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Executive Functioning in--Neuro-Developmental and Psychiatric Disorders

11/22/2021

Conjecture

I think that some of the BIG TALENTS one sees in NEURO-DIVERSITY may be the result of:

Differences in Information and Sensory Processing AS WELL AS
The need to OVERCOME EXECUTIVE FUNCTIONING DIFFERENCES, CHALLENGES or DEFICITS.

Further, this is on a CONTINUUM and most people probably are dealing with SOME LEVEL of EXECUTIVE DISFUNCTION --- Professor Graham Rook from King's College London estimates the level of LOW GRADE INFLAMMATION in the US POPULATION is--- 95%.I think that may be why there is not a lot of SYMPATHY for bad behavior tied to neurodevelopmental or psychiatric disorders and associated poor executive functioning --- on some level most people are dealing with some of these executive functioning issues.

Further, there are MILLIONS of PEOPLE with some category of NEURO-DEVELOPMENTAL and/or PSYCHIATRIC DISORDER that are not homeless or justice involved.

WHAT's the DIFFERENCE? Generally 2 big issues:
- People who are Justice-Involved or Homeless can be a lot further along on that CONTINUUM, and/or
- Accessing Support may be more difficult if :
  - you are poor and marginalized, and
  - it is certainly more difficult if one has greater needs.

Addressing EXECUTIVE FUNCTIONING is the BIG NEED in Mental Health.
- Partly, that is rehabilitative attempts, BUT
- A much BIGGER PART is finding WORK-AROUNDS that even High IQ patients may be struggling with due to DEVELOPMENTAL EXECUTIVE FUNCTIONING DIFFERENCES.

Neurocognitive insight and executive functioning in schizophrenia (2015)

Affiliation
1a "Psychologie, Santé et Qualité de vie" , Univ Bordeaux ,Bordeaux , France.

Conclusion:

These results provide support for the hypothesis that executive dysfunctioning is a limiting factor for NI (neuro-cognitive insight), independently from depressive and anxiety symptoms.

Executive functioning but not IQ or illness severity predicts occupational status in bipolar disorder (2020)

Affiliations
1Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Blå Stråket 15, 413 45, Gothenburg, Sweden.
2Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Blå Stråket 15, 413 45, Gothenburg, Sweden.
3Department of Psychology, University of Pennsylvania, 3720 Walnut Street, Philadelphia, PA, 19104, USA.
4Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
5Center for Autism Research, The Children's Hospital of Philadelphia, 2716 South St, Philadelphia, PA, 19104, USA.

Conclusions:

Executive functioning was a more powerful predictor of occupational status in bipolar disorder patients than IQ and other clinical factors, including illness severity.

Executive function deficits and neurodevelopmental disorders in childhood and adolescence (2019)

Affiliations
1Universidad Pública de Navarra, Pamplona, España.
2Hospital San Juan de Dios, Pamplona, España.
3Hospital Universitario Marqués de Valdecilla, Santander, España.

Neurodevelopmental disorders are diverse, and even though they are independent diagnostic entities they share common manifestations in people with brain damage or dysfunction of the prefrontal cortex; that is, neurodevelopmental disorders present different alterations in executive functions.

Conclusions:

The dimensions of executive functioning are affected to a variable degree in different neurodevelopmental disorders.

We can hypothesis that the dimensions that are affected in the different neurodevelopmental disorders can be characterized in terms of the existence of a continuum, and occasionally those dimensions are too complex to establish categorical limits when comparing different neurodevelopmental disorders.

The structure of adult ADHD (2017)

Affiliations
1Department of Psychiatry and Child and Adolescent Psychiatry, New York University Langone School of Medicine and Psychiatry Service, New York, NY, USA.
2Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.
3Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
4Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
5Hofstra Northwell School of Medicine, Hofstra University, Hempstead, NY, USA.
6Department of Health Care Policy, Harvard Medical School, Boston, MA, USA.

Although DSM-5 stipulates that symptoms of attention-deficit hyperactivity disorder (ADHD) are the same for adults as children, clinical observations suggest that adults have more diverse deficits than children in higher-level executive functioning and emotional control.

These results show that executive dysfunction is as central as DSM-5 symptoms to adult ADHD, while emotional dyscontrol is more distinct but nonetheless part of the combined presentation of adult ADHD.

Autoimmunity in Neurodiversity and Psychiatric Disorders and Maternal Immune Activation

11/14/2021

Maternal Immune Activation as a Risk Factor for Schizophrenia: Evidence From Preclinical and Clinical Studies

Maternal immune activation and neuroinflammation in human neurodevelopmental disorders (Nature Reviews Neurology -- Aug. 2021)

The Future of Psychiatry and Neurodevelopmental Disorders: A Paradigm Shift (2018)
- Abstract
  "A paradigm shift is now taking place in psychiatry with the emphasis on neurodevelopmental disorders with a neurobiologic emphasis and early onset including autism, ADHD, learning disability, schizophrenia and bipolar disorder.

"This paradigm superseded the attachment paradigm of the second half of the twentieth century with so many misguided theories such as, “blaming the mother”—the so-called refrigerated mother and the schizophrenogenic mother.

"The new paradigm allows more focused treatment interventions."

RIFFING

If you want to know why we are not on top of the Mental Health Crisis --- just read the abstract above.
I'll be 60 in 2023 -- and I've lived the bad paradigms of the late 20th Century and early 21st Century --- only now it's ----COPING SKILLS and RESILIENCE.
1. When I say "I've lived the bad paradigms" --- what do I mean?
  1. A movement disorder that is not really Tourette's but did come on at childhood and family members and co-workers (especially at The Legal Center --- now Disability Law Colorado -- were aware of --- "TOUCHDOWN" --- that's me with my arms in the air as I'm thinking)
  2. Two or Three Trips to the Psychologist in 4th Grade --- ultimate verdict -- my mom should chill out about my wardrobe choices and let me be me.
  3. Saw a therapist three or four times for depression when I was about 37 while pregnant.
  4. A psychotic episode when I was 43 that was potentially extremely dangerous.
  5. At 50, a diagnosis of ADHD.

[With the current paradigms--- it's pretty hard to do much with that.

But with the NEW PARADIGMS, we're bringing in:

Maternal Immune Activation
BLURRED DIAGNOSTIC CATEGORIES
DEVELOPMENTAL INFLAMMATION
The ENDOCRINE SYSTEM is involved
Etc.

-----With the NEW PARADIGMS --- we have a much better handle on what's going on --- even though it's not perfect.

Of course, knowing what the hell you're talking about is right up there, too.
1. This may seem IRONIC to say for someone who engages in as much CONJECTURE as I do
But we haven't known about DEVELOPMENTAL INFLAMMATION.
In 2021 many of our researchers do know --- BUT that hasn't been effectively transmitted to CLINICIANS, FAMILY MEMBERS, INDIVIDUALS and the SOCIETY at large,

Mental Health Patients have been written off for a long time as having "SOMATIC COMPLAINTS" in which the mental health professional often couldn't find a physical source.

At least in a significant number of cases, Maternal Immune Activation is not only often contributing to related IMMUNE DYSREGULATION such as THYROID DISORDERS and other IMMUNE DISORDERS, but that Maternal Immune Activation is a PRIMARY SOURCE of the NEURO-DIVERSITY and/or PSYCHIATRIC DISORDER .

This isn't saying that PSYCHIATRIC DISORDERS are not a brain disease, but many researchers are conceptualizing PSYCHIATRIC DISORDERS as MULTI-SYSTEM DYSREGULATIONS --- and certainly as well as the Central Nervous System --- the IMMUNE SYSTEM, MICROBIOME and the ENDOCRINE SYSTEM are prime systems associated with these DYSREGULATIONS.

I think it is going to take the NAMIs and Mental Health Americas to make bringing this research to clinicians a PRIORITY --- because it certainly doesn't seem to be a PRIORITY.

A few years ago, NAMI Montana did take on mental health's beleaguered diagnostic system. 

These new understandings can fuel policy reform even as they are INCOMPLETE. Knowledge is always incomplete.

The On-Going and Unfinished Pursuit of Knowledge is why a robust PUBLIC HEALTH APPROACH to CRIMINAL JUSTICE is needed:

Psychiatric PARADIGMS are changing and we don't have the systems to incorporate those new understandings and consider the implications in a timely manner, AND
Those new understandings are going to keep coming and at a faster and faster pace --- we need something both more nimble and sophisticated than what we currently have to keep up.

Wrong Jungle --- But Can We Get Out Without the Knockout Treatment?

11/10/2021

Researchers are yelling "Wrong Jungle" when it comes to psychiatric disorders
Namely, in 2021 it is hard to understand psychiatric disorders without understanding the role of the IMMUNE SYSTEM --- BUT CLINICIANS are not up to speed on that.
One of the reasons for that is that Researchers don't understand how important these new conceptualizations are for policymaking --- even without the knockout treatment.
For a lot of people in the Criminal Justice System and Homeless who essentially have an IMMUNE DISORDER that affects the BRAIN ---
- These new conceptualizations are a GAME-CHANGER.

New theory suggests blood immune and clotting components could contribute to psychosis

A scientific review has found evidence that a disruption in blood clotting and the first line immune system could be contributing factors in the development of psychosis.

Immune dysregulation in depression: Evidence from genome-wide association -- 2020

Abstract

A strong body of evidence supports a role for immune dysregulation across many psychiatric disorders including depression, the leading cause of global disability.

Recent progress in the search for genetic variants associated with depression provides the opportunity to strengthen our current understanding of etiological factors contributing to depression and generate novel hypotheses.

Here, we provide an overview of the literature demonstrating a role for immune dysregulation in depression, followed by a detailed discussion of the immune-related genes identified by the most recent genome-wide meta-analysis of depression.

These genes represent strong evidence-based targets for future basic and translational research which aims to understand the role of the immune system in depression pathology and identify novel points for therapeutic intervention.

Immune dysregulation in depression: Evidence from genome-wide association -- 2020

Conclusions: The link between immune dysregulation, autoimmunity, and bipolar disorder may be closer than previously thought.

Psychiatrists should be vigilant for autoimmunity in presentations of bipolar disorder due to its high morbidity and therapeutic implications.

Advances in neuroimaging and biomarker identification related to immune dysregulation and neuroinflammation will contribute to our knowledge of the pathophysiology of bipolar disorder.

Neuroinflammation in Mood Disorders: Role of Regulatory Immune Cells ---2021

Abstract

Mood disorders are associated with chronic low-grade systemic (sterile) inflammation, with increased plasma levels of pro-inflammatory mediators targeting all tissues including the brain. Importantly, pro-inflammatory cytokines (ex., tumor-necrosis factor alpha [TNF-α], interleukin [IL]-6) regulate mood behavior and cognition by influencing neurotransmitter levels, activating stress-responsive endocrine axes, among other effects.

However, the mechanisms underlying this enhanced inflammation are not well understood.

There is increasing evidence indicating that impaired immunoregulatory mechanisms may play a role in this context.

Patients with mood disorders (major depression [MDD] and bipolar disorder [BD]) have reduced numbers of major regulatory cells of both innate (natural killer regulatory cells and myeloid-derived suppressor cells [MDSCs]) and adaptive immune responses (CD4+CD25+FoxP3+, B regulatory cells).

Dysfunctional regulatory immune cells might contribute to systemic and neuroinflammation observed in mood disorders via different mechanisms, such as:
(i) failure to develop adequate stress-related responses,
(ii) indirectly through microglial activation,
(iii) lack of trophic support and pro-cognitive functions of T cells in the brain, and
(iv) dysbiosis.

In conclusion, maladaptive immunoregulatory mechanisms seem to be involved with both onset and progression of mood disorders.

A deeper understanding of these mechanisms may lead to the development of new therapeutic strategies

The immune system and psychiatric disease: a basic science perspective -- 2019

Summary

Mental illness exerts a major burden on human health, yet evidence-based treatments are rudimentary due to a limited understanding of the underlying pathologies.

Clinical studies point to roles for the immune system in psychiatric diseases, while basic science has revealed that the brain has an active and multi-cellular resident immune system that interacts with peripheral immunity and impacts behavior.

In this perspective, we highlight evidence of immune involvement in human psychiatric disease and review data from animal models that link immune signaling to neuronal function and behavior.

We propose a conceptual framework for linking advances in basic neuroimmunology to their potential relevance for psychiatric diseases, based on the subtypes of immune responses defined in peripheral tissues.

Our goal is to identify novel areas of focus for future basic and translational studies that may reveal the potential of the immune system for diagnosing and treating mental illnesses

Migraines, Sensory Processing, Neuro-Diversity and Psychiatric Disorders

11/9/2021

Two BIG LINKS:

Migraines are more and more associated with psychiatric disorders;
- What is the link between migraine and psychiatric disorders? From epidemiology to therapeutics
Sensory / Information Processing Differences and Disorders are associated with NEURO-DIVERSITY
- Sensory processing related to attention in children with ASD, ADHD, or typical development: results from the ELENA cohort
- Sensory hypersensitivity in Tourette syndrome: A review

A BIG PART OF BETTER TREATMENT IS BETTER PREVENTION & DIAGNOSTICS.

A BIG PART OF BETTER TREATMENT IS BETTER PREVENTION & DIAGNOSTICS.

People who are NEURO-DIVERSE and/or have MIGRAINES are at high risk for PSYCHIATRIC DISORDERS.

On the other hand, because of their SENSORY PROCESSING DIFFERENCES, NEURO-DIVERSE people often have BIG STRENGTHS in ACADEMIC, ATHLETIC and/or CREATIVE pursuits.

NEURO-DIVERSE people who can look like such OPPOSITES -- often have in common SENSORY PROCESSING DIFFERNCES that DIVERGE FROM THE NORM.

Pathophysiology of Migraine: A Disorder of Sensory Processing
(2017)

Affiliations

Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom;
Department of Neurology, University of California, San Francisco, San Francisco, California;
Department of Neurology, University of Hamburg-Eppendorf, Hamburg, Germany; and
Department of Neurology, University Hospital Bern-Inselspital, University of Bern, Bern, Switzerland.

Abstract

Plaguing humans for more than two millennia, manifest on every continent studied, and with more than one billion patients having an attack in any year, migraine stands as the sixth most common cause of disability on the planet.

The pathophysiology of migraine has emerged from a historical consideration of the "humors" through mid-20th century distraction of the now defunct Vascular Theory to a clear place as a neurological disorder.

It could be said there are three questions: why, how, and when?

Why:
migraine is largely accepted to be an inherited tendency for the brain to lose control of its inputs.

How:
the now classical trigeminal durovascular afferent pathway has been explored in laboratory and clinic; interrogated with immunohistochemistry to functional brain imaging to offer a roadmap of the attack.

When:
migraine attacks emerge due to a disorder of brain sensory processing that itself likely cycles, influenced by genetics and the environment.

In the first, premonitory, phase that precedes headache, brain stem and diencephalic systems modulating afferent signals, light-photophobia or sound-phonophobia, begin to dysfunction and eventually to evolve to the pain phase and with time the resolution or postdromal phase.

Understanding the biology of migraine through careful bench-based research has led to major classes of therapeutics being identified: triptans, serotonin 5-HT1B/1D receptor agonists; gepants, calcitonin gene-related peptide (CGRP) receptor antagonists; ditans, 5-HT1F receptor agonists, CGRP mechanisms monoclonal antibodies; and glurants, mGlu5 modulators; with the promise of more to come.

Investment in understanding migraine has been very successful and leaves us at a new dawn, able to transform its impact on a global scale, as well as understand fundamental aspects of human biology.

Translational Medicine Friday

Executive Functioning in--Neuro-Developmental and Psychiatric Disorders

Autoimmunity in Neurodiversity and Psychiatric Disorders and Maternal Immune Activation

Wrong Jungle --- But Can We Get Out Without the Knockout Treatment?

Migraines, Sensory Processing, Neuro-Diversity and Psychiatric Disorders

Translational Medicine Friday

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