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Schizophrenia as a progressive brain disease

Published online by Cambridge University Press:  16 April 2020

N.E.M. van Haren ,
W. Cahn ,
H.E. Hulshoff Pol  and
R.S. Kahn
N.E.M. van Haren*
Affiliation:
Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
W. Cahn
Affiliation:
Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
H.E. Hulshoff Pol
Affiliation:
Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
R.S. Kahn
Affiliation:
Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
*
∗Corresponding author. Department of Psychiatry, A.01.126, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Tel.: +31 30 2507130; fax: +31 30 2505443. E-mail address: n.e.m.vanharen@umcutrecht.nl (N.E.M. van Haren).
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Abstract

There is convincing evidence that schizophrenia is characterized by abnormalities in brain volume. At the Department of Psychiatry of the University Medical Centre Utrecht, Netherlands, we have been carrying out neuroimaging studies in schizophrenia since 1995. We focused our research on three main questions. First, are brain volume abnormalities static or progressive in nature? Secondly, can brain volume abnormalities in schizophrenia be explained (in part) by genetic influences? Finally, what environmental factors are associated with the brain volume abnormalities in schizophrenia?

Based on our findings we suggest that schizophrenia is a progressive brain disease. We showed different age-related trajectories of brain tissue loss suggesting that brain maturation that occurs in the third and fourth decade of life is abnormal in schizophrenia. Moreover, brain volume has been shown to be a useful phenotype for studying schizophrenia. Brain volume is highly heritable and twin and family studies show that unaffected relatives show abnormalities that are similar, but usually present to a lesser extent, to those found in the patients. However, also environmental factors play a role. Medication intake is indeed a confounding factor when interpreting brain volume (change) abnormalities, while independent of antipsychotic medication intake brain volume abnormalities appear influenced by the outcome of the illness.

In conclusion, schizophrenia can be considered as a progressive brain disease with brain volume abnormalities that are for a large part influenced by genetic factors. Whether the progressive volume change is also mediated by genes awaits the results of longitudinal twin analyses. One of the main challenges for the coming years, however, will be the search for gene-by-environment interactions on the progressive brain changes in schizophrenia.

Keywords

SchizophreniaNeuroimagingProgressionOutcomeAntipsychotic medicationGenetics
Type
Original article
Information
European Psychiatry , Volume 23 , Issue 4 , June 2008 , pp. 245 - 254
Copyright
Copyright © European Psychiatric Association 2008

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