Historical context

A neurodevelopmental model of schizophrenia

The existence of pre- and perinatal risk factors for schizophrenia as outlined in this chapter is central to the notion of schizophrenia as a neurodevelopmental disorder. The ‘neurodevelopmental hypothesis’ of schizophrenia proposes a subtle deviance in early brain development, the full adverse consequences of which are not manifest until adolescence or early adulthood. The hypothesis came to prominence in the late 1980s (Murray and Lewis, 1987; Weinberger, 1987), though similar models had been proposed by other researchers decades, even centuries, earlier (Clouston, 1891, 1892; Southard, 1915; Pasamanick et al., 1956).

The 1980s version of the neurodevelopmental hypothesis originated from a number of strands of evidence available at that time, including retrospective studies revealing a pattern of abnormalities in neurological and behavioural characteristics during childhood (Watt, 1978; Aylward et al., 1984), histopathological studies indicating developmental abnormalities in the hippocampus (Kovelman and Scheibel, 1984; Jakob and Beckman, 1986) and neuroimaging studies showing cerebral ventricular enlargement (Johnstone et al., 1976; Weinberger et al., 1979), even at the time of the first episode (Turner et al., 1986). Not all of this evidence has withstood the test of time, particularly the original histopathological findings. However, new, convincing information to support the neurodevelopmental hypothesis has emerged from epidemiological investigations, longitudinal studies of high-risk offspring, imaging studies and recent, robust neuropathological investigations (for review see Marenco and Weinberger, 2000; McDonald et al., 2000).