The Immune System and Mental Health

Hymie Anisman, Shawn Hayley, Alexander W. Kusnecov, Alexander Kusnecov

• Publisher: Academic Press
• Year: 2018
• Print ISBN: 9780128113516
• eBook ISBN: 9780128113523
• Topic: Biological Sciences
• Subtopic: Psychiatry & Mental Health
• Index: Biological Sciences

The Immune System and Mental Health fully investigates how immune-related cellular, molecular and anatomical changes impact mental functioning. The book combines human and animal studies to reveal immunological changes related to mental-health problems. In addition, users will find comprehensive information on new research related to the microbial composition of the gut, aka, the microbiome, and how it influences brain function and mental health. Common comorbidities with mental illness and their inherent immunological or inflammatory components are also covered. Written by leaders in the field, the book synthesizes basic and clinical research to provide a thorough understanding on the role of immunity in neuropsychiatry.Sociology, psychology, psychiatry, neuroscience and genetics have provided considerable explanations and solutions to some of the most intractable mental-health problems. But researchers are increasingly relying on investigations of the immune system to identify factors that can undermine and impair mental health. This book covers devastating mental-health conditions, such as depression, anxiety, schizophrenia, and autism-like spectrum disorders. In addition, degenerative disorders of the brain, such as Parkinson's and Alzheimer's-like dementia are explored.- Considers both basic human and animal studies that address immunological changes relating to mental health problems across the lifespan- Incorporates techniques, concepts and ideas from a variety of social, behavioral and life sciences- Explores the relatively new area of the microbiome and how the microbial composition of the gut influences brain function and mental health

Chapter 1

Multiple Pathways Linked to Mental Health and Illness

Abstract

Mental illnesses and behavioral disorders affect an inordinately large number of people worldwide, accounting for a greater burden of illness than any other condition regardless of whether this is considered in terms of years lived with disability or disability-adjusted life-years. Vulnerability and resilience to these illnesses is affected by a broad range of psychosocial and experiential factors, prenatal and developmental influences, genetic and epigenetic processes, and a constellation of hormonal, neurotransmitter, neurotrophin, microbial, and inflammatory immune factors. The latter includes both peripheral inflammatory processes, and those linked to brain microglia. A broad overview is provided as to how such processes, independently and in conjunction with one another may influence various disease states and their comorbid conditions. These varied influences are provided in the context of a precision (personalized) medicine treatment approach to mental illness that incorporates neurobiological, psychosocial, and developmental factors, even if this approach may not yet be ready for prime time.

Keywords

Depression; anxiety; PTSD; pain; genetic; neurochemical; inflammatory; microbiota; prenatal development; early postnatal development

Broad impact of mental illness

Despite the best efforts of scientists and clinicians, mental illnesses are often resistant to pharmacological and to behavioral/cognitive treatments. Moreover, even when a positive response is obtained, residual features of the illness may persist, and illness recurrence is notably high. Making matters worse, mental illnesses are frequently comorbid with other psychological problems, as well as numerous physical disorders. In some instances, the comorbid conditions may be reciprocally perpetuating, whereas in other cases they might be promoted by common elements. These include growth factors and inflammatory immune processes that have been implicated in various mental illnesses and neurological disorders, as well as heart disease, diabetes, stroke, cancer, and an array of immune-related conditions. Treatments for many physical illnesses have been advancing, even if a bit slowly, and the potential for still better outcomes have been bolstered by the recognition that a precision (personalized) medicine approach may be instrumental in determining which patients will be most responsive to particular treatments. This perspective opened the door to precision public health that could potentially predict the most efficacious interventions to benefit whole communities or populations. With new perspectives, new approaches, and new technologies, the modes of treatment and their effectiveness are becoming progressively better.

Yet, there’s another side to mental illnesses that needs to be addressed. Despite many treatment advances, and the understanding that psychiatric disturbances are medical conditions and not a personal failing, attitudes concerning mental illness have considerable stigma attached to them. This is all the more remarkable given that mental illness affects more than 20% of people at some time in their life, which means that an awful lot of families are affected by these illnesses. It’s hard enough on individuals to deal with their mental illness, but when this is compounded by various forms of stigma, as well as insufficient or ineffective social support, maintaining a positive quality of life becomes much more difficult (Corrigan, Rafacz, & Rüsch, 2011). If nothing else, reducing the stigmatization of individuals with mental health problems will increase the likelihood that those at risk will seek treatment early.

Aside from public stigma, it isn’t unusual for self-stigma to occur, frequently accompanied by shame and humiliation, social devaluation, internalization of a negative self-concept, a need to maintain secrecy (Corrigan, Rafacz, & Rüsch, 2011) and a decline of help-seeking. If this weren’t sufficiently diminishing, individuals with mental health issues frequently have to deal with “structural stigma” which is manifested as inordinately extended waits for treatment as well as a variety of biases when they actually do seek help. Diminished care for other physical illnesses is not uncommon, being misattributed to the manifestation of mental illness. Is it any wonder that life span of patients with mental illness is reduced?

Over the past decade, there has been a decline in overt stigma, possibly reflecting political correctness, but the problem is still extensive. Attempting to “educate” people about mental illness has not been especially effective in eliminating stigma (Adams, Lee, Pritchard, & White, 2010). Even health professionals aren’t immune from maintaining stigmatizing attitudes concerning mental illness, and they are also likely to self-stigmatize when they experience symptoms of a mental health problem. It isn’t unusual for health professionals to have serious concerns about exposing themselves to the judgment of their peers, and they may also be reluctant to seek treatment (Givens & Tjia, 2002). Given that health professionals are affected in this manner, it’s hardly surprising that negative attitudes occur in so many others.

A General Perspective of Mental Illness

Considerable efforts have been devoted to the identification of specific brain regions and neuronal processes that are responsible for the provocation or inhibition of particular behavioral phenotypes. There is merit to this approach, as critical neuronal pathways and brain regions have been identified that contribute to cognitive and emotional functioning, and a variety of behaviors, as well as to mental and neurological illnesses. At the same time, complex behaviors involve complicated neural circuits that won’t readily be discerned by simply assessing single brain regions (Northoff, 2013). Consistent with this perspective, a systems approach is frequently adopted that involves analyses of the functional connectivity among neural circuits that subserve normal behaviors and that of psychological illnesses. It has become increasingly apparent that the activity and functioning of neuronal circuits within the brain are influenced by peripheral and brain hormones, sympathetic nervous system activity, immune factors within the periphery, and immune-like factors that act within the brain (e.g., released by microglia) as well as processes associated with gut bacteria (e.g., Cryan & Dinan, 2012; Dantzer, O’Connor, Freund, Johnson, & Kelley, 2008). In essence, there has been a push toward analysis of mental illnesses within the context of a broader systems-based approach.

This opening chapter introduces multiple systems that may contribute to the evolution of physical, neurological, and psychological disorders, and why some individuals may be more vulnerable (or resilient) to such illnesses. As a particular illness may come about owing to any of several factors, it may be understandable that a treatment that is effective for one individual may not be equally effective for a second. Accordingly, the concept of personalized (precision medicine) treatment strategies are introduced as these have been used for several physical illnesses, and are being incorporated in the treatment of mental health disturbances.

In considering mental illnesses, it is essential to assess not only the diverse processes and mechanisms that are operative within the central nervous system (CNS) itself, but also those apparent across several other systems. The focus in this book is on brain-immune system interactions as they pertain to health, which is consistent with the literature of the past decade or so, wherein inflammatory factors have moved from being a marginal consideration, to one that is a primary player in a range of brain conditions. Indeed, it is now evident that inflammatory immune cells, such as macrophages and microglial cells, and the inflammatory messengers they produce (cytokines), can influence neurotransmission, hormonal release, and even neuronal survival. The involvement of these systems (and their interactions) will be considered in relation to mental health processes as well as comorbid physical illnesses. Finally, genetic, prenatal, and early life experiences, environmental challenges and life-style factors all feed into these illness-related biological processes, and thus need to be considered within any systems-based approach.

It is generally accepted that psychosocial factors, such as early negative life experiences (e.g., parental neglect, abuse), living in poverty, or other types of psychologically toxic environments, together with a failure to cope effectively, would be at or near the top of the list of damaging experiences that can lead to mental illness (Shonkoff, Boyce, & McEwen, 2009). In concert with these psychological stressors are the many other “physical” (neurogenic), systemic, and environmental stressors that affect well-being, including chemical toxicants, industrial contaminants, food additives, and bacterial or viral agents. Given this spectrum of differing challenges, it is easy to get lost in all the specifics, which we wanted to avoid. Thus, we focus on some of the mechanistic commonalities of these varied challenges insofar as they pertain to mental and neurological illness.

Inherent in a systems approach is that in addition to pharmacologically based strategies, psychosocial influences ought to be considered in dealing with at least some psychiatric illnesses (Cruwys, Haslam, Dingle, Haslam, & Jetten, 2014). Moreover, while the treatments of neurodegenerative diseases are obviously not amenable to psychological approaches alone, their comorbid features include depression and anxiety, which may be affected by these treatments. Accordingly, in considering the development and recovery from mental illness, “systems” not only encompass intrinsic biological processes, but also those related to the individual in the context of their social and physical environment, their experiences, and the influence of their ethnic (including cultural) background (Matheson, Bombay, & Anisman, 2018)

In evaluating the multiple factors that are involved in mental illnesses, it is also important to rely on a constellation of “omics” that might be used to decipher how diverse systems come together to produce different phenotypes. Piecing together the interactions of multiple biological networks, at different levels of analysis, can provide a fuller picture of what’s going on in the body (see Table 1.1). Unlike the research conducted a decade or two earlier, data sets are now immense and becoming progressively larger. There are some 3 billion chemical coding units that form an individual’...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Preface
• Acknowledgments
• Chapter 1. Multiple Pathways Linked to Mental Health and Illness
• Chapter 2. The Immune System: An Overview
• Chapter 3. Bacteria, Viruses, and the Microbiome
• Chapter 4. Life-Style Factors Affecting Biological Processes and Health
• Chapter 5. Stressor Processes and Effects on Neurobiological Functioning
• Chapter 6. Stress and Immunity
• Chapter 7. Prenatal and Early Postnatal Influences on Health
• Chapter 8. Depressive Disorders
• Chapter 9. Anxiety Disorders
• Chapter 10. Posttraumatic Stress Disorder
• Chapter 11. Pain Processes
• Chapter 12. Autism
• Chapter 13. Schizophrenia
• Chapter 14. Inflammatory Roads to Parkinson’s Disease
• Chapter 15. A Neuroinflammatory View of Alzheimer’s Disease
• Chapter 16. Comorbidities in Relation to Inflammatory Processes
• References
• Index