Picture
Val Corzine
Sebastian Yatra
Tacones Rojos

Working to Eliminate Homelessness & Criminal Justice Involvement of People with Cognitive Disabilities


  • Current Scientific Research
  • Legal Analysis, and
  • Authenticity & Lived Experience

Frank Capra, "Manic Depression," and "It's a wonderful LIfe"

Val's Take/Conjecture
  • I had generally viewed "It's A Wonderful Life" as a feel good, sweet movie --- and it is.
  • It was only after learning that Frank Capra had "Manic Depression" or Bipolar Disorder (or was thought to) --- that I started to appreciate how much "It's A Wonderful Life" is about mental illness.
  • One of the most affecting scenes is an out of control bullying George Bailey --- shaking the forgetful Uncle Billy.
  • Mr. Gower, Potter, Violet, Mary and even George's mother all have their issues.
  • Addressing lower level executive functioning issues (and fatigue) --- has the potential to make all of this a lot more manageable.
    • ​​What we don't want is people defaulting to "AGGRESSION" to access the ENERGY they need.
Executive dysfunction, violence and aggression (2020)
Frank Capra --- 1897 - 1991
It's A Wonderful LIfe (1946)

One of the things that is so interesting about this portrayal of Uncle Billy --- he's not some wild and crazy guy --- he's a very nice guy with memory and executive functioning challenges.

One of the things we learn during the course of the movie --- if George hadn't been there, Uncle Billy would be in a mental institution.

​Further, George has his problems  and suicidality is one of them.

Maternal Immune Activation and MIcroglia dysregulation

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

Val's Take/Conjecture
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."

TRANSLATIONAL JusTICE as "A THING" 

Val's Take/Conjecture
  • ​The article to the right addresses Translational Justice in Healthcare.
  • When I'm referring to "TRANSLATIONAL JUSTICE" --- I'm generally referring to the need to appreciate the ramifications of Medical Research through a Criminal Justice Lens.
    • ​Might also be Translational Justice in Criminology or Translational Criminology.
  • Even more specifically, addressing biological and or developmental issues of Criminal Behavior vis a vis BURDEN OF PROOF.
    • Punishment vs. Mental Health, Substance Use or Disability Certification.
Building Better Medicine: Translational Justice and the Quest for Equity in US Healthcare (2025)
Affiliations
1Mayo Clinic.
2University of Toronto.
3University of Miami.
4Case Western Reserve University.
5University of Pennsylvania.
6ETH Zurich.
7Stanford University.

"Micro-Credentialling" in Behavioral Health

& the crying need for more advanced care in immuno-psychiatry
​

Val's Take/Conjecture
  • ​The Colorado Community College System is promoting "micro-credentialing" in Behavioral Health.
  • There have been work force problems in mental health for a long time --- and there are immediate, practical issues and needs.
  • Providing a more thorough understanding of Neuro-Developmental and Psychiatric Disorders with New and Modified Paradigms is also critical to addressing "work force" issues.
  • Neuro-Developmental and Psychiatric Disorders are more and more seen through a lens of "Neuro-Immunology" and "Brain, Behavior & Immunity."
Jonathan Kipnis
Pioneer in Neuro-Immunology

This isn't to say that everyone should be a world-renowned researcher --- but if you want to--- go for it.

Kipnis talks about how ideas can become entrenched and self-perpetuating even if they are wrong --- and that is a problem in Mental Health.

Further, out-dated paradigms are not irrelevant to the mental health profession's work force problems.

PREVIEW: Neuro-Diversity Wednesday

Do we have the right professional?

From PSYCHOLOGY to integrative immunobiology

Val's Take/Conjecture
  • When all the research gets sorted out ---- Societal Responses won't be the Ethical & Moral Nightmare they are today.
  • BUT right now the research continues to corroborate Developmental  multi-system Neuro-Immune Disorders.
  • ​Further, that is a refinement from a decade ago.
What has not been corroborated by the research is the DSM categorical system.
NAMI Montana
It's Time to Improve the Mental Illness Diagnostic Process (2013)

PREVIEW

What is a Neuro-Immune Transcriptome?

Val's Take/Conjecture
Neuroimmune transcriptome changes in patient brains of psychiatric and neurological disorders (2023)

*Chinese, American [SUNY -- State University of New York] & Australian Researchers

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?

Preview

The Ethics of Mitochondrial Replacement Therapy & Transplantation

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
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

Preview:  Neuro-Diversity Wednesday

Neuro-Diversity and Thyroid Problems

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)

Preview

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

​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.

​PREVIEW

Trans-Cranial Magnetic Stimulation  AS A Treatment for MICROGLIAL Dysregulation

[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)

Preview:  Neuro-Diversity Wednesday

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

"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. T

hese 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."

​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-Developmental Disorders, Criminal Justice & An Emerging Global Consensus

Val's Take/Conjecture
  • The Connection between ADHD and greater risk of Criminal Justice involvement has been around at least since the 1990s.
  • Sweden led this at one point.
  • ​There has been more and more work on this in the UK and with this latest 2025 article in the International Journal of Law & Psychiatry --- Italy.​
  • It does seem that European academic articles and government reports are asking more interesting questions:
    • What should the law be?
    • What should the range of services be?
  • I do think that American Academic articles can get bogged down in the finer points of Not Guilty by Reason of Insanity and Competency ---
    • I'm not saying we can ignore current law.
    • But we need to be thinking about what "ought to be" not just what "is."
On the other hand, I think the American Legal System by and large would be happy to hand over the oversight of Defendants with various aspects of "ADHD" and "Co-Morbidities" to the Public Health System ----
  • Not only are the RESOURCES not there to handle that in PUBLIC HEALTH;
  • The UNDERSTANDINGS are getting a lot better but they're not perfect and it's not clear that you can get out of some kind of "CUSTODIAL CARE" in every case.
  • It's exceedingly inconvenient to know that there are actual biological mechanisms.
  • Further, these "Social Concerns" affect people's biology, too and are often diverse forms of "Chronic Stress."
ADHD in adults and criminal behavior: The role of psychiatric comorbidities and clinical and sociodemographic factors in a clinical sample (2025)
[Italian Researchers]

Conclusions: Adult ADHD, particularly in males, with combined presentation and in the presence of comorbidities such as oppositional defiant disorder and alcohol use disorder, is associated with an increased risk of criminal behavior.

The findings highlight the need for personalized and multimodal interventions to mitigate these risks.

​Future studies should adopt longitudinal designs to explore causal dynamics and evaluate the effectiveness of therapeutic strategies in forensic contexts.

​Offending and clinical characteristics of adults with autism spectrum disorder: Experience at forensic psychiatry center in Türkiye between 2012 and 2022 (2025)

​[Turkish Researchers]

PREVIEW:  Neuro-Diversity Wednesday

metabolic dysregulation and neuro-developmental and Psychiatric disorders

Val's Take/Conjecture
  • "Metabolic Dysregulation" like a lot of this is on a "Spectrum." 
​​ ​
  • 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)

It's not just access To care ---

​It's access to Up-to-Date Translational medicine

Re-allocating resources Responsibly

Val's Take/Conjecture
  • There are news reports of 500 mental health professionals in Colorado being laid off and 3 mental hospitals being closed.​ ​
  • Mental Health does need SIGNIFICANT TRANSFORMATION and INTEGRATION with the rest of Health Care.
    • ​​Better Systems and Support to Keep Up with the Research.
  • For me this is akin to the "Defund the Police" or "Cost Shift to the Police" debates and realities --- BUT re-purposing law enforcement to gain even more safety and humane treatment --- yes, that is worthy of doing.
    • ​And perhaps providing law enforcement an expanded career ladder into Public Health and Medicine.
I am not for FUNDING THE STATUS QUO in mental health.

On the other hand, I'm not for people summarily losing their jobs either.

That's a lot of chaotic, unpredictable stress that is not going to be good for patients, clinicians or the community.

Five Books

addressing New understandings of Neuro-Developmental & Psychiatric disorders

Val's Take/Conjecture
  • One of the things that has come out of the research ---- the DSM 5 Categories are not distinct but blurred.
  • Neuro-Inflammation acquired IN UTERO and additionally during the life span are the keys to understanding Neuro-Developmental and Psychiatric Disorders.​
  • To me, the big issue is the perinatal inflammation and the long list of Neuro-Immune consequences that flow from that.
Part of: Progress in Inflammation Research (50 books)

Preview:  Translational Medicine Friday

Maternal Immune Activation Activates Inflammatory Genes in the Fetus

​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)

Reasoning to reform without perfect information

Val's Take
  • ​Those of us living now will not see the full benefit of research on Neuro-Developmental and Psychiatric Disorders that is such a long- term, multi-generational effort.

  • In 2025, most people can live in the Community with current treatment but some can't.

  • It's time to get rid of Medicaid's Exclusion of Payment for Institutes of Mental Disease (IMD) Rule while also:
    • Bringing Intensive Community Supports to Scale.
I posted the study to the right because it represents a different take on the research.

The point is not so much the Conclusion --- as that the researchers are still working on this and it is not done.

On the other hand, we have plenty of people with Schizophrenia and other Neuro-Developmental and Psychiatric Disorders incarcerated.

We have substantial reason to believe we are punishing people for a not sympathetic underlying biology.

It's not like we're not doing anything, but we're not doing enough.
​Genetic contribution to microglial activation in schizophrenia (2024)

"We conclude that microglia of the patients with SCZ (Schizophrenia) have gene expression aberrations related to inflammation response and extracellular matrix without contributing to increased microglial activation."

Anti-Social Personality Disorder as a

​Neuro-Developmental Disability
Associations of the immune system in aggression traits and the role of microglia as mediators (2024)

Policy Challenges

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