Historical Development of the Dopamine Hypothesis of Schizophrenia

This review examines the history of discoveries that contributed to development of the dopamine hypothesis of schizophrenia. The origin of the hypothesis is traced to the recognition that neuroleptic drugs interfere with brain dopamine function. This insight was derived from two distinct lines of research. The first line originated from the discovery in 1956 that reserpine depletes brain serotonin. This finding resulted in a sequence of studies that led to the discovery that brain dopamine is involved in neuroleptic-induced extrapyramidal motor disturbances. The second line of research was aimed at determining the mechanism of action of psychomotor stimulants. This research produced evidence that stimulants directly or indirectly activate brain dopamine receptors. Because nonreserpine neuroleptics such as chlorpromazine block stimulant-induced movement, these findings suggested that neuroleptics were dopamine antagonists. Most previous accounts of the development of the dopamine hypothesis of schizophrenia emphasize the first line of research and ignore the second.     

A case study of possible differential diagnoses of a medieval skeleton from Denmark: leprosy,ergotism, treponematosis,sarcoidosis or smallpox?

This paper uses macroscopic and radiological examinations to provide differential diagnoses of pathological lesions in the skeleton of a young woman, 20–25 years of age, which triggered the Danish palaeopathologist Vilhelm Møller‐Christensen's interest in leprosy. The skeleton was incomplete, but the majority of bones of the upper body, as well as the skull, were present. The pathological changes consisted of medullary and cortical lytic foci, periosteal reaction and enhanced cortical density. The lesions were most extensive on the left side, especially around the elbow, wrist and scapula. Treponematosis, leprosy, smallpox, ergotism, rheumatoid arthritis, tuberculosis and sarcoidosis are all reviewed with regard to bone and joint pathology and their likelihood of being the correct diagnosis. We concluded that the most plausible diagnosis is treponematosis, but neither sarcoidosis nor smallpox can be completely excluded. Copyright © 2007 John Wiley & Sons, Ltd.