<![CDATA[Orchid Advocacy - Translational Medicine Friday]]>Fri, 17 May 2024 06:19:43 -0700Weebly<![CDATA[Maternal Immune activation, Mitochondria Dysfunction, Innate & adaptive Immunity, Epigenetics and Neuro-Developmental and Psychiatric disorders]]>Thu, 09 May 2024 15:07:09 GMThttps://orchidadvocacy.org/translational-medicine-friday/maternal-immune-activation-mitochondria-dysfunction-innate-adaptive-immunity-epigenetics-and-neuro-developmental-and-psychiatric-disordersVal's Note:  There is some important information here --- even if it's jumbled.

The main thing is to start thinking of other systems and processes than we are used to with regard to neuro-developmental & 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.
"In the near future, we might be able to replace chronological age with biological age, based on the epigenetic clock, with the promise of providing greater therapeutic benefits.

"A wide range of epigenetic drugs are currently under development at various stages.

"Although their full effectiveness is yet to be realized, they show great potential in the treatment of cancer, psychiatric disorders, and other complex diseases."
"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.
Energy Constraints on Brain Network Formation (2021)

Val's Take/Conjecture:  I think we could all benefit from eating a better diet, but I think the "hyper-connected brains" of people with neuro-developmental and psychiatric disorders are putting a big strain on the energy needs of the brain.

Unfortunately, this is often coupled with Mitochondrial Dysfunction that seems also to arise from Maternal Immune Activation.

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<![CDATA[Mitochondria dysfunction in Depression, Suicide, CANCER & Beyond]]>Tue, 07 May 2024 13:56:07 GMThttps://orchidadvocacy.org/translational-medicine-friday/mitochondria-dysfunction-in-depression-suicide-cancer-beyond
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.
Researchers around the world are focusing on Mitochondria.
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.
"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"
Naviaux Lab
 The story behind this is fascinating --- in seeking to address
"orphan" mitochondrial diseases that affect few people, Naviaux Lab and others discovered that the problem of mitochondrial dysfunction was actually shared across many disease and disorder categories.
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<![CDATA[Research Seems to be on the road to better understandingings]]>Sun, 21 Apr 2024 19:03:49 GMThttps://orchidadvocacy.org/translational-medicine-friday/research-seems-to-be-on-the-road-to-better-understandingings
Val's Take/Conjecture
  • These new understandings are not perfect --- but they are BETTER than what we've been using.
  • There is a lot to INTEGRATE -- and people are doing the work of that.
    • Generational Issues
    • Maternal Immune Activation
    • Mitochondrial Dysfunction
    • the Immune System
    • the Microbiome
    • the Endocrine System
    • Epigenetics
    • the Exposome
    • the Inflammasome
    • etc.
  • Mental Health has relied on some pretty sloppy analysis --- BUT they didn't really have anything else even if the logical problems were there --- for anyone brave enough to acknowledge them--
    • that is changing
    • More and more professionals know the status quo is not good enough.
[P]renatal activation of the maternal immune system has been connected with both increased risk of ASD [Autism Spectrum Disorder] and with mitochondrial dysfunction

It has been demonstrated that the mitochondria have a noteworthy relationship with the immune system, as they can impact the immune response and vice versa.
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<![CDATA[Mitochondria and Neuro-Developmental & Psychiatric disorders]]>Thu, 18 Apr 2024 20:15:04 GMThttps://orchidadvocacy.org/translational-medicine-friday/mitochondria-and-neuro-developmental-psychiatric-disorders
Val's Take/Conjecture
  • These are some big, important new understandings.
  • Neuro-Developmental & Psychiatric Disorders are NOT UNCOMMON in this society ---- maybe they have never been uncommon, but we had some ASSUMPTIONS that didn't pan out when it came to "intelligence," executive functioning, etc.
    • For some of us, this has been brutally hard.
  • Further, our hierarchies still protect some people from ever having to face the music.
  • Metabolomic biomarkers and other biomarkers, I think will ultimately be freeing and medically helpful and give us quite a different perspective on our social structures.
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<![CDATA[The World of MaTernal Immune Activation & EpigeneticS]]>Sat, 06 Apr 2024 22:06:45 GMThttps://orchidadvocacy.org/translational-medicine-friday/the-world-of-maternal-immune-activation-epigenetics
Val's Take/Conjecture
  • there is a LARGE DEVELOPMENTAL COMPONENT  to the Neuro-Developmental Psychiatric Continuum. 
  • It is focusing not so much on specific genes (although they may be important) as Maternal Immune Activation during Fetal Development.

BUT THAT IS NOT THE END OF THE STORY.

Epigenetics is playing a BIG ROLE on HIGHLY REACTIVE CELLS.

Additionally, Auto-Immune Diseases, especially Thyroid Disorders, affect a lot of people with "mental Illness" and EPIGENETICS is being viewed as a critical component in the understanding of Auto-Immune Diseases,
The epigenetics of autoimmunity | Cellular & Molecular Immunology (2011)
  1. Alterations in the post-translational modification of histones and DNA methylation are the two major epigenetic mechanisms that may potentially cause a breakdown of immune tolerance and the perpetuation of autoimmune diseases.
Epigenetics and ADHD: Reflections on Current Knowledge, Research Priorities and Translational Potential (2022)

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.

In this Current Opinion, we discuss the relevance of epigenetics (specifically DNA methylation) for ADHD research and clinical practice, starting with the current state of knowledge, what challenges we have yet to overcome, and what the future may hold in terms of methylation-based applications for personalized medicine in ADHD.
Additionally, people with "Autism" seem to be more at risk for Cancer, and cancer is more and more understood to have epigenetic components.
Epigenetics and Cancer - Introduction to Epigenetics (2021)
Alterations in chromatin function and epigenetic mechanisms are a hallmark of cancer. The disruption of epigenetic processes has been linked to altered gene expression and to cancer initiation and progression. Recent cancer genome sequencing projects revealed that numerous epigenetic regulators are frequently mutated in various cancers.
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<![CDATA[the new paradigm is getting stronger all the time]]>Sat, 06 Apr 2024 18:59:01 GMThttps://orchidadvocacy.org/translational-medicine-friday/the-new-paradigm-is-getting-stronger-all-the-time
Val's Take/Conjecture
  • The Normal Science of the DSM 5 is not worthless BUT it is not adequate to the task of our current mental health crisis and there are serious errors.
  • It became more and more apparent there was a lot we were missing:
    • Maternal Immune Activation
    • the Neuro-Developmental Psychiatric Continuum
    • Dysregulation of Multiple Systems of the Body, and
    • Mitochondrial Dysfunction.
From my perspective the EVIDENCE has been there well over a decade that Mental Health Clinical was on shaky ground.
On the other hand, there were no Interim Procedures and apart from someone like myself crying in the Colorado Wilderness, most professionals on all sides seem to be fine putting this Burden of Ignorance on very ill individuals.

That is UNETHICAL.

Neuroinflammation and Oxidative Stress in the Pathogenesis of Autism Spectrum Disorder (2023)
  • MIA [Maternal Immune Activation]  is one of the common environmental risk factors for the onset of ASD during pregnancy. It induces an immune reaction in the pregnant mother’s body, resulting in further inflammation and oxidative stress in the placenta and fetal brain.
Psychopathology of attention deficit/hyperactivity disorder: from an inflammatory perspective. (2022)
  • A growing body of evidence shows that maternal inflammatory status during pregnancy is associated with diagnosis of ADHD in the offspring, whereas oxidative stress, inflammatory biochemical markers and immune-mediated diseases have been observed in individuals with ADHD
Mitochondrial Oxidative Stress—A Causative Factor and Therapeutic Target in Many Diseases (2021)
The main source of free radicals responsible for oxidative stress is mitochondrial respiration. The deleterious effects of ROS [Reactive Oxygen Species] on cellular biomolecules, including DNA, is a well-known phenomenon that can disrupt mitochondrial function and contribute to cellular damage and death, and the subsequent development of various disease processes.
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<![CDATA[maternal Immune Activation and Mitochondria]]>Sat, 06 Apr 2024 02:12:59 GMThttps://orchidadvocacy.org/translational-medicine-friday/maternal-immune-activation-and-mitochondriaMaternal Inflammation During Pregnancy and Offspring Brain Development: The Role of Mitochondria (2022)
In summary, we argue that mitochondrial function is a promising mechanism through which MIA/inflammation during pregnancy can affect the risk for neurodevelopmental and psychiatric disorders.

Elucidating the role of mitochondria as a mediator of MIA-induced alterations in brain development and neurodevelopmental disease risk may not only provide new insight into the pathophysiology
of mental health disorders but may also offer new therapeutic targets

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<![CDATA[Metabolic aspects of mental health & Dietitians]]>Sun, 31 Mar 2024 00:59:34 GMThttps://orchidadvocacy.org/translational-medicine-friday/metabolic-aspects-of-mental-health-dietitians
Val's Take/Conjecture
  • I think as the "METABOLIC" aspects of Mental Health come more into focus there's going to be a need for Dieticians to provide specialized care.
  • One of the challenges of being "NEURO-DIVERSE" is sometimes what works for everyone else doesn't work for you.
  • This is also why BIOMARKERS are so important --- as opposed to subjective symptom clusters.  Of course, most mental health professionals are not relying on subjective symptom clusters because they want to.

  • A Ketogenic Diet is being promoted by Metabolic Mind and the Researchers at Harvard and other places for Bipolar Disorder, etc.
    • There are plenty of CAVEATS to that, even as people are experiencing a range of outcomes with current treatments.

Getting PERSONALIZED, INDIVIDUAL Dietary Advice and Monitoring is likely to be very important.
Mission

Provide resources and support which empower Behavioral Health Nutrition (BHN) Members to excel in the areas of addictions, eating disorders, intellectual and developmental disabilities, mental health.

Vision

Optimize the physical and cognitive health of those we serve through nutrition education and behavioral health counseling.
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<![CDATA[FAT Metabolism and ATP Production]]>Sun, 24 Mar 2024 23:11:23 GMThttps://orchidadvocacy.org/translational-medicine-friday/fat-metabolism-and-atp-production
Today Show
How Following the Keto Diet Improved this Man's Mental Health

SIGNIFICANTLY, no one is claiming a Keto Diet is a CURE-ALL.

But there are reasons to believe it could help address some of the METABOLIC ASPECTS of Mental Illness.  Keto is lower carbs, high fat and moderate protein.

Fat can lead to greater ATP Production.  Is it heart healthy, maybe not.

People with Mental Illness are often faced with various "CATCH-22s" when it comes to treatment.
Metabolic Mind --- Feb. 22, 2024
New Harvard Study Explores Brain Energy Metabolism in Bipolar Disorder
Fatty acid metabolism consists of various metabolic processes involving or closely related to fatty acids, a family of molecules classified within the lipid macronutrient category. These processes can mainly be divided into (1) catabolic processes that generate energy and (2) anabolic processes where they serve as building blocks for other compounds.  
In catabolism, fatty acids are metabolized to produce energy, mainly in the form of adenosine triphosphate (ATP). When compared to other macronutrient classes (carbohydrates and protein), fatty acids yield the most ATP on an energy per gram basis, when they are completely oxidized to CO2 and water by beta oxidation and the citric acid cycle.[2] Fatty acids (mainly in the form of triglycerides) are therefore the foremost storage form of fuel in most animals, and to a lesser extent in plants.  

In anabolism, intact fatty acids are important precursors to triglycerides, phospholipids, second messengers, hormones and ketone bodies. For example, phospholipids form the phospholipid bilayers out of which all the membranes of the cell are constructed from fatty acids. Phospholipids comprise the plasma membrane and other membranes that enclose all the organelles within the cells, such as the nucleus, the mitochondria, endoplasmic reticulum, and the Golgi apparatus. In another type of anabolism, fatty acids are modified to form other compounds such as second messengers and local hormones. The prostaglandins made from arachidonic acid stored in the cell membrane are probably the best-known of these local hormones.

------Wikipedia
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<![CDATA[ATP, Parkinson's and the neuro-developmental/Psychiatric continuum]]>Fri, 15 Mar 2024 22:24:57 GMThttps://orchidadvocacy.org/translational-medicine-friday/atp-parkinsons-and-the-neuro-developmentalpsychiatric-continuum
"The use of oxygen enables a net production of 38 molecules of ATP from one molecule of glucose. Without oxygen, net production is only 2 molecules of ATP.

Because oxygen-requiring reactions (aerobic metabolism) take place only in the mitochondria, it’s clearly advantageous in terms of energy production for cells to contain mitochondria."

Reference:
11.6: Aerobic Metabolism and the Mitochondria - Medicine ...
Parkinson's Disease in now being viewed as a failure to produce ATP.

  • "ATP is essential in human activities and health. We hypothesize that maintaining ATP levels may help to preserve vulnerable brain cells in neurodegenerative diseases like Parkinson's disease (PD). For this purpose, we developed and tested two types of chemical compounds, one for limiting ATP consumption and the other for enhancing ATP production."
ATP Maintenance via Two Types of ATP Regulators ... - ScienceDirect

Parkinson's is interesting because we think of it as a disorder of mobility, but it also has PSYCHIATRIC SYMPTOMS.
Psychiatric Symptoms Associated With Parkinson Disease

Many nonmotor aspects of PD, including depression, drug-induced psychosis and impulse control disorders, cognitive impairment, anxiety, and sleep disturbances, are common and are associated with a variety of poor outcomes. 2 These nonmotor symptoms complicate the clinical management of the disorder and are significant determinants of poor quality of life for patients and their caregivers. 3
Are hallucinations a symptom of Parkinson's disease?
  • Hallucinations and delusions are potential complications of Parkinson’s disease (PD). They may be severe enough to be classified as PD psychosis. Hallucinations are perceptions that aren’t really there. Delusions are beliefs that aren’t based in reality. One example is paranoia that persists even when a person is presented with contrary evidence.
Parkinson’s Hallucinations: Delusions and More - Healthline
Currently we estimate the "normal" Brain uses 20% of the oxygen of the body --- the brain uses more oxygen than any other organ of the body.
AUTISM

Autism Spectrum Disorders: The Mitochondria Connection

ourworldandautism.com
Why are Autistic People So Tired? Exploring Fatigue in Autism


Sep 21, 2023 · Fatigue in autism can be caused by sleep problems, such as difficulties falling asleep or staying asleep. Additionally, sensory overwhelm, which is common in autism, can lead to

ADHD

Response variability in Attention-Deficit/Hyperactivity ...

"The immediate effects of deficient ATP production and slow restoration of ionic gradients across membranes of rapidly firing neurons have implications for daily functioning: For individuals with ADHD, performance efficacy would be enhanced if repetitive and lengthy effortful tasks were segmented to reduce concurrent demands for speed and accuracy of response (introduction of breaks into lengthy/effortful activities such as examinations, motorway driving, assembly-line production)."

www.verywellhealth.com › adhd-fatigue-8407263ADHD Fatigue: Understanding the Connection - Verywell Health
Jan 4, 2024 · Fatigue is a common symptom in those with ADHD. Fatigue often brings tiredness and stress and can lead to burnout. Though the exact cause can be unknown and vary from person
MOOD DISORDERS

More recent studies showed that a decrease in the astrocytic release of ATP in the prefrontal cortex and hippocampus is a major cause of mood disorders. It is an attractive hypothesis that compensatory increases in P2X7Rs in these areas of the brain are the immediate actuators of MD and BD.
www.frontiersin.org › articles › 10Frontiers | Pathological ATPergic Signaling in Major ...

www.ncbi.nlm.nih.gov › pmc › articles
The relationship between fatigue and psychiatric disorders ...
(2009)


Fatigue and psychiatric disorders frequently occur comorbidly and share similar phenomenological features. There has been debate as to whether chronic fatigue, or neurasthenia, should be
SCHIZOPHRENIA

www.ncbi.nlm.nih.gov › pmc › articles
Schizophrenia as metabolic disease. What are the causes?

Jan 19, 2023 · Purigenic signaling as a mechanism is Schizophrenia. ATP and adenosine work as neurotransmitters. ATP plays the role of the excitatory transmitter, while adenosine plays the


trialsjournal.biomedcentral.com › articles › 10Assessment of the efficacy of a fatigue management therapy in ...
Sep 17, 2020 · First, lack of energy, one of the main characteristics of fatigue, is frequently encountered in individuals with schizophrenia. Second, fatigue is a common and severe symptom
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