Multimodal voxel-based meta-analysis of structural and functional magnetic resonance imaging studies in those at elevated genetic risk of developing schizophrenia

Psychiatry Res. 2014 Jan 30;221(1):69-77. doi: 10.1016/j.pscychresns.2013.07.008. Epub 2013 Nov 14.


Computational brain-imaging studies of individuals at familial high risk for psychosis have provided interesting results, but interpreting these findings can be a challenge due to a number of factors. We searched the literature for studies reporting whole brain voxel-based morphometry (VBM) or functional magnetic resonance imaging (fMRI) findings in people at familial high risk for schizophrenia compared with a control group. A voxel-wise meta-analysis with the effect-size version of Signed Differential Mapping (ES-SDM) identified regional abnormalities of functional brain response. Similarly, an ES-SDM meta-analysis was conducted on VBM studies. A multi-modal imaging meta-analysis was used to highlight brain regions with both structural and functional abnormalities. Nineteen studies met the inclusion criteria, in which a total of 815 familial high-risk individuals were compared to 685 controls. Our fMRI results revealed a number of regions of altered activation. VBM findings demonstrated both increases and decreases in grey matter density of relatives in a variety of brain regions. The multimodal analysis revealed relatives had decreased grey matter with hyper-activation in the left inferior frontal gyrus/amygdala, and decreased grey matter with hypo-activation in the thalamus. We found several regions of altered activation or structure in familial high-risk individuals. Reliable fMRI findings in the right posterior superior temporal gyrus further confirm that alteration in this area is a potential marker of risk.

Keywords: Functional MRI; Genetic; Multimodal; Relatives; Schizophrenia; Voxel based morphometry.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Amygdala / pathology
  • Brain / pathology*
  • Case-Control Studies
  • Female
  • Frontal Lobe / pathology
  • Genetic Predisposition to Disease
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging / methods*
  • Male
  • Multimodal Imaging / methods*
  • Neuroimaging
  • Psychotic Disorders / genetics
  • Psychotic Disorders / pathology*
  • Risk Factors
  • Schizophrenia / genetics
  • Schizophrenia / physiopathology
  • Temporal Lobe / pathology