Working Memory in Unaffected Relatives of Patients With Schizophrenia: A Meta-Analysis of Functional Magnetic Resonance Imaging Studies

Schizophr Bull. 2016 Jul;42(4):1068-77. doi: 10.1093/schbul/sbv221. Epub 2016 Jan 5.


Working memory deficits, a core cognitive feature of schizophrenia may arise from dysfunction in the frontal and parietal cortices. Numerous studies have also found abnormal neural activation during working memory tasks in patients' unaffected relatives. The aim of this study was to systematically identify and anatomically localize the evidence for those activation differences across all eligible studies. Fifteen functional magnetic resonance imaging (fMRI) manuscripts, containing 16 samples of 289 unaffected relatives of patients with schizophrenia, and 358 healthy controls were identified that met our inclusion criteria: (1) used a working memory task; and (2) reported standard space coordinates. Activation likelihood estimation (ALE) identified convergence across studies. Compared to healthy controls, patients' unaffected relatives showed decreases in neural activation in the right middle frontal gyrus (BA9), as well as right inferior frontal gyrus (BA44). Increased activation was seen in relatives in the right frontopolar (BA10), left inferior parietal lobe (BA40), and thalamus bilaterally. These results suggest that the familial risk of schizophrenia is expressed in changes in neural activation in the unaffected relatives in the cortical-subcortical working memory network that includes, but is not restricted to the middle prefrontal cortex.

Keywords: dorsolateral prefrontal cortex; endophenotype; functional magnetic resonance imaging (fMRI); intermediate phenotype; meta-analyses.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Endophenotypes*
  • Family*
  • Female
  • Functional Neuroimaging / statistics & numerical data*
  • Humans
  • Magnetic Resonance Imaging / statistics & numerical data*
  • Male
  • Memory, Short-Term / physiology*
  • Middle Aged
  • Prefrontal Cortex / physiopathology*
  • Schizophrenia / physiopathology*
  • Young Adult