Welcome To Orchid Advocacy

PREVIEW:  Translational Medicine Friday

Maternal Immune activation, Mitochondria Dysfunction, Innate & adaptive Immunity, Epigenetics

and Neuro-Developmental and Psychiatric disorders

The epigenetic encoded memory of the innate immune system (2020)

How do innate immune cells affect epigenetic changes?
  • Stimulation or infection of innate immune cells induces profound epigenetic changes, including the induction of histone modifications and alterations in DNA methylation levels.

Mitochondrial dysfunction as a trigger of innate immune responses and inflammation (2017)
  • Much research on mitochondrial control of immunity now centers on understanding how mitochondrial constituents released during cellular damage simulate the innate immune system.
  • When mitochondrial integrity is compromised, mitochondrial damage-associated molecular patterns engage pattern recognition receptors, trigger inflammation, and promote pathology in an expanding list of diseases.
 
Epigenetics and the Adaptive Immune Response (2013)

" Cells of the adaptive immune response undergo dynamic epigenetic changes as they develop and respond to immune challenge.

"Plasticity is a necessary prerequisite for the chromosomal dynamics of lineage specification, development, and the immune effector function of the mature cell types."
Mitochondrial dysfunction in psychiatric disorders (2022)

"Growing evidence indicates that mitochondrial function plays an important role in developing psychiatric disorders."

And Mitochondrial dysfunction also plays an important role in other deseases:
Mitochondrial dysfunction and psychiatric disorders (2009)
  • Damage to the mitochondrial electron transport chain has been suggested to be an important factor in the pathogenesis of a range of psychiatric disorders.
  • Tissues with high energy demands, such as the brain, contain a large number of mitochondria, being therefore more susceptible to reduction of the aerobic metabolism.-
  • Mitochondrial dysfunction results from alterations in biochemical cascade and the damage to the mitochondrial electron transport chain has been suggested to be an important factor in the pathogenesis of a range of neuropsychiatric disorders, such as bipolar disorder, depression and schizophrenia.
More Later Today


Epigenetics and ADHD: Reflections on Current Knowledge, Research Priorities and Translational Potential (2022)

"Attention-deficit/hyperactivity disorder (ADHD) is a common and debilitating neurodevelopmental disorder influenced by both genetic and environmental factors, typically identified in the school-age years but hypothesized to have developmental origins beginning in utero."

. . .

"Epigenetic processes that regulate gene expression, such as DNA methylation, have emerged as a promising molecular system in the search for both biomarkers and mechanisms to address this
challenge. "
Epigenetic mechanism of SETDB1 in brain: implications for neuropsychiatric disorders (2020)

Neuropsychiatric disorders are a collective of cerebral conditions with a multifactorial and polygenetic etiology.

Dysregulation of epigenetic profiles in the brain is considered to play a critical role in the development of neuropsychiatric disorders.

SET domain, bifurcate 1 (SETDB1), functioning as a histone H3K9 specific methyltransferase, is not only critically involved in transcriptional silencing and local heterochromatin formation, but also affects genome-wide neuronal epigenetic profiles and is essential for 3D genome integrity.

Here, we provide a review of recent advances towards understanding the role of SETDB1 in the central nervous system during early neurodevelopment as well as in the adult brain, with a particular focus on studies that link its functions to neuropsychiatric disorders and related behavioral changes, and the exploration of novel therapeutic strategies targeting SETDB1.

Preview:  Neuro-diversity Wednesday

Mitochondria, Fatigue and chronic Homelessness

Val's Take
  • It's the extreme, sensational aspects of Neuro-Diversity that make the news.
  • The low grade fatigue and/or mild to moderate executive functioning challenges have until recently flown under the radar.---
  • What we may see is the person has a hard time holding a job or with relationships --- and maybe they need some motivational interviewing.
  • Mental Health didn't get everything wrong, but they got a lot wrong and that is why it is so important to bring these new understandings to the forefront.
  • These new understandings will get us out of Mental Health America's --- STAGE 4 DIAGNOSIS.
ADHD Fatigue: Understanding the Connection (2024)


Our World And Autism

Why are Autistic People So Tired? Exploring Fatigue in Autism (2023)
Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders (2010)

"For many years, a deficiency of monoamines including serotonin has been the prevailing hypothesis on depression, yet research has failed to confirm consistent relations between brain serotonin and depression.

"High degrees of overlapping comorbidities and common drug efficacies suggest that depression is one of a family of related conditions sometimes referred to as the "affective spectrum disorders", and variably including migraine, irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia and generalized anxiety disorder, among many others."
The relationship between fatigue and psychiatric disorders: Evidence for the concept of neurasthenia (2009)    

"Previous cross-sectional studies have demonstrated a close association between chronic fatigue and psychiatric disorders .

"Up to two thirds of people reporting fatigue lasting longer than 6 months will also be suffering from a comorbid psychiatric disorder."
TedxTalk: 
Solving the Housing Crisis for Neurodiverse Adults
Lyric Rivera --- Neurodivergent Rebel
Stop Asking Neurodivergent People to Keep A Neurotypical Pace at Work
CBS Colorado
Denver Councilwoman Shontel Lewis calling for more accountability at newest homeless shelter
In Schizophrenia, Chronic Fatigue Syndrome- and Fibromyalgia-Like Symptoms are Driven by Breakdown of the Paracellular Pathway with Increased Zonulin and Immune Activation-Associated Neurotoxicity (2023)

Mitochondria dysfunction and it's relation to other systems of the body

[this does implicate the neuro-developmental/psychiatric continuum --- it also implicates other chronic Diseases, Auto-immune disorders and neuro-degenerative diseases]

Draft 2

Researchers around the world are focusing on Mitochondria.
Mitochondrial Dysfunction:  A Fatal Blow in Depression  (2023)

Affiliations
  • 1 Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
  • 2 Cancer Center of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
  • 3 Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China; Key Laboratory of Vascular Aging (HUST), Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Hubei, China.
Picture
"In most cells, mitochondria (green) form complex tubular networks that help them distribute energy throughout the cell. Disruption of these mitochondrial networks is a hallmark of many human diseases"

Blood Testing Identifies Biomarkers of Suicidal Thoughts (2023)

UC San Diego study

One of the things that Orchid is committed to is a "ROOT CAUSE ANALYSIS."

Much of the Neuro-Developmental / Psychiatric Continnuum appears to begin with Maternal Immune Activation and Mitochondrial Dysfunction ----
  • and that in turn has many cascading effects over the lifespan.
  • including dysfunction of mitochondria in T-Cells which appears to lead to greater deterioration that would generally be associated with age.

So there "may" be some pre-mature aging as the result of maternal immune activation..

Honing in on Mitochondria Dysfunction appears to be a key to Integrating Developmental, Physical and Mental Health.

Many physical health issues have psychiatric symptoms and many mental health issues do have physical symptoms.
Maternal Immune Activation and Neuropsychiatric Illness: A Translational Research Perspective (2018)


Epidemiologic studies, including prospective birth cohort investigations, have implicated maternal immune activation in the etiology of neuropsychiatric disorders.

Maternal infectious pathogens and inflammation are plausible risk factors for these outcomes and have been associated with schizophrenia, autism spectrum disorder, and bipolar disorder.
The Significance of Mitochondrial Dysfunction in Cancer (2020)

Val's Tables

FEATURED

Significant Reports

Gene-Based Therapy Restores Cellular Development and Function in Brain Cells From People With Timothy Syndrome
"Our study showed that we can correct cellular deficits associated with Timothy syndrome," said Dr. Pasca.

"We are now actively working towards translating these findings into the clinic, bringing hope that one day we may have an effective treatment for this devastating neurodevelopmental disorder."

KOAA 5

Colorado Mental Health Institute at Pueblo (CMHIP) operating with 1/2 its psychologists positions
Learn More
Val's Note:  The Staffing Problems at CMHIP are long standing and resulted in the Neiberger decision some twenty years ago.

It's our opinion that Pueblo is not a good place to staff a large mental health institute.

Colorado should keep what it can staff in Pueblo and probably move the rest to Ft. Logan in Denver.


GUEST OPINION: Public safety, justice, and mental health

As a state, our lack of behavioral health resources hurts a lot of people and makes our communities less safe.

This crisis requires an immediate and thorough response that the Legislature must address.

Contributors: District Attorney Michael Dougherty (20th JD), District Attorney Michael J. Allen (4th JD), District Attorney John Kellner (18th JD), District Attorney Brian Mason (17th JD).
Learn More
Val's Note:
  • Measurable Goals
  • Reasonable Time Frames, &
  • Funding to Support the Plan

If Colorado would comply with the 1999 US Supreme Court Olmstead decision --- it would probably help.

What's New

Olmstead Condensed
Mitochondria Dysfunction and Neuro-Developmental & Psychiatric Disorders
Intelligence as a Symptom