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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)

The Kynurenine Pathway and multi-System Neuro-Developmental & Psychiatric disorders

6/19/2025

"The immune-KYN-neuroendocrine interaction"

Val's Take/Conjecture

One of the big paradigm shifts of the 21st Century is recognizing Neuro-Developmental and Psychiatric Disorders as MULTI-SYSTEM DISORDERS, not just BRAIN DISORDERS.

In 1987, the Psychoneuroimmunology Research Society (PNIRS) established the Brain, Behavior, and Immunity Journal --- that also now includes the Endocrine System.

The KYNURENINE PATHWAY has emerged not only as a common molecular pathway for Neuro-Developmental, Psychiatric and Neuro-Degenerative Disorders --- but also much of our chronic disease epidemic of Diabetes, Auto-Immune Disorders, Cancer, etc.

Maternal Immune Activation is associated with increased risk of Type 1 and Type 2 Diabetes and Cancer and thought to increase the risk of adult on-set Auto-Immune Disease in offspring.
- Further, those illnesses often come with psychiatric symptoms.

Diet and Exercise are important, but if we're not recognizing "NEURO-DEVELOPMENTAL IMPAIRMENT" of MULTIPLE SYSTEMS OF THE BODY through various biological mechanisms such as:

Maternal Immune Activation
Paternal Immune Activation
Microglia Dysregulation
Immune Dysregulation
Endocrine Dysregulation
Dysregulation of the KYNURENINE PATHWAY
Microbiota Dysregulation
Metabolic Dysregulation
Etc.

---- We're going to have an incomplete and highly misleading understanding of what's going on.

Diverse Physiological Roles of Kynurenine Pathway Metabolites: Updated Implications for Health and Disease (2025)

Abstract

Tryptophan is an essential amino acid critical for human health. It plays a pivotal role in numerous physiological and biochemical processes through its metabolism.

The kynurenine (KYN) pathway serves as the principal metabolic route for tryptophan, producing bioactive metabolites, including KYN, quinolinic acid, and 3-hydroxykynurenine.

Numerous studies are actively investigating the relationship between tryptophan metabolism and physiological functions.

These studies are highlighting the interactions among metabolites that may exert synergistic or antagonistic effects, such as neuroprotective or neurotoxic, and pro-oxidative or antioxidant activities.

Minor disruptions in the homeostasis of these metabolites can result in immune dysregulation, contributing to a spectrum of diseases.

These diseases include neurological disorders, mental illnesses, cardiovascular conditions, autoimmune diseases, and chronic kidney disease.

[See also Targeting the kynurenine pathway: another therapeutic opportunity in the metabolic crosstalk between cancer and immune cells (2025)]

Therefore, understanding the physiological roles of the KYN pathway metabolites is essential for elucidating the contribution of tryptophan metabolism to health regulation.

The present review emphasizes the physiological roles of KYN pathway metabolites and their mechanisms in disease development, aiming to establish a theoretical basis for leveraging dietary nutrients to enhance human health.

Implications of Kynurenine Pathway Metabolism for the Immune System, Hypothalamic-Pituitary-Adrenal Axis, and Neurotransmission in Alcohol Use Disorder (2024)

Abstract

In recent years, there has been a marked increase in interest in the role of the kynurenine pathway (KP) in mechanisms associated with addictive behavior.

Numerous reports implicate KP metabolism in influencing the immune system, hypothalamic-pituitary-adrenal (HPA) axis, and neurotransmission, which underlie the behavioral patterns characteristic of addiction.

An in-depth analysis of the results of these new studies highlights interesting patterns of relationships, and approaching alcohol use disorder (AUD) from a broader neuroendocrine-immune system perspective may be crucial to better understanding this complex phenomenon.

In this review, we provide an up-to-date summary of information indicating the relationship between AUD and the KP, both in terms of changes in the activity of this pathway and modulation of this pathway as a possible pharmacological approach for the treatment of AUD.

The correlation of inflammation, tryptophan-kynurenine pathway, and suicide risk in adolescent depression (2024)

Accumulating evidence suggests a role for the tryptophan-kynurenine pathway (TKP) in the psychopathology of major depressive disorder (MDD).

Abnormal inflammatory profile and production of TKP neurotoxic metabolites appear more pronounced in MDD with suicidality. . . .

"Our findings indicated that serum inflammatory cytokines were robustly associated with IDO and KMO activity, along with significantly decreased serum level of TRP, increased level of 3-HK, and higher suicide risk in adolescent depression."
Accumulating evidence suggests a role for the tryptophan-kynurenine pathway (TKP) in the psychopathology of major depressive disorder (MDD).

Abnormal inflammatory profile and production of TKP neurotoxic metabolites appear more pronounced in MDD with suicidality. . . .

"Our findings indicated that serum inflammatory cytokines were robustly associated with IDO and KMO activity, along with significantly decreased serum level of TRP, increased level of 3-HK, and higher suicide risk in adolescent depression."

Maternal immune activation induces neurodevelopmental impairments of adult offspring through alterations in tryptophane-kynurenine pathway in the placenta (2024)

The kynurenine pathway: a finger in every pie (2020)

Abstract

The kynurenine pathway (KP) plays a critical role in generating cellular energy in the form of nicotinamide adenine dinucleotide (NAD+).

Because energy requirements are substantially increased during an immune response, the KP is a key regulator of the immune system.

Perhaps more importantly in the context of psychiatry, many kynurenines are neuroactive, modulating neuroplasticity and/or exerting neurotoxic effects in part through their effects on NMDA receptor signaling and glutamatergic neurotransmission.

As such, it is not surprising that the kynurenines have been implicated in psychiatric illness in the context of inflammation.

However, because of their neuromodulatory properties, the kynurenines are not just additional members of a list of inflammatory mediators linked with psychiatric illness, but in preclinical studies have been shown to be necessary components of the behavioral analogs of depression and schizophrenia-like cognitive deficits.

Further, as the title suggests, the KP is regulated by, and in turn regulates multiple other physiological systems that are commonly disrupted in psychiatric disorders, including endocrine, metabolic, and hormonal systems.

This review provides a broad overview of the mechanistic pathways through which the kynurenines interact with these systems, thus impacting emotion, cognition, pain, metabolic function, and aging, and in so doing potentially increasing the risk of developing psychiatric disorders.

Novel therapeutic approaches targeting the KP are discussed.

Moreover, electroconvulsive therapy, ketamine, physical exercise, and certain non-steroidal anti-inflammatories have been shown to alter kynurenine metabolism, raising the possibility that kynurenine metabolites may have utility as treatment response or therapeutic monitoring biomarkers.

Neuro-Diversity and Thyroid Problems

6/15/2025

Val's Take/Conjecture

In 2025, part of understanding Neuro-Developmental and Psychiatric Disorders is understanding them as MULTI-SYSTEM DISORDERS.
"Thyroid Disorders" and other Auto-Immune Diseases are also often implicating more than one Generation.
- Maternal Auto-Immune Disorders are a source of Maternal Immune Activation during pregnancy.
- And that Maternal Immune Activation can disrupt multiple systems of the body in offspring, including the ENDOCRINE SYSTEM and the THYROID.

Causal relationship between graves' disease and mental disorders: A bidirectional Mendelian randomization study (2025)

Conclusions: This bidirectional MR [Mendelian Randomized] study supports the role of GD [Graves Disease] in the causal association with an increased risk of bipolar disorder, which guides us to pay attention to the mental diseases of GD patients in the clinic.

Dr. Daniel Amen -- Brain Warrior's Way
10 Signs Thyroid Problems May Be Impacting Your Mental Health

Hormonal disorders in autism spectrum disorders (2025)

The Potential Role of Thyroid Hormone Therapy in Neural Progenitor Cell Differentiation and Its Impact on Neurodevelopmental Disorders (2024)

Maternal Immune Activation and MIcroglia dysregulation

6/13/2025

Understanding the developmental beginnings of Many Neuro-Developmental & Psychiatric Disorders

Val's Take/Conjecture

Maternal Immune Activation and MIcroglia Dysregulation (Dysregulation of the Brain's Innate Immune Cells) are 2 important pieces to the puzzle of Neuro-Developmental and Psychiatric Disorders.
Mitochondria, Microglia, and the Immune System—How Are They Linked in Affective Disorders? (2019)
Dysfunctional Mitochondria is a hallmark of aging.

WHAT'S THE POINT?

These paradigms and understandings don't look like the DSM.
Now, there appear to be plans to get the DSM 6 on a more biologically sound footing.
There are many legal and policy ramifications of these new understandings--- we need a concerted effort to address them.

The roles of immune factors in neurodevelopment (2025)

A microglia-containing cerebral organoid model to study early life immune challenges (2025)

Prenatal Immune Stress: Its Impact on Brain Development and Neuropsychiatric Disorders (2025)

"Many epidemiological studies have indicated that prenatal immune stress, frequently elicited by maternal immune activation, underlies a major risk for neuropsychiatric disorders of neurodevelopmental origin, such as schizophrenia and autism spectrum disorders."

metabolic dysregulation and neuro-developmental and Psychiatric disorders

6/12/2025

Val's Take/Conjecture

"Metabolic Dysregulation" like a lot of this is on a "Spectrum."

I'm going to be adding "Catch-22" on the "Orchid Theme's and Symbols" page -- I've already used it a lot and I'm going to use it now.

I think the Crux of the "Catch-22" for many people with Neuro-Developmental and Psychiatric Disorders is:

They often have more synapses and brain hyper-plasticity which require more ENERGY, BUT
Due to dysregulation of Microglia IN UTERO as a result of Maternal Immune Activation (and Paternal Immune Activation), Metabolism is dysregulated with Mitochondrial dysregulation and insufficient ATP.
So they actually need more ENERGY than the average person to supply their brains --- but their bodies have less ability to efficiently convert Glucose into ATP.

Lauren Kennedy West with Dr. Chris Palmer

Are Mental Illnesses Really Metabolic Disorders?

Dysregulation of immune and metabolism pathways in maternal immune activation induces an increased risk of autism spectrum disorders (2023)

Mitochondria at the crossroad of dysregulated inflammatory and metabolic processes in bipolar disorders (2024)

Microglia in Central Control of Metabolism (2023)

Glucose dysregulation in antipsychotic-naive first-episode psychosis: in silico exploration of gene expression signatures (2024)

Neuroimmunometabolism: how metabolism orchestrates immune response in healthy and diseased brain (2025)

Neuro-Immuno-Metabolism

Cleveland Clinic -- Continuing Medical Education (2015)

Metabolic Comorbidities in Autism Spectrum Disorder – Part Two

The BRAIN Foundation

Metabolic Autism Prediction (MAP) Study - John Slattery, BioROSA Technologies @Synchrony (2021)

Glucose transporter 1 deficiency, AMP-activated protein kinase activation and immune dysregulation in autism spectrum disorder: Novel biomarker sources for clinical diagnosis (2023)

The Ethics of Mitochondrial Replacement Therapy & Transplantation

6/11/2025

Val's Take/Conjecture

The United Kingdom and Australia are the only countries to specifically approve the use of Mitochondrial Replacement Therapy.
- Both the UK and Australia are using Mitochondrial Replacement Therapy in the context of Reproductive Medicine and IVF (In Vitro Fertilization).
The US Food & Drug Administration (FDA) is prohibited from approving Mitochondrial Replacement Therapy research and clinical applications.

What's the point?

The main point is that researchers around the world are honing in on potential new therapeutics based on new paradigms.

Mitochondrial Transplantation in Animal Models of Psychiatric Disorders: A Novel Approach to Psychiatric Treatment (2025)

*Japanese Researchers

Researchers are targeting pro-inflammatory microglia --- including wholesale replacement

Mitochondrial transplantation in brain disorders: Achievements, methods, and challenges (2025)

*Swiss Researchers

Mitochondria in the Central Nervous System in Health and Disease: The Puzzle of the Therapeutic Potential of Mitochondrial Transplantation (2024)

*Israeli Researchers

Mitochondrial Replacement Therapy: In Whose Interests? (2022)

*Canadian & US Authors

Dr. Michael Burton and Neuro-Immunology and Behavior

6/8/2025

Dr. Michael Burton, PhD
Center for Brain Health
University of Texas

Neuroimmunology and Behavior (2025)

For a much shorter video click HERE

Trauma, Bessel van der kolk and Concern about what is happening in the us

6/6/2025

See also: Trauma, trust and triumph: psychiatrist Bessel van der Kolk on how to recover from our deepest pain

"The reality, of course, is that being traumatised does make you a difficult person to get along with."

Experts in traumatic stress are concerned about global impact of what is happening in U.S (2025)

Bessel van der Kolk
Your reality narrows after trauma — here’s how to expand it

"UNreasonable Fatigue" & Mitochondrial dysfunction in NEuro-Developmental & Psychiatric Disorders

5/30/2025

Val's Take/Conjecture

One of the amazing accomplishments of Modern psychiatric drugs of the past few decades --- they could resolve a psychosis in many cases.

Just get the medication right and add some Cognitive Behavioral Therapy (CBT) --- and you're good to go.

Well, sort of.

It's been within the past 10 to 15 years that there has been a significant recognition that people with Neuro-Developmental and Psychiatric disorders have differences in EXECUTIVE FUNCTIONING.

It's been more recently that we are linking Executive Functioning challenges to Mitochondria Dysfunction and Microglia Dysregulation -- dysregulation of the brain's innate immune cells.

This is not just Psychiatry or Neurology --- this is also Immunology (and other bodily systems and disciplines as well).

Mitochondrial dysfunction in psychiatric disorders (2024)

Inflammation-induced mitochondrial and metabolic disturbances in sensory neurons control the switch from acute to chronic pain (2023)

Mitochondrial dysfunction: A fatal blow in depression (2023)

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

Elena Carroll
What Autism Fatigue Really Looks Like in High Maskers

"UNREASONABLE FATIGUE"

More and more Neuro-Diverse youtubers are tackling the topics of FATIGUE and BURNOUT.
Certainly, it looks like TIREDNESS, but it can also look like:
- IRRITABILITY
- PAIN --- maybe that associated with Migraines
- Etc.

Innate immune dysfunction and neuroinflammation in autism spectrum disorder (ASD) (2023)

Mitochondria and Mood: Mitochondrial Dysfunction as a Key Player in the Manifestation of Depression (2018)

Dr Naglaa Elmongy ----The Role of Inflammation in Depression & Fatigue

5/29/2025

Val's Take: Neuro-Developmental and Psychiatric Disorders are starting to look much more like other illnesses.

Neuro-Developmental and Psychiatric Disorders involve the Immune System, Cytokines, and Macrophages.

Many other illnesses have psychiatric symptoms.

Derma Immunology---
Dr Naglaa Elmongy
The Role of Inflammation in Depression & Fatigue

<<Previous

Translational Medicine Friday

Trans-Cranial Magnetic Stimulation AS A Treatment for MICROGLIAL Dysregulation

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

The Kynurenine Pathway and multi-System Neuro-Developmental & Psychiatric disorders

"The immune-KYN-neuroendocrine interaction"

Neuro-Diversity and Thyroid Problems

Maternal Immune Activation and MIcroglia dysregulation

Understanding the developmental beginnings of Many Neuro-Developmental & Psychiatric Disorders

metabolic dysregulation and neuro-developmental and Psychiatric disorders

The Ethics of Mitochondrial Replacement Therapy & Transplantation

Dr. Michael Burton and Neuro-Immunology and Behavior

Trauma, Bessel van der kolk and Concern about what is happening in the us

"UNreasonable Fatigue" & Mitochondrial dysfunction in NEuro-Developmental & Psychiatric Disorders

Dr Naglaa Elmongy ----The Role of Inflammation in Depression & Fatigue

Translational Medicine Friday

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