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Although the establishment of the field of Immunology dates back many decades, psychoimmunology is generally viewed as a relatively recent discovery in medicine. This discovery is based on the evidence that the immune, endocrine and neurotransmitter systems are interdependent in health and disease states. They are invariably dysfunctional in all major psychiatric disorders. The basic concepts of psychoimmunology have depended largely on knowledge of the changes in these interactive and interdependent systems because of recent technical advances in immunology and molecular neurobiology. For example, the immunotransmitters, cytokines, that play a critical role in the pathophysiology of mental illnesses were only discovered about 30 years ago following the development of sensitive assay techniques, such as ELISA, that permitted their detection.

The fundamental concept that endogenous factors are responsible for cognitive, affective and behavioral dysfunction can be traced back to antiquity. Hippocrates, about 400 BC, formulated the concept of black bile which he held responsible for melancholia, and was associated with the autumn season - shades of seasonal affective disorder perhaps? Some 500 years later, the Roman physician Galen wrote a thesis on black bile (‘De atrabile’) which described its pathological properties that are now identified as melancholic depression. Undoubtedly the most well-known thesis on melancholia was published in the late Middle

Ages by Robert Burton of Oxford (1577-1640) and titled ‘The Anatomy of Melancholy.’ In his thesis, Burton described ‘melancholia flatulosa’, a disease caused by black bile that ‘affects the brain and causes fear, sorrow, dullness and heaviness which troubles the imagination’. Like many ancient commentators, melancholia was considered to be a disease of scholars due to their ‘sedentary life and excessive exertion of the brain’.

Clearly, the concept of disease has changed decidedly from the prescientific to the modern, scientific era. In the former era, medicine was essentially viewed in a holistic way. With the development of scientific medicine in the 19th and 20th centuries, specialized disciplines came to dominate Medicine and the holistic, integrated aspects were often ignored. Nowhere is this more apparent than in psychoimmunology. To the immunologist, the brain was considered to be a privileged organ uninfluenced by the immune system; to the psychiatrist, the immune system was restricted to the peripheral organs and therefore of no importance to psychiatry.

How relevant are such views to the subject of inflammation? These reductionist views have been largely rejected by the discoveries in the past 25 years. Inflammation is involved in most aspects of mental health and mental diseases. It is now apparent that chronic, low-grade inflammation not only plays a major role in the pathophysiology of most major psychiatric disorders, but it also has an important evolutionary significance [1-3].

This volume seeks to highlight the intricate link between psychiatry and psychoimmunology and to underscore the central role of inflammation in furthering our understanding of the pathophysiology underlying mental health and mental illness. The choice of specific topics and authors who have contributed to this volume was dictated by the realization that this area of scientific endeavor is rapidly maturing and deserves broader dissemination across disciplines and specialty areas in medicine. Inflammation research is advancing our knowledge of the pathology of depression, schizophrenia, chronic fatigue syndrome, posttraumatic stress disorder and a host of comorbid conditions, notably diabetes, cardiovascular and cerebrovascular disease. Stress is a major contributor to mental illness. Stress initiates pathological changes by activating the immune and endocrine systems. The possible mechanisms underlying the bidirectionality of co-morbid medical and psychiatric disorders can be viewed as a consequence of inflammatory changes. These emerging novel concepts illustrate how the knowledge of inflammation can enable meaningful integration of psychopathology with physical comorbidity. Thus, the black bile of Hippocrates can now be identified as a number of factors that are derived from the inflammatory changes that form part of the psychopathology of major psychiatric disorders.

In conclusion, it must be remembered that a theory goes through 3 major stages. First stage it is ignored. Second stage it is vehemently opposed. Third stage it is accepted as being self-evident! We believe psychoimmunology has reached stage 3. Unlike false hopes raised by earlier theories of mental illness, we are confident that this relatively young subspecialty will have staying power. We base this belief on the fact that psychoimmunology provides a previously unsuspected powerful integrative link between autonomic nervous system function and dysfunction, neurochemical transmission, endocrine function and phenomenology. We trust the readers of this volume will agree with us.

Angelos Halaris, Chicago, Ill. Brian E. Leonard, Galway

Crespi B, Summers K, Dorus S: Adaptive evolution of genes underlying schizophrenia. Proc Biol Sci 2007;274:2801-2810
McDade TW: Life history theory and immune system: steps towards a human ecological immunology. Am J Phys Anthropol 2003;(suppl 37)100-125
Raison CL, Miller AH: The evolutionary significance of depression in pathogen host defense (PATHOS-D). Mol Psychiatry 2012;

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