Blog Archives

Maternal Immune Activation, above average intelligence & above Average Inflammation

2/28/2025

Val's Take/Conjecture

It is interesting that AI is coming to the fore, just as we are recognizing significant limits of Human Intelligence.
We're only processing a fraction of the information out there ---- and it's taking an enormous amount of energy to process what we are processing.
Contrary to what we might think --- it takes a lot of energy to think.
Sensory Processing is associated with Intelligence and the Immune System.
The challenge for many neurodivergent people is that they are taking in more information --- but it is taking them more energy to process it --- and various dysfunctions including microglial dysfunction and mitchondrial are making that difficult.

Tonic on Demand
Bipolar Disorder (2016)

See 3:18: Bipolar linked to the EXCEPTIONALITIES in the Humanities -- above average, below average -- the main thing -- NOT AVERAGE.

Maternal immune activation and its multifaceted effects on learning and memory in rodent offspring: A systematic review (2024)

Highlights

•  Maternal immune activation (MIA) can impair offspring learning and memory.

•  MIA negatively impacts cognition in rodents.

•  Males are more susceptible to cognitive deficits.

•  Some studies show improved cognition after MIA.

•  Sex differences in immune responses may explain cognitive outcomes.

Lactoferrin alleviates the adverse effects of early-life inflammation on depression in adults by regulating the activation of microglia (2025)

Inflammation, Fatigue, Aggression and Neuro-Diversity

2/28/2025

Val's Take/Conjecture

FATIGUE is a driving issue in many Neuro-Diverse challenges.
We are starting to recognize the association between Neuro-Diversity and other disorders and diseases involving fatigue such as:
- ME/CFS (Chronic Fatigue Syndrome),
- Fibromyalgia
- Multiple Sclerosis
- Hyper-Mobility Syndromes
- etc.
The disorders listed above tend to hit women much harder than men, although there are exceptions.

When it comes to some Neuro-Diverse men and energy and aggression, the conversation is complicated.

It's not that women aren't using AGGRESSION as well to gin their energy up, but they may not be getting away with it and even women who are getting away with it---

those women are not likely to be as physically aggressive.

So when someone like Elon Musk says --- "Hey, I'm this high energy, aggressive Neuro-Diverse guy"

Yeah, but
You wouldn't be so aggressive, if you had the energy not to be.

Further, the aggression doesn't create energy, it mobilizes what energy is there by the release of stress hormones.

Prolonged exertion of self-control causes increased sleep-like frontal brain activity and changes in aggressivity and punishment (2024)

Childhood neurodivergent traits, inflammation and chronic disabling fatigue in adolescence: a longitudinal case–control study (2024)

Conclusions: Our results indicate higher risk of chronic disabling fatigue for children with neurodivergent traits, likely linked to higher levels of inflammation. The implementation of transdiagnostic screening criteria to inform support strategies to counteract risk early in life is recommended.

Stress, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis, and aggression (2024)

All adolescents need support making the transition to Adulthood, and Neuro-Diverse kids with an IQ over 70 need support in order to avoid Homelessness or Criminal Justice involvement.

That "Executive Functioning" from ages 4-6 may undergo previously unpredicted upheavals due to complex dysregulations of the brain's immune cells, among many other things.

CATCH 22: DO You have enough ATP to run all those synapses & that 'Hyper-Plastic' brain?

2/23/2025

Val's Take/Conjecture

It was just a few years ago that everyone was talking about "Brain Plasticity."
I thought that was so cool UNTIL I came across the research that people with ADHD & Autism often have HYPER-PLASTIC BRAINS.

This idea of "BRAIN ENERGY" is linking some things together such as MICROGLIA DYSTREGULATION and EMOTIONAL DYSREGULATION,

Neuro-Diverse folks are often very bright in one or more respects and struggling to keep it together.

Neuron-Glia Interactions in Neurodevelopmental Disorders (2020)

Abstract

Recent studies have revealed synaptic dysfunction to be a hallmark of various psychiatric diseases, and that glial cells participate in synapse formation, development, and plasticity.

Glial cells contribute to neuroinflammation and synaptic homeostasis, the latter being essential for maintaining the physiological function of the central nervous system (CNS).

In particular, glial cells undergo gliotransmission and regulate neuronal activity in tripartite synapses via ion channels (gap junction hemichannel, volume regulated anion channel, and bestrophin-1), receptors (for neurotransmitters and cytokines), or transporters (GLT-1, GLAST, and GATs) that are expressed on glial cell membranes.

In this review, we propose that dysfunction in neuron-glia interactions may contribute to the pathogenesis of neurodevelopmental disorders.

Understanding the mechanisms of neuron-glia interaction for synapse formation and maturation will contribute to the development of novel therapeutic targets of neurodevelopmental disorders.

Glutamate and microglia activation as a driver of dendritic apoptosis: a core pathophysiological mechanism to understand schizophrenia (2021)

Val's Take: What I'm trying to say is that there is a DISCONNECT between the ENERGY NEEDS of NEURO-DIVERSE BRAINS and the ENERGY that is actually available to them due to dysregulation of Microglia and Mitchondria IN UTERO.

Further, there are other Glial cells such as Astrocytes and they seem to be maintaining glutamate homeostasis in the Central Nervous System.

Surprise, Surprise --- This also seems to be DYSREGULATED for those who experienced Maternal Immune Activation.

Abnormal Brain Bioenergetics in First-Episode Psychosis (2021)

In addition to understanding:

Maternal Immune Activation
BRAIN ENERGY &
Microglia ----

How does this relate to "HOMEOSTASIS"?

One of the things the researchers are doing is they are getting to the CELLULAR and MOLECULAR PATHWAY LEVEL and finding that:

Dysregulations occurred IN UTERO via Maternal Immune Activation which had epigenetic consequences and various "DYSREGULATIONS" pre-natally.
This often involves:
- Microglia,
- Mitchondria (and ATP production),
- Astrocytes,
- And Glutamate which is associated with "NEURONAL EXCITOTOXITY"

Why do Neuro-Diverse folks have excess Glutamate?

Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders (2024)

Astrocytes Maintain Glutamate Homeostasis in the CNS by Controlling the Balance between Glutamate Uptake and Release (2019)

Specialized astrocytes mediate glutamatergic gliotransmission in the CNS (2023)

Maternal Immune Activation imprints translational dysregulation and differential MAP2 phosphorylation in descendant neural stem cells (2024)

Neuro-Diversity, microglia, Synapses & Energy

2/15/2025

Val's Take/Conjecture

BIO-ENERGETICS is expressed in many DIVERSE ways in Neuro-Diverse people.
Further, a common strategy for Neuro-Diverse folks is "HYPER-FOCUS."
That can look like ENORMOUS MENTAL ENERGY ---
- which in some ways it is.
- BUT it is also a strategy to CONSERVE ENERGY and REDUCE TRANSITIONS.

Synapses: The Brain's Energy-Demanding Sites (2022)

Abstract

The brain is one of the most energy-consuming organs in the mammalian body, and synaptic transmission is one of the major contributors.

To meet these energetic requirements, the brain primarily uses glucose, which can be metabolized through glycolysis and/or mitochondrial oxidative phosphorylation.

The relevance of these two energy production pathways in fulfilling energy at presynaptic terminals has been the subject of recent studies.

In this review, we dissect the balance of glycolysis and oxidative phosphorylation to meet synaptic energy demands in both resting and stimulation conditions.

Besides ATP output needs, mitochondria at synapse are also important for calcium buffering and regulation of reactive oxygen species.

These two mitochondrial-associated pathways, once hampered, impact negatively on neuronal homeostasis and synaptic activity.

Therefore, as mitochondria assume a critical role in synaptic homeostasis, it is becoming evident that the synaptic mitochondria population possesses a distinct functional fingerprint compared to other brain mitochondria.

Ultimately, dysregulation of synaptic bioenergetics through glycolytic and mitochondrial dysfunctions is increasingly implicated in neurodegenerative disorders, as one of the first hallmarks in several of these diseases are synaptic energy deficits, followed by synapse degeneration.

Metabolome subtyping reveals multi-omics characteristics and biological heterogeneity in major psychiatric disorders (2023)

Abstract
Growing evidence suggests that major psychiatric disorders (MPDs) share common etiologies and pathological processes. However, the diagnosis is currently based on descriptive symptoms, which ignores the underlying pathogenesis and hinders the development of clinical treatments.

This highlights the urgency of characterizing molecular biomarkers and establishing objective diagnoses of MPDs.

Here, we collected untargeted metabolomics, proteomics and DNA methylation data of 327 patients with MPDs, 131 individuals with genetic high risk and 146 healthy controls to explore the multi-omics characteristics of MPDs.

First, differential metabolites (DMs) were identified and we classified MPD patients into 3 subtypes based on DMs.

The subtypes showed distinct metabolomics, proteomics and DNA methylation signatures.

Specifically, one subtype showed dysregulation of complement and coagulation proteins, while the DNA methylation showed abnormalities in chemical synapses and autophagy.

Integrative analysis in metabolic pathways identified the important roles of the citrate cycle, sphingolipid metabolism and amino acid metabolism.

Finally, we constructed prediction models based on the metabolites and proteomics that successfully captured the risks of MPD patients.

Our study established molecular subtypes of MPDs and elucidated their biological heterogeneity through a multi-omics investigation.

These results facilitate the understanding of pathological mechanisms and promote the diagnosis and prevention of MPDs [Major Psychiatric Disorders].

The Underlying Neurobiological Mechanisms of Psychosis (2024):

Focus on

Neurotransmission Dysregulation,
Neuroinflammation,
Oxidative Stress, and
Mitochondrial Dysfunction

Synaptic elimination by microglia and disturbed higher brain functions (2021)

Highlights

Microglia engage in synaptic elimination by phagocytosis in mature brains.

Selective synaptic elimination changes excitatory/inhibitory (E/I) balance.

Microglia modulate neuropsychiatric disorders by synaptic elimination.

This review discusses Parkinson's and Alzheimer's diseases, ASD [Autism Spectrum Disorder], ADHD, and schizophrenia.

Errant gardeners: glial-cell-dependent synaptic pruning and neurodevelopmental disorders (2017)

Key Points

Brain development is associated with the formation of excessive synapses that have to be removed in a controlled and timely manner to achieve refined mature circuitry.

Glial cells, including microglia and astrocytes, are the effectors of synaptic pruning, identifying and eliminating superfluous synapses.

Synaptic pruning depends on various molecules, including those controlling glial chemotaxis, target recognition and phagocytosis.

Autism spectrum disorders are associated with excessive synapses, autophagy and dysregulated microglial function.

Schizophrenia is linked to exaggerated synaptic pruning owing to elevated levels of complement proteins and microglial activation.

Epilepsy is thought to arise owing to immature circuitry that was not refined via synaptic pruning.

This initial epileptiform activity is followed by microglial activation and upregulation of complement components.

Synapses & Neuro-Developmental & Psychiatric Disorders

Synaptic changes in psychiatric and neurological disorders: state-of-the art of in vivo imaging (2024)

The stressed synapse 2.0: pathophysiological mechanisms in stress-related neuropsychiatric disorders (2022)

Immune synaptopathies: how maternal immune activation impacts synaptic function during development (2023)

"In the present review, we highlight this concept, which we define by the term “immune‐synaptopathy,” and we discuss recent evidence suggesting a bi‐directional link between the genetic architecture of individuals and maternal activation of the immune system in modulating brain developmental trajectories in health and disease."

Giftedness, Atypical Sexual Differentiation, and Neuro-developmental disorders

2/10/2025

Val's Take/Conjecture

When I was growing up and still today, INTELLIGENCE was some unqualified good and it had to do with the BRAIN.
It does have to do with the BRAIN --- but it also has to do with the IMMUNE SYSTEM, the ENDOCRINE SYSTEM and the MICROBIOME.

Interestingly, Neuro-Developmental and Psychiatric Disorders also involve more than the Brain and involve the Immune System, the Endocrine System and the Microbiome.

"SENSORY PROCESSING ATYPICALITY" in "GIFTED" people often involves:

Maternal Immune Activation
Dysregulated Glial Cells, affecting among other systems the IMMUNE SYSTEM, ENDOCRINE SYSTEM and the MICROBIOME as well as the BRAIN and the CENTRAL NERVOUS SYSTEM.
More Synapses
A Hyper-Plastic Brain
Mitochondrial Dysfunction --- there's not enough ATP to run those Synapses and Hyper-Plastic Brain
- Neither you, nor the people around you, nor the Society seem to understand these BIO-ENERGETIC ISSUES, and
- And you don't understand the idiosyncratic BIO-ENERGETIC ISSUES of Others
Emotional Dysregulation

This is a complicated picture --- and we're bringing into CONSCIOUS AWARENESS a more sophisticated conceptualization of "GIFTEDNESS" than "Mr. or Ms. PERFECT" or the "EVIL GENIUS."

"Gifted," Neuro-Diverse, Emotionally Dysregulated people with INSUFFICIENT BIOENERGETICS are problematic.

There are some BIG TRADE-OFFS that many people would like to avoid making.

Giftedness, Neuro-Diversity, Bipolar Disorder & Inflammation

Integrative Thinking & the Current Trade-Offs of Neuro-Diversity

The Epidemic of Misdiagnosis of Mental Health Problems in the Gifted Community

Intelligence as a Symptom

Giftedness and atypical sexual differentiation: enhanced perceptual functioning through estrogen deficiency instead of androgen excess (2024)

"Exploring the possibility that estrogen deficiency since early development interrupts GABA shift, causing sensory processing atypicality, it helps to evaluate the co-occurrence of ASC [Autism Spectrum Conditions] with attention deficit hyperactivity disorder, dyslexia, and schizophrenia based on phenotypic and physiological bases.

"It also provides clues for understanding the common underpinnings of these neurodevelopmental disorders and gifted populations."

Intelligence and Executive Functions: A Comprehensive Assessment of Intellectually Gifted Children (2023)

Conclusions

Contrary to expectations, high intellectual level does not appear to be associated with superior EFs (Executive Functions).

Surprisingly, parents and teachers of IGC (Intellectually Gifted Children) reported more complaints about their executive functioning in everyday life.

We put forward different hypotheses to explain this contrast.

Further research is needed to better understand this phenomenon, in which neuropsychology has a fundamental role to play.

High Intelligence & High Executive Functioning often don't go together

Neuro-Diversity, Gender & Sexuality

More on Neuro-Diversity, Gender & Sexuality --- Getting Beyond the Culture Wars in 2023

High iq and Psycho-Neuro-Immunology

Emotional Dysregulation & Neuro-Diversity

2/7/2025

Val's Take - Conjecture

Maternal Immune Activation is associated with dysregulation of Microglia in the yok-sac.
Dysregulated microglia is associated with "anxiety" and "anxiety-like behaviors."
We need Microglia to manage Stress over the lifespan.
I think it is actually Neuro-Diverse people who have often come up with various practices to alleviate out-sized Stress --- and a lot of those strategies can help.
We're still at this in 2025 because "Anxiety" is not innocuous --- in humans and other animals.
Further, it is not just a handful of humans who are dealing with serious emotional dysregulation, and it's not just people who don't have any power.

MicroRNA-dependent control of neuroplasticity in affective disorders (2021)

Emerging role of non-coding RNAs in neuroinflammation mediated by microglia and astrocytes (2023)

Emotional dysregulation (ED) is a transdiagnostic variable underlying various psychiatric disorders, including addictive behaviors (ABs) (2024)

miRNAs and Substances Abuse: Clinical and Forensic Pathological Implications: A Systematic Review (2023)

When I think of Anxiety -- I think of Monk--- but Anxiety often comes with Anger and Aggression.

Some concept of "Justice" is often what we use to manage that -- but that can become more difficult than we realized.

Emotional Dysregulation and Adaptive Functioning in Preschoolers With Autism Spectrum Disorder or Other Neurodevelopmental Disorders (2022)

miRNA regulation of social and anxiety-related behaviour (2020)

MicroRNAs as potential diagnostic biomarkers for bipolar disorder (2025)

Inhibition of NKCC1 Ameliorates Anxiety and Autistic Behaviors Induced by Maternal Immune Activation in Mice (2024)

Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male mice (2024)

NEURODiversity Wednesday

Maternal Immune Activation, above average intelligence & above Average Inflammation

Inflammation, Fatigue, Aggression and Neuro-Diversity

CATCH 22: DO You have enough ATP to run all those synapses & that 'Hyper-Plastic' brain?

Neuro-Diversity, microglia, Synapses & Energy

Giftedness, Atypical Sexual Differentiation, and Neuro-developmental disorders

Emotional Dysregulation & Neuro-Diversity

Neuro-Diversity
Wednesday

(with variable spellings of Neurodiversity)

Archives

Categories

​ NEURODiversity Wednesday

Maternal Immune Activation, above average intelligence & above Average Inflammation

Inflammation, Fatigue, Aggression and Neuro-Diversity

CATCH 22: DO You have enough ATP to run all those synapses & that 'Hyper-Plastic' brain?

Neuro-Diversity, microglia, Synapses & Energy

Giftedness, Atypical Sexual Differentiation, and Neuro-developmental disorders

Emotional Dysregulation & Neuro-Diversity

Neuro-DiversityWednesday(with variable spellings of Neurodiversity)

Archives

Categories

NEURODiversity Wednesday

Neuro-Diversity
Wednesday

(with variable spellings of Neurodiversity)