<![CDATA[Orchid Advocacy - Translational Medicine Friday]]>Fri, 21 Feb 2025 21:05:18 -0800Weebly<![CDATA[the neuro-immune system and  substance use]]>Sat, 22 Feb 2025 01:00:07 GMThttps://orchidadvocacy.org/translational-medicine-friday/the-neuro-immune-system-and-substance-use
​Val's Take/Conjecture​
  • The "Neuro-Immune System" is a relatively new concept and it has taken off in the last 5 to 10 years.
  • It involves Glial Cells (including the Brain's Innate Immune Cells in Microglia) and various Molecular Pathways.
  • Researchers are identifying the "Neuro-Immune System" as a critical player in many diseases and disorders, including:
    • Neuro-Developmental Disorders
    • Psychiatric Disorders, and
    • Substance Use Disorders
  • Researchers are zeroing in on "Microglia" and its relationship to Substance Use Disorders.

  • In Criminal Justice, there are a lot of People with Neuro-Developmental Disorders, Psychiatric Disorders, Substance Use Disorders and Brain Injury.
    • Further, many people are contending with more than one issue.
​
  • "NEURO-INFLAMMATION" is a big common denominator.
​On the other hand, one of the reasons why the issues are so complex and expensive to treat is they are not identical and often require a fair amount of individualized medicine and treatment.
There's a reason why these disorders have tended to cluster in the Criminal Justice System --- these disorders do have the potential to become dangerous.
  • There have been Criminal Justice Rehabilitation Efforts for hundreds of years --- going back to England even before the US was a country.
  • But the way they conceptualized the "ROOT CAUSE" of the problem was often a MORAL FAILURE. [History of the Penitentiary]
  • And that is still going on.  Some kind of  "Religious and/or Moral Education" probably can help manage excess ANXIETY, ANGER,  AGGRESSION, and EMOTIONAL DYSREGULATION.just as DIET and EXERCISE can help with managing some of that NEURO-INFLAMMATION.
There is evidence that Diet and Exercise can improve Cognitive Dysfunction and Neuro-Inflammation and the regulation of Microglia.​ 


  • ​BUT in many cases these strategies can help but fall woefully short of solving the problem for some people.
​
  • We've been PUSHED to understand the underlying BIOLOGY of Substance Use and other issues -- because what we we're doing wasn't sufficient.
The Neuroimmune System and the Cerebellum (2023)

​[provides a good overview of the Neuro-Immune System]
Microglia NLRP3 Inflammasome and Neuroimmune Signaling in Substance Use Disorders (2023)
"During the last decade, substance use disorders 
(SUDs) have been increasingly recognized as neuroinflammation-related brain diseases. ...Recently, inflammasome-mediated signaling has been identified as playing critical roles in the microglia activation …"
Transcriptional and epigenetic regulation of microglia in substance use disorders.  (2023)
​"Microglia are widely known for their role in immune surveillance and for their ability to refine neurocircuitry during development, but a growing body of evidence suggests that microglia may also play a complementary role to neurons in regulating the ​behavioral aspects of substance use disorders."
CONTINUED

​For me, a big issue from a "Moral Education" standpoint is that many people are coming with SIGNIFICANT NEURO-DEVELOPMENTAL INFLAMMATION and AFTER-ACQUIRED INFLAMMATION (including TRAUMA but many other things as well) and significantly reduced abilities to manage STRESS.
  •  and if we don't understand their personal individual biology and situation -- a big default is often a punitive response.
  • That punitive response is meant to reassure the Community --- and it often does --- but it also sends a powerful message that we SACRIFICE people in our community.
]]><![CDATA[New diagnostic framework, glutamate-mediated Excitotoxity in Neuro-Developmental & psychiatric disorDers]]>Sun, 16 Feb 2025 22:33:14 GMThttps://orchidadvocacy.org/translational-medicine-friday/new-diagnostic-framework-glutamate-mediated-excitotoxity-in-neuro-developmental-psychiatric-disorders

​Towards a consensus roadmap for a new diagnostic framework for mental disorders (2024)

"In general, the meeting indicated a crucial need for a biology-informed framework to establish more precise diagnosis and treatment for mental disorders to facilitate bringing the right treatment to the right patient at the right time."
​Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders (2024)
Disruption of the mechanisms responsible for glutamate homeostasis may result in
  • the accumulation of excessive glutamate levels,
  • which in turn leads to increased calcium levels,
  • mitochondrial abnormalities,
  • oxidative stress, and
  • eventually cell atrophy and death.

This condition is known as glutamate-induced excitotoxicity and is considered as a pathogenic mechanism
  • in several diseases of the central nervous system,
  • including neurodevelopmental,
  • substance abuse, and
  • psychiatric disorders.
]]><![CDATA[What is Excitotoxicity?]]>Sat, 15 Feb 2025 23:42:14 GMThttps://orchidadvocacy.org/translational-medicine-friday/what-is-excitotoxicity
Val's Take / Conjecture
  • "Excitotoxity" is actually associated with CELL DEATH across a wide range of diseases and disorders.
  • That wide range includes Neuro-Developmental & Psychiatric Disorders.
  • It does seem that dysregulated microglia that can result from Maternal Immune Activation, could promote inflammation and excess glutamate release and neurotoxity.
  • Further, there can be more overlap than we often appreciate.
  • Further, we talk so much about the lack of BIOMARKERS in Mental Health -- but that is a perennial battle in Medicine.
    • ​Other areas of Medicine have more BIOMARKERS than Mental Health.
    • But Mental Health is getting Metabolomic Biomarkers and others, and
    • At least in the last few years, people have seen the Trifecta of Neuro-Developmental, Psychiatric and Neuro-Degenerative Disorders and researchers have been exploring the relationships among them to a greater and greater degree.
    • More and more we're seeing relationships with other Disorders and Diseases as well.
RIPK1 activation in Mecp2-deficient microglia promotes inflammation and glutamate release in RTT (2024)
Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders (2024)
Discovery of the therapeutic potential of naltriben against glutamate-induced neurotoxicity (2025)
Editorial: Glutamate-Related Biomarkers for Neuropsychiatric Disorders (2019)
What Happens When You Have Too Much Glutamate?
What happens when you have too much glutamate?

Too much glutamate in the brain can cause nerve cells to become overexcited.

Overexcitement can lead to brain cell damage and/or death. In this case, glutamate is called an excitotoxin.

Having too much glutamate in the brain is associated with some conditions, including:
​*Amyotrophic lateral sclerosis (Lou Gehrig’s disease).

*Multiple sclerosis.

*Alzheimer’s disease.

*Parkinson’s disease.

*Huntington’s disease.

*Stroke.

*Fibromyalgia.

​*Chronic fatigue syndrome
Glutamate and microglia activation as a driver of dendritic apoptosis [a type of cell death]: a core pathophysiological mechanism to understand schizophrenia (2021)
The role of glutamate receptors in the regulation of the tumor microenvironment (2023)
Glutamate-induced excitotoxicity in Parkinson's disease: The role of glial cells (2020)
]]><![CDATA[The Greatest Human diversity is in our immune systems]]>Thu, 13 Feb 2025 04:02:48 GMThttps://orchidadvocacy.org/translational-medicine-friday/the-greatest-human-diversity-is-in-our-immune-systems
​Kendrick Lamar
DNA
University of Manchester Professor Dan Davis (UK)

The vast majority of Human DNA is the same.

The greatest human diversity is in our Immune Systems
]]><![CDATA[Metabolomics, immuno-methylomics, Biomarkers ​And slowly moving to better diagnostics]]>Fri, 07 Feb 2025 17:53:11 GMThttps://orchidadvocacy.org/translational-medicine-friday/metabolomics-immuno-methylomics-biomarkers-and-slowly-moving-to-better-diagnostics
​Val's Take/Conjecture
  • The New Insight that Neuro-Developmental and Psychiatric Disorders are not just disorders of the Brain -- is opening up new opportunities for biomarkers.
    • ​Brain surgery is not required.
  • It is also profoundly re-conceptualizing what Neuro-Developmental & Psychiatric Disorders are and understanding relationships with:
    • ​Auto-Immune Disease
    • Cancer, and
    • ​Neurodegenerative Disorders
​Metabolomic Biomarker Signatures for Bipolar and Unipolar Depression (2024)
Infant microbes and metabolites point to childhood neurodevelopmental disorders (2024)
Association Between Human Blood Metabolome and the Risk of Psychiatric Disorders (2023)
The microRNA profile of brain-derived extracellular vesicles: A promising step forward in developing pharmacodynamic biomarkers for psychiatric disorders (2025)
​"[A]nalyzing the miRNA expression profile of brain-derived EVs in blood may allow us to non-invasively assess miRNA dysregulation and thus to gain knowledge about the pathophysiology of psychiatric disorders and identify potential new predictive targets.
​miRNA regulation of social and anxiety-related behaviour (2020)
​"[O]verview of recent expression profiling and genetic association studies in human patient-derived samples in an attempt to highlight the most promising candidates for biomarker discovery and therapeutic intervention."
Dissecting depression symptoms: Multi-omics clustering uncovers immune-related subgroups and cell-type specific dysregulation (2025)
Exploring the use of immunomethylomics in the characterization of depressed patients: A proof-of-concept study (2025)
​"DNA-methylation based cell-type profiles may be valuable in the immunological characterization and stratification of patients with MDD [Major Depressive Disorder].

"Future models should consider the inclusion of more cell-types and cytokines for better prediction of treatment outcomes."
Claudin-5 and occludin levels in patients with psychiatric disorders - A systematic review (2025)
​"Recent research has underscored the critical role of blood-brain barrier (BBB) integrity in psychiatric disorders, highlighting disruptions in tight junction (TJ) proteins, specifically claudin-5 and occludin.

"These proteins are pivotal in maintaining the BBB's selective permeability, which is essential for brain homeostasis.

​"Altered levels of the TJ proteins have been observed in various psychiatric conditions, suggesting potential as biomarkers for the pathophysiology of these disorders."
Large-scale metagenomic analysis of oral microbiomes reveals markers for autism spectrum disorders (2024)
MicroRNA-dependent control of neuroplasticity in affective disorders (2021)
Plasma and CSF neurofilament light chain distinguish neurodegenerative from primary psychiatric conditions in a clinical setting (2024)
Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder (2025)
]]><![CDATA[Towards a consensus roadmap for a new diagnostic framework for mental disorders (2024)]]>Fri, 07 Feb 2025 16:54:17 GMThttps://orchidadvocacy.org/translational-medicine-friday/towards-a-consensus-roadmap-for-a-new-diagnostic-framework-for-mental-disorders-2024
Towards a consensus roadmap for a new diagnostic framework for mental disorders (2024)
​Val's Take/Conjecture
  • It's been over a decade since the US National Institute of Mental Health said the DSM 5 lacked scientific validity.
  • Since then, researchers around the world have corroborated that concern and begun their own efforts to address it.
  • There are more and more entities and researchers around the world articulating the "crucial need" for a "biology-informed framework."​
  • This has implications for Criminal Justice and State Disability Housing, Placement and Service provision.
​Abstract

Current nosology claims to separate mental disorders into distinct categories that do not overlap with each other.

This nosological separation is not based on underlying pathophysiology but on convention-based clustering of qualitative symptoms of disorders which are typically measured subjectively.

Yet, clinical heterogeneity and diagnostic overlap in disease symptoms and dimensions within and across different diagnostic categories of mental disorders is huge.

While diagnostic categories provide the basis for general clinical management, they do not describe the underlying neurobiology that gives rise to individual symptomatic presentations.

The ability to incorporate neurobiology into the diagnostic framework and to stratify patients accordingly will be a critical step forward for the development of new treatments for mental disorders.

Furthermore, it will also allow physicians to provide patients with a better understanding of their illness's complexities and management.

To realize this ambition, a paradigm shift is needed to build an understanding of how neuropsychiatric conditions can be defined more precisely using quantitative (multimodal) biological processes and markers and thus to significantly improve treatment success.

The ECNP [European College of Neuropharmacology] New Frontiers Meeting 2024 set out to develop a consensus roadmap for building a new diagnostic framework for mental disorders by discussing its rationale, outlook, and consequences with all stakeholders involved.

This framework would instantiate a set of principles and procedures by which research could continuously improve precision diagnostics while moving away from traditional nosology. In this meeting report, the speakers' summaries from their presentations are combined to address three key elements for generating such a roadmap, namely:
​
​* the application of innovative technologies,
​
*understanding the biology of mental illness, and

*translating biological understanding into new approaches.

In general, the meeting indicated a crucial need for a biology-informed framework to establish more precise diagnosis and treatment for mental disorders to facilitate bringing the right treatment to the right patient at the right time.
]]><![CDATA[2025 Research:  Neo-Natal Inflammation, Microglia, and  Investigation of New Treatments]]>Fri, 07 Feb 2025 16:27:00 GMThttps://orchidadvocacy.org/translational-medicine-friday/2025-research-neo-natal-inflammation-microglia-and-investigation-of-new-treatments
​2025 is bringing a continued focus on:
  • Neo-Natal Inflammation
  • Microglia (the Brain's Innate Immune Cells), and
  • More Investigation of New Treatments
Remimazolam attenuates lipopolysaccharide-induced neuroinflammation and cognitive dysfunction (2025)
​Ginsenoside reprogramming microglia through the FGF/FGFR1 inhibits post traumatic stress disorder (2025)
Neonatal inflammation impairs developmentally-associated microglia and promotes a highly reactive microglial subset (2025)
]]><![CDATA[Chronic Fatigue Syndrome & Neuro-developmental / Psychiatric Disorders]]>Fri, 07 Feb 2025 00:59:33 GMThttps://orchidadvocacy.org/translational-medicine-friday/chronic-fatigue-syndrome-neuro-developmental-psychiatric-disorders
Val's Take:   IT TAKES A LOT OF TIME AND ENERGY to UNDERSTAND THESE DISORDERS, especially if they have not been easily resolved with current understandings.

What's left is pretty darn complicated --- Health Disorders such as:
  • Neuro-Developmental and Psychiatric Disorders
  • ME/CFS
  • Cancer
  • Autoimmune Diseases
  • Neuro-Degenerative Disorders
  • Neuro-Immune Disorders
  • Etc.

Most "Neuro-Developmental" and "Psychiatric" diagnoses at this point are conceptualized as NEURO-DEVELOPMENTAL, MULTI-SYSTEM DISORDERS in the Research. 
  • How many People know that?
  • How many Clinicians know that?
  • How many Policymakers?
University of Michigan School of Medicine
Dr. Melvin McInnis

The Cells of People with Bipolar Disorder are Developmentally Different (2017)
​Columbia Public Health
​Dr. Mady Hornig

Scientists Discover Robust Evidence That Chronic Fatigue Syndrome (ME/CFS) Is a Biological Illness (2015)
​Broken Battery

ME/CFS -- The Greatest Medical Scandal of the 21st Century (2024)
​Many people with Neuro-Developmental & Psychiatric Disorders have issues with Burnout, Melt Downs & Shut Downs.  BIO-ENERGETICS is turning out to be a big issue in Neuro-Developmental & Psychiatric Disorders.

In fact, some type of Mitochondrial Dysfunction and Fatigue is associated with many diseases and disorders.

A lot of people in the Homeless Population get tagged with being "LAZY" or "UNMOTIVATED," and I think what is going on is much more complicated.
]]><![CDATA[Astrocytes in Depression and a complicated biological universe for criminal justice]]>Wed, 05 Feb 2025 15:06:57 GMThttps://orchidadvocacy.org/translational-medicine-friday/astrocytes-in-depression-and-a-complicated-biological-universe-for-criminal-justice
Various types of GLIAL CELLS  in both the Central Nervous System (CNS) and the Peripheral Nervous System (PNS) seem critical in Neuro-Developmental Disorders, Psychiatric Disorders, Neuro-Degenerative Disorders as well as other Diseases and Disorders.

This is exceedingly complicated in 2025. 

What happens if we have a Criminal Justice System that is unable to deal honestly and effectively with this COMPLEXITY?

Well, you might live in the most incarcerated country in the world that still has significant safety problems.
NeuroLingo

Liam Anuj O'Leary
McGill University (Canada)
McGill Group for Suicide Studies

Fewer astrocytes in depression
Picture
Astrocytic Neuroligin-3 influences gene expression and social behavior, but is dispensable for synapse number (2025)
Picture
​Widespread Decrease of Cerebral Vimentin-Immunoreactive Astrocytes in Depressed Suicides (2021)
]]><![CDATA[Microglia, Neuro-Degenerative Diseases & Neuro-Developmental Disorders]]>Fri, 31 Jan 2025 11:33:59 GMThttps://orchidadvocacy.org/translational-medicine-friday/microglia-neuro-degenerative-diseases-neuro-developmental-disorders
Dr. Melanie Capasso
DZNE, Bonn, Germany

Overactive Microglia in the Aging Brain
"Not only neurons exist in the brain, but also immune cells, the microglia. These microglia form our 'brain security' and protect the brain from pathogens.

"But with increasing age, the microglia, which are supposed to protect the brain, permanently raise the alarm and become chronically active.

"Inflammation occurs: this is an excessive immune reaction. The microglia turn against the brain and then secrete pro-inflammatory substances themselves.

"This violent over-activation in turn contributes to the progression of a neurodegenerative disease such as Alzheimer's – because inflammatory processes in the brain accelerate neurodegeneration, i.e. the death of neurons."
Lior Brimberg
Feinstein Institute for Medical Research

Captopril Reduces Microglial Activation in Autism and Improves Social Behavior
​​"As the primary brain immune cells, microglia are critical for maintaining a healthy brain and are recognized as important sculptors of neuronal development.

"Exposure in utero to maternal brain reactive antibodies may perturb microglia programing leading to neurodevelopmental disorder."
]]>