Criminal Justice ---​
    • ​They often are referring to COMMUNITY-BASED CARE.
    • But in extremely serious cases it may be Custodial Care, just as it might be for other very serious health conditions.
  • Neuro-Developmental and Psychiatric Disorders are complex NEURO-IMMUNE DISORDERS affecting multiple systems of the body.
    • ​They are often the result of DEVELOPMENTAL IMMUNE DYSREGULATIONS incurred in IN UTERO as the result of Maternal Immune Activation.
    • We need Integrated Health Care not only of Physical and Mental Health, but also Developmental Health.
  • In some ways, "Psychiatry" has been "BACK-DOORING" highly complex IMMUNE ISSUES.
  • Google AI didn't give the US credit for a Public Health Approach to Criminal Justice --- but it's there along with being the Most Incarcerated Country in the World.
  • Some of our Public Health Approaches to Criminal Justice are PRIMATIVE.  
Tom Abbott, 44 Communications, Ltd.
countries with a public health approach to criminal justice

There's a growing global movement to integrate public health principles into criminal justice systems, moving away from solely punitive approaches towards more rehabilitative and preventative measures. 

​Here are some examples of countries implementing such approaches:

Portugal: Known for decriminalizing personal drug use and focusing on treating addiction as a health issue, with positive impacts like plummeting drug-induced death rates.

Netherlands: Emphasizes harm reduction and prevention in its approach to drug use and other criminal justice matters.

Switzerland: Implemented the "Four Pillars Law" encompassing prevention, harm reduction, treatment, and law enforcement for drug-related issues, according to foundationswellness.net.

Norway and Finland: Their justice systems prioritize rehabilitation and focus on the inherent humanity of individuals involved in the system, viewing prisons as environments for learning a life without crime.

United Kingdom: Has utilized hospital-based violence surveillance to inform prevention strategies, sharing anonymized data with police and local government partners to reduce violence-related hospital admissions.

Canada: Introduced legislative reforms in British Columbia to support the decriminalization of drug use and possession.

Australia: Has adopted harm reduction measures like syringe service programs.

Certain Countries in the Caribbean Community (CARICOM): Recognizing the link between violence and public health, CARICOM hosted a symposium on crime and violence as a public health issue, exploring a public health approach to reduce violence.

Ukraine, Philippines, Nigeria, and Peru: Are developing addiction public health infrastructure with support from international organizations, focusing on regulatory changes, workforce development, and resource allocation, according to the National Institutes of Health (NIH).

Republic of Moldova: Introduced in-prison therapeutic communities for addiction treatment and post-release mentorship programs.

Germany, France, Finland, Estonia, and the Netherlands: Have successfully implemented alternative punishments such as community service, probation, electronic monitoring, and fines, leading to reduced incarceration rates and recidivism.

Indonesia: Is also pursuing alternatives to incarceration, including supervision and social work, aiming to reduce prison overcrowding and support reintegration. 

Key aspects of a public health approach to criminal justice
Treating addiction and mental illness as public health concerns: Focusing on prevention, treatment, and harm reduction instead of solely relying on criminal penalties.
Investing in social services and community programs: *Addressing the root causes of crime like poverty, lack of education, and limited access to healthcare.
*Diverting individuals with mental health or substance use disorders away from incarceration: Utilizing drug courts, mental health courts, and community-based treatment programs.

Focusing on rehabilitation and reintegration: Providing support and resources to individuals exiting the criminal justice system to reduce recidivism.

Using data to inform policies and practices: Employing evidence-based strategies and evaluating their effectiveness in reducing crime and improving public health.

Collaboration between law enforcement and public health agencies: Sharing data, expertise, and resources to implement effective interventions. 

This shift towards a public health approach aims to create a more just and effective criminal justice system that promotes public safety while also improving the health and well-being of individuals, families, and communities. 

AI responses may include mistakes. Learn more

PREVIEW:  Translational Medicine Friday

Mitochondrial Dysfunction, Calcium Homeostasis & Aggression

Val's Take/Conjecture
  • If there is an acceptance of the algebra of the biological basis of behavior, one already knows there are biological reasons for aggression even if we don't know the specifics.
  • But, ultimately we do need the specifics to address dangerous dysregulations with more than custodial care and with treatments that actually change people's lives and protect the community.
  • It appears that AGGRESSION is related to Mitchodrial Dysfunction and disruption of CALCIUM HOMEOSTASIS.
  • With Calcium as with many things, it appears we do not want too little or too much.
  • At the same time that we're recognizing common mechanisms of disorder and disease --- and "psychiatric disorders" across  illness categories ---
    • ​​the COMPLEXITY of this requires PRECISION MEDICINE
Deletion of the P/Q-Type Calcium Channel from Serotonergic Neurons Drives Male Aggression in Mice (2022)
SIGNIFICANCE STATEMENT
​ 
In this study, we show that P/Q-type calcium channel is mediating aggression in serotonergic neurons from the dorsal raphe nucleus via monosynaptic projections to the ventrolateral part of the ventromedial hypothalamus.

More importantly, silencing these projections reduced aggressive behavior in mice and may serve as a therapeutic approach for treating aggression in humans.
Molecular mechanisms of mitochondrial dynamics (2025)
Mitochondria not only:
  • synthesize energy required for cellular functions
  • but are also involved in numerous cellular pathways including
    • apoptosis [programmed cell death],
    • calcium homoeostasis,
    • inflammation and
    • immunity. 

​*Bullets added.
Aggressiveness, violence, homicidality, homicide, and Lyme disease (2018)
Conclusion:  LD [Lyme Disease] and the immune, biochemical, neurotransmitter, and the neural circuit reactions to it can cause impairments associated with violence.

Many LD patients have no aggressiveness tendencies or only mild degrees of low frustration tolerance and irritability and pose no danger; however, a lesser number experience explosive anger, a lesser number experience homicidal thoughts and impulses, and much lesser number commit homicides.

​Since such large numbers are affected by LD, this small percent can be highly significant. Much of the violence associated with LD can be avoided with better prevention, diagnosis, and treatment of LD.

Why immunology for psychiatric Disorders?

*Maternal immune activation
*Atypical response to viruses

preview

Epstein Barr Virus and Atypical Neuro-inflammation

In Neuro-Developmental Disorders, Psychiatric Disorders, Auto-immune Disorders, Cancer  & Aging

Val's Take/Conjecture
  • Developmental Atypical Inflammation as a result of Maternal Immune Activation (MIA) In Utero is a BIG CLUE to Neuro-Developmental and Psychiatric Disorders.
  • Another BIG CLUE is that People with Neuro-Developmental and Psychiatric Disorders have an Atypical Response to the Epstein Barr Virus.
    • Epstein Barr Virus has over 90% exposure in the human population.
    • It's not rare.
    • It's the response that can be rare, and more damaging. 
MULTIPLE SCLEROSIS is all about Epstein Barr.

3rd BIG CLUE:  Bipolar Disorders and Mood Disorders are common in Multiple Sclerosis.

Protein intake is associated with cognitive functioning in individuals with psychiatric disorders (2020)
Shared interactions of six neurotropic viruses with 38 human proteins: a computational and literature-based exploration of viral interactions and hijacking of human proteins in neuropsychiatric disorders (2025)

*Turkish Researchers
Did the Turkish Researchers discover one of the reason why HIGH PROTEIN DIETS are important for people with Neuro-Developmental & Psychiatric Disorders?

Targeting GzmB in maternal NK cells alleviates MIA-induced neuroimmune disorders

Plus diagnosis & Management of Atypical neuro-Inflammation

​

​Val's Take/Conjecture
  • We're getting a narrative that hangs together with respect to MIA-induced neuro-developmental and psychiatric disorders.
  • Chinese researchers have made a big breakthrough.

  • Additionally, we need diagnosis and management of atypical neuro-inflammation across the lifespan.​
  • Moleculera Labs developed the Cunningham Panel to diagnose some auto-immune psychiatric disorders.
    • ​The Cunningham Panel, now known as the Autoimmune Brain Panel, is often ordered through Neurology as opposed to Psychiatry.
    • This is looking like a traditional medical approach with biomarkers.
    • ​BUT not everyone has the auto-immune psychiatric disorders that the Cunningham Panel tests for.
  • That's one of the reasons why the paper Diagnosis and Management of Children With Atypical Neuroinflammation is so important. 
    • Researchers are focusing more broadly on ATYPICAL NEURO-INFLAMMATION.
Genetic evidence for causal effects of immune dysfunction in psychiatric disorders: where are we? (2024)
Maternal natural killer cells drive neuroimmune disorders in offspring through aberrant secretion of extracellular granzyme B (2025)

*Chinese Researchers
Highlights
•Stressed maternal NK [Natural Killer] cells drive activated macrophage accumulation in fetal brains
•CD49a+ trNK-derived GzmB promotes the propagation of immune signals in MIA [Maternal Immune Activation]
•Maternal GzmB induces ISGshi macrophage accumulation and microglial activation
•Targeting GzmB in maternal NK cells alleviates MIA-induced neuroimmune disorders
Diagnosis and Management of Children With Atypical Neuroinflammation (2025)
Pediatric neuroimmune disorders comprise a heterogeneous group of immune-mediated CNS inflammatory conditions.

Some, such as multiple sclerosis, are well defined by validated diagnostic criteria.

Others, such as anti-NMDA receptor encephalitis, can be diagnosed with detection of specific autoantibodies.

This review addresses neuroimmune disorders that neither feature a diagnosis-defining autoantibody nor meet criteria for a distinct clinicopathologic entity.

A broad differential in these cases should include:
* CNS infection,
*noninflammatory genetic disorders,
*toxic exposures,
*metabolic disturbances, and
​*primary psychiatric disorders.

Neuroimmune considerations addressed in this review include:
* seronegative autoimmune encephalitis,
*seronegative demyelinating disorders such as neuromyelitis optica spectrum disorder, and
*genetic disorders of immune dysregulation or secondary neuroinflammation.

In such cases, we recommend a broad diagnostic workup:
* to support the presence of neuroinflammation,
* exclude non-neuroimmune disorders,
* detect autoantibodies and other biomarkers of known diseases,
* identify any potential genetic drivers of neuroinflammation, and
​*provide case-specific insights into pathophysiologic mechanisms of inappropriate immune pathway activation or dysregulation.

This review includes an extensive list of useful diagnostic tests and potential implications thereof, as well as a proposed algorithm for the diagnosis and management of the pediatric patient with atypical neuroimmune disorders

Bullets added.
Author Affiliations
​
1Division of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, CA.
2Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles.
3Children's Neurosciences, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, United Kingdom.
4Department of Women and Children's Health, School of Life Course Sciences (SoLCS), King's College London, United Kingdom.
5Department of Neurology, Boston Children's Hospital, Harvard Medical School, MA.
6Department of Neurology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; and.
7Department of Neuroinflammation, Institute of Neurology, University College London, United Kingdom.

Preview:  Olmstead law & Order Thursday

Pres. Trump's new executive order on Homelessness and 

Denver Mayor Mike Johnston's Triumphant program pairing housing with case management

Val's Take/Conjecture
  • It doesn't appear that Democrats and Republicans are that far apart on addressing homelessness.​
  • For Mental Health Advocates, two issues of note under Trump's Executive Order are
    • ​A robust return to Civil Commitment, and
    • A Disavowal of "Harm Reduction" practices.
I consider current TRADITIONAL MENTAL HEALTH TREATMENT ---- "HARM REDUCTION."
  • is it IDEAL --- NO 
  • can it be harmful -- YES
  • BUT given TREATMENT LIMITATIONS --- it is often the best option.
CIVIL COMMITMENT, OUT-DATED UNDERSTANDINGS &  TREATMENTS 
  • Basically, we generally favor Civil Commitment over Incarceration in Jails or Prisons.
  • ​Civil Commitment is still a significant deprivation of liberty.
  • Further, we have been very critical of Colorado Amendments to the Civil Commitment Statute in lieu of an ADEQUATE CONTINUUM OF CARE.
  • Civil Commitment will not save us from having an INADEQUATE CONTINUUM OF CARE and OUT-DATED UNDERSTANDINGS & TREATMENTS.
ENDING CRIME AND DISORDER ON AMERICA’S STREETS (July 24, 2025)
DENVER MAYOR MIKE JOHNSTON
ALL IN MILE HIGH

Preview:  Neuro-Diversity WednesDay

Val's Take/Conjecture
  • One of the reasons so many people are MISSED in screening for mental health concerns ---
    • They don't necessarily fit neatly into current DSM Categories.​
  • Beyond that -- there is not an appreciation for the importance of definitions.

La, La, La . . .
When we talk about getting to the ROOT CAUSE of some of these policy and treatment challenges in mental health ---
  • the fact that the DSM is not a scientifically valid diagnostic manual is HUGE.
Theoretically, WE KNEW OR SHOULD HAVE KNOWN  that the problems with the DSM meant BIG PROBLEMS for Competency Evaluations in Criminal Justice.

The US National Institute of Mental Health identified the problem with the current DSM categories as not sufficiently tied to the "UNDERLYING BIOLOGY."

So this is about getting to DEEPER LEVELS OF ANALYSIS --- with respect to Mental Health ---
  • Getting to the CELLULAR & MOLECULAR  Levels of Analysis

With respect to THE LAW, it is uncovering UNDERLYING ASSUMPTIONS within Mens Rea or Intent.
  • If biological explanations for intent go beyond "PSYCHOSIS" and include Neuro-Developmental Disorders and IN UTERO DYSREGULATIONS of Microglia --- the Brain's Immune Cells, and
  • Highly complex and idiosyncratic underlying biology ---
  • We've got a problem.


​The problem for THE LAW is that a RATIONAL BASIS for Punishment is being effectively undermined by:
  • the Biological Basis of Behavior
  • the Developmental Origins of Health and Disease (DOHaD)
  • the reconceptualization of Neuro-Developmental and Psychiatric Disorders as Neuro-Immune Disorders affecting Multiple Systems of the body.
  • the reconceptualization of Anti-Social Personality Disorder and Borderline Personality Disorder as Neuro-Developmental Disorders.
  • the need for PRECISION MEDICINE --- one size doesn't fit all.
The High Rates of Comorbidity among Neurodevelopmental Disorders:

Reconsidering the Clinical Utility of Distinct Diagnostic Categories  (2024)
Abstract

​The boundaries between neurodevelopmental disorders are often indistinct, even among specialists.

But do these boundaries exist, or do experts struggle to distinguish and categorize symptoms in order to arrive at a dominant diagnosis while comorbidity continually leaves questions about where each disorder ends and begins?

What should be reconsidered?

The introduction of the term ‘spectrum of neurodevelopmental disorders’ could pave the way for a re-appraisal of the clinical continuum of neurodevelopmental disorders.

This study aims to highlight the problems that emerge in the field of the differential diagnosis of neurodevelopmental disorders and propose a renegotiation of the distinctiveness criteria.
Voegelin View:  The Roman Law's Contribution to Modern Legal Systems
The Criminal Law's underlying purpose to maintain SAFETY is as strong as ever if not stronger ----
  • but how we achieve that may be more about addressing underlying developmental immunological dysregulations than what was previously understood.​

PREVIEW TRANSLATIONAL JUSTICE​


​
​Neuro-immune, Baby,
​Neuro-Immune
"The origin of some neuropsychiatric diseases, such as autism, bipolar disorder, or depression, and certain neurodegenerative diseases, Alzheimer’s and Parkinson’s, can be found in very early stages of brain formation in the fetus."

​Early developmental origins of cortical disorders modeled in human neural stem cells (July 9, 2025)
These diseases encompass cortical alterations commonly associated with neuronal dysfunctions.

To map the expression patterns of these risk gene sets in the early fetal human brain, we performed expression-weighted cell type enrichment (EWCE) analysis on single-cell RNA-sequencing (RNA-seq) data from telencephalic regions spanning the first trimester44 .

Consistent with our previous findings in macaque brain and other studies, genes associated with NDDs  [Neuro-Developmental Disorders]  were enriched in both inhibitory and excitatory neuronal signatures.

Similarly, LIS, FCD, and dyslexia genes showed neuronal enrichment, while MIC- and HC-associated genes were enriched in RG cells and glioblasts, MIC-, POLYM-, and rare MCD-associated genes in intermediate progenitor cells (IPCs), and AD genes in immune cell signatures.
​​Could Mental Illness Begin Before You’re Born?  (July 25, 2025)
Key Facts:
  • Early Origins: Key disease-related genes are active in fetal neural stem cells.
  • Wide Disease Range: Genes linked to autism, schizophrenia, Alzheimer’s, and more show early activation.
  • Therapeutic Potential: Findings may guide early interventions and gene-targeted treatments.

Preview:  Neuro-Diversity Wednesday

Accommodating IDIOSYNCRATIC
*Big Strengths,
*BIO-ENERGETICS &
*Executive Functioning

In Employment & ENTREPRENEURSHIP

Val's Take/Conjecture
  • This is about Employment and Entrepreneurship for Neuro-Diverse People who are not savants and have an IQ over 70.  
  • Two of the Big Ideas are:
    • Awareness, and 
    • Try Smarter, Not Harder
    • Understood.org does a great job of articulating these concepts.
  • One of the caveats to "AWARENESS" is that we can think we know, and we don't, or we don't know enough.​
  • As more and more Neuro-Developmental Disorders, Psychiatric Disorders, and Addiction Disorders are conceptualized as
    • Neuro-Immune Disorders
    • Brain Energy Issues, and
    • Mitochondrial Dysfunction
  • Potentially, we could do this much SMARTER.
Art Station -- Individuality

Preview: Neuro-Diversity, Love & Relationships

Hyper-excitability, melt-downs and Relationships

Val's Take/Conjecture
  • Paul MiCallef talks about being in "SURVIVAL MODE" ----
    • He asked for help (or something),
    • Couldn't get it,
    • At this point, he can't communicate rationally about the issue,
    • He is too angry to talk, and
    • Those around him may assume he is fine with the Status Quo  ---​
    • And he is not fine with the Status Quo.
  • The person on the receiving end of this "Silent Meltdown" may feel that they tried to communicate why they couldn't provide help or something ---
    • ​It wasn't accepted,
    • And now the person can't or won't talk about the issue.
The role of ANGER in Neuro-Diverse Relationships is often related to:
  • INDIVIDUAL ENERGY ISSUES and Mitochondrial Dysfunction.
  • And the DYNAMIC of that with the other person's challenges.
If there are two Neuro-Diverse people, that can get complex fast.
Autoimmune Diseases are associated with
​ Neuro-Diversity
WHEN RELATIONSHIP PROBLEMS ARE MASKING SERIOUS HEALTH ISSUES
  • Relationships are so important to us that we may think everything revolves around the RELATIONSHIP --- for good or ill.
  • Accommodations are essential, as they can lessen stress and reduce pro-inflammatory cytokines.
  • But we must understand that we have complex NEURO-IMMUNE DISORDERS, and our partner may too.​​
LEVELS OF ANALYSIS
  • We need to get to the CELLULAR and MOLECULAR LEVELS of:
    • ​Neuro-Developmental
    • Psychiatric, and
    • Addiction Disorders
  • In some ways, this may sound "BORING" or even "COLD."
    • ​But if we want SOCIETAL EMPATHY or even the EMPATHY of a FAMILY MEMBER or FRIEND ---
    • We need to understand what is going on from a biological standpoint as best we can.
  • Moving to Precision Psychiatry doesn't mean that other levels of analysis can't be helpful.
  • But we need to provide the CLINICAL and PUBLIC EDUCATION to make the JUMP to understand the CELLULAR and MOLECULAR LEVELS of:
    • Neuro-Developmental Disorders
    • Psychiatric Disorders and
    • Addiction Disorders
Autism from the Inside
The Danger of Silent Meltdowns
If we're Neuro-Diverse, we are probably already carrying a significant amount of systemic neuro-inflammation.​

SILENT MELTDOWNS can be a RED FLAG signifying many things ---- including worsening underlying health issues.
Paul MiCallef considers himself to be stereotypically "Autistic."
The BLURRED and INACCURATE CATEGORIES of the DSM are driving the need for PRECISION PSYCHIATRY.

​Further, there are often SEX DIFFERENCES.
Neurodivergent Therapist Louise Taylor
Neurodiversity & Empathy
Extracellular ATP Is a Homeostatic Messenger That Mediates Cell-Cell Communication in Physiological Processes and Psychiatric Diseases  (2025)
Abstract

​Neuronal activity is the basis of information encoding and processing in the brain.

During neuronal activation, intracellular ATP (adenosine triphosphate) is generated to meet the high-energy demands.

Simultaneously, ATP is secreted, increasing the extracellular ATP concentration and acting as a homeostatic messenger that mediates cell-cell communication to prevent aberrant hyperexcitability of the nervous system.

In addition to the confined release and fast synaptic signaling of classic neurotransmitters within synaptic clefts, ATP can be released by all brain cells, diffuses widely, and targets different types of purinergic receptors on neurons and glial cells, making it possible to orchestrate brain neuronal activity and participate in various physiological processes, such as sleep and wakefulness, learning and memory, and feeding.

​Dysregulation of extracellular ATP leads to a destabilizing effect on the neural network, as found in the etiopathology of many psychiatric diseases, including depression, anxiety, schizophrenia, and autism spectrum disorder.

In this review, we summarize advances in the understanding of the mechanisms by which extracellular ATP serves as an intercellular signaling molecule to regulate neural activity, with a focus on how it maintains the homeostasis of neural networks.

In particular, we also focus on neural activity issues that result from dysregulation of extracellular ATP and propose that aberrant levels of extracellular ATP may play a role in the etiopathology of some psychiatric diseases, highlighting the potential therapeutic targets of ATP signaling in the treatment of these psychiatric diseases.

​Finally, we suggest potential avenues to further elucidate the role of extracellular ATP in intercellular communication and psychiatric diseases.

NARCISSISM, immaturity or
A Kind of pre-mature aging

in Neuro-Developmental, Psychiatric &/or ADDICTION Disorders

developmental mitochondrial dysfunction & 
ImmunoSENESCENCE [Aging of the immune System]

Val's Take/Conjecture
  • I'm defining "Pre-Mature Aging" as jump-starting "Mitochondrial Dysfunction," often through MATERNAL IMMUNE ACTIVATION.​
  • "Mitochondrial Dysfunction" is ubiquitous in:
    • Sensory Processing Abnormalities,
    • Disease,
    • Chronic Pain,
    • Aging,
    • Cell Death,
    • etc.
  • So Mitochondrial Dysfunction is not unique to Neuro-Developmental, Psychiatric or Addiction Disorders.
    • Further, there is more and more focus on the Developmental Origins of Health & Disease (DOHaD).
MITOCHONDRIAL DYSFUNCTION & IMMUNOSENESCENCE
Influence of Immune System Abnormalities Caused by Maternal Immune Activation in the Postnatal Period  (2024)

*Japanese Researchers

Evaluating the link between immune characteristics and attention deficit hyperactivity disorder through a bi-directional Mendelian randomization study  (2024)

*Chinese Researchers
Correlations between personality traits, personality disorders, and immunometabolic markers  (2024)

*Swedish Researchers
De Staat
Witch Doctor
For the person who is PRE-MATURELY AGING --- that can look like ASYNCHRONY.

Additionally, the DYNAMICS of this PRE-MATURE AGING and ASYNCHRONY are not necessarily playing out the way we might think.
LEVELS of ANALYSIS & DEFINITIONS
  • DEFINING PEOPLE IN and OUT of Diagnostic Categories, Age, and "Morality"
    • ​Much of recent research is considering Anti-Social Personality Disorder as a Neuro-Developmental Disorder.
    • In some quarters, this is controversial-- the diagnostic criteria themselves reference age.
Antisocial Personality Disorder DSM-5-TR [Text Revision] Criteria 
  1. The presence of a pervasive pattern of disregard for and violation of the rights of others. This behavior begins by age 15 and is present in various contexts. Clinical features include ≥3 of the following:
    1. Failure to conform to social norms concerning lawful behaviors, such as performing acts that are grounds for arrest.
    2. Deceitfulness, repeated lying, use of aliases, or conning others for pleasure or personal profit.
    3. Impulsivity or failure to plan.
    4. Irritability and aggressiveness, often with physical fights or assaults.
    5. Reckless disregard for the safety of self or others.
    6. Consistent irresponsibility, failure to sustain consistent work behavior, or honor monetary obligations.
    7. Lack of remorse, indifference to or rationalizing having hurt, mistreated, or stolen from another person.
  3. The individual is at least age 18.
  4. There is evidence of conduct disorder with onset before age 15.
  5. The occurrence of antisocial behavior is not exclusively during the course of schizophrenia or bipolar disorder. 

​Adults who do not have evidence of conduct disorder in childhood and adolescence but otherwise meet the diagnostic criteria for ASPD can be diagnosed with adult antisocial behavior.

While adult antisocial behavior is not a formal DSM-5-TR diagnosis, the DSM-5-TR lists it as a V code, used in the DSM and International Classification of Diseases, Ninth Revision (ICD-9), or Z code used in the ICD-10. 
See Antisocial Personality Disorder (2024) on StatPearls.

PREVIEW

Maternal immune responses, Gut MIcrobiota and Sexuality?

Male Homosexuality, Precocious puberty and Female Obesity​

Val's Take/Conjecture
  • ​20 years ago, if you were talking about the biological basis of behavior ---- it was GENETICS.
  • It became apparent that genetics wasn't explaining everything.
    • So there was the conclusion ---THIS IS ENVIRONMENTAL.
  • As it turned out there were other important BIOLOGICAL  FACTORS.   Additionally, the WHEN was important ---
    • We recognized first that Childhood Abuse or Neglect could affect the child's biology, and broader ADVERSE CHILDHOOD EXPERIENCES (ACES) could have long-lasting effects.
    • Alcohol, Smoking and Drug Use during pregnancy have been recognized for having potentially long-lasting, lifelong effects. 
    • Now we're at
      • Maternal Immune Responses,
      • Maternal Immune Activation, and
      • Maternal Gut Microbiota,
      • all of which have a long-lasting impacts on the person throughout the lifespan.
And there's a lot more.
Picture
Venus, Mars and Cupid c.1635 Peter Paul Rubens (1577–1640)

​Art UK:  Rubens & Women:  Whose Afraid of Peter Paul Rubens?  (2023)

​CBS News:  ADHD linked to obesity in girls  (2016)

Val's Take
  • The common explanation for greater obesity in ADHD and Autism is "impulsivity."
  • Further, males with Neuro-Developmental Disorders have obesity issues, too --- but they are more common in women.

More recently, we've recognized MITOCHONDRIAL DYSFUNCTION AND ​DYSREGULATED ATP PRODUCTION as issues in Neuro-Developmental and Psychiatric Disorders.​

For the woman with MITOCHONDRIAL DYSFUNCTION and DYSREGULATED ATP [Energy] PRODUCTION ---- 
Were her children surviving if she had more stored energy?

In some cases (though not all), there must have been an evolutionary advantage.

But evolutionary pressure in Modern Times for both men and women to be "THIN" or some version of "FIT" is INTENSE.

At least some of the current diet drugs seem to have an effect on MITOCHONDRIAL DYSFUNCTION.
Tempo Bioscience
Bridging ADHD and Metabolic Disorders: Insights into Shared Mechanisms and Clinical Implications (2025)
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, impulsivity and/or hyperactivity.

In recent years, metabolic alterations, primarily obesity, insulin resistance, and diabetes, have emerged as frequent comorbidities in individuals with ADHD, suggesting a bidirectional relationship between neurodevelopmental and metabolic  dysfunctions​
Picture
in Canada

​New research solidifies idea that sexual orientation is biological (2017)
Bogaert, an internationally recognized expert in human sexuality, said the study is groundbreaking for at least two major reasons:

  • It supports the conclusion, suggested by previous studies, that genes alone do not completely account for homosexuality.
  • ​​​​It suggests that immunological factors should be considered along with genetic and hormonal factors as possible biological influences on sexual orientation. 

​​​Bogaert said that since the older brother effect was first discovered two decades ago, many studies have replicated it, including cross-cultural ones.

But when a Bogaert research project 10 years ago strongly indicated that the older brother effect in men was likely biological in origin, he saw the need to look at prenatal factors, and set out to test the major biological theory explaining this effect through a lab study.
Precocious puberty and microbiota: The role of the sex hormone-gut microbiome axis (2022)

​The Association between Autism Spectrum Disorder and Precocious Puberty: Considering Effect Modification by Sex and Neuropsychiatric Comorbidities  (2024)
We found that patients with ASD were prone to precocious puberty, regardless of sex or comorbid neuropsychiatric disorders.

Girls with ASD are at a particularly higher risk of developing precocious puberty.
A Multi-Perspective Qualitative Study About Working With Autistic Individuals in Prison-Based Interventions to Address Sexual Offending (2025)

*UK Researchers
​Maternal gut microbiota influences immune activation at the maternal-fetal interface, affecting pregnancy outcome (2025)
A SUMMING UP
  • In the words of Leonard Cohen --- "Everyone has something."
  • When it comes to Neuro-Developmental & Psychiatric Disorders  ---
    • ​There's both a lot of DIVERSITY and a lot of DYSREGULATION
    • In the midst of all that, there are often gifts.
  • In some research quarters and patient quarters, there has been a recognition for a long time that there needed to be MAJOR PARADIGM SHIFTS in:
    • Mental Health​
As we get those MAJOR PARADIGM SHIFTS in Mental Health --- it starts to shift our views on other issues that we might have considered unrelated.

PREVIEW


Anti-Social Personality Disorder as a

​Neuro-Developmental Disability
Associations of the immune system in aggression traits and the role of microglia as mediators (2024)

Policy Challenges

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​At this time, we generally do not provide INDIVIDUAL ADVOCACY.  Further, we do not address Individual Requests for Information and Referral --- See the Orchid Indexes for OTHER RESOURCES.