ABSTRACT
This chapter explores the disease state and disease basis of schizophrenia, summarizes experimental disease models of the disorder, and focuses largely on the putative role of H3 receptor antagonists/inverse agonists as potential therapies. Schizophrenia is a complex, heterogeneous psychiatric disorder that affects between 0.5 and 1.5% of the worldwide population. Despite the number of antipsychotic medications available, there remains a significant unmet need in the treatment of schizophrenia. To understand the proposed role of the histaminergic system in the etiology of schizophrenia and the potential capacity of H3 receptor antagonists to treat aspects of the disorder, it is first important to review the most widely accepted theories on the neurological bases of schizophrenia. The neurodevelopmental hypothesis states that “schizophrenia is the behavioral outcome of an aberration in neurodevelopmental processes that begins long before the onset of clinical symptoms and is caused by a combination of environmental and genetic factors”.
