What causes the onset of psychosis? Matthew R. Broome a, T , James B. Woolley a , Paul Tabraham a , Louise C. Johns a , Elvira Bramon a , Graham K. Murray b , Carmine Pariante a , Philip K. McGuire a , Robin M. Murray a a Division of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK b Department of Psychiatry, University of Cambridge, Box 189, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK Received 21 December 2004; received in revised form 10 February 2005; accepted 12 February 2005 Available online 31 March 2005 Abstract It has become increasingly clear that the simple neurodevelopmental model fails to explain many aspects of schizophrenia including the timing of the onset, and the nature of the abnormal perceptions. Furthermore, we do not know why some members of the general population have anomalous experiences but remain well, while others enter the prodrome of psychosis, and a minority progress to frank schizophrenia. We suggest that genes or developmental damage result in individuals vulnerable to dopamine deregulation. In contemporary society, this is often compounded by abuse of drugs such as amphetamines and cannabis, which then propel the individual into a state of dopamine-induced misinterpretation of the environment. Certain types of social adversity such as migration and social isolation, as well as affective change can also contribute to this. Thereafter, biased cognitive appraisal processes result in delusional interpretation of the abnormal perceptual experiences. Thus, a plausible model of the onset of psychosis needs to draw not only on neuroscience, but also on the insights of social psychiatry and cognitive psychology. D 2005 Elsevier B.V. All rights reserved. Keywords: Psychosis; Schizophrenia; Prodromal; Aetiology/Etiology; Epidemiology; Imaging 1. Introduction In this paper we consider what initiates psychosis. We start by describing the developmental and epidemiological context of prodromal symptoms. Then we discuss dopaminergic mechanisms impli- cated in the onset of functional psychosis as well as the role of social factors, and how cognitive psycho- logical models may help to integrate these seemingly disparate lines of research. 1.1. The developmental perspective It has been apparent for almost two decades that there is a developmental component to schizophrenia. 0920-9964/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2005.02.007 T Corresponding author. Tel.: +44 20 7848 0355; fax: +44 20 7848 0976. E-mail address: m.broome@iop.kcl.ac.uk (M.R. Broome). Schizophrenia Research 79 (2005) 23 – 34 www.elsevier.com/locate/schres