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The aim of this paper was to investigate differences in brain structure volumes between schizophrenia and affective psychoses, and whether cumulative lifetime antipsychotic or benzodiazepine doses relate to brain morphology in these groups. We conducted two systematic reviews on the topic and investigated 44 schizophrenia cases and 19 with affective psychoses from the Northern Finland Birth Cohort 1966. The association between lifetime antipsychotic and benzodiazepine dose and brain MRI scans at the age of 43 was investigated using linear regression. Intracranial volume, sex, illness severity, and antipsychotic/benzodiazepine doses were used as covariates. There were no differences between the groups in brain structure volumes. In schizophrenia, after adjusting for benzodiazepine dose and symptoms, a negative association between lifetime antipsychotic dose and the nucleus accumbens volume remained. In affective psychoses, higher lifetime benzodiazepine dose associated with larger volumes of total gray matter and hippocampal volume after controlling for antipsychotic use and symptoms. It seems that in addition to antipsychotics, the severity of symptoms and benzodiazepine dose are also associated with brain structure volumes. These results suggest, that benzodiazepine effects should also be investigated also independently and not only as a confounder., (Copyright © 2018. Published by Elsevier B.V.)

Clozapine is known as the first 'atypical' medication and is effective in people who have treatment-resistant schizophrenia. Its 1990 emergence in the USA was marked by considerable controversy over its high cost, due in large part to having been both the first new antipsychotic medication to come to market in over a decade and the need for comprehensive safety monitoring within a decentralized health system. This paper traces the history of clozapine's discovery and development in Europe, its part in the 1975 Finnish agranulocytosis scare, and its subsequent volatile emergence in the USA. Analyses examine peripheral forces at the time, particularly the influence of political, corporate, medical and societal forces which shaped its market course.