Translational Medicine Friday

Multi-Factoral Disease & Disorders and Epstein-barr Virus

6/26/2025

Predisposing and Precipitating Factors in Epstein-Barr Virus-Caused Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (2025)

Does Epstein-Barr virus and intracellular Toll-like receptors affect the course of Hashimoto disease? Findings from studies on newly-diagnosed patients (2025)

"Epstein-Barr virus (EBV) reactivation is increasingly recognized as a potential exacerbator of autoimmune diseases, including Hashimoto thyroiditis (HT)."

Epstein-Barr Virus BARF1 Is Expressed in Lung Cancer and Is Associated with Cancer Progression (2024)

Elevated Epstein-Barr Virus Antibody Level is Associated with Cognitive Decline in the Korean Elderly (2017)

Schizophrenia is Associated With an Aberrant Immune Response to Epstein-Barr Virus (2019)

Microglia as potential key regulators in viral-induced neuroinflammation (2024)

[What gets dysregulated in Maternal Immune Activation ---- MICROGLIA]

Unraveling the links between neurodegeneration and Epstein-Barr virus-mediated cell cycle dysregulation (2022)

Study identifies how Epstein-Barr virus triggers multiple sclerosis (updated 2025)

Epstein-Barr virus infection increases the risk of depression: A cross-sectional study and Mendelian randomization analysis (2025)

Shared interactions of six neurotropic viruses with 38 human proteins: a computational and literature-based exploration of viral interactions and hijacking of human proteins in neuropsychiatric disorders (2025)

New insights on the link between Epstein‑Barr virus infection and cognitive decline in neurodegenerative diseases (Review) (2024)

Awakening the sleeping giant: Epstein–Barr virus reactivation by biological agents (2024)

Chronic Fatigue Syndrome

6/25/2025

Val's Take: It is more and more obvious that many Neuro-Developmental and Psychiatric Disorders are BLURRED and not distinct.

It is becoming more and more obvious that physical health issues are BLURRING with Neuro-Developmental and Psychiatric Disorders.

Three of the most obvious are Thyroid Disorders, Chronic Fatigue Syndrome and Long Covid.

Probably patients with Chronic Fatigue Syndrome more than any other have fought a "PSYCHIATRIC LABEL" ---

"I've got a REAL ILLNESS --- not a Mental Illness"

Patients with Chronic Fatigue Syndrome do have REAL PHYSICAL FATIGUE and they often do have cognitive or psychiatric symptoms.

People with "MENTAL ILLNESS" often do have REAL PHYSICAL FATIGUE (not always to the extent of CFS -- but enough to greatly affect their quality of life).

AND that FATIGUE is complicated.

Childhood neurodivergent traits, inflammation and chronic disabling fatigue in adolescence: a longitudinal case-control study (2025)

The impact of autoimmune thyroid disease on cognitive and psychiatric disorders: focus on clinical, pre-clinical and molecular studies (2025)

Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (2025)

Dr. Sanil Rege
Chronic Fatigue Syndrome (CFS) or Myalgic Encephalomyelitis (ME)

"Correction: 14:19 Graded Exercise Therapy NOT Graded Exposure Therapy. Graded exercise therapy is a term used in varying ways by different services supporting people with ME/CFS. (NICE).

"In this guideline, graded exercise therapy is defined as first establishing an individual's baseline of achievable exercise or physical activity, then making fixed incremental increases in the time spent being physically active.

"This definition of graded exercise therapy reflects the descriptions given in the evidence that was reviewed, and it is this approach that the guideline says should not be undertaken.

"Correction: 14:25 Graded Exercise Therapy NOT Graded Exposure Therapy"

Medical Secrets
Dr. Anthony Kaveh
Chronic Fatigue Syndrome

Association of preexisting psychiatric disorders with post-COVID-19 prevalence: a cross-sectional study (2023)

Paradigm Shift: Cytokine Therapeutics In Mental Health

6/24/2025

Val's Take/Conjecture

The most striking thing about conceptualizing Neuro-Developmental and Psychiatric Disorders as Neuro-Immune Disorders affecting Multiple Systems of the Body ----
- It's illuminating not only Neuro-Developmental and Psychiatric Disorders but also many other diseases and disorders as well.

Google AI Overview

What Medical Disciplines Generally Target Cytokines?

Multiple medical disciplines focus on or utilize cytokines due to their crucial role as signaling molecules in the immune system and their involvement in various disease processes.

Cytokines regulate inflammation, cell growth and differentiation, and immune responses.

Here are some of the key disciplines:

Immunology: Cytokines are fundamental to understanding immune responses, and immunologists investigate their function in both healthy and diseased states.
Rheumatology: Cytokines are central to the pathogenesis of rheumatoid arthritis and other inflammatory diseases, with therapies targeting cytokines like TNF-α and IL-6 having revolutionized treatment.
Oncology (Cancer Treatment): Cytokine therapy, including the use of interferons and interleukins like IL-2, is used to boost the immune system's ability to fight cancer cells.
Dermatology: Cytokine-based treatments are employed for various skin conditions, including melanoma, psoriasis, and vitiligo.
Gastroenterology: Cytokine-targeted therapies are transforming the management of inflammatory bowel diseases (IBD) like Crohn's disease.
Infectious Disease: Cytokines play a critical role in the inflammatory response to infections, and cytokine-based therapies can be used to manage infectious diseases, such as Kaposi's sarcoma associated with HHV-8 virus.
Psychiatry: Evidence suggests that cytokines may be involved in certain psychiatric conditions, and research is ongoing in this area.

Causal relationship between psoriasis and psychiatric disorders with the potential mediating factors: a two-step Mendelian Randomization study (2025)

*Chinese researchers

Background: Psoriasis (PsO) is a chronic, recurrent inflammatory skin disorder, with a high prevalence of psychiatric comorbidities.

Although various studies explore the association between the two diseases, the causal relationship and underlying mechanisms remain poorly understood.

PsO may be linked to the aberrant secretion of circulating cytokines, and disturbances in peripheral inflammatory factors are considered substantial contributors to central pathophysiological abnormalities.

Thus circulating inflammatory cytokines may serve as potential mediators in the association of PsO and psychiatric comorbidities.

Targeting Cytokine-Mediated Inflammation in Brain Disorders: Developing New Treatment Strategies (2025)

*Researchers from Finland, India, Sweden, Bangladesh, Texas, Mexico and Norway

Abstract

Cytokine-mediated inflammation is increasingly recognized for playing a vital role in the pathophysiology of a wide range of brain disorders, including neurodegenerative, psychiatric, and neurodevelopmental problems.

Pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) cause neuroinflammation, alter brain function, and accelerate disease development.

Despite progress in understanding these pathways, effective medicines targeting brain inflammation are still limited.

Traditional anti-inflammatory and immunomodulatory drugs are effective in peripheral inflammatory illnesses.

Still, they face substantial hurdles when applied to the central nervous system (CNS), such as the blood-brain barrier (BBB) and unwanted systemic effects.

This review highlights the developing treatment techniques for modifying cytokine-driven neuroinflammation, focusing on advances that selectively target critical cytokines involved in brain pathology.

Novel approaches, including cytokine-specific inhibitors, antibody-based therapeutics, gene- and RNA-based interventions, and sophisticated drug delivery systems like nanoparticles, show promise with respect to lowering neuroinflammation with greater specificity and safety.

Furthermore, developments in biomarker discoveries and neuroimaging techniques are improving our ability to monitor inflammatory responses, allowing for more accurate and personalized treatment regimens.

Preclinical and clinical trial data demonstrate the therapeutic potential of these tailored techniques.

However, significant challenges remain, such as improving delivery across the BBB and reducing off-target effects.

As research advances, the creation of personalized, cytokine-centered therapeutics has the potential to alter the therapy landscape for brain illnesses, giving patients hope for better results and a higher quality of life.

***Physical Health Issues, the Immune System and Mental Health

Multiple Sclerosis and Mood Disorders

6/23/2025

Val's Take

One of the big discoveries of the last decade or so is that many Neuro-Developmental and Psychiatric Disorders are blurred --- not distinct.

Further, that among other things is driving the need for PRECISION MEDICINE.

Additionally. many other chronic illnesses have psychiatric symptoms.

Integrating Physical and Mental Health Care has already begun --- and there is more to do.

National MS Society
Mood Changes in MS

Clinical Immunology is slowly But Surely Stepping Up

6/21/2025

Val's Take/Conjecture

Over 100 years ago medical researchers began speculating about a role for the Immune System in psychiatric disorders.
Now with better technology those suppositions are proving to be true.
Especially in the last 10 to 15 years--- the research linking neuro-developmental and psychiatric disorders to the Immune System has exploded.

When we talk about integrating Physical and Mental Health
- What does that Care Team look like?
We're talking about idiosyncratic Neuro-Immune Disorders that impact multiple systems of the body.

What are the ramifications of these new understandings for people who are Homeless and/or Justice-Involved?

THE HISTORY OF LINKING THE IMMUNE SYSTEM TO PSYCHIATRIC DISORDERS

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

Editorial: Peripheral Markers of Immune Response in Major Psychiatric Disorders: Where Are We Now and Where Do We Want to Be? (2019)

Conventional and new immunotherapies for immune system dysregulation in postpartum mood disorders: comparisons to immune system dysregulations in bipolar disorder, major depression, and postpartum autoimmune thyroid disease. (2025)

Abstract

Introduction: Postpartum mood disorders are heterogenous disorders and comprise postpartum psychosis and postpartum depression.

Evidence is accumulating that systemic monocyte/macrophage activation, low-grade inflammation and (premature senescence related) T cell defects increase the risk for mood disorders outside pregnancy by affecting the function of microglia and T cells in the emotional brain (the cortico-limbic system) leading to inadequate mood regulation upon stress.

Areas covered: The evidence in the literature that similar immune dysregulations are present in postpartum mood disorders.

Results: The physiological postpartum period is characterized by a rapid T cell surge and a mild activation of the monocyte/macrophage system.

Postpartum mood disorder patients show a diminished T cell surge (including that of T regulatory cells) and an increase in low grade inflammation, that is, an increased inflammatory state of monocytes/macrophages and higher levels of serum pro-inflammatory cytokines.

Expert opinion: Anti-inflammatory agents (e.g. COX-2 inhibitors) and T cell boosting agents (e.g. low-dose IL-2 therapy) should be further investigated as treatment.

The hypothesis should be investigated that postpartum mood disorders are active episodes (triggered by changes in the postpartum immuno-endocrine milieu) in ongoing, dynamically fluctuating aberrant neuro-immune-endocrine trajectories leading to mood disorders in women (inheritably) vulnerable to these disorders.

Immune Disorders, Neuro-Developmental Disorders and Biomarkers

6/21/2025

Association of aging related genes and immune microenvironment with major depressive disorder (2025)

Conclusion: The process of aging, immune dysregulation, and MDD [Major Depressive Disorder] closely interconnected.

MMP9, IL7R, S100B, and EGF may be used as novel diagnostic biomarkers and potential therapeutic targets for MDD, especially MMP9.

Shared molecular mechanisms and transdiagnostic potential of neurodevelopmental disorders and immune disorders (2024)

Highlights

•Neurodevelopmental disorders share a common genetic foundation with immune disorders but exhibit a higher degree of polygenicity.
•This study identified thirty genomic loci with significant associations in both types of diseases, including eight novel loci.
•The shared loci were mapped to genes enriched in three classes of pathways.
•The pleiotropic loci show a significant association with blood cell traits, potentially serving as more accessible and feasible biomarkers for patient stratification.

Maternal Immune Activation Activates Inflammatory Genes in the Fetus

6/21/2025

Maternal Immune Activation Alters Fetal Brain Development and Enhances Proliferation of Neural Precursor Cells in Rats (2020)

"Maternal immune activation (MIA) caused by exposure to pathogens or inflammation during critical periods of neurodevelopment is a major risk factor for behavioral deficits and psychiatric illness in offspring. . . .

"We identified a robust increase in expression of genes related to antiviral inflammation following maternal PolyI:C exposure, and a corresponding decrease in transcripts associated with nervous system development."

Impact of maternal immune activation and sex on placental and fetal brain cytokine and gene expression profiles in a preclinical model of neurodevelopmental disorders (2024)

What is a Neuro-Immune Transcriptome?

6/21/2025

Neuroimmune transcriptome changes in patient brains of psychiatric and neurological disorders (2023)

The Australian Researcher Cynthia Shannon Weickert participated in this --- she has been on the forefront of research involving the immune system and psychiatric disorders.

She has a twin brother with "Schizophrenia."

Professor Cyndi Shannon Weickert (Neuroscience Research Australia) talks with ABC Radio National's Dr Norman Swan on the Health Report (2012)

Is an Overactive Immune System a Cause of Schizophrenia?

Paradigm shift: Mood Disorders are not just brain disorders, they are multi-System Disorders

6/21/2025

Val's Take/Conjecture

The lead author of the article to the right is Dr. Antonio Teixeira at the University of Texas.
Dr. Teixeira literally edited the book on Immunopsychiatry -- published by Oxford University Press.

Dr. Antonio L Teixeira

This book is designed to be a clinician's introduction. It was published by Oxford University Press in 2019.

Neuro-Developmental & Psychiatric Disorders as Multi-System Disorders

Addressing Multi-System Developmental Neuro-Immune Disorders --- Is the Mental Health Profession up to addressing this alone?

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 [age-related decline in functionality of the immune system].

[bullets added]

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

REGULATING AGGRESSION THROUGH THE IMMUNE SYSTEM

6/21/2025

Val's Take/Conjecture

Stephen Hawking maintained that addressing Aggression was the top problem facing humanity.
But the biological basis of the challenge doesn't necessarily match with the MYSTIQUE we may have imagined.

Link Between the Immune System and Aggression

The Role of Interleukin 1β in Aggression in Animal Models (2023)

Study: Antibiotics in Infancy Linked to Increased Aggression (2024)

Plasma and cerebrospinal fluid inflammatory markers and human aggression (2023)

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

*Japanese Researcher

Abstract

There is an important relationship between the immune system and aggressive behavior.

Aggressive encounters acutely increase the levels of proinflammatory cytokines, and there are positive correlations between aggressive traits and peripheral proinflammatory cytokines.

Endotoxin lipopolysaccharide (LPS) treatment, which results in peripheral immune activation, decreases aggressive behavior as one of the sickness behavioral symptoms.

In contrast, certain brain infections and chronic interferon treatment are associated with increased aggression.

Indeed, the effects of proinflammatory cytokines on the brain in aggressive behavior are bidirectional, depending on the type and dose of cytokine, target brain region, and type of aggression.

Some studies have suggested that microglial activation and neuroinflammation influence intermale aggression in rodent models.

In addition, pathological conditions as well as physiological levels of cytokines produced by microglia play an important role in social and aggressive behavior in adult animals.

Furthermore, microglial function in early development is necessary for the establishment of the social brain and the expression of juvenile social behaviors, including play fighting.

Overall, this review discusses the important link between the immune system and aggressive traits and the role of microglia as mediators of this link.

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