Research Topics

The Translational Immunopsychiatry Unit (TIU) studies immune processes that contribute to neuropsychiatric illness.he TIU is interested particularly in identifying autoimmune B and T cell reactivities that cause behavioral pathology.

One aim of the lab is to identify rare psychiatric subgroups whose illness is defined by an antigen-specific autoimmune response—thereby helping to parse the staggering heterogeneity of psychiatric illness.

A second aim is to develop technologies that demarcate cells and circuits that are vulnerable to autoimmune responses in the human central nervous system.

A third focus of the TIU is, in collaboration, to study the pathobiological consequences of immune-antigen interactions at different levels of analysis: structure and biochemistry, neurophysiology, and behavior.

The bit that I've been particularly sort of interested in is how we have had these two separate worlds ---  mental health over here  and the disability system ---

And when I went to work in Mental Health I just saw people with almost identical needs to the people I had worked [with] and known in the disability system.

In fact, if you went to some of the less desirable community living alternatives and boarding houses and hostels and all that --- these people were practically indistinguishable almost.

Research has demonstrated that microglia, especially those in the gray matter of the brain, are activated in schizophrenia.

Upon activation, microglia release key proinflammatory cytokines and free radicals, which are well-recognized neurotoxic factors contributing to cognitive decline.

Thus, we propose that the inhibition of microglial activation holds potential for the prevention and treatment of cognitive deficits in patients with schizophrenia.

This review identifies potential targets for the development of new treatment strategies and eventually the improvement of care for these patients.

It might also help psychologists and clinical investigators in planning future research.

Summary

Microglia are implicated in all stages of multiple sclerosis (MS).

Microglia alterations are detected by positron emission tomography in people living with MS prior to the formation of structural lesions determined through magnetic resonance imaging. In histological specimens, clusters of microglia form in normal-appearing tissue likely predating the development of lesions.

Features of degeneration-associated/pro-inflammatory states of microglia increase with chronicity of MS.

However, microglia play many beneficial roles including the removal of neurotoxins and in fostering repair.

The protector-gone-rogue microglia in MS is featured herein.

We consider mechanisms of microglia neurotoxicity and discuss factors, including aging, osteopontin, and iron metabolism, that cause microglia to lose their protective states and become injurious. 

. . . The framework of microglia-turned-destroyers may instigate new approaches to counter microglia-driven neurodegeneration in MS.

Activation of the maternal immune system may affect innate and adaptive immune responses in the next generation and may therefore have implications for vaccine efficacy and dietary immune modulation by feed additives . . .

Despite variabilities in the outcomes of the two experiments, the observations of both suggest a link between the maternal innate immune system and the immune system of the offspring.

Furthermore, our results may imply that maternal activation of the innate immune system can influence immune modulating dietary interventions and vaccine strategies in the next generation. 

The Dust Bowl. Image Credit: National Drought Mitigation Center, University of Nebraska

Sensory processing abilities are highly variable within and across people diagnosed with autism and attention-deficit/hyperactivity disorder (ADHD).

This study examined the transdiagnostic nature of sensory processing …

[I]ndividuals with autism, who may present with 'atypical' features (e.g. severe irritability).

Risk factors for mood problems in autism appear to be largely overlapping with those identified in the general population, including shared genetic, environmental, cognitive, physiological/neurobiological mechanisms.

The proposed neuropathology is hyper-functioning of local neural microcircuits, best characterized by hyper-reactivity and hyper-plasticity. 

• The sensory nervous system possesses the ability to integrate exogenous threats and endogenous signals to mediate downstream effector functions.
• Sensory neurons have been shown to activate or suppress host defense and immunity against pathogens, depending on the tissue and disease state.

Conclusions:

The prevalence of bipolar disorder is markedly higher in patients with autoimmune disease.

Yet, more basic research is needed to verify the special significance of immune mechanisms in bipolar disorder. 

Microglia are the predominant resident immune cells in the brain and exhibit a critical role in depression.

Conclusion

Herein we show that autistic children and their mothers share an intrinsic responsiveness to in vitro microenvironmental changes in expressing HERVs [Human Endogenous Retroviruses] and pro-inflammatory cytokines.

Remarkably, the antiretroviral drug Efavirenz restores the expression of specific HERV families to values similar to those of the controls, also reducing the expression of proinflammatory cytokines but keeping the regulatory ones high.

Our findings open new perspectives to study the role of HERVs in the biological mechanisms underlying Autism.

[V]accination implementation is critically significant.

However, growing evidence suggests that COVID-19 vaccination may cause new-onset autoimmune diseases, including autoimmune glomerulonephritis, autoimmune rheumatic diseases, and autoimmune hepatitis.

Nevertheless, the causal relationship between COVID-19 vaccines and these autoimmune diseases remains to be demonstrated.

In this review, we provide evidence that vaccination induces autoimmunity and summarize possible mechanisms of action, such as molecular mimicry, activation by bystanders, and adjuvants.

Our objective is not to refute the importance of vaccines, but to raise awareness about the potential risks of COVID-19 vaccination. In fact, we believe that the benefits of vaccination far outweigh the possible risks and encourage people to get vaccinated.

Our objective is not to refute the importance of vaccines, but to raise awareness about the potential risks of COVID-19 vaccination. In fact, we believe that the benefits of vaccination far outweigh the possible risks and encourage people to get vaccinated.

Susceptible individuals would then expectedly have an increased risk of DNA damage, chronic autoinflammation, autoimmunity and cancer.

In light of the current mass administration of nms-mRNA vaccines, it is essential and urgent to fully understand the intracellular cascades initiated by cellular uptake of synthetic mRNA and the consequences of these molecular events.

• Another protective variant has been associated with an increased risk of two autoimmune diseases. Thus, the Black Death and other past pandemics may have shaped humans’ immune systems in ways both good and bad.
  

While we acquired better protection against infections, we became more susceptible to autoimmune diseases.

We report that the risk of developing most AI-CTDs  [autoimmune connective tissue diseases] did not increase following mRNA vaccination, except for systemic lupus erythematosus with a 1.16-fold risk in vaccinated individuals relative to controls.

Comparable results were reported in the stratified analyses for age, sex, mRNA vaccine type, and prior history of non-mRNA vaccination.

However, a booster vaccination was associated with an increased risk of some AI-CTDs [autoimmune connective tissue diseases] including alopecia areata, psoriasis, and rheumatoid arthritis.

Overall, we conclude that mRNA-based vaccinations are not associated with an increased risk of most AI-CTDs, although further research is needed regarding its potential association with certain conditions.

Combined, our data document spontaneous numtogenesis in human cells and demonstrate an association between brain cortical somatic Numts and human lifespan.

These findings open the possibility that mito-nuclear horizontal gene transfer among human post-mitotic tissues produce functionally-relevant human Numts over timescales shorter than previously assumed.

University of Michigan School of Medicine

Colombia University Irving Medical Center

The insertions are called nuclear-mitochondrial segments—NUMTs ("pronounced new-mites")—and have been accumulating in our chromosomes for millions of years.

"As a result, all of us are walking around with hundreds of vestigial, mostly benign mitochondrial DNA segments in our chromosomes that we inherited from our ancestors," Mills says.

Key points

    Human studies are uncovering a role for maternal immune activation (MIA) in the pathogenesis of common neurodevelopmental disorders, such as autism spectrum disorder, attention-deficit/hyperactivity disorder and Tourette syndrome, in the offspring.

    Prenatal, in utero and postnatal embedding of environmental factors in the epigenetic architecture of both the brain and the peripheral immune system can modulate individual susceptibility to neurodevelopmental disorders.

    The effects of MIA, mediated by acute and chronic inflammation in pregnancy, are transduced to the fetus through inflammatory cell signalling pathways and epigenetic mechanisms.

    Pathogen-associated molecular patterns, damage-associated molecular patterns and Toll-like receptors represent a convergent cellular pathway between heterogeneous environmental factors and innate immune activation.

    In conjunction with individual genetic risk, sex-related factors and second ‘immune’ hits during life, MIA-induced aberrant immune programming results in a loss of immune homeostasis, which is associated with behavioural abnormalities in animal models.