A Review of the Neurodevelopmental Hypothesis of Schizophrenia

complications have all been suggested based on epidemiological evidence. Murray and Lewis examined various schizophrenic epiphenomena suggesting that a neurodevelopmental model may serve to connect and elucidate them.3 The various neurodevelopmental hypotheses share three main assumptions: 1.The primary pathogenic defect is an early derangement of the orderly development of the central nervous system (CNS). 2.The period of active operation of the causative agent is of short duration, so the process is essentially static. 3.The behavioural consequences of this static process remain relatively latent until long after the primary pathogenetic process has run its course.4 There is no direct evidence of a pre- or peri-natal lesion associated with schizophrenia but indirect evidence of impaired development can be seen in macroscopic anatomical variations as well as microscopic immunohistochemical anomalies. The Evidence Over the past decade, the most consistently demonstrated phenomenon on CT or MRI, is that schizophrenic patients have larger third and lateral ventricles than controls matched for age and sex, even in the case of monozygotic twins discordant for schizophrenia.5,6 This phenomenon is not specific for schizophrenia, however, and is only identified in six to 40 percent of subjects.7 Ventricular enlargement is presumed to take place at the expense of cerebral tissue and may be interpreted as indicating functional disorder in the adjacent brain substance. Widened third ventricles, in particular, may cause damage to diencephalic and limbic structures which are involved in excitatory autonomic functioning. This is evidenced by the relationship to premorbid reduction in electrodermal responses and heart rate in a study of high-risk individuals.8 This is significant in light of evidence linking diminished autonomic responsiveness with negative symptoms of schizophrenia. Ventricular enlargement is present at the onset of disease and has been found in most cases to be non-progressive, supporting a neuro