chapter  1
16 Pages

The neurodevelopmental hypothesis of schizophrenia

WithKATHERINE H. KARLSGODT, LAUREN M. ELLMAN

Schizophrenia has an insidious onset, with full manifestation of the disorder occurring in late adolescence and early adulthood. Onset is complex and includes cognitive and social changes in early childhood as well as a more proximal prodromal phase in which functioning undergoes a pronounced deterioration and subpsychotic symptoms emerge. Based on this trend of slow change, it was initially thought that schizophrenia might be degenerative, similar to other gradually emerging disorders such as Alzheimer’s disease. However, with an increased understanding of the associated neural changes, a neurodegenerative process appeared less likely. For instance, despite early findings (Weinberger, Wagner, & Wyatt, 1983), it became evident that any gliosis present in schizophrenia could not explain the degree of neuroanatomical changes observed (Harrison, 1999). Further, findings that ventricular enlargement (originally presumed to be evidence of neural degeneration) positively correlated with a history of obstetric complications (OCs; Reveley, Reveley, & Murray, 1984) supported the importance of environmental influences on early development. Simultaneously, a deeper understanding of later neurodevelopmental processes began to emerge, notably that normal development includes a natural pruning process that can in itself cause a decrease in cortical thickness or brain volume (Huttenlocher, 1979) and that in areas critical for schizophrenia, such as the prefrontal cortex, these processes reach completion around the age of disease onset (Huttenlocher, 1990; Pfefferbaum et al., 1994). The confluence of these findings, with work by Robin Murray at the forefront, lead to the emergence of the widely influential neurodevelopmental hypothesis of schizophrenia, in which a subtle, static brain lesion (caused by a combination of genetic and environmental factors) later interacts with normal maturational processes in the brain to result in schizophrenia (Murray & Lewis, 1987).