Blog Posts

New study shows adults with Autism Need More Support

1/24/2025

Val's Take: First, I think Taylor Heaton does such important work and she reaches so many people on YouTube.

I do want to say that the increase in Neuro-Developmental & Psychiatric Diagnoses is in part AWARENESS, but it's not just that.

Further, there is a great need for INTEGRATIVE THINKING to address the wicked problems of Giftedness/Sensory Processing Differences and Emotional Dysregulation in Neuro-Developmental & Psychiatric Disorders.

Additionally, Neuro-Developmental Disorders involve Developmental Inflammation and a kind of Premature Aging affecting multiple systems of the body resulting in Dysregulated Stress Responses and in many cases serious negative health consequences across the lifespan.

Taylor Heaton ---
Mom on the Spectrum
New Study Shows Adults with Autism Need More Support

Glial-Neuronal Networks & Neuro-Developmental & Psychiatric Disorders

1/20/2025

Val's Take: This video is from 14 years ago. The whole Glial, Neuron, Mental Health connection is "NEW" in a broad sense, but some researchers have been working on this for awhile --- and the number of researchers working on understanding the importance of Glial Cell Types in Neuro-Developmental and Psychiatric Disorders has increased exponentially over the last 5 years.

One of the points that Professor Hickie makes and I have tried to make although I'm not necessarily the best messenger for this --- we need to integrate Clinical and Research practice.

If you spend a lot of time trolling PubMed like I do --- there do seem to be big gulfs among the Researchers, the Clinicians and the Public with regard to basic understandings that greatly affect TREATMENT and POLICY.

Professor Ian Hickie, Brain Mind Centre (Australia)
Glial-Neuronal Networks: Dysfunction in Youth Mental Health

"Resilience," The Immune System & "Second Hits"

1/12/2025

Val's Take/Conjecture

"Maternal Immune Activation" involves the Immune System and occurs In Utero.
Among other things, Maternal Immune Activation impacts Adult Behavior.
So the first hit is "Maternal Immune Activation."
But during the course of our lives we have many and varied experiences of INFLAMMATION and STRESS.
It's a BRAVE NEW WORLD out there and some researchers are already proposing:
- "immunomodulatory" treatments for depression, and
- targeting microglia in treatment efforts.
The point I want to make is that when we talk about "RESILENCE" --- there are actually very complicated mechanics to that.

Additionally, UNPREDICTED CHRONIC STRESS seems to be an issue for mammals and us.

The Unpredictability of Neuro-Developmental and Psychiatric Disorders is taking a huge toll on Individuals, Families, Communities and Societies.
There is CONSCIOUS AWARENESS of the need for:
- Updated Paradigms
- Biomarkers, and
- Better Treatments that address Multi-System Disorders

Genes Participating in the Ensheathment of Neurons Are Affected by Postnatal Stress and Maternal Immune Activation in the Pituitary Gland (2023)

Fetal brain response to maternal inflammation requires microglia
(2024)

In utero infection and maternal inflammation can adversely impact fetal brain development.

Maternal systemic illness, even in the absence of direct fetal brain infection, is associated with an increased risk of neuropsychiatric disorders in affected offspring. . .

Using a rodent maternal immune activation (MIA) model in which polyinosinic:polycytidylic acid is injected into pregnant mice, we demonstrate long-lasting transcriptional changes in fetal microglia that persist into postnatal life.

We find that MIA induces widespread gene expression changes in neuronal and non-neuronal cells; importantly, these responses are abolished by selective genetic deletion of microglia, indicating that microglia are required for the transcriptional response of other cortical cell types to MIA.

These findings demonstrate that microglia play a crucial durable role in the fetal response to maternal inflammation, and should be explored as potential therapeutic cell targets.

The inflammatory underpinning of depression: An historical perspective (2024)

"Synthesizing insights from this extensive research, the review presents an integrative model of the biological foundations of inflammation-associated depression.

"It posits that we have reached a critical juncture where the translation of this knowledge into personalized immunomodulatory treatments for depression is not just possible, but imperative."

Microglial TREM 2 Gene

1/11/2025

*Neuro-Degeneration
*Cancer
*Neuro-Developmental Disorders &
*Psychiatric Disorders

TREM2 in Neuro-Degeneration

TREM2 regulates BV2 microglia activation and influences corticosterone-induced neuroinflammation in depressive disorders (2024)

TREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK signaling pathway (2024)

A multi-omics study of brain tissue transcription and DNA methylation revealing the genetic pathogenesis of ADHD (2024) [includes TREM2]

Trem2 expression in microglia is required to maintain normal neuronal bioenergetics during development (2024)

Engineered Microglia and More

1/10/2025

Val's Take/Conjecture

A collection of articles featuring:
- Engineered Microglia as a Treatment
- The Role of Glial Cells in Mental Illness
- Maternal Immune Activation Generates "Anxiety" in Offspring.
- ADHD as "Dysregulated not Deficit" and
- Maternal Type-I interferon signaling adversely affects Microglia resulting in increased Sensitivity to Stress.

This new research requires significant modification of our paradigms.

Taming microglia: the promise of engineered microglia in treating neurological diseases (2024)

The role of glial cells in mental illness: a systematic review on astroglia and microglia as potential players in schizophrenia and its cognitive and emotional aspects (2024)

Maternal immune activation generates anxiety in offspring (2021)

“Dysregulated not deficit”: A qualitative study on symptomatology of ADHD in young adults (2023)

Maternal Type-I interferon signaling adversely affects the microglia and the behavior of the offspring accompanied by increased sensitivity to stress (2019)

Addiction

1/5/2025

Val's Take: U2's "Bad" is from 1984. I actually didn't hear it until working on it this past year with the Ukulele and Percussion Ensemble at Swallow Hill Music in Denver.

It meant a lot more to me now than I think it would have meant to me in 1984.

It is about Addiction and how morally implicated and powerless the people witnessing that feel. You know you're not helping or solving things --- but you don't know what to do and there is GUILT.

To make matters even more morally fraught, it is not just you or Bono who are lamenting, "If I could, yes I would. If I could, I would" --- it is often the person themselves.

Further, you are NOT PERFECT --- maybe you don't have an illegal substance problem -- as you're guzzling your 7th Diet Coke of the day.

Further, your intended recipient of this angst might be grateful they don't have some of your problems -- "There but for the grace of God go I."

At the end of the day, this is about IMPERFECT PEOPLE HELPING IMPERFECT PEOPLE.

Dr. Mizra talks about the connection between ADHD & Substance Use Issues.

Dr. Sulman Aziz Mirza, MD is Board Certified physician in Adult Psychiatry, Child & Adolescent Psychiatry and Addiction Medicine.

Val's Take: Just as I think it is important to recognize the NEURO-DEVELOPMENTAL/PSYCHIATRIC CONTINUUM --- it is important to include SUBSTANCE USE ISSUES.

There are many aspects to that. Two of those aspects seem to include:

having enough ENERGY to run the brain and the synapses; and
dealing with AFFECTIVE PAIN that may be HIGHLY DYSREGULATED.

This is Neurobiologist David Anderson's 2013 TedTalk. He has a lab at Caltech bearing his name.

He is an amazingly accomplished researcher.

I've posted this video on Orchid several times for various purposes.

Here, he makes many salient points, including:

we need psychiatric medications that are precise and do not affect the brain globally.
Additionally, we need to understand the specific biology of various components of these disorders --- because they don't always go together.

Translational medicine in Glial protection

12/31/2024

Val's Take/Conjecture

In 2013, the National Institute of Mental Health (NIMH) proclaimed the DSM 5 "lacked validity" because it was based on clusters of symptoms and not the underlying biology.
The American Psychiatric Association said, "Well, what is your alternative?"
NIMH said, "We'll get back to you on that."
Since then the basic research has exploded.
On the other hand, the Translational Research and Medicine perhaps predictably has lagged behind.
That is slowly starting to change.
Part of that is recognizing the glial protective aspects of current medications (which may not work for everyone) and
Pursuing Novel Therapeutic Medications and Approaches.

Regulation of Zbp1 by miR-99b-5p in microglia controls the development of schizophrenia-like symptoms in mice (2024)

The Janus face of antipsychotics in glial cells: Focus on glioprotection (2023).

"[C]onverging lines of evidence indicate that psychiatric disorders are commonly associated with the triad

neuroinflammation,
oxidative stress, and
excitotoxicity, and

that glial cells may contribute to the gliotoxicity process.

"Conversely, glioprotective molecules attenuate glial damage by generating specific responses that can protect glial cells themselves and/or neurons, resulting in improved central nervous system (CNS) functioning.

"In this regard, resveratrol is well-recognized as a glioprotective molecule, including in clinical studies of schizophrenia and autism."
"[C]onverging lines of evidence indicate that psychiatric disorders are commonly associated with the triad

neuroinflammation,
oxidative stress, and
excitotoxicity, and

that glial cells may contribute to the gliotoxicity process.

"Conversely, glioprotective molecules attenuate glial damage by generating specific responses that can protect glial cells themselves and/or neurons, resulting in improved central nervous system (CNS) functioning.

"In this regard, resveratrol is well-recognized as a glioprotective molecule, including in clinical studies of schizophrenia and autism." "[C]onverging lines of evidence indicate that psychiatric disorders are commonly associated with the triad

neuroinflammation,
oxidative stress, and
excitotoxicity, and

Microglia and cognitive impairment in schizophrenia: translating scientific progress into novel therapeutic interventions (2023).

Suicide in bipolar disorder patients is associated with hippocampal microglia activation and reduction of lymphocytes-activation gene 3 (LAG3) microglial checkpoint expression (2023).

Role of Microglial Modulation in Therapies for Perinatal Brain Injuries Leading to Neurodevelopmental Disorders (2024).

Editorial

Special Issue "Microglia Heterogeneity and Its Relevance for Translational Research" (2021)

Val's Take: One of the things that happened with NIMH and Researchers around the world: They started saying these neuro-developmental & psychiatric disorders are "BLURRED."

Since that time, it has become more obvious that there are common mechanisms in a range of CHRONIC DISEASE --- the actual "dysregulation" may be different --- but those new understandings are multiplying to benefit a range of illnesses.

Lead and Psychiatric Disorders

12/16/2024

Val's Take/Conjecture

"Lead" in gasoline in the 20th Century is currently being identified as a "CAUSE" of poor mental health.
At least at one point, Lead was identified with the Fall of the Roman Empire.
- I think most historians would identify a range of factors --- but "Lead" may come back in popularity as a factor with regard to the fall of ancient Rome.

To me when people say --- "Hey, I think this is a factor in mental health" ---- I think they are generally right.

To me, this is really about Developmental and After Acquired INFLAMMATION --- so it can be a lot of things and a lot of combinations of things.

There's realization in Medicine and Psychiatry for the need for INDIVIDUALIZED PRECISION MEDICINE.

20th Century Lead Exposure Damaged American Mental Health
Dec. 4, 2024

IT IS NOT JUST LEAD

There are any number of environmental toxins that can impair mental health.

The exposomeThe role of the exposome is to understand how the totality of an individual's exposures throughout the lifetime can impact human health.

Immune System Gene and Neurodevelopmental Disorders

11/29/2024

It's not intuitive, but the Immune System plays critical roles in Neuro-Developmental and Psychiatric Disorders. That has been highlighted in the last 10 to 15 years, and it is continuing to be corroborated.

This is transforming our understerstanding of Neuro-Developmental and Psychiatric Disorders.

Immune System Gene Linked to Hyperactivity, ADHD and Autism

Nov. 21, 2024
Duke University Study

from the one-man show of genetics to lots of cross-talk & a Cast of Thousands -----(actually a cast of Trillions)

11/29/2024

Val's Take/Conjecture

The Ancient Greeks had the "Four Humors" and Chinese Medicine has the "Five Elements."
- These conceptualizations are not necessarily stictly accurate.
- BUT they give people a way of understanding a monumentally complex biology --- that is within their grasp.
In 2013, Thomas Insel, head of the National Institute of Mental Health, said the DSM "lacks validity" --- and we'll be using it as our "DICTIONARY" --- until we can get something better. --- Hmmm . . . BUT it probably is going to take 20 to 30 years to flesh out something better that it based on the underlying biology rather than clusters of symtoms.
That is happening.

Professor Graham Rook
"We Are Ecosystems"

We are conceptualizing neurodevelopmental and psychiatric disorders as:

Developmental, in many cases as a result of Maternal Immune Activation
Involving:
- the Immune System
- the Central Nervous System
- the Endocrine System
- the Metabolism, and
- the Microbiome
It is a form of premature aging
Individuals often have processings differences that can confer benefits and challenges.

Endocrine cross-talk between the gut microbiome and glial cells in development and disease. 2021)

"Glial cells make up the major cellular component of the nervous system. Glial development is usually investigated through perturbations of host genetics, although non-host-derived signalling molecules can also regulate glial cells. ..."

Investigating the “two-hit hypothesis”: Effects of prenatal maternal immune activation and adolescent cannabis use on neurodevelopment in mice (2023)

Val's Take/Conjecture: I think Cannabis Use is an issue, BUT to me the larger issue is Secondary Inflammatory Hits during the lifetime.

People with psychiatric disorders are much more vulnerable to Long Haul Covid.

We know that childhood illnesses can be much more serious in Adults. For some people, that period in utero led to perhaps years worth of inflammation as compared to someone who did not experience Maternal Immune Activation.

The lifespan for people with psychiatric disorders is reduced.

Life expectancy and years of potential life lost in people with mental disorders: a systematic review and meta-analysis (2023)

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Translational Medicine Friday

New study shows adults with Autism Need More Support

Glial-Neuronal Networks & Neuro-Developmental & Psychiatric Disorders

"Resilience," The Immune System & "Second Hits"

Microglial TREM 2 Gene

Engineered Microglia and More

Addiction

Translational medicine in Glial protection

Lead and Psychiatric Disorders

Immune System Gene and Neurodevelopmental Disorders

from the one-man show of genetics to lots of cross-talk & a Cast of Thousands -----(actually a cast of Trillions)

Translational Medicine Friday

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