Blog Posts

"UNreasonable Fatigue" & Mitochondrial dysfunction in NEuro-Developmental & Psychiatric Disorders

5/30/2025

Val's Take/Conjecture

One of the amazing accomplishments of Modern psychiatric drugs of the past few decades --- they could resolve a psychosis in many cases.

Just get the medication right and add some Cognitive Behavioral Therapy (CBT) --- and you're good to go.

Well, sort of.

It's been within the past 10 to 15 years that there has been a significant recognition that people with Neuro-Developmental and Psychiatric disorders have differences in EXECUTIVE FUNCTIONING.

It's been more recently that we are linking Executive Functioning challenges to Mitochondria Dysfunction and Microglia Dysregulation -- dysregulation of the brain's innate immune cells.

This is not just Psychiatry or Neurology --- this is also Immunology (and other bodily systems and disciplines as well).

Mitochondrial dysfunction in psychiatric disorders (2024)

Inflammation-induced mitochondrial and metabolic disturbances in sensory neurons control the switch from acute to chronic pain (2023)

Mitochondrial dysfunction: A fatal blow in depression (2023)

Associations of the immune system in aggression traits and the role of microglia as mediators (2024)

Elena Carroll
What Autism Fatigue Really Looks Like in High Maskers

"UNREASONABLE FATIGUE"

More and more Neuro-Diverse youtubers are tackling the topics of FATIGUE and BURNOUT.
Certainly, it looks like TIREDNESS, but it can also look like:
- IRRITABILITY
- PAIN --- maybe that associated with Migraines
- Etc.

Innate immune dysfunction and neuroinflammation in autism spectrum disorder (ASD) (2023)

Mitochondria and Mood: Mitochondrial Dysfunction as a Key Player in the Manifestation of Depression (2018)

Dr Naglaa Elmongy ----The Role of Inflammation in Depression & Fatigue

5/29/2025

Val's Take: Neuro-Developmental and Psychiatric Disorders are starting to look much more like other illnesses.

Neuro-Developmental and Psychiatric Disorders involve the Immune System, Cytokines, and Macrophages.

Many other illnesses have psychiatric symptoms.

Derma Immunology---
Dr Naglaa Elmongy
The Role of Inflammation in Depression & Fatigue

We don't need another Celebrity diet doctor

5/29/2025

Val's Take/Conjecture

I think when we see someone who we think needs to lose weight --- we think --- if that person would just lose the weight --- their problems would be solved.
Further, we're often focused on different types of diets and exercise programs ---- which can be helpful. This is an issue for a dietitian or a personal trainer.
BUT what if a person has a DEVELOPMENTAL DYSREGULATION of their MICROGLIA, MITOCHONDRIA --- and they are not as good as the average person at producing ATP.

I don't think it is any accident that the most deadly psychiatric disorders are Eating Disorders.

While there are definitely bi-directional relationships, often the MICROGLIA DYSREGULATION came first IN UTERO.

My Dad was 200 pounds when he was 12 and he was not a tall guy.

He lost that weight.
He ultimately died of Parkinson's and Lewy Body Dementia --- NO ATP.

A younger male relative of mine was overweight as a child.

He developed eating disorders --- seemingly starving himself.
He seemed to have gotten past that --- was trim --- looked great and healthy --- and committed suicide in March of this year.

Historian Daniel Boorstin made a distinction between Celebrities and Heroes.

We don't need another Celebrity Diet Doctor or The Biggest Loser --- we need Medical Professionals/Heroes who can deal with the complexity of this problem.

Of course now we have Weight Loss Drugs ---- but why do so many people need them?

Some of these drugs are thought to:

contribute to more efficient ATP production within cells, and
improve Mitochondrial Energy efficiency
there seem to be both Mental Health concerns and hopeful aspects with regard to Wegovy and Ozempic.

Stressed Mitochondria: How the Powerhouse May Be Involved in Mental Health (2023)

By Tara Lago

"Patients with mitochondrial disorders arising from deletions in the mtDNA have comorbidities with mood disorders and experience symptoms like phobias and panic attacks (Filiou & Sandi, 2019).

"A study done on children with oxidative phosphorylation disorders, a type of mitochondrial disease, found that they displayed significantly more depressive behavior compared to healthy controls (Morava et al., 2010).

"Another study confirmed that 70% of the participants diagnosed with mitochondrial dysfunction met the criteria for mental illness (Fattal et al., 2006)."

Eating disorders and neurodivergence

"Once thought of primarily as social diseases, eating disorders are now much better understood, with researchers increasingly discovering biological drivers of these conditions.

"And studies have shown that, in many cases, eating disorders commonly occur in people considered neurodivergent. "

If Medieval people filled in the blanks of human bad or problematic behavior with DEMONS --- we do it with Psychology's PRO SOCIAL COMPETENCY RELIGION or LIFESTYLE CHOICES.

The fact that these equations are incredibly complicated is incredibly inconvenient.

HINT: Neurodivergence is DEVELOPMENTAL ---- It's not a lifestyle choice.

Mitochondria, Energy & Life --- Martin Picard

5/24/2025

Val's Take/Conjecture:

Colombia University Researcher Martin Picard is not just proposing a paradigm shift in mental health --- but in our view of life itself!

Many who now view mental illness as a Metabolic Disorder are proposing a KETO DIET.

Human beings have been trying to find the Magic Diet or Elixir for thousands of years and they have often come up short.

One of the concerns that I have is that when treatments don't work as well as we hoped --- we often blame the patient. That is true across board --- but menta health patients are uniquely vulnerable because of the stigma in the society.

So I think a KETO DIET may very well help some people --- while focusing on PRECISION MEDICINE and the right treatment, at the right time, for the right patient.

Scientific American
Could Mitochondria Be Rewriting the Rules of Biology?
(May 2025)

Additionally, I have had concerns that NEURO-DEVELOPMENTAL and PSYCHIATRIC DISORDERS are not sufficiently recognized as DEVELOPMENTAL with IN-UTERO DYSREGULATION of MICROGLIA.

It seems as though repair of Mitochondria can influence the regulation of Microglia in a positive way. (See: Mitochondrial Regulation of Microglial Immunometabolism in Alzheimer’s Disease)

mitochondria link to mental illness -- Dr. Ana Andreazza

5/23/2025

Val's Note: This is a long video from 2 months ago.

Understanding MITOCHONDRIAL DYSFUNCTION and its relationship to MENTAL ILLNESS is a fairly significant paradigm shift and the research of the last decade or so does support this focus on MITOCHONDRIA.

This has the potential to be TRANSFORMATIVE in our UNDERSTANDINGS and TREATMENT of Mental Illness.

I've seen a lot of people who have been criminally shamed and/or punished for essentially mitochondria dysfunction. Further, not understanding MITOCHONDRIA DYSFUNCTION leads us to write off people who are homeless as lazy or just needing a break when they actually have serious systemic biological dysregulations.

The Intersection of Mitochondrial Function and Psychiatric Disorders: Biomarkers, Gene Variants, and Patient Stratification

Metabolic Health Summit
The Mitochondrial Link to Mental Illness | Ana Andreazza, PhD

This video is highly technical and it certainly doesn't present that all the questions are answered.

On the other hand, this research is RELEVANT to individuals and our systems, even if the research is not completed. It raises REASONABLE DOUBT about current approaches and paradigms.

Mitochondrial Dysfunctionin neuro-Developmental & Psychiatric Disorders

5/19/2025

Val's Take/Conjecture

When we think of "SUPPORTED EMPLOYMENT" we may think of someone with an IQ under 70 working at "menial work" that is often ESSENTIAL.
For many people with Neuro-Developmental and Psychiatric Disorders --- they may have:
- an average or above average IQ
- expanded Sensory Processing, and
- MITOCHONDRIAL DYSFUNCTION
- The employment needs to ACCOMMODATE --- all 3 of those things.

Bob Dylan
The Times They Are A Changin'

Mitochondrial dysfunction in psychiatric disorders (2024)

Abstract

Psychiatric disorders are a heterogeneous group of mental disorders with abnormal mental or behavioral patterns, which severely distress or disable affected individuals and can have a grave socioeconomic burden.

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

This review discusses the neuropsychiatric consequences of mitochondrial abnormalities in both animal models and patients.

We also discuss recent studies associated with compromised mitochondrial function in various psychiatric disorders, such as schizophrenia (SCZ), major depressive disorder (MD), and bipolar disorders (BD).

These studies employ various approaches including postmortem studies, imaging studies, genetic studies, and induced pluripotent stem cells (iPSCs) studies.

We also summarize the evidence from animal models and clinical trials to support mitochondrial function as a potential therapeutic target to treat various psychiatric disorders.

This review will contribute to furthering our understanding of the metabolic etiology of various psychiatric disorders, and help guide the development of optimal therapies.

Moving beyond "Personality analysis" to Biomarkers

5/18/2025

Val's Take/Conjecture

Mental Health got caught up in symptom clusters and personality analysis by necessity --- the biomarkers were not available.
That's changing BUT even I have argued for the need for INTERIM PROCEDURES with regard to an Out-of-Date DSM.
- This isn't quite the same thing --- but they both represent the need to deal with practical realities.

This new study is out of the University of Michigan --- I'm a huge fan of the work they have done on bipolar disorder --- they were one of the first to demonstrate that Bipolar Disorder was DEVELOPMENTAL.

I think the study is not so much to diagnose bipolar disorder but to predict severity and based on personality.

It's pretty much what one would expect. [How much money was spent on this?]
We really need to focus on those biomarkers.
P.S. Researchers from the University of Cambridge have found biomarkers for bipolar disorder and depression and it was reported in JAMA Psychiatry in 2024.

With Bipolar Disorder, we really are talking about Developmental Multi-System Neuro-Immune Disorders.

If all there is --- is TALK THERAPY --- maybe that is better than nothing --- but it doesn't seem to be the most appropriate therapy or treatment for a Neuro-Immune Disorder.

Personality Could Help Predict Bipolar Disorder (May 2025)

University of Michigan
The Study of Bipolar Disorder is the Study of Humanity (2017)

The cells of people with bipolar disorder are developmentally different than the cells of people without bipolar disorder.

the Big Catch 22 ---- Hey now . . . MicrogliaL Dysregulation, idiosyncratic Sensory Processing & an Insufficient energy Supply

5/17/2025

Val's Take/Conjecture

The CATCH-22 is that Microglial Dysregulation as a result of Maternal Immune Activation:
- Ramps up Sensory Processing with INCREASED ENERGY NEEDS
- While at the same time Microglia is playing a role in Mitochondria Dysfunction.
  - Making ENERGY production LESS EFFICIENT.

So what you end up with are people with IDIOSYNCRATIC Sensory Processing --- that does have the potential to benefit the society and themselves --- BUT

those kids, adolescents and adults are more vulnerable to BURNOUTS and BREAKDOWNS.

BUT that is very hard for the Society to understand --- because you look fine or fine enough.

Further, it is generally not clear to the person either --- which can result in the person pushing themselves more --- only to find that they are making things worse.

Understood
ADHD, Dyslexia Advice for Kids:
Try Smarter, Not Try Harder

MIGRAINE

Migraine has a documented association with Neuro-Developmental & Psychiatric Disorders.
Neuro-Developmental & Psychiatric Disorders often come with Sensory Processing Disorders.
Migraine is now viewed as a "LOSS OF CONTROL" by the Hypothalamus over the limbic system.
Further, some researchers have maintained that "Migraine" is a "LOSS OF CONTROL OF INPUTS."

I had 3 or 4 years of MIGRAINES that I certainly found painful and inconvenient --- but didn't view them as a precursor to more serious psychiatric problems.

Then I had something that may or may not have been a MINI STROKE ---- but created a situation in which I was unable to tell the difference between fantasy and reality.
- THAT IS DANGEROUS.

At the time, I was hospitalized and had a kind of crash landing to reality with the help of various anti-psychotics.

That was 18 years ago, and I haven't had a similar episode.
- But it does illustrate the problem that Mental Health America identified which was STAGE 4 diagnosis of serious mental health problems.

It is why we need biomarkers and we're getting them. I also think we need to take MIGRAINES more seriously than we do.

Finally, Microglial Dysregulation, Sensory Processing and Mitochondria Dysfunction are keys to understanding Neuro-Developmental & Psychiatric Disorders.

Migraine as an inflammatory disorder with microglial activation as a prime candidate (2023)

The status of knowledge on migraines: The role of microglia (2023)

Migraine attacks as a result of hypothalamic loss of control (2021)

"The hypothalamus as a metronome of internal processes is suggested to control these limbic circuits: migraine attacks may occur as a result of the hypothalamus losing control over the limbic system."

Grateful Dead
IKO IKO

Atypical Sensory Processing in Neurodevelopmental Disorders: Clinical Phenotypes in Preschool-Aged Children (2024)

"A positive correlation was found between sensory processing abnormalities and behavioral problems.

. . .

"Our results suggest that sensory processing difficulties should be considered regardless of developmental level and in children with behavioral problems."

Sensory processing difficulties in psychiatric disorders: A meta-analysis (2022)

Highlights

• Many individuals with psychiatric disorders report difficulties in sensory processing.

*  This meta-analysis examined sensory processing patterns in psychiatric conditions.

•  We detected a general pattern of sensory processing difficulties in psychopathology.

•  Sensory processing difficulties are considered to be a transdiagnostic phenotype.

•  Further research may improve long-term prognosis and treatment in psychiatry.

"In clinical practice, many individuals with psychiatric disorders report difficulties in sensory processing, including increased awareness or sensitivity to external stimuli.

. . .

"In conclusion, sensory processing difficulties can be considered as a non-specific transdiagnostic phenotype associated with a broad spectrum of psychiatric conditions.

"Further research into the relevance and role of sensory processing difficulties in psychiatric disorders may improve long-term prognosis and treatment."

Development and sensory experience dependent regulation of microglia in barrel cortex (2020)

*Researchers at City University of New York

"Findings suggest that both developmental age and sensory experience has profound impact on microglia morphology.

"Following chronic sensory deprivation, microglia undergo a morphological transition from a monitoring or resting state to an altered morphological state, by exhibiting expanded cell body size and retracted processes.

. . .

"Our results indicate that microglia may be recruited to participate in the modulation of neuronal structural remodeling during developmental critical periods and in response to alteration in sensory input."

Researcher Staci Bilbo: prenatal inflammation alters Microgial phenotype and behavior

5/15/2025

Staci D. Bilbo, PhD
Director of Research, Lurie Center for Autism
MassGeneral Hospital for Children
Lurie Family Associate Professor of Pediatrics, and Program in Neuroscience, Harvard Medical School
[Currently at Duke University]

Prenatal inflammation by combined environmental stressors alters microglial phenotype and behavior (2018)

Researcher Jonathan Kipnis --- A pioneer in Neuro-immunology

4/25/2025

Val's Note: Kipnis was formerly at the University of Virginia, now at the Washington University in St. Louis.

He is also an academic editor of the Journal of Experimental Medicine which publishes papers on immunology, cancer biology, vascular biology, microbial pathogenesis, neuroscience and stem cell biology.

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Translational Medicine Friday

"UNreasonable Fatigue" & Mitochondrial dysfunction in NEuro-Developmental & Psychiatric Disorders

Dr Naglaa Elmongy ----The Role of Inflammation in Depression & Fatigue

We don't need another Celebrity diet doctor

Mitochondria, Energy & Life --- Martin Picard

mitochondria link to mental illness -- Dr. Ana Andreazza

Mitochondrial Dysfunctionin neuro-Developmental & Psychiatric Disorders

Moving beyond "Personality analysis" to Biomarkers

the Big Catch 22 ---- Hey now . . . MicrogliaL Dysregulation, idiosyncratic Sensory Processing & an Insufficient energy Supply

Researcher Staci Bilbo: prenatal inflammation alters Microgial phenotype and behavior

Researcher Jonathan Kipnis --- A pioneer in Neuro-immunology

Translational Medicine Friday

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