Longitudinal gray matter change in young people who are at enhanced risk of schizophrenia due to intellectual impairment

T. William J. Moorhead*, Andrew C. Stanfield, Andrew G. McKechanie, Maria R. Dauvermann, Eve C. Johnstone, Stephen M. Lawrie, David G. Cunningham Owens

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Background: Existing studies of brain structural changes before the onset of schizophrenia have considered individuals with either familial risk factors or prodromal symptomatology. We aimed to determine whether findings from these studies are also applicable to those at enhanced risk of developing schizophrenia for another reason - intellectual impairment. 

Methods: Participants with intellectual impairment (mean IQ: 78.2) received magnetic resonance imaging of the brain at baseline (mean age: 16 years old) and again 6 years later. The Positive and Negative Syndrome Scale was used to assess psychotic symptoms. Participants were dichotomized using their Positive and Negative Syndrome Scale scores at follow-up and gray matter changes were compared between the groups using tensor based morphometry and semiautomated region of interest analysis. 

Results: Forty-six individuals had scans of sufficient quality to be included in the study. The tensor based morphometry analyses revealed that those with psychotic symptoms at follow-up showed significantly greater gray matter reductions over 6 years in the medial temporal lobes bilaterally. Region of interest analyses revealed that those individuals with psychotic symptoms at follow-up showed a reduced right hippocampal volume at age 16 and reduced bilateral hippocampal volumes at follow-up. 

Conclusions: This unique study of individuals vulnerable to schizophrenia due to intellectual impairment highlights aberrant development in the medial temporal lobe associated with the occurrence of psychotic symptoms. These developmental changes are also evident in populations at enhanced risk of schizophrenia for familial and symptomatic reasons, suggesting they are central to the development of the disorder regardless of the nature of the vulnerability state.

Original languageEnglish
Pages (from-to)985-992
Number of pages8
JournalBiological Psychiatry
Issue number10
Early online date17 Jan 2013
Publication statusPublished - 15 May 2013

Bibliographical note

Funding Information:
This project was funded by a program Grant from the Medical Research Council of Great Britain with additional support from the RS McDonald Trust. The scans were acquired at the Brain Research Imaging Centre ( http://www.bric.ed.ac.uk/ ), which is supported by the Scottish Imaging Network, A Platform for Scientific Excellence Collaboration ( http://www.sinapse.ac.uk/ ). The investigators also acknowledge the support of National Health Service Research Scotland, through the Scottish Mental Health Research Network ( www.smhrn.org.uk ), who provided assistance with subject recruitment and cognitive assessments. During this work, TWJM and MRD received support from the Dr. Mortimer and Theresa Sackler Foundation. During this work, ACS was supported by a Wellcome Trust Clinical Research Training Fellowship.

The authors TWJM and SML have received financial support from Pfizer (formerly Wyeth) in relation to imaging studies of people with schizophrenia and bipolar disorder. ACS and AGM have received funding from Novartis Pharmaceuticals. These received funds do not present a conflict of interest with the present study. None of the other authors has any biomedical financial interests or potential conflicts of interest to disclose.


  • Hippocampus
  • learning disability
  • longitudinal change
  • psychotic symptoms
  • schizophrenia high risk
  • tensor based morphometry

ASJC Scopus subject areas

  • Biological Psychiatry


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