Vol 5 n° 2 - Psychiatric disorders in somatic medicine
Past issues Contributors How to publish Contributions and comments Home
 
A short history of PNI he  first  evidence  suggesting  an  interaction between the brain and the immune system came from studies performed 80 years ago by Russian investigators. Derived directly from a Pavlovian perspective on the con- ditioning of behavioral and physiological responses, a con- ditioned stimulus (CS) was repeatedly paired with injec- tions of foreign proteins. Subsequent exposure to the CS, alone, was purported to induce antibody production in addition to a conditioned increase in a variety of non- specific defense responses.1 As this research attracted very little attention outside the Soviet Union, the commonly accepted beginning of research in the field of psycho- neuroimmunology (PNI) is associated with the experi- ments of Ader, who was studying taste aversion condi- tioning in rats in the 1970s. Conditioned animals that were reexposed to a CS, previously paired with the immuno- suppressive effects of cyclophosphamide showed an atten- uated antibody response to sheep red blood cells.2 The results of these initial experiments demonstrated that the immune system was subject to classical conditioning. A more complex research direction in the field of PNI was the study of behavioral influences on immunity, start- ing in the 1950s with the research on stress and infectious disease.3 During the 1970s, Besedovsky was beginning to systematically investigate the neuroendocrine–immune system network with his studies on the effects of immune responses  on  neural  and  endocrine  function.4  Felten described the direct contact of noradrenergic sympathetic nerve fibers with lymphocytes and macrophages.5 He showed that these nerve fibers were localized in specific compartments of lymphoid organs, forming close, synap- tic-like neuroeffector junctions with T lymphocytes and macrophages.6 These “hard-wired” connections between the brain and the immune system have since been shown B a s i c   r e s e a r c h 1 3 9 Cytokines, neurophysiology, neuropsychology, and psychiatric symptoms Markus J. Schwarz, MD T Keywords:  psychoneuroimmunology;  cytokine;  schizophrenia;  major  depression; sickness behavior; immunogenetics Author   affiliations:   Psychiatric   Hospital,   Ludwig-Maximilians-University Munich, Munich, Germany Address   for   correspondence:   Psychiatric   Hospital,   Ludwig-Maximilians University Munich, Nußbaumstr 7, D-80336 Munich, Germany
(e-mail: mschwarz@helios.med.uni-muenchen.de) Recent research has overcome the old paradigms of the brain as an immunologically privileged organ, and of the exclusive role of neurotransmitters and neuropeptides as signal transducers in the central nervous system. Growing evidence suggests that the signal proteins of the immune system—the cytokines—are also involved in modulation of behavior and induction of psychiatric symptoms. This article gives an overview on the nature of cytokines and the pro- posed mechanisms of immune-to-brain interaction. The role of cytokines in psychiatric symptoms, syndromes, and disor- ders like sickness behavior, major depression, and schizo- phrenia are discussed together with recent immunogenetic findings. Dialogues Clin Neurosci. 2003;5:139-153.