Blog Posts

Mitochondrial DNA CoPy Number in Neuro-Developmental & Psychiatric Disorders -----Cellular Aging

6/13/2024

Val's Take

Mitochondrial DNA plays a role in many chronic illnesses.
It is less clear if Mitochondrial DNA Copy Number can serve as a biomarker in any or some of these chronic diseases.
Many researchers are devoted to addressing these questions throughout medicine, including neuro-developmental and psychiatric disorders, cardio-vascular issues, auto-immune issues, cancer, etc.
Additionally, many of these other illnesses and disorders can have psychiatric symptoms and neuro-developmental and psychiatric disorders often do involve some aspect of fatigue.

Telomere length and mitochondrial DNA copy number in bipolar disorder: identification of a subgroup of young individuals with accelerated cellular aging (2022)

Association between mitochondrial DNA levels and depression: a systematic review and meta-analysis (2023)

Mitochondrial DNA copy number in autism spectrum disorder and attention deficit hyperactivity disorder: a systematic review and meta-analysis (2023)

Leukocyte mitochondrial DNA copy number in schizophrenia (2020)

Cells dispose of cytoplasmic mitochondrial DNA by nucleoid-phagy (May 2024)

Mitochondrial damage in stress conditions results in the release of mitochondrial DNA (mtDNA), causing inflammation that is linked to various diseases.

We discovered a mechanism for the elimination of this harmful mtDNA — ‘nucleoid-phagy’.

Targeting this process represents another way to treat mitochondrial damage-related diseases.

Inflammation and mitophagy are mitochondrial checkpoints to aging (April 2024)

Cellular and organismal aging have been consistently associated with mitochondrial dysfunction and inflammation.

Accumulating evidence indicates that aging-related inflammatory responses are mechanistically linked to compromised mitochondrial integrity coupled with mtDNA-driven CGAS activation, a process that is tonically inhibited by mitophagy.

Faulty DNA disposal system causes inflammation (Feb. 2024)

"Salk scientists outline mouse cell inflammation pathway from mitochondrial stress to leaking endosomes to immune system initiation, revealing new potential therapeutic targets to reduce inflammation in aging and disease."

Mitochondrial DNA Copy Number as a Biomarker of Multiple Sclerosis (2023)

Mitochondrial DNA copy number and lung cancer risk in a prospective cohort study (2010)

Connecting the Dots: Maternal immune activation, Neuro-Developmental Disorders and Chronic Disease

6/11/2024

Val's Take: We are connecting the dots among Neuro-Diverse "categories" --- we're also connecting the dots of Chronic Disease including autoimmune disorders and cancer with Neuro-Diversity.

JAMA: More Evidence Linking Autoimmune Diseases to ADHD (2021)
The evidence for bidirectional links between the immune system and the central nervous system has accumulated over the last few decades.

Down Syndrome Is an Immune Disorder (2018)
Researchers from the University of Colorado School of Medicine are conducting breakthrough research indicating that Down syndrome could be considered a disorder of the immune system. The findings announced in the journals eLife and Scientific Reports are a significant development in understanding Down syndrome.

Immune synaptopathies: how maternal immune activation impacts synaptic function during development (2023)

Genomic Medicine: Neurodevelopmental disorders and cancer networks share pathways, but differ in mechanisms, signaling strength, and outcome (2023)
Epidemiological studies suggest that individuals with neurodevelopmental disorders (NDDs) are more prone to develop certain types of cancer. Notably, however, the case statistics can be impacted by late discovery of cancer in individuals afflicted with NDDs, such as intellectual disorders, autism, and schizophrenia, which may bias the numbers.

Kings College London
Thinking Twice About ADHD & Autism Spectrum Disorder

Ehlers Danlos Society / Jane Green
2023 Connecting The Dots between Autism, ADHD, Dyspraxia and EDS (Ehlers Danlos Syndromes) and HSD (Hypermobility Spectrum Disorders)

Selective Timing of Maternal Immune Activation Alters Developmental Milestones, Behavior, and Blood-Brain Barrier Integrity (May 2024)

***Physical Health Issues, the Immune System & Mental Health Index

Science Up

New Science Is Amazing and It has Huge Moral Implications NOW

Mental Health Is going to have to change a whole lot to be effective --- a big part of that is appreciating the large role of the immune system in mental & brain disorders

New Research & Changing Paradigms raise tough questions

5/28/2024

Val's Take/Conjecture

A lot of people got BLIND-SIDED by serious Psychiatric Disorders or Neuro-Developmental Disorders in Adulthood.
- When we're not using any kind of bio-marker that can happen quite frequently.
Paradigms are shifting and if we truly understand the ramifications of those shifts --- it may very well feel like the world has changed.

Once you get to the point of Mitochondrial Dysfunction as it relates to illness and aging, including neuro-developmental and psychiatric disorders---- you are pretty far from the DSM 5.

A lot of researchers are pretty far from the DSM 5.
If we want clinicians and policymakers to catch-up -- we have to provide the SUPPORT for that.

Mental Health Systems and Criminal Justice Systems are inter-dependent. If we have Mental Health Systems that are significantly behind the research --- we're going to have Criminal Justice Systems that are significantly behind the research.

What jumps out to me in the research is the need to understand:

The Neuro-Developmental/Psyschiatric Disorder Continuum and the ramifications of that, including Maternal Immune Activation and Epigenetics
Mitochondrial Dysfunction
Dysregulation of Multiple Systems of the Body, including
- Innate and Adaptive Immunity
- The Microbiome, and
- The Endocrine System

Mitochondria: A Unifying Link for Psychiatric Illness (2024)

In the past few years, as researchers have begun measuring such factors, more and more preclinical and clinical studies have reported abnormalities in brain energy metabolism, electron activity, and genes associated with mitochondrial functions in stress-related disorders, anxiety, depression, bipolar, schizophrenia, and autism spectrum disorders.

Val's Take: Mitochondria is not just arising as a unifying link for psychiatric illness but for illness and aging in general.

For people with neuro-developmental disorders and/or psychiatric disorders -- Maternal Immune Activation and Epigenetics over the lifespan appear to account for Mitochondrial Dysfunction in many cases.

This does include "psychological stress" but it is more than that.

Erechtheion in Athens
A Symbol of Support in Western Civilization

Draft Mitochondria and Neuro-Developmental & Psychiatric Disorders

Neuro-developmental & Psychiatric Disorders as forms of premature aging

5/22/2024

Val's Take/Conjecture

We have worked our way to some fundamental questions regarding chronic illness.
To me, the Maternal Immune Activation that is often characteristic of Neuro-Developmental and Psychiatric Disorders is a form of pre-mature aging.
- which is not normally how we think of it --- the person needs better coping skills.
- the person is acting "immaturely"

The study above says we should be looking for the beginnings of Alzheimer's in younger people and I think the research supports going back in utero.
Some researchers are actually saying that we need to understand the GENERATIONAL ASPECTS of Maternal Immune Activation.
- Transgenerational Sex-dependent Disruption of Dopamine Function Induced by Maternal Immune Activation (2022)

Antecedent ADHD, dementia, and metabolic dysregulation: A U.S. based cohort analysis (2018)

Neuroimmune nexus of depression and dementia: Shared mechanisms and therapeutic targets (2019)

Mitochondrial Boost Reverses Protein Clumping in Aging and Alzheimer’s (2024)

Neurodevelopmental and Neurodegenerative Illnesses: Autism, Fragile X Syndrome, Parkinson's Disease, and Dementia (2022)

The Complex Link Between Schizophrenia and Dementia: Targeting Ca2+/cAMP Signalling (2020)

Bipolar disorder and frontotemporal dementia: A systematic review (2021)

More reactive cells and energy issues

5/21/2024

Val's Take/ Conjecture

One of the things that CMS did was they partnered with the National Institute of Mental Health for protocols to treat First Episode Psychosis.
It would be good for CMS to partner with the National Institute of Mental Health on addressing energy issues in Neuro-Developmental and Psychiatric Disorders.
It would be good for HUD to partner with states to provide housing for people with neuro-developmental disorders, psychiatric disorders and brain injury who are at risk of institutionalization such as is inherent in homelessness.

See also:

Arizona College of Medicine

The Epigenetics of Homelessness

University of Michigan School of Medicine
The Study of Bipolar Disorder is the Study of Humanity

I think the Study of Bipolar Disorder can also be instructive with regard to other mental disorders --- because there often is a fair amount of overlap.

This video is from 2017.

Dr. McInnis discusses people with bipolar disorder literally having "more reactive cells" and this has a life of its own --- which I would say is epigenetics.

So you can come off as very "reactive" --- because you are.

On the other hand, many people with neuro-developmental and psychiatric "disorders" --- struggle to have enough ATP so that their brains and the rest of their bodies have enough energy to function "neuro-typically" throughout the day.

Maternal Immune activation, Mitochondria Dysfunction, Innate & adaptive Immunity, Epigenetics and Neuro-Developmental and Psychiatric disorders

5/9/2024

Val'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.

Epigenetics of Ageing and Psychiatric Disorders (2024)

"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."

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.

Maternal inflammation during pregnancy and offspring brain development: the role of mitochondria (2022)

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.

Mitochondria dysfunction in Depression, Suicide, CANCER & Beyond

5/7/2024

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.

Val's Tables

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.

The Significance of Mitochondrial Dysfunction in Cancer (2020)

"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

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.

Research Seems to be on the road to better understandingings

4/21/2024

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.

Cell Death: All Roads Lead to Mitochondria (2022)

Mitochondria and Neuro-Developmental & Psychiatric disorders

4/18/2024

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.

The World of MaTernal Immune Activation & EpigeneticS

4/6/2024

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)

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.

Epigenomic signatures reveal mechanistic clues and predictive markers for autism spectrum disorder (2023)

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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Translational Medicine Friday

Mitochondrial DNA CoPy Number in Neuro-Developmental & Psychiatric Disorders -----Cellular Aging

Connecting the Dots: Maternal immune activation, Neuro-Developmental Disorders and Chronic Disease

New Research & Changing Paradigms raise tough questions

Neuro-developmental & Psychiatric Disorders as forms of premature aging

More reactive cells and energy issues

Maternal Immune activation, Mitochondria Dysfunction, Innate & adaptive Immunity, Epigenetics and Neuro-Developmental and Psychiatric disorders

Mitochondria dysfunction in Depression, Suicide, CANCER & Beyond

Research Seems to be on the road to better understandingings

Mitochondria and Neuro-Developmental & Psychiatric disorders

The World of MaTernal Immune Activation & EpigeneticS

Translational Medicine Friday

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