Executive functioning-related brain abnormalities associated with the genetic liability for schizophrenia: an activation likelihood estimation meta-analysis

Psychol Med. 2011 Jun;41(6):1239-52. doi: 10.1017/S0033291710001972. Epub 2010 Oct 14.


Background: Relatives of schizophrenia patients demonstrate abnormalities in prefrontal cortical activation during executive processing as measured by functional neuroimaging, albeit not consistently. A meta-analysis was conducted to determine whether reliable patterns of brain hypo- and hyperactivity, especially in the middle frontal region, were present in the relatives of patients.

Method: Seventeen studies, containing 18 samples of relatives and controls, were included in this meta-analysis. Studies were included if relatives of schizophrenia patients were compared to controls, an executive processing task was used, and standard space coordinates were reported for the functional activations. Activation likelihood estimation (ALE) was implemented to find convergence across functional neuroimaging experiment coordinates. A separate analysis was conducted to assess the potential impact of a priori hypothesis testing used in region-of-interest (ROI) approaches on the meta-analysis results.

Results: Relatives demonstrated hypo- and hyperactivity in statistically overlapping right middle frontal regions [Brodmann area (BA) 9/10]. Use of an ROI analysis that a priori focused on prefrontal regions resulted in more findings of reduced activity in the middle frontal region.

Conclusions: The cortical regions identified by this meta-analysis could potentially serve as intermediate biological markers in the search for candidate genes for schizophrenia. As neurocognitive deficits are related to functional impairments in patients, a better understanding of neural and genetic vulnerabilities would be beneficial in our efforts to remediate these important deficits.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / abnormalities*
  • Brain / physiopathology*
  • Brain Mapping
  • Executive Function / physiology*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Image Interpretation, Computer-Assisted*
  • Likelihood Functions
  • Magnetic Resonance Imaging*
  • Phenotype
  • Prefrontal Cortex / abnormalities
  • Prefrontal Cortex / physiopathology
  • Schizophrenia / genetics*
  • Schizophrenia / physiopathology*
  • Schizophrenic Psychology*