Neurodevelopmental Hypothesis of Schizophrenia: Reappraisal
Neurodevelopmental Hypothesis of Schizophrenia: Reappraisal
Neurodevelopmental Hypothesis of Schizophrenia: Reappraisal
Reappraisal
173
Owen et al
174
Implications
What is clear is that there is now an urgent need to re-examine
and reappraise the relationships between these various syndromes.
There has been much recent interest in the relationship between
schizophrenia and bipolar disorder,5,9 but there is now a need to
focus upon the relationships among the neurodevelopmental
syndromes that typically present in childhood and between these
and the disorders that typically present in adulthood. There is a
need for studies examining the clinical and familial overlap
between these syndromes. Such studies would benefit from a focus
on specific symptoms as well as cognitive and neurocognitive
endophenotypes with the confounding effects of diagnostic
practices removed. This needs to be coupled with more detailed
analyses of the familial and molecular genetic relationships
between each syndrome and the less severe manifestations that
appear in relatives. Indeed, understanding the modifying and
compensatory mechanisms that underlie variable expressivity
and penetrance might point the way to new therapeutic
opportunities. This work will need to take a developmental
perspective since it is likely that the manifestations of these
phenotypes will vary with age, and longitudinal studies will
certainly be required. Aetiological research, including genetics,
should now end its exclusive love affair with DSM and ICD
categories. The goal now must be to relate research on aetiology
and pathogenesis to specific psychopathological syndromes and
phenotypes defined by studies of cognition and neuroimaging,
and to place these in a developmental context.
Although recent genetic findings certainly challenge the
aetiological basis of current diagnostic groupings, it would be
premature to suggest a radical overhaul of diagnostic practices
until more evidence accumulates. However, these findings do
inform attempts as part of the DSM5 and ICD11 processes to
create a meta-structure for psychiatric disorders based on
aetiological and/or pathophysiological grounds.31 They suggest
that varying degrees of neurodevelopmental impairment might
contribute across a broad spectrum of disorders with the final
phenotype depending upon a complex dynamic of risk, protective,
modifying and compensatory factors. These findings also have
important implications for clinicians by suggesting that we should
break down some of the service structures that currently serve to
partition the management of individuals based upon current
diagnostic categories. An obvious example is the separation
between services treating general psychiatric disorders and
intellectual disability.20 The recent genetic data also add to
evidence of continuities between childhood and adult psychiatric
disorders13 and suggest that greater communication and
continuity between child and adult services is required.
In conclusion, the neurodevelopmental hypothesis of
schizophrenia provided a valuable framework that allowed a
Funding
We are members of the MRC Centre for Neuropsychiatric Genetics and Genomics and the
Neuroscience and Mental Health Research Institute in Cardiff University. Our research in
this area is supported by the MRC and the Wellcome Trust (076113).
Acknowledgements
M.J.O. is a member of the DSM5 Work Group on Psychotic Disorders. The opinions
expressed in this article do not necessarily reflect the consensus of the DSM5 Work Group
or Task Force.
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