Blog Posts

"ADHD" and Epigenetics

8/4/2024

Val's Take

Epigenetics is more and more seen as a crucial player in Auto-Immune Diseases.
When we talk about Neuro-Developmental Disorders, they often begin with Maternal Immune Activation (MIA).
That MIA can result from many things, including infection, obesity, smoking, auto-immune disease, etc.
Since Epigenetics plays a large role in Auto-Immune and Inflammatory Diseases, it not surprising that Epigenetics would also play a large role in Neuro-Developmental Disorders.
Frontiers in Neuroscience: The Epigenome in Neurodevelopmental Disorders (2021)

"There is increasing evidence that dysregulated epigenetic mechanisms of gene expression are involved in the pathogenesis of attention deficit hyperactivity disorder (ADHD)."

The Role of Epigenetics in the Pathogenesis and Potential Treatment of Attention Deficit Hyperactivity Disorder (2022)

Recent Research on Cognitive Disability

8/2/2024

Conduct Disorder Linked to Widespread Brain Structure Changes (2024)

Val's Take/Conjecture

The Criminal Law has at least to some extent dealt with the Defendant with an IQ under 70.
Further, we do have supports for people with an IQ under 70 and Developmental Disabilities.
The challenge in 2024, is the Defendant with an IQ over 70 and Developmental Disabilities.
- They may be tagged with ADHD, Autism, Conduct Disorder, and/or Anti-Social Personality Disorder, etc.
Further, people with ADHD are more likely to incur a brain injury (2015 study supports link between ADHD and traumatic brain injury)
People with brain injury make-up generally over 50% of the justice-involved population, with some estimates at 80%.
The Council of State Governments Justice Center found that the prevalence of brain injury in the criminal justice population was around 60%. (2024)

University of Southern California

Enigma Working Groups Around the World

The ENIGMA Consortium has grown to include over 1400 participating scientists from over 200 institutions, across 43 countries worldwide. ENIGMA is organized as a set of 50 WGs [Working Groups], studying 26 major brain diseases (see color key).

Each group works closely with the others and consists of worldwide teams of experts in each brain disorder as well as experts in the major methods used to study each disorder.

The diseases studied include major depressive disorder, bipolar disorder, schizophrenia, substance use disorder, post-traumatic stress disorder, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and autism spectrum disorder, and several neurological disorders, including Parkinson's disease, epilepsy, ataxia, and stroke.

In recent years, new WGs were created that grew into worldwide consortia on epilepsy (Whelan et al. 9 ), eating disorders (King et al. 104 ), anxiety disorders (Groenewold et al. 107 ), antisocial behavior, and infant neuroimaging.

"ADHD" and "ANTI-SOCial Personality Disorder"

8/2/2024

Val's Take/Conjecture

So "ADHD" is a Neuro-Developmental Disorder
It is part of a Neuro-Developmental/Psychiatric Continuum in which Epigenetics is playing a large role.
It is important to understand the "Generational" aspects to ADHD which often involve some type of maternal auto-immunity.
Additionally, this is often going back more than one generation.
In the case of "smoking," that can go back to the 3rd Generation (maybe more) --- so if your maternal grandmother smoked, you have a higher risk for ADHD.
ADHD, Autism and other Psychiatric Disorders are much more FULL BODY DISORDERS than we generally appreciate.
The Immune System is important as one might expect if ADHD is often seen with maternal auto-immunity and maternal immune activation during pregnancy.
As psychiatry and psychology slowly move to biomarkers --- that will bring a dimension of clarity that we just haven't had in mental health.
Further, the assumption was often that to get those biomarkers one essentially needed brain surgery.
Now, researchers are more and more finding biomarkers in the blood.

THIS IS SERIOUS STUFF

The rates of ADHD and Autism are increasing --- and if one appreciates the many causes of Maternal Immune Activation that is not surprising.
Boys and Men with ADHD, of color and poor are highly represented in Jails and Prisons in Colorado, the US and Countries around the world.
This is a Disability Rights Issue --- it's also a competent assessment and care issue .
Nobody's for sacrificing safety --- but we can't keep punishing a neuro-developmental disorder.

Does ADHD Cause Antisocial Personality Disorder? - WebMD

Studies suggest that as many as 90% of adults with ADHD have other mental health disorders. ASPD is one of the most common mental disorders that happens with ADHD. One study showed that men with ADHD were more likely to have antisocial personality disorder than women with ADHD.

Autoimmune Diseases and ADHD: Is There a Link?

The risk for attention-deficit/hyperactivity disorder is increased with a personal or maternal history of autoimmune disease, particularly with type 1 diabetes and parental autoimmune diseases.

Mitochondrial DNA Copy Number is Associated with Attention Deficit Hyperactivity Disorder. (2020)

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is the most common psychiatric disorder in children. ...Mitochondrial dysfunction (MD) is suggested to be one of the causes of Attention Deficit Hyperactivity …

Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity (2024)

Single-cell RNA-seq identified common alterations in fetal microglial and Hofbauer cell gene expression induced by maternal obesity, as well as sex differences in these alterations.

We propose that Hofbauer cells, which are easily accessible at birth, provide insights into fetal brain microglial programs and may facilitate the early identification of offspring vulnerable to neurodevelopmental disorders.

Recognizing and treating obesity as a disease | 60 Minutes

We have a long tradition of wanting to blame Mom --- and Maternal Immune Activation is often a key precursor to neuro-developmental disorders.

We need to strenuously resist the temptation to scapegoat Mom or anyone else as we work for more comprehensive understandings and treatments.

Policy Challenges & the complicated intersection between Developmental & Psychiatric disorders

7/11/2024

Val's Take/Conjecture

I am supportive of the State's desire to reserve premium ABTU space to those who really need it.
We do have some categories that we have traditionally thought of as quite distinct and most research in 2024 would identify a Neuro-Developmental / Psychiatric Continuum.
There are specialists, but many mental health professionals are not competent to address Neuro-Developmental Disorders, and if these kids, adolescents, adults have an IQ over 70 --- they are ironically quite at risk.
Historically, a lot of kids and adults with neuro-developmental disorders have ended up in the Juvenile Justice System and the Adult Justice System.
So where in the "rich, abundant resources in the community" are these kids with neuro-developmental disorders going?

The influence of neurodevelopmental impairment on youth crime. (2017)

"The disproportionately high prevalence of neurodevelopmental disorders among young people in custody in numerous countries suggests a heightened vulnerability to serious and/or persistent offending coupled with a failure of various policy and practice systems to address complex needs in seeking to prevent offending and re-offending."

Updated adolescent admissions to the Colorado Mental Health Hospital in Pueblo
June 27, 2024

Good afternoon,
I am writing to inform you of the updated admissions policy and procedures for the adolescent behavioral treatment unit (ABTU) at the Colorado Mental Health Hospital in Pueblo (CMHHIP).

Review of recent admissions to ABTU show that many of the youth ordered to inpatient competency restoration are not in need of inpatient psychiatric care and that the factors impacting competency are often related to learning or developmental disorders, young age, and/or attentional problems, for example, rather than a psychiatric illness.

Youth without a need for intensive/inpatient psychiatric treatment would be best served, and have their developmental needs best met, in settings where there are more opportunities for these youth to develop their skills and abilities socially, academically, and recreationally while continuing treatment in a safe and secure environment.

Jill Marshall
Chief Executive Officer
Colorado Mental Health Hospital in Pueblo (CMHHIP)

Higher levels of Bioactive Lipids are arising as another biomarker of mental Disorders

7/2/2024

Val's Take, Conjecture

Illness is a scary thing --- especially when there are a lot of unknowns. With something like "Mental Illness," the symptoms can be very subtle until they are not.
We are constantly telling ourselves stories about how the world works --- until we have the basis for a new story.
"Mental Disorders" do involve the brain --- but they involve a lot more and often have prenatal origins.
We are starting to be able to see this in the Circulatory System in the Blood and the Mitochondria and in the Lymphatic System with Increased levels of Bioactive Lipids.
We're maybe not that far from getting a more comprehensive understanding of neuro-developmental and psychiatric disorders . Given the level of human suffering --- that would be a very good thing.
A lot of Energy in this society is going to trying to understand these issues and integrate the understandings we do have.
Better understandings (and treatments) will almost assuredly improve the "dynamics" of how we handle neuro-developmental and psychiatric disorders in the society.

University of Cologne in Germany

Lipid Signaling in Brain Linked to Mental Disorders (June 6, 2024)

"Increased levels of bioactive lipids produced naturally in the body, which affect excitatory transmission between brain cells, promote mental disorders."

Autotaxin activates the lipids.

Autotaxin is also recognized as a factor in heart disease and stroke, cancer, immune regulation, and autoimmune disorders.

[Val's Take: Mental Health has gone a long time without biomarkers. Things are breaking. We will likely have many biomarkers in the next 30 years]

Why are BioMarkers so important?

7/2/2024

Val's Take

"Seeing is Believing" and many people don't know what to make of our "Mental Health Crisis."
- Are we just a Society of Victims?
- Do we need more Positivity?
- Is this more complicated than what we thought?
  - What did we think: If we just have medication adherence this will all work out.
Dr. Chris Palmer is developing this idea of "Brain Energy" and I think it can be expanded to the Society in general.
It is taking a lot of time, energy and resources to analyze these issues and their ramifications.

One of the things that has been surprising is the rise of biomarkers in the blood for psychiatric disorders.

It's one of those things that if you are not looking for it or you don't know what to look for, you don't see it.
But if you hit upon a new conceptualization, you may be looking for something different and looking for it in a different place.

University of Indiana School of Medicine
Indianapolis VA Medical Center

Global Health Today
Blood Testing Identifies Biomarkers in Suicidal Thoughts

Blood Testing Identifies Biomarkers of Suicidal Thoughts (2023)
UC San Diego study

The point I want to make is this idea of "Blood Biomarkers" for Suicidality and at least some research to support it has been out there for over a decade.

How many people know that?

I would submit it is important that we know there are blood biomarkers for suicidality.

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)