<![CDATA[Orchid Advocacy - Translational Medicine Friday]]>Mon, 16 Dec 2024 06:17:49 -0800Weebly<![CDATA[Immune System Gene and Neurodevelopmental Disorders]]>Sat, 30 Nov 2024 01:56:29 GMThttps://orchidadvocacy.org/translational-medicine-friday/immune-system-gene-and-neurodevelopmental-disorders
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
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<![CDATA[from the one-man show of genetics to lots of cross-talk & a Cast of Thousands -----(actually a cast of Trillions)]]>Sat, 30 Nov 2024 00:07:54 GMThttps://orchidadvocacy.org/translational-medicine-friday/from-the-one-man-show-of-genetics-to-lots-of-cross-talk-a-cast-of-thousands-actually-a-cast-of-trillions
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.
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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. ..."
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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.
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<![CDATA[Major Paradigm shifts:  ​Maternal immune Activation, Microglia (& other glia) & Human Endogenous Retro Viruses]]>Wed, 27 Nov 2024 23:00:49 GMThttps://orchidadvocacy.org/translational-medicine-friday/major-paradigm-shifts-maternal-immune-activation-microglia-other-glia-human-endogenous-retro-viruses
Val's Take/Conjecture
  • The Immune Connection to the Neuro-Developmental/Psychiatric Disorder Continuum is HUGE.
  • It is also COMPLICATED --- we're talking about something that begins IN UTERO and continues with:
    • ​molecular "CROSSTALK", as well as
    • DYSREGULATION of MOLECULAR PATHWAYS
  • ​"Microglia" --- immune cells in the brain are also associated with "emotional regulation."
Ancient Viruses Linked to Mental Illness (2024)​

New research led by King's College London has found that thousands of DNA sequences originating from ancient viral infections are expressed in the brain, with some contributing to susceptibility for psychiatric disorders such as schizophrenia, bipolar disorder, and depression.  
Moreover, growing evidence supports the involvement of HERVs (Human Endogenous Retro Viruses) in neurodevelopmental disorders, such as autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and schizophrenia (SCZ) .
​"MIA alters placental and fetal expression of endogenous retroviral elements. MIA-induced alterations in endogenous retrovirus expression persist into adulthood. Differential expression of endogenous retroviruses defines MIA subgroups."
Val's Take:  There is a gulf between Researchers and US Clinicians.

I think that had been there for awhile but the 2013  "invalid" DSM 5 sanctioned gross incompetence in a public way.

England is probably 10 or 20 years ahead of us in understanding the Immune Connection to Psychiatric Disorders.

I do think the proprietary nature of the American Psychiatric Association is in part to blame for incompetence in the US Mental Health Profession.
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<![CDATA[The complicated domino effects of Maternal Immune Activation]]>Wed, 27 Nov 2024 20:27:04 GMThttps://orchidadvocacy.org/translational-medicine-friday/the-complicated-domino-effects-of-maternal-immune-activation
Val's Take/Conjecture
  • There are several factors that can result in Maternal Immune Activation (MIA).
  • MIA is associated with Neuro-Developmental and Psychiatric Disorders in the Child.
    • Why is that?
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Influence of Immune System Abnormalities Caused by Maternal Immune Activation in the Postnatal Period  (2023)

"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 activatio …"
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"Evidence from human and animal studies indicates that maternal immune activation programmes the
fetal brain and immune system through inflammatory and
epigenetic mechanisms during key periods
  • of CNS [Central Nervous System],
  • microglial and
  • immune system development, and
  • colonization of gut microbiota."
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Mid-pregnancy maternal immune activation increases Pax6-positive and Tbr2-positive neural progenitor cells and causes integrated stress response in the fetal brain in a mouse model of maternal viral infection (2021)

​"Mid-pregancy maternal immune
activation increases Pax6-positive and Tbr2-positive neural progenitor cells and causes integrated stress response in the fetal brain in a mouse model of . . ."
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Paliperidone Reversion of Maternal Immune
Activation-Induced Changes on Brain Serotonin and Kynurenine Pathways
 
​(2021)


"Inflammation can alter the metabolism of tryptophan through the oxidative kynurenine pathway to compounds with neurotoxic and neuroprotective activity and compromise serotonin (5-HT) synthesis. Here we investigate the role of serotonergic and kynurenine …"
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Maternal Immune Activation Disrupts Dopamine System in the Offspring (2016) 

"
Our study, the first to combine electrophysiological and microdialysis experiments on the dopamine system in a maternal immune activation model of schizophrenia, reveals that . . ."
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Dysregulation of immune and metabolism pathways in maternal  (2023)

"
Maternal immune activation regulates the dysregulation of four key risk KEGG pathways related to immunity, metabolism, and nervous system leading to abnormal embryonic . . ."
Val's Take
  • Compared to where we have been in our knowledge of the Neuro-Developmental/Psychiatric Continuum ---
  • Researchers around the world are providing a COHERENT UNDERSTANDING with a LEVEL of DETAIL that is MIND-BLOWING.
  • Neuro-Transmitters like Serotonin and Dopamine are still there ---- BUT the Context and Complexity has been expanded Exponentially.
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<![CDATA[Astrocytes -- Another Glial Cell involved with the Neuro-Developmental / Psychiatric Continuum]]>Wed, 27 Nov 2024 19:29:14 GMThttps://orchidadvocacy.org/translational-medicine-friday/astrocytes-another-glial-cell-involved-with-the-neuro-developmental-psychiatric-continuum
Val's Take/Conjecture
  • introducing "ASTROCYTES." -- another Glial Cell associated with the Immune response and Neuro-Developmental & Psychiatric Disorders.
Almost a century ago, Julius Wagner-Jauregg first reported the impact of immunological disturbance on psychological function.

This finding stirred up researchers' enthusiasm about bidirectional communication between immunological dysfunction and mental disorders.

To date, understanding the etiology of mental disorders, such as schizophrenia, autism spectrum disorder, anxiety disorder, as well as mood disorders, is one of the most actively explored topics in immunology.
We're starting to get more than a rough idea about what is going on with the Neuro-Developmental/Psychiatric Continuum:
  • It often starts in utero with Maternal Immune Activation (MIA).
  • That MIA dysregulates Microglia in the yok-sak in the placenta.
    • Microglia are innate immune cells in the brain.
  • This ultimately leads to abnormal development of neurons.
  • Additionally, other glial cells seem to create abnormal "myelation" of the neurons.
    • To me that sounds very much like Multiple Sclerosis.
    • One of the things I heard a researcher say a few years ---- the Immune System seemed to be involved with psychiatric disorders but it wasn't a classic autoimmune disease.
    • On the other hand, some MIA is the result of mom's auto-immune disease and people on the Neuro-Developmental/Psychiatric Continuum do have autoimmune diseases such as Thyroid Disorders.
  • Really understanding that we are talking about Developmental Disorders that involve multiple systems of the body and a BIG DRIVER is the IMMUNE SYSTEM is the key to real PROGRESS.
Astrocyte involvement in metabolic regulation and disease (2024)

​Val's Take:  Astrocytes are involved with thyroid disorders --- and those are very common among people with psychiatric disorders.
See Also:
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<![CDATA[Post-traumatic Stress Disorder and --- the Immune system]]>Wed, 27 Nov 2024 17:33:41 GMThttps://orchidadvocacy.org/translational-medicine-friday/post-traumatic-stress-disorder-and-the-immune-system
Val's Take/Conjecture
  • I remember by Father-in-Law Dick Bayles, Jr. -- was part of the force that liberated Dachau.
  • He was also quite fond of saying, "No kiddin' when confronted with some true but unlikely statement.
  • To me that is very much the situation when it comes to the large role of the immune system and various forms of the Neuro-Developmental/ Psychiatric Continuum.
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<![CDATA[T-Cells, Anxiety, Anger & Aggression]]>Tue, 26 Nov 2024 22:29:23 GMThttps://orchidadvocacy.org/translational-medicine-friday/t-cells-anxiety-anger-aggression
Brain Foundation/ Kalil Alves de Lima, Washington University (2020)
T cells regulate anxiety-like behavior
Maternal Immune Activation is often associated with anxiety in offspring.

T-Cells are immune cells and the video below argues that T-Cells regulate anxiety-like behavior.  

One of the big challenges of "anxiety" is that it is often associated with anger and aggression in animals and humans.

Most people mask  anger and aggression as much as possible and they are not involved in the criminal justice system.  Many people in the criminal justice system are dealing with high levels of anxiety.

If we addressed T-Cell issues in people in the Criminal Justice System, could that help?
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<![CDATA[​Exploring Biomarker Technology to Enhance the Diagnosis and Treatment of PTSD in Justice-Involved Veterans -- 2024]]>Mon, 25 Nov 2024 20:23:44 GMThttps://orchidadvocacy.org/translational-medicine-friday/exploring-biomarker-technology-to-enhance-the-diagnosis-and-treatment-of-ptsd-in-justice-involved-veterans-2024
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Click Image to go to Article
Val's Take/Conjecture

​We are starting to get Biomarkers in Mental Health.

Metabolomic Biomarker Signatures for Bipolar and Unipolar Depression -- JAMA Psychiatry 2023.

Biomarkers are desperately needed in Criminal Justice.

Clinicians have tried to exercise the best judgement they could --- it is subjective.

Researchers are working to provide those ALTERNATIVES.

Not only that they are putting forth Major Paradigm Shifts in our understanding of neuro-developmental & psychiatric disorders.

Those paradigm shifts include in utero maternal immune activation and dysregulation of the immune system, the central nervous system, the metabolism, the endocrine system and the microbiome.
  • Researchers are building out a much more complete understanding of what is going on in the neuro-developmental/psychiatric continuum.
  • This has the potential to transform Mental Health Practice and get the many stakeholders on the same page.

What's important about the Council on Criminal Justice article --- this major, mainstream organization seems to appreciate the important need to move to biomarkers even if we're not quite there yet.
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<![CDATA[Keto diet, Mental Illness, Metabolic Disregulation and Microglia]]>Wed, 20 Nov 2024 11:54:23 GMThttps://orchidadvocacy.org/translational-medicine-friday/keto-diet-mental-illness-metabolic-disregulation-and-microglia
The Metabolic Mind folks have gone to great lengths to provide a nuanced view of Keto and in fact recommending "Medical Keto."

That is important because "Keto" can be an extremely unhealthy diet.

Unfortunately, "Medical Keto" is not available to most people with mental illness --- something the Metabolic Mind folks are aware of.

One of the things that really helped me understand one of the benefits of Keto --- a study found Keto could improve Microglia functioning.

I would love to have access to Medical Keto.

On the other hand, human beings have been trying to use Highly Prescriptive Diets for EONS to manage their physical and mental health.

For people on the Neuro-Developmental/Psychiatric Continuum ---- we're really talking about "DEVELOPMENTAL HEALTH."

Further, "Metabolic Dysregulation" can be another feature of Maternal Immune Activation.

Theoretically "Medical Keto" could be a safe option for people to access.  I'm a big proponent of that.

On the other hand, I'm also greatly interested in the development of treatments that more directly address dysregulated microglia than KETO.
But repair and replacement of Microglia may be down the road and researved for the most serious brain injuries at least initially.
Metabolic Mind
​Who should use Keto for Mental Illness?
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<![CDATA[In Born errors in Metabolism]]>Sun, 20 Oct 2024 21:32:44 GMThttps://orchidadvocacy.org/translational-medicine-friday/in-born-errors-in-metabolism
Val's Take/Conjecture
  • We tend to have a view that traits are either the result of GENETICS or LIFESTYLE CHOICES.
  • That is a FALSE DICHOTOMY.
  • Many Neuro-Divergent People are evidence that PRE-NATAL INFLAMMATION as well as other factors can have dramatic influence over the life course.
  • Further, our researchers are doing the heavy lifting of understanding multiple systems of the body and the "CROSSTALK" between those systems of the body that are relevant to our most difficult chronic diseases.
    • This includes the Neurodevelopmental/Psychiatric Continuum, but it also includes:
    • Autoimmune Diseases
    • Cancer,
    • Neuro-Degenerative Diseases,
    • Etc.
Microglia and lipids: how metabolism controls brain innate immunity (2021)

In the last years, single-cell analyses have revealed that microglia exhibit diverse phenotypes during development, growth and disease. Emerging evidence suggests that such phenotype transitions are mediated by reprogramming of cell metabolism. Indeed, metabolic …
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