Many neuropsychiatric diseases still elude full understanding and effective therapy. It has become increasingly obvious that some of the prevailing explanations of their pathology are overly simplistic since only a small fraction of patients appear to be successfully helped, at best. One possibility is that the role of lymphocytes and neuroimmune interactions in the central nervous system (CNS) have been largely neglected,1 except in clear cases that are autoimmune in nature, as in multiple sclerosis (MS).2 Much can be learned from rare diseases about apparent links between the immune and the nervous system. For example, systemic mastocytosis is characterized by mast cell proliferation and activation in most organs, including the CNS.3 The prevalence of psychiatric problems in these patients is much higher than the general population, and acute stress is known to exacerbate their symptoms.3
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