Blog Posts

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.

How can microglia (the brain's immune cells) affect Mental States?

6/21/2025

Microglia-Derived Interleukin-6 Triggers Astrocyte Apoptosis [Cell Death] in the Hippocampus and Mediates Depression-Like Behavior
(2025)

Chinese Researchers

Microglia Sing the Prelude of Neuroinflammation-Associated Depression (2025)

Chinese Researchers

Abstract

Major depressive disorder (MDD) is a psychiatric condition characterized by sadness and anhedonia and is closely linked to chronic low-grade neuroinflammation, which is primarily induced by microglia.

Nonetheless, the mechanisms by which microglia elicit depressive symptoms remain uncertain.

This review focuses on the mechanism linking microglia and depression encompassing the breakdown of the blood-brain barrier, the hypothalamic-pituitary-adrenal axis, the gut-brain axis, the vagus and sympathetic nervous systems, and the susceptibility influenced by epigenetic modifications on microglia.

These pathways may lead to the alterations of microglia in cytokine levels, as well as increased oxidative stress.

Simultaneously, many antidepressant treatments can alter the immune phenotype of microglia, while anti-inflammatory treatments can also have antidepressant effects.

This framework linking microglia, neuroinflammation, and depression could serve as a reference for targeting microglia to treat depression.

Neuro-Diversity, Inflammation, Sensory Processing Differences --- and Trauma

6/21/2025

Val's Take/Conjecture

People with Neuro-Developmental and Psychiatric Disorders are more vulnerable to POST TRAUMATIC STRESS DISORDER.
There may be many reasons for that --- and the 3Ms are relevant:
- Maternal Immune Activation
- Dysregulation of MIcroglia, and
- MItochondrial Dysfunction.

Maternal immune activation and neuroinflammation in human neurodevelopmental disorders (2021)

Investigating the effects of maternal immune activation on sensory processing: Timing, immune mechanisms, and gene-environment interactions (2021)

By Faraj Haddad
University of Western Ontario

Mitochondrial dysfunction as a possible trigger of neuroinflammation at post-traumatic stress disorder (PTSD) (2023)

*Ukrainian and Canadian Researchers

Sensory alterations in post-traumatic stress disorder (2024)

Genetic insights into the role of mitochondria-related genes in mental disorders: An integrative multi-omics analysis (2025)

*Chinese Researchers

Conclusions: These findings suggested that dysfunction in mitochondria-related genes may underlie the molecular mechanisms of ADHD and SCZ, providing novel biomarkers for diagnosis and therapeutic interventions.

[Val's Take: At least in some to many cases, it is likely that dysfunction in mitochondria-related genes began IN UTERO with Maternal Immune Activation.

This also goes to the idea of a Neuro-Developmental - Psychiatric Continuum that is BLURRED and not distinct as the DSM.]

Trans-Cranial Magnetic Stimulation AS A Treatment for MICROGLIAL Dysregulation

6/20/2025

[Microglia are the innate immune cells of the brain & central Nervous system]

Val's Take/Conjecture

These studies provide more corroboration that Neuro-Developmental & Psychiatric Disorders are NEURO-IMMUNE DISORDERS.
Further, many of our current treatments are being re-evaluated in light of new understandings and paradigms.
Additionally, researchers are working to refine treatments such as Transcranial Magnetic Stimulation (TMS) to make them more targeted and effective based on these new understandings and paradigms.

Low-frequency repetitive transcranial magnetic stimulation alleviates abnormal behavior in valproic acid rat model of autism through rescuing synaptic plasticity and inhibiting neuroinflammation
(2024)

"Prenatal VPA exposure increased the level of inflammation cytokines and promoted the excessive activation of microglia.

"rTMS significantly alleviated the prenatal VPA-induced abnormalities including behavioral and synaptic plasticity deficits, and excessive neuroinflammation.

"TMS maybe a potential strategy for autism therapy via rescuing synaptic plasticity and inhibiting neuroinflammation."

Neuroprotective and plasticity promoting effects of repetitive transcranial magnetic stimulation (rTMS): A role for microglia (2025)

"Given their critical involvement in neurodegenerative and neuropsychiatric disorders, modulating microglial function presents a promising therapeutic avenue.

"In this context, rTMS is emerging as a potential strategy to influence microglial activity, suggesting that these cells serve as both targets and key mediators of rTMS-induced plasticity, neuroprotection, and therapeutic outcomes.

"Findings from in vitro and in vivo studies highlight how these interactions contribute to the therapeutic benefits of rTMS across various neuropsychiatric disorders."

Microglial Cytokines Mediate Plasticity Induced by 10 Hz Repetitive Magnetic Stimulation (2023)

"We conclude that rTMS affects neural excitability and plasticity by modulating the release of cytokines from microglia."

Transcranial Magnetic Stimulation for Developmental Neuropsychiatric Disorders with Inflammation (2023)

<<Previous

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Translational Medicine Friday

Multiple Sclerosis and Mood Disorders

Clinical Immunology is slowly But Surely Stepping Up

Immune Disorders, Neuro-Developmental Disorders and Biomarkers

Maternal Immune Activation Activates Inflammatory Genes in the Fetus

What is a Neuro-Immune Transcriptome?

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

REGULATING AGGRESSION THROUGH THE IMMUNE SYSTEM

How can microglia (the brain's immune cells) affect Mental States?

Neuro-Diversity, Inflammation, Sensory Processing Differences --- and Trauma

Trans-Cranial Magnetic Stimulation AS A Treatment for MICROGLIAL Dysregulation

[Microglia are the innate immune cells of the brain & central Nervous system]

Translational Medicine Friday

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