Childhood onset schizophrenia: support for a progressive neurodevelopmental disorder

► Converging evidence points to progressive structural brain abnormalities in schizophrenia. ► Childhood-onset schizophrenia is a sever, treatment refractory phenotype with more salient genetic features. ► This review covers longitudinal anatomic brain development in childhood-onset schizophrenia. S...

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Published inInternational journal of developmental neuroscience Vol. 29; no. 3; pp. 251 - 258
Main Authors Rapoport, Judith L., Gogtay, Nitin
Format Journal Article
LanguageEnglish
Published United States Elsevier Ltd 01.05.2011
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Abstract ► Converging evidence points to progressive structural brain abnormalities in schizophrenia. ► Childhood-onset schizophrenia is a sever, treatment refractory phenotype with more salient genetic features. ► This review covers longitudinal anatomic brain development in childhood-onset schizophrenia. Structural brain abnormalities have become an established feature of schizophrenia and increasing evidence points towards the progressive nature of these abnormalities. The brain abnormalities are most profound in early onset cases, which have a severe, treatment refractory phenotype and more salient genetic features. Unique insights could thus be gained in schizophrenia pathology from studying the earliest manifestations of the illness. This paper reviews and updates the findings on anatomic brain development in patients with very early onset schizophrenia while showing preliminary data from ongoing studies. Collectively, our studies demonstrate that childhood-onset schizophrenia (COS) subjects show progressive loss of gray matter, delayed/disrupted white matter (WM) growth, and a progressive decline in cerebellar volume, some of which are shared by their healthy siblings. The developmental patterns or the ‘trajectories’ of brain development are often more striking than anatomic brain differences at any one point in time; highlighting the importance of longitudinal studies. The sibling findings of partially shared gray matter (GM) deficits which appear to normalize with age, along with other genetic analyses, provide evidence that the brain developmental ‘patterns/trajectories’ for several regions at particular ages could be useful endophenotypes (trait markers).
AbstractList Structural brain abnormalities have become an established feature of schizophrenia and increasing evidence points towards the progressive nature of these abnormalities. The brain abnormalities are most profound in early onset cases, which have a severe, treatment refractory phenotype and more salient genetic features. Unique insights could thus be gained in schizophrenia pathology from studying the earliest manifestations of the illness. This paper reviews and updates the findings on anatomic brain development in patients with very early onset schizophrenia while showing preliminary data from ongoing studies. Collectively, our studies demonstrate that childhood-onset schizophrenia (COS) subjects show progressive loss of gray matter, delayed/disrupted white matter (WM) growth, and a progressive decline in cerebellar volume, some of which are shared by their healthy siblings. The developmental patterns or the ‘trajectories’ of brain development are often more striking than anatomic brain differences at any one point in time; highlighting the importance of longitudinal studies. The sibling findings of partially shared gray matter (GM) deficits which appear to normalize with age, along with other genetic analyses, provide evidence that the brain developmental ‘patterns/trajectories’ for several regions at particular ages could be useful endophenotypes (trait markers).
► Converging evidence points to progressive structural brain abnormalities in schizophrenia. ► Childhood-onset schizophrenia is a sever, treatment refractory phenotype with more salient genetic features. ► This review covers longitudinal anatomic brain development in childhood-onset schizophrenia. Structural brain abnormalities have become an established feature of schizophrenia and increasing evidence points towards the progressive nature of these abnormalities. The brain abnormalities are most profound in early onset cases, which have a severe, treatment refractory phenotype and more salient genetic features. Unique insights could thus be gained in schizophrenia pathology from studying the earliest manifestations of the illness. This paper reviews and updates the findings on anatomic brain development in patients with very early onset schizophrenia while showing preliminary data from ongoing studies. Collectively, our studies demonstrate that childhood-onset schizophrenia (COS) subjects show progressive loss of gray matter, delayed/disrupted white matter (WM) growth, and a progressive decline in cerebellar volume, some of which are shared by their healthy siblings. The developmental patterns or the ‘trajectories’ of brain development are often more striking than anatomic brain differences at any one point in time; highlighting the importance of longitudinal studies. The sibling findings of partially shared gray matter (GM) deficits which appear to normalize with age, along with other genetic analyses, provide evidence that the brain developmental ‘patterns/trajectories’ for several regions at particular ages could be useful endophenotypes (trait markers).
Structural brain abnormalities have become an established feature of schizophrenia and increasing evidence points towards the progressive nature of these abnormalities. The brain abnormalities are most profound in early onset cases, which have a severe, treatment refractory phenotype and more salient genetic features. Unique insights could thus be gained in schizophrenia pathology from studying the earliest manifestations of the illness. This paper reviews and updates the findings on anatomic brain development in patients with very early onset schizophrenia while showing preliminary data from ongoing studies. Collectively, our studies demonstrate that childhood-onset schizophrenia (COS) subjects show progressive loss of gray matter, delayed/disrupted white matter (WM) growth, and a progressive decline in cerebellar volume, some of which are shared by their healthy siblings. The developmental patterns or the 'trajectories' of brain development are often more striking than anatomic brain differences at any one point in time; highlighting the importance of longitudinal studies. The sibling findings of partially shared gray matter (GM) deficits which appear to normalize with age, along with other genetic analyses, provide evidence that the brain developmental 'patterns/trajectories' for several regions at particular ages could be useful endophenotypes (trait markers).Structural brain abnormalities have become an established feature of schizophrenia and increasing evidence points towards the progressive nature of these abnormalities. The brain abnormalities are most profound in early onset cases, which have a severe, treatment refractory phenotype and more salient genetic features. Unique insights could thus be gained in schizophrenia pathology from studying the earliest manifestations of the illness. This paper reviews and updates the findings on anatomic brain development in patients with very early onset schizophrenia while showing preliminary data from ongoing studies. Collectively, our studies demonstrate that childhood-onset schizophrenia (COS) subjects show progressive loss of gray matter, delayed/disrupted white matter (WM) growth, and a progressive decline in cerebellar volume, some of which are shared by their healthy siblings. The developmental patterns or the 'trajectories' of brain development are often more striking than anatomic brain differences at any one point in time; highlighting the importance of longitudinal studies. The sibling findings of partially shared gray matter (GM) deficits which appear to normalize with age, along with other genetic analyses, provide evidence that the brain developmental 'patterns/trajectories' for several regions at particular ages could be useful endophenotypes (trait markers).
Author Rapoport, Judith L.
Gogtay, Nitin
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Snippet ► Converging evidence points to progressive structural brain abnormalities in schizophrenia. ► Childhood-onset schizophrenia is a sever, treatment refractory...
Structural brain abnormalities have become an established feature of schizophrenia and increasing evidence points towards the progressive nature of these...
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SubjectTerms Age of Onset
Anatomic
Brain
Brain - growth & development
Brain - pathology
Child
Childhood-onset
Cohort Studies
Developmental Disabilities - pathology
Developmental Disabilities - physiopathology
Disease Progression
Humans
Imaging
Longitudinal Studies
Magnetic Resonance Imaging
MRI
Phenotype
Progressive
Schizophrenia
Schizophrenia - pathology
Siblings
Title Childhood onset schizophrenia: support for a progressive neurodevelopmental disorder
URI https://dx.doi.org/10.1016/j.ijdevneu.2010.10.003
https://onlinelibrary.wiley.com/doi/abs/10.1016%2Fj.ijdevneu.2010.10.003
https://www.ncbi.nlm.nih.gov/pubmed/20955775
https://www.proquest.com/docview/861593222
https://www.proquest.com/docview/867749213
https://pubmed.ncbi.nlm.nih.gov/PMC5157162
Volume 29
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