Psychological Medicine

Original Article

Brain MRI abnormalities in schizophrenia: same genes or same environment?

F. V. RIJSDIJK a1c1, N. E. M. van HAREN a2, M. M. PICCHIONI a3, C. McDONALD a3, T. TOULOPOULOU a3, H. E. HULSHOFF POL a2, R. S. KAHN a2, R. MURRAY a3 and P. C. SHAM a1a3a4
a1 Social, Genetic & Developmental Psychiatry Research Centre, Institute of Psychiatry, London, UK
a2 Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Centre Utrecht, The Netherlands
a3 Division of Psychological Medicine, Section of General Psychiatry, Institute of Psychiatry, London, UK
a4 Department of Psychiatry, University of Hong Kong, Queen Mary Hospital, Hong Kong

Article author query
rijsdijk fv   [PubMed][Google Scholar] 
van haren ne   [PubMed][Google Scholar] 
picchioni mm   [PubMed][Google Scholar] 
mcdonald c   [PubMed][Google Scholar] 
toulopoulou t   [PubMed][Google Scholar] 
pol he   [PubMed][Google Scholar] 
kahn rs   [PubMed][Google Scholar] 
murray r   [PubMed][Google Scholar] 
sham pc   [PubMed][Google Scholar] 


Background. Structural brain volume abnormalities are among the most extensively studied endophenotypes in schizophrenia. Bivariate genetic model fitting (adjusted to account for selection) was used to quantify the genetic relationship between schizophrenia and brain volumes and to estimate the heritability of these volumes.

Method. We demonstrated by simulation that the adjusted genetic model produced unbiased estimates for endophenotype heritability and the genetic and environmental correlations. The model was applied to brain volumes (whole brain, hippocampus, third and lateral ventricles) in a sample of 14 monozygotic (MZ) twin pairs concordant for schizophrenia, 10 MZ discordant pairs, 17 MZ control pairs, 22 discordant sibling pairs, three concordant sibling pairs, and 114 healthy control subjects.

Results. Whole brain showed a substantial heritability (88%) and lateral ventricles substantial common environmental effects (67%). Whole brain showed a significant genetic correlation with schizophrenia, whereas lateral ventricles showed a significant individual specific correlation with schizophrenia. There were significant familial effects for hippocampus and third ventricle, but the analyses could not resolve whether these were genetic or environmental in origin (around 30% each).

Conclusions. Using genetic model fitting on twin and sibling data we have demonstrated differential sources of covariation between schizophrenia and brain volumes, genetic in the case of whole brain volume and individual specific environment in the case of lateral ventricles.

c1 SGDP Centre, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. (Email: