Wrong Jungle --- But Can We Get Out Without the Knockout Treatment?

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• Researchers are yelling "Wrong Jungle" when it comes to psychiatric disorders
• Namely, in 2021 it is hard to understand psychiatric disorders without understanding the role of the IMMUNE SYSTEM --- BUT CLINICIANS are not up to speed on that.
• One of the reasons for that is that Researchers don't understand how important these new conceptualizations are for policymaking --- even without the knockout treatment.
• For a lot of people in the Criminal Justice System and Homeless who essentially have an IMMUNE DISORDER that affects the BRAIN ---
  • ​These new conceptualizations are a GAME-CHANGER.

New theory suggests blood immune and clotting components could contribute to psychosis

A scientific review has found evidence that a disruption in blood clotting and the first line immune system could be contributing factors in the development of psychosis.

Immune dysregulation in depression: Evidence from genome-wide association -- 2020

​Abstract

A strong body of evidence supports a role for immune dysregulation across many psychiatric disorders including depression, the leading cause of global disability.

Recent progress in the search for genetic variants associated with depression provides the opportunity to strengthen our current understanding of etiological factors contributing to depression and generate novel hypotheses.

Here, we provide an overview of the literature demonstrating a role for immune dysregulation in depression, followed by a detailed discussion of the immune-related genes identified by the most recent genome-wide meta-analysis of depression.

​These genes represent strong evidence-based targets for future basic and translational research which aims to understand the role of the immune system in depression pathology and identify novel points for therapeutic intervention.

Immune dysregulation in depression: Evidence from genome-wide association -- 2020

Conclusions: The link between immune dysregulation, autoimmunity, and bipolar disorder may be closer than previously thought.

​Psychiatrists should be vigilant for autoimmunity in presentations of bipolar disorder due to its high morbidity and therapeutic implications.

​Advances in neuroimaging and biomarker identification related to immune dysregulation and neuroinflammation will contribute to our knowledge of the pathophysiology of bipolar disorder.

Neuroinflammation in Mood Disorders: Role of Regulatory Immune Cells ---2021

Abstract
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Mood disorders are associated with chronic low-grade systemic (sterile) inflammation, with increased plasma levels of pro-inflammatory mediators targeting all tissues including the brain. Importantly, pro-inflammatory cytokines (ex., tumor-necrosis factor alpha [TNF-α], interleukin [IL]-6) regulate mood behavior and cognition by influencing neurotransmitter levels, activating stress-responsive endocrine axes, among other effects.

However, the mechanisms underlying this enhanced inflammation are not well understood.

There is increasing evidence indicating that impaired immunoregulatory mechanisms may play a role in this context.

Patients with mood disorders (major depression [MDD] and bipolar disorder [BD]) have reduced numbers of major regulatory cells of both innate (natural killer regulatory cells and myeloid-derived suppressor cells [MDSCs]) and adaptive immune responses (CD4+CD25+FoxP3+, B regulatory cells).

Dysfunctional regulatory immune cells might contribute to systemic and neuroinflammation observed in mood disorders via different mechanisms, such as:
(i) failure to develop adequate stress-related responses,
(ii) indirectly through microglial activation,
(iii) lack of trophic support and pro-cognitive functions of T cells in the brain, and
(iv) dysbiosis.

In conclusion, maladaptive immunoregulatory mechanisms seem to be involved with both onset and progression of mood disorders.

A deeper understanding of these mechanisms may lead to the development of new therapeutic strategies

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

Summary

Mental illness exerts a major burden on human health, yet evidence-based treatments are rudimentary due to a limited understanding of the underlying pathologies.

Clinical studies point to roles for the immune system in psychiatric diseases, while basic science has revealed that the brain has an active and multi-cellular resident immune system that interacts with peripheral immunity and impacts behavior.

In this perspective, we highlight evidence of immune involvement in human psychiatric disease and review data from animal models that link immune signaling to neuronal function and behavior.

We propose a conceptual framework for linking advances in basic neuroimmunology to their potential relevance for psychiatric diseases, based on the subtypes of immune responses defined in peripheral tissues.

​Our goal is to identify novel areas of focus for future basic and translational studies that may reveal the potential of the immune system for diagnosing and treating mental illnesses​