The neurodevelopmental hypothesis proposes that adverse environmental events during fetal life impairs and subsequendy alter neural development, leading to mental illness in adulthood.10'14" Like all good theories, it has a long history. As early as 1891, the founding father of adolescent psychiatry, Scottish psychiatrist Thomas Storer Clouston, proposed that there was a developmental component to "adolescent or developmental insanity". He considered it a disorder of cortical development; "the last cortical disease", and that the onset of psychotic symptoms was due to maturation during adolescence "of certain parts of the brain which had lain dormant before",20"23 This concept was subsequendy superseded by the hypothesis proposed by Emil Kraeplin, much influenced by Alzheimer and his study of adult dementia, that the illness was a neurodegenerative organic brain disease;24 a view Clouston "strenuously" objected to,22 but one which held sway for a considerable number of years.17'19'25 Even Kraeplin acknowledged, however, that there might be a developmental origin, at least in some cases where evidence of the illness existed in childhood,23 as did Eugene Bleuler, who in 1911 coined the term schizophrenia; a term chosen to express the presence of schisms between thought, emotion and behaviour which characterises the "schizophrenias".26 Bleuler reported that behavioural difficulties could be observed in childhood in more than half the patients who eventually developed schizophrenia.
This observation is fundamental, since it demonstrates that the underlying disorder that leads to schizophrenia evolves in some cases at least from early childhood if not before birth. In subsequent years these childhood clues about the potential developmental origins of schizophrenia were forgotten or dismissed, but subsequendy rediscovered in the 1980s.27'28 Prospect lve follow-up studies of birth cohorts have confirmed that significant impairments in neuromotor, receptive language, and cognitive development are present among children later diagnosed as having schizophreniform disorder.29"33 These premorbid behavioural changes can be seen as early as three years of age.29 There is also an early childhood onset version of schizophrenia.34 Thus, while schizophrenia typically manifests in its full form in adulthood, there is now good evidence to show that the illness is already in progress much earlier and is progressive in nature.
One key conceptual difficulty is reconciling the dining between origin and onset of the disorder: how can it be that an illness which manifests in adolescent or adult life could have its origins so long ago, in fetal life?5,25 This apparent paradox may be resolved by understanding that neurodevelopment is a continuum started at conception, but not completed until adulthood. Disturbances in particular critical windows of maturation can thus have very long lasting effects.
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