Immunology of Eating Disorders

Eating disorders (EDs) are characterized by dysregulation in eating behavior leading to extreme increase or decrease in food intake that, in turn, changes body weight, adiposity, and physical health. Anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) are the three major eating disorders. Peculiar immune abnormalities occur in these conditions. Previous studies have reported a higher number of CD4+ T lymphocytes in patients with AN, which are related to a relative resistance to viral infections, even in the presence of leukopenia. It has also been proposed that a cluster of cytokines is altered in these patients. A chronic low-grade inflammation has been observed in obese people with BED and in patients with AN, but with a different profile in each condition. In this context, antagonist drugs of specific cytokines, such as anti-TNF, showed improvement of AN-related symptoms, but increased weight gain in obese subjects. The identification of specific molecules and/or immune cells that impair neuronal circuits implicated in eating behaviors may contribute to the development of pharmacological strategies for eating disorders.

Immune-Based Biomarkers and Therapies in Psychiatry

Research has established the role of complex immune-inflammatory signalling pathways within the brain during psychiatric disorders and associated development of cognitive deficits, anxiety, depression, dementia, and loss of social and communication skills. Various immune changes such as changes in the expression of cytokines, chemokines, T and B cell subsets, and increases in the levels of pro-inflammatory eicosanoids in the brain have been reported. However, the intricacies associated with the molecular pathways and biophysiological measures for the investigation of mental illnesses have posed a multitude of questions to our scientific community when devising the treatment and management strategies for the brain to return to its healthy state. Although antidepressants, mood-stabilisers, and atypical antipsychotic medications have shown great potential to treat psychiatric disorders, adjunctive treatment with anti-inflammatory agents can augment the overall therapeutic efficacy of antipsychotic drugs by downregulating the immune-inflammatory signalling pathways.

Immunology of Bipolar Disorder

Bipolar disorder (BD) is a severe, chronic, and recurrent psychiatric illness. It has been associated with a high prevalence of medical and psychiatric comorbidities, cognitive impairment, and a progressive course of illness. Its neurobiology is not completely understood, but recent evidence has shown a wide range of immune changes. Here we review several data supporting the presence of immunological dysfunction in BD: (1) increased frequency of autoimmune diseases; (2) distinct immune cell profile; (3) altered release of cytokines by stimulated mononuclear cells; (4) elevated levels of circulating immune markers; (5) inflammatory changes in the central nervous system; (6) relationship with clinical comorbidities; and (7) the effect of current treatments on the immune system and the role of immunomodulatory agents.

Immune Mechanisms and Central Nervous System (CNS) Development

Multiple factors and mechanisms may influence the healthy development of the embryo and fetus during the gestational period. Inflammation is a physiological response that mediates the clearance of cellular debris and release of neurotrophic factors. Inflammation also eludes or minimizes threats. The same developmental mechanisms that promote plastic changes may expose the organism to adverse outcomes. Several mechanisms related to the immune system, including the release of cytokines and activation of T cells, may contribute to neuroinflammation. An exacerbated inflammatory response has been associated with the occurrence of central nervous system (CNS) injuries that may determine, in the short term and/or long term, structural and functional consequences for CNS development. Evidence suggests that immune dysfunction may affect brain development and may play a role in several neurodevelopmental/psychiatric disorders.

Immune Mechanisms Affecting the Functioning of the Central Nervous System (CNS)

This chapter presents an overview of the immune mechanisms affecting the functioning of the central nervous system (CNS). The cross-talk between the immune system and the CNS is established by three independent pathways: the humoral, neural, and cellular (leukocyte) routes. Of note, increased circulating pro-inflammatory cytokines and concomitant activation of brain-resident microglia can lead to impaired cognition and depressive behavioral symptoms. The activated microglia phenotype has been associated with neuroinflammation reported in neurodegenerative and psychiatric disorders. This chapter also reviews novel physiological roles for adaptive immunity (especially T cells) during health and disease. T cells support hippocampal neurogenesis, cognition, mood, resilience to stress, and are protective against the development of psychiatric disorders.

Immune System Dysregulation and Schizophrenia

Schizophrenia is a common disease with a lifetime prevalence of 1% and a complex etiopathogenesis, probably involving multiple and heterogeneous genetic and environmental factors. Stress and immune system reactivity are implicated in both the pathogenesis and exacerbation of psychotic symptoms in schizophrenia. Exposure to environmental stressors in genetically susceptible individuals may alter brain processes and potentially have long-term consequences leading to the onset of schizophrenia. Here we discuss the role that genetic architecture, in combination with environmental stimuli, plays in immune system regulation and the development of schizophrenia, and review recent and accumulating evidence of associations between immune system genes with schizophrenia.

Immunology of Substance Use Disorders

As in other psychiatric disorders, the role of the immune system is gathering increasing attention as an important mechanism in substance use disorders. Addiction is a complex condition in which a person engages in drug-seeking and drug-taking behaviors to accentuate the reward processes in the brain and avoid negative withdrawal states. Due in part to the activation of stress responses during drug withdrawal, high levels of peripheral pro-inflammatory cytokines are observed in this phase, and these immune changes might contribute to the behavioral negative reinforcing effects of the drug. This and other observations suggest that the immune system might play a role in the development of substance use disorders, also representing a potential target for biomarker and therapeutic strategy development (e.g., vaccines).

Immune Dysfunction

Immune dysfunction plays an important etiological role in several psychiatric disorders, thus appearing as a transnosological feature potentially associated with worse clinical outcomes such as early onset, severity of symptoms, treatment resistance, and suicide, as well as with the development of other metabolic and autoimmune comorbidities. In this chapter, evidence for the existence of a chronic low-grade inflammation and oxidative and nitrosative stress in major psychiatric disorders is documented. In addition, elements likely to be the consequence of this immune dysfunction and suggesting that psychiatric disorders should be considered as multisystem disorders are discussed, such as the comorbidity with metabolic and autoimmune disorders, alterations of gut permeability and microbiota, and the reactivation of human endogenous retroviruses. In this context, potential constitutive (genetic) and environmental determinants (childhood stress and early-life infection) of immune dysfunction are discussed.

Overview of the Immune System

This chapter presents an overview of the immune system, presenting its organization, major cellular and molecular components, as well as functional responses. The main objective of this chapter is to provide the reader the basic information necessary to understand the immunological terms in the following chapters. More in-depth information can be found in several excellent basic immunology books. In addition to the well-known roles in generating immunity against infections, cells of the immune system are also involved in regulating non-immune physiological processes, including tissue remodeling and brain functions. The generation of sterile inflammation and the role of T-lymphocyte subsets are important hallmarks discussed here.

Immunology of Late-Life Psychiatric Disorders and Dementias

Aging is a complex process associated with significant physiological functions across all body systems, especially the immune system. The age-related changes in the immune system are collectively known as immunosenescence. As a consequence of immunosenescence, advanced age is characterized by a decrease in the ability to cope with stressors. The multifaceted immunosenescence profile includes a constitutive low-grade inflammation, a phenomenon known as inflammaging. This low-grade chronic inflammation observed in aging may contribute to the development and/or progression of age-related chronic diseases, including neuropsychiatric disorders. Herein, we discuss the age-related immune/inflammatory changes observed in late-life psychiatric disorders.