Schizophrenia Bulletin Advance Access originally published online on January 22, 2008
Schizophrenia Bulletin 2008 34(2):310-311; doi:10.1093/schbul/sbm166
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Progressive Brain Changes in Schizophrenia
2 Unidad de Adolescentes, Department of Psychiatry, Hospital General Universitario Gregorio Marañón, Madrid, Spain
3 Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht, The Netherlands
For this theme issue, we have called upon experts in the field of study of brain changes in high-risk patients with prodromal symptoms or with a first episode of schizophrenia, whether it takes place in childhood, adolescence, or adulthood. The evidence—or lack thereof—that currently exists for progressive brain changes is discussed in this theme issue by some of the leading groups in the field.
The set of reviews starts with an elegant historical background on the cyclical issue of progressive brain changes in schizophrenia. The longitudinal magnetic resonance imaging studies from Edinburgh and Melbourne in prodromal subjects and subjects at increased genetic risk are then reviewed by their investigators. And finally, bringing us full circle, progressive changes after a first schizophrenia episode and in children and adolescents with early-onset psychosis are the last 2 reviews of this theme issue.
Overall, the different lines of evidence suggest that some structures appear abnormal before the first sign of any symptom and therefore during a first episode, while some of these same structures and others show a higher than expected volume loss over time and thus appear different at follow-up when compared with healthy controls. These progressive changes seem to be present during the initial years after the first episode and continue even in the more chronic phase of the illness.
The results of the different studies reviewed here could be explained by separate disease processes taking place at different times in the lives of patients with schizophrenia or a single ongoing process beginning during brain development and accelerating after maximum cranial volume is reached.1,2 Brain insults early in development, either in utero or ex utero, may affect maturational processes. In turn, early and late maturational processes, eg, regressive or pruning processes, result in dynamic changes in the structure of the brain well into the second and third decade of life and even later.3 These normal processes of brain maturation, leading to decreased cortical volume, could be exaggerated in patients with schizophrenia and lead to greater than expected decreases in cortical volume and increases in sulcal cerebrospinal fluid, in the absence of neurodegeneration. Excessive brain volume loss occurring may also be a consequence rather than a cause of illness, with variables such as psychosis, stress, and drug treatment playing a role in brain volume loss.4–6 Therefore, if we attempt to integrate the findings from the studies reviewed in this issue, we would suggest that early and late neurodevelopmental abnormalities may be present in varying degrees in patients with schizophrenia. Some of these may be under genetic control, other may be the result of environmental effects. Finally, progressive changes need to be addressed, not only from the aspect of volumetric brain changes but also at the molecular, cellular, and neurochemical level, and the findings will need to be related to the influence of genetic and environmental factors.7–10
 |
Footnotes |
|---|
1 To whom correspondence should be addressed; tel: +344265006; fax: +344265005; e-mail: CArango{at}mprc.umaryland.edu.
|
References |
|---|
 Top References |
|---|
- Woods BT. Is schizophrenia a progressive neurodevelopmental disorder? Toward a unitary pathogenetic mechanism. Am J Psychiatry (1998) 155::1661–1670.
[Abstract/Free Full Text] - Woods BT, Yurgelun-Todd D, Goldstein JM, Seidman LJ, Tsuang MT. MRI brain abnormalities in chronic schizophrenia: one process or more? Biol Psychiatry (1996) 40::585–596.[CrossRef][Web of Science][Medline]
- Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW. Mapping cortical change across the human life span. Nat Neurosci (2003) 6::309–315.[CrossRef][Web of Science][Medline]
- Cannon TD, Huttunen MO, Dahlstrom M, Larmo I, Rasanen P, Juriloo A. Antipsychotic drug treatment in the prodromal phase of schizophrenia. Am J Psychiatry (2002) 159::1230–1232.
[Abstract/Free Full Text] - Weinberger DR, McClure RK. Neurotoxicity, neuroplasticity, and magnetic resonance imaging morphometry: what is happening in the schizophrenic brain? Arch Gen Psychiatry (2002) 59::553–558.
[Free Full Text] - Lieberman JA, Tollefson GD, Charles C, et al. Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch Gen Psychiatry (2005) 62::361–370.
[Abstract/Free Full Text] - Salisbury DF, Kuroki N, Kasai K, Shenton ME, McCarley RW. Progressive and interrelated functional and structural evidence of post-onset brain reduction in schizophrenia. Arch Gen Psychiatry (2007) 64::521–529.
[Abstract/Free Full Text] - Rapoport JL, Addington AM, Frangou S, Psych MR. The neurodevelopmental model of schizophrenia: update 2005. Mol Psychiatry (2005) 10::434–449.[CrossRef][Web of Science][Medline]
- Rapoport JL, Gogtay N. Brain neuroplasticity in healthy, hyperactive and psychotic children: insights from neuroimaging. Neuropsychopharmacology (2008) 33::181–197.[Web of Science][Medline]
- Whitford TJ, Grieve SM, Farrow TF, et al. Progressive grey matter atrophy over the first 2-3 years of illness in first-episode schizophrenia: a tensor-based morphometry study. Neuroimage (2006) 32::511–519.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Janssen, A. Diaz-Caneja, S. Reig, I. Bombin, M. Mayoral, M. Parellada, M. Graell, D. Moreno, A. Zabala, V. G. Vazquez, et al. Brain morphology and neurological soft signs in adolescents with first-episode psychosis The British Journal of Psychiatry, September 1, 2009; 195(3): 227 - 233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Thompson, G. Bartzokis, K. M. Hayashi, A. D. Klunder, P. H. Lu, N. Edwards, M. S. Hong, M. Yu, J. A. Geaga, A. W. Toga, et al. Time-Lapse Mapping of Cortical Changes in Schizophrenia with Different Treatments Cereb Cortex, May 1, 2009; 19(5): 1107 - 1123. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||