Abstract

The three main theories explaining major mental illness, namely mood disorders, psychoses and dementias, have been partially discredited.

Alongside this, there are emerging links between perturbations of the immune system and the onset and phenotypic features of these disorders.

This article outlines the alternative pathophysiology and suggests potential treatments which could improve disease burden and avoid the need for psychotropic medication, with their associated side effects and relapse following withdrawal.

Szasz argued throughout his career that mental illness is a metaphor for human problems in living, and that mental illnesses are not "illnesses" in the sense that physical illnesses are, and that except for a few identifiable brain diseases, there are "neither biological or chemical tests nor biopsy or necropsy findings for verifying DSM diagnoses."

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Inflammation during prenatal development can be detrimental to neurodevelopmental processes, increasing the risk of neuropsychiatric disorders.

Prenatal exposure to maternal viral infection during pregnancy is a leading environmental risk factor for manifestation of these disorders.

Together, our results suggest that MIA [Maternal Immune Activation] in late pregnancy has the potential to affect cognitive functions and prefrontal gene expression patterns in multiple generations, highlighting its role in shaping disease risk across generations.

Abstract

Prenatal exposure to infectious or inflammatory insults is increasingly recognized in the etiology of neuropsychiatric diseases, including schizophrenia, autism, depression and bipolar disorder.

New discoveries highlight that maternal immune activation can lead to pathological effects on brain and behavior in multiple generations.

This review describes the transgenerational consequences of maternal immune activation in shaping brain and behavior anomalies and disease risk across generations.

We discuss potential underlying mechanisms of transmission, by which prenatal immune activation can mediate generation-spanning changes in brain development and functions and how external influences could further determine the specificity of the phenotype across generations.

The identification of the underlying mechanisms appears relevant to infection-related neuropsychiatric illnesses independently of existing diagnostic classifications and may help identifying complex patterns of generation-spanning transmission beyond genetic inheritance.

The herein described principles emphasize the importance of considering ancestral infectious histories in clinical research aiming at developing new preventive treatment strategies against infection-related neurodevelopmental disorders and mental illnesses.

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.