Drug Addiction, Microglia and Neuro-Immuno-pharmacology

Val's Take/Conjecture

• ​Less than 10 years ago, Dual Diagnosis -- psychiatric disorders and substance use were considered "2 Distinct Disorders."
• That is not as true today.
• Further, some Neuro-Diverse people are very prone to use particular drugs, and others are highly unlikely to use recreational drugs.

• This idea of "Distinct Disorders" when it comes to Neuro-Developmental and Psychiatric Disorders started to obviously breakdown with the findings of the National Institute of Mental Health in 2013--- that 5 disorders (ADHD, Autism, Bipolar Disorder, Depression, and Schizophrenia) shared common genes and also involved immune epigenetics and calcium channels.

The breaking down of "Distinct Disorders" has also seen the rise of more sophisticated understandings of biological mechanisms such as the microbiome and glial cells and the role of innate immunity in Neuro-Developmental, Psychiatric and Substance Use Disorders as well as Autoimmune Disorders, Cancer, etc.

• ​There is a move away from "Symptom Clusters" to "Mechanism-Based Sub-Typing."

Shared Genes & Psychiatric Disorders

All of this is highly relevant to our out-dated, half-right DSM 5 conceptualization of "Anti-Social Personality Disorder" which in the Research is now being conceptualized as a Neuro-Developmental Disorder.

​​​Association patterns of antisocial personality disorder across substance use disorders (2024)

​"The present study expands our understanding of polysubstance addiction and co-occurring mental health disorders.

"Our findings support personalized interventions targeting mechanism-based subtyping in relation to ASPD-SUD comorbidities."

​Maternal immune activation and adolescent alcohol exposure increase alcohol drinking and disrupt cortical-striatal-hippocampal oscillations in adult offspring (2022)

​Neuroimmune Mechanisms as Novel Treatment Targets for Substance Use Disorders and Associated Comorbidities
(2021)

​Microglia in neuroimmunopharmacology and drug addiction (2024)

Affiliations

• 1Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China.
• 2Department of Psychology and Neuroscience, and the Center for Neuroscience, University of Colorado Boulder, Boulder, CO, 80309, USA.
• 3Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China. 
• 4School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China. 
• 5Beijing National Laboratory for Molecular Sciences, Beijing, 100190, China.

​Abstract

Drug addiction is a chronic and debilitating disease that is considered a global health problem.

Various cell types in the brain are involved in the progression of drug addiction.

​Recently, the xenobiotic hypothesis has been proposed, which frames substances of abuse as exogenous molecules that are responded to by the immune system as foreign "invaders", thus triggering protective inflammatory responses.

An emerging body of literature reveals that microglia, the primary resident immune cells in the brain, play an important role in the progression of addiction.

​Repeated cycles of drug administration cause a progressive, persistent induction of neuroinflammation by releasing microglial proinflammatory cytokines and their metabolic products.

This contributes to drug addiction via modulation of neuronal function.

In this review, we focus on the role of microglia in the etiology of drug addiction.

​Then, we discuss the dynamic states of microglia and the correlative and causal evidence linking microglia to drug addiction.

Finally, possible mechanisms of how microglia sense drug-related stimuli and modulate the addiction state and how microglia-targeted anti-inflammation therapies affect addiction are reviewed.

​Understanding the role of microglia in drug addiction may help develop new treatment strategies to fight this devastating societal challenge.

​Substance Use Disorders Are Psychiatric Disorders (2023)