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"FATIGUE" ---A Huge issue in Neuro-developmental & Psychiatric disordeRs

5/20/2025

Val's Take/Conjecture

Obviously, we want good treatments for fatigue
BUT just getting it on everyone's radar screen would help a lot.

When someone is subject to ENERGY ISSUES that are NOT NORMAL and are impacting the person's ability to perform "NORMALLY" ---

That person may be subject to considerable SHAME and EMOTIONAL ABUSE.

On the other hand, we're not always sympathetic to the "fatigue" and "executive functioning" issues of others --- that may look different than our own.

The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders (2015)

* Welsh and Australian Researchers

[Autism and burnout] (2025)

*Argentine Researcher

Florence + Machine
Free

Florence Welch invokes the crucified Christ and she herself is pictured on a kind of cross --- a suffering that she is hiding and is not understood by others.

This video captures the hyper sensitivity, the hidden pain, the selective energy and the grinding fatigue that often accompany Neuro-Diversity.

Residual Fatigue in Unipolar and Bipolar Depression: A Systematic Review (2025)

*Polish researchers

The relationship between central fatigue and Attention Deficit/Hyperactivity Disorder of the inattentive type (2022)

*Japanese Researcher

Accommodating "Spikiness"

5/15/2025

Val's Take/Conjecture

When we think of accommodating "DISABILITIES" we think of accommodating the weaknesses.
But it is just as important to accommodate the STRENGTHS.

We have not appreciated how important it is for people to EXERCISE their STRENGTHS.

On the other hand, neuro-diverse people cannot SURVIVE if we don't get our weaknesses such as idiosyncratic
- Bioenergetics, and
- Executive Functioning
- Etc.

out on the table.

Strength-Based Approach

19th Century Painters and Imagine Dragons --- "I'm Gonna say all the words inside my head"

Dr. Saltz recommends 80% of the time spent on STRENGTHS DEVELOPMENT and 20% of the time on WORK-AROUNDS for WEAKNESSES.

"WORK-AROUNDS for WEAKNESSES" for DEVELOPMENTAL DIFFERENCES in Neuro-Developmental & Psychiatric Disorders is a lot different than "Behavioral Modification."

Further, addressing:

pro-inflammatory cytokine levels,
dysregulated microglia and
dysfunctional mitochondria

might be the more direct medical approaches to improve behavior and well-being in people with Neuro-Developmental and Psychiatric Disorders.

Autism, Disorder or Different --- Dr. Chris Palmer

4/20/2025

Val's Take: Dr. Chris Palmer has been a major leader in re-conceptualizing Neuro-Developmental & Psychiatric Disorders as "Brain Energy" issues.

Dr. Chris Palmer is a Harvard Medical School psychiatrist, researcher, educator, and author of Brain Energy.

Once again Dr. Palmer is taking on the Tough Issues, bringing Clarity and Respect.

Importantly, Dr. Palmer understands these issues as "DEVELOPMENTAL" often beginning IN UTERO and some traits becoming "FIXED" by Adulthood ---

[Further, a lot of people with "Autism" or some form of Neuro-Developmental/Psychiatric Disorder have "Hyper-Plastic Brains" so the idea that Neuro-Plasticity is going to solve everything is a lot more complicated than even professionals can think --- many Neuro-Diverse people are "MAXXED OUT" --- so we need to either Expand the Capacity or Work Within Our Limits]

The Criminal Justice System has become the Disability Provider of Last Resort really as a Default because we haven't had the Systems to deal with the RANGE of DEVELOPMENTAL ISSUES with which people are contending.

We do understand now that we need a CONTINUUM OF CARE and we need to marry that with more up to date understandings of Neuro-Developmental and Psychiatric Disorders.

P.S. "Person-First Language" would be "a person with autism."

Executive Functioning Challenges as an Energy --- ATP Issue

4/18/2025

Val's Take/Conjecture

We are starting to hone in on Developmental Mitochondrial Dysfunction as a result of Maternal Immune Activation.
These Energy issues are CRITICAL. Societies, Professionals and Families are often perplexed by the IDIOSYNCRATIC ENERGY ISSUES of the person with a neuro-developmental and or psychiatric disorder.
The failure to Treat and/or Accommodate those Energy Issues generally makes the person worse.

Brain levels of high-energy phosphate metabolites and executive function in geriatric depression (2016)

Conclusions: These findings suggest two independent sources of executive function dependence on bioenergetic state in the aging brain.

The dependence of executive function performance in subjects with late life depression on ATP in white matter may be associated with mitochondrial impairment and is consistent with predictions of the vascular depression hypothesis.

Further research with wider neuropsychological testing targeting bioenergetic markers could help clarify the scope of these effects.

Prenatal immune activation in mice induces long-term alterations in brain mitochondrial function (2024)

Dr. Chris Palmer advocates a Metabolic Theory of Brain Disorder.

He and the Metabolic Mind folks advocate for a Keto Diet.

Impaired mitochondrial function in bipolar disorder and alcohol use disorder: a case study using 18F-BCPP-EF PET imaging of mitochondrial Complex I (2024)

Conclusions: Despite mounting evidence implicating mitochondria in BD [Bipolar Disorder], this study represents the first PET imaging study to investigate this mechanistic connection.

There were key limitations in the form of comorbid alcohol use disorder, limited statistical power inherent to a case study, no sex matched controls, and the absence of a comprehensive psychiatric history.

However, even with these limitations in mind, the significant overlap between dysfunction previously demonstrated on functional MRI and this imaging provides compelling preliminary evidence that strengthens the mechanistic link between mitochondrial dysfunction and BD [Bipolar Disorder].

Florence & the Machine
Free

Florence Welch is a person with Dyslexia and Dyspraxia and she's been open about substance issues.

I love this video. Her Anxiety is being personified as an Old Man.

The video begins with Her Anxiety handing her a cup of coffee/caffeine for some Energy.

[As an aside, comedian and mental health advocate Maria Bamford, often says, "I need another frickin' Diet Coke" --- something I can very much relate to.

Further, some ADHD advocates do talk about using Caffeine medicinally.

There's even a sweatshirt on Etsy saying "I need a Diet Coke."]

When Florence is Dancing --- she has plenty of Energy, but most of the time she is running to catch-up.

She's presenting a complicated, confusing picture --- a picture that many people with Neurodevelopmental & Psychiatric Disorders present.

Extracellular ATP Is a Homeostatic Messenger That Mediates Cell–Cell Communication in Physiological Processes and Psychiatric Diseases (2025)

Dysregulation of extracellular ATP leads to a destabilizing effect on the neural network, as found in the etiopathology of many psychiatric diseases, including depression, anxiety, schizophrenia, and autism spectrum disorder.

In this review, we summarize advances in the understanding of the mechanisms by which extracellular ATP serves as an intercellular signaling molecule to regulate neural activity, with a focus on how it maintains the homeostasis of neural networks.

In particular, we also focus on neural activity issues that result from dysregulation of extracellular ATP and propose that aberrant levels of extracellular ATP may play a role in the etiopathology of some psychiatric diseases, highlighting the potential therapeutic targets of ATP signaling in the treatment of these psychiatric diseases.

Finally, we suggest potential avenues to further elucidate the role of extracellular ATP in intercellular communication and psychiatric diseases.

The multifaceted role of mitochondria in autism spectrum disorder (2025)

Normal brain functioning relies on high aerobic energy production provided by mitochondria.

Failure to supply a sufficient amount of energy, seen in different brain disorders, including autism spectrum disorder (ASD), may have a significant negative impact on brain development and support of different brain functions.

Mitochondrial dysfunction, manifested in the abnormal activities of the electron transport chain and impaired energy metabolism, greatly contributes to ASD.

The aberrant functioning of this organelle is of such high importance that ASD has been proposed as a mitochondrial disease.

Pre-Natal Inflammatory Exposure (PIE), Neuro-Diversity and Disease

4/11/2025

Val's Take/Conjecture

Even as we're identifying Mechanism Sub-Types in Neuro-Developmental & Psychiatric Disorders ---
Those Mechanism Sub-Types are often relevant for other chronic diseases such as Autoimmune Disorders and Cancer.

Pre-Natal Inflammatory Exposure (PIE) is relevant for:

Neuro-Developmental & Psychiatric Disorders
Auto-Immune Disorders, and
Cancer

Is PIE relevant for every single case --- maybe not. But it is relevant for many, many cases.

Additionally, there is a need to marry a concern for "Lifestyle Choices" with the long-term ramifications of "Pre-Natal Inflammatory Exposure."

Prenatal inflammation exposure accelerates lung cancer tumorigenesis in offspring mouse: possible links to IRE1α/XBP1-mediated M2-like polarization of TAMs and PD-L1 up-expression (2024)

PBS
The Brain with David Eagleman

A One-Word Label is Enough to Change Your Brain's Pre-Conscious Response to Someone in Pain

The fetal programming effect of maternal immune activation (MIA) on the offspring’s immune system (2024)

American Authors, Zac Barnett & "Deep Water"

4/11/2025

Val's Take: I have posted this video several times ---- it is very much what having a psychiatric disorder can feel like.

Zac Barnett, the lead singer for American Authors, is a Mental Health Advocate and he has talked about getting therapy ----- he's also talked about caring for his mother with Bipolar Disorder and the importance of that.

The reality of premature aging with a Neuro-Developmental and/or Psychiatric Disorder is that it is not just affecting the person with the disorder --- it is affecting the rest of the family and the person's ability to work in a traditional work environment.

One of the great verses in "Deep Water" is:

"I was going for the title
Got hit by a tidal wave,
Can't stay in the shallows
Please, tell me I won't wash away"

The experience of being a Neuro-Diverse person can be quite Surreal both with great gifts and devastating health challenges.

ADHD, Autism, Bipolar Disorder, Depression & Schizophrenia As Multi-System Disorders

4/8/2025

Val's Take/Conjecture

This view of Neuro-Developmental and Psychiatric Disorders as multi-system conditions is relatively new and has many ramifications.
In addition, Neuro-Degenerative Disorders such as Parkinson's, Huntington's Disease and Alzheimer's are now viewed as multi-system disorders.

What are the ramifications of Neuro-Developmental & Psychiatric Disorders as Multi-System Disorders?

For Treatment
For Criminal Justice Involvement
and Homelessness

If we don't know, who bears the burden?

Burden of Proof

Schizophrenia, a disease of impaired dynamic metabolic flexibility: A new mechanistic framework (2024)

"Mounting evidence from a variety of transcriptomic, proteomic, metabolomics and brain imaging studies points toward the possibility that schizophrenia is a systemic disorder and involves abnormal glucose and energy metabolism both in the periphery and in brain."

Pathway Network Analyses for Autism Reveal Multisystem Involvement, Major Overlaps with Other Diseases and Convergence upon MAPK and Calcium Signaling (2016)

Psychoneuroimmunology of Mood Disorders (2025)

Abstract

Recent research has shed light on the intricate relationship between mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BD), and inflammation.

This perspective underscores the notion that MDD [Major Depressive Disorder] and BD [Bipolar Disorder] are not solely brain disorders, highlighting their nature as multi-system conditions.

ADHD symptoms in neurometabolic diseases: Underlying mechanisms and clinical implications (2016)

Neuro-Developmental & Psychiatric disorders as Multi-system disorders

3/17/2025

Val's Take/Conjecture

Most of us understand that Down Syndrome is a "MULTI-SYSTEM DISORDER."
Neuro-Developmental Disorders such as Autism, and/or ADHD and Psychiatric Disorders such as Bipolar Disorder, Schizophrenia and Depression are also MULTI-SYSTEM DISORDERS.
Further, Bipolar Disorder, Schizophrenia and Depression are now recognized as NEURO-DEVELOPMENTAL DISORDERS.
Additionally, Down Syndrome, Autism, ADHD, Bipolar Disorder, Schizophrenia and Depression are all NEURO-IMMUNE DISORDERS.

Maternal Immune Activation and Schizophrenia–Evidence for an Immune Priming Disorder (2021)

"Schizophrenia is a complex neurodevelopmental disorder affecting around 19. 8 million people worldwide."

Towards a neurodevelopmental model of bipolar disorder: a critical review of trait- and state-related functional neuroimaging in adolescents and young adults (2025)

Minor physical anomalies in schizophrenia and bipolar I disorder and the neurodevelopmental continuum of psychosis (2014)

Psychoneuroimmunology of Mood Disorders (2025)

Abstract

Recent research has shed light on the intricate relationship between mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BD), and inflammation.

This chapter explores the complex interplay involving immune and metabolic dysfunction in the pathophysiology of these disorders, emphasizing their association with autoimmunity/inflammatory conditions, chronic low-grade systemic inflammation, T cell overactivation, and immunosenescence.

This perspective underscores the notion that MDD [Major Depressive Disorder] and BD [Bipolar Disorder] are not solely brain disorders, highlighting their nature as multi-system conditions.

Brain methylome remodeling selectively regulates neuronal activity genes linking to emotional behaviors in mice exposed to maternal immune activation (2023)

"Thus, MIA [Maternal Immune Activation] induces maladaptive methylome remodeling in brain and selectively regulates neuronal activity gene methylation linking to emotional behavioral abnormalities in offspring."

How we unwittingly put ourselves and others in catch 22s

The Legal System, Trauma-Informed Care and the Living Hell of Catch 22s

Commonalities among Disorders

3/3/2025

Val's Take/Conjecture

A significant percentage of Neuro-Diverse YouTubers were identified "gifted" as kids and subsequently got a LATE DIAGNOSIS of a Neuro-Developmental Disorder in Adulthood.
- May have done very well Academically, and/or
- Had some Special Ability or Talent.
That Adulthood was often a lot different than they expected and often different than what the people around them expected of them.

What researchers are discovering is that Neuro-Diverse "BURNOUT" issues and "MELTDOWN" issues are related to ENERGY ISSUES.

Further, this isn't happening in a VACUUM in which there are nice, neat distinctions between people with Neuro-Developmental Disorders and those without --- this often involves Neuro-Developmental Inflammation and how that impacted one person.

There are many gradations and combinations -- but biomarkers are being identified.

Further, it is not necessarily that hard to recognize associations among Neuro-Developmental, Psychiatric and Neuro-Degenerative Disorders in 2025.

Researchers also recognize Psychiatric Components of other disease and/or disorder issues such as:

Multiple Sclerosis
Myalgic Encephalomyelitis (Chronic Fatigue Syndrome)
Type 1 Diabetes
Cancer
Down Syndrome

All the biological components are NOT IDENTICAL --- but some of the biological components are IDENTICAL or SIMILAR.

People with Neuro-Developmental &/or Psychiatric issues are often facing PHYSICAL issues that are not as dramatic as other diseases or disorders but nonetheless relevant and significant.

The need to integrate PHYSICAL HEALTH & MENTAL HEALTH & DEVELOPMENTAL HEALTH is great.

From Neuro-developmental to Neuro-degenerative Disorders: The Vascular Continuum (2021)

Structural and functional integrity of the cerebral vasculature ensures proper brain development and function, as well as healthy aging.

The inability of the brain to store energy makes it exceptionally dependent on an adequate supply of oxygen and nutrients from the blood stream for matching colossal demands of neural and glial cells.

Key vascular features including a dense vasculature, a tightly controlled environment, and the regulation of cerebral blood flow (CBF) all take part in brain health throughout life.

As such, healthy brain development and aging are both ensured by the anatomical and functional interaction between the vascular and nervous systems that are established during brain development and maintained throughout the lifespan.

During critical periods of brain development, vascular networks remodel until they can actively respond to increases in neural activity through neurovascular coupling, which makes the brain particularly vulnerable to neurovascular alterations.

The brain vasculature has been strongly associated with the onset and/or progression of conditions associated with aging, and more recently with neurodevelopmental disorders.

Our understanding of cerebrovascular contributions to neurological disorders is rapidly evolving, and increasing evidence shows that deficits in angiogenesis, CBF [Cerebral Blood Flow] and the blood-brain barrier [BBB] re causally linked to cognitive impairment.

Moreover, it is of utmost curiosity that although neurodevelopmental and neurodegenerative disorders express different clinical features at different stages of life, they share similar vascular abnormalities.

In this review, we present an overview of vascular dysfunctions associated with neurodevelopmental:

autism spectrum disorders,
schizophrenia,
Down Syndrome

And neurodegenerative

multiple sclerosis,
Huntington’s,
Parkinson’s, and
Alzheimer’s diseases) disorders,

Maternal Immune Activation, above average intelligence & above Average Inflammation

2/28/2025

Val's Take/Conjecture

It is interesting that AI is coming to the fore, just as we are recognizing significant limits of Human Intelligence.
We're only processing a fraction of the information out there ---- and it's taking an enormous amount of energy to process what we are processing.
Contrary to what we might think --- it takes a lot of energy to think.
Sensory Processing is associated with Intelligence and the Immune System.
The challenge for many neurodivergent people is that they are taking in more information --- but it is taking them more energy to process it --- and various dysfunctions including microglial dysfunction and mitchondrial are making that difficult.

Tonic on Demand
Bipolar Disorder (2016)

See 3:18: Bipolar linked to the EXCEPTIONALITIES in the Humanities -- above average, below average -- the main thing -- NOT AVERAGE.

Maternal immune activation and its multifaceted effects on learning and memory in rodent offspring: A systematic review (2024)

Highlights

•  Maternal immune activation (MIA) can impair offspring learning and memory.

•  MIA negatively impacts cognition in rodents.

•  Males are more susceptible to cognitive deficits.

•  Some studies show improved cognition after MIA.

•  Sex differences in immune responses may explain cognitive outcomes.

Lactoferrin alleviates the adverse effects of early-life inflammation on depression in adults by regulating the activation of microglia (2025)

<<Previous

NEURODiversity Wednesday

"FATIGUE" ---A Huge issue in Neuro-developmental & Psychiatric disordeRs

Accommodating "Spikiness"

Autism, Disorder or Different --- Dr. Chris Palmer

Executive Functioning Challenges as an Energy --- ATP Issue

Pre-Natal Inflammatory Exposure (PIE), Neuro-Diversity and Disease

American Authors, Zac Barnett & "Deep Water"

ADHD, Autism, Bipolar Disorder, Depression & Schizophrenia As Multi-System Disorders

Neuro-Developmental & Psychiatric disorders as Multi-system disorders

Commonalities among Disorders

Maternal Immune Activation, above average intelligence & above Average Inflammation

Neuro-Diversity
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Neuro-DiversityWednesday(with variable spellings of Neurodiversity)

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NEURODiversity Wednesday

Neuro-Diversity
Wednesday

(with variable spellings of Neurodiversity)