Relationship between prefrontal gray matter volumes and working memory performance in schizophrenia: A family study

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21 Scopus citations


Diffuse structural abnormalities in the prefrontal cortex have been reported in both schizophrenia patients and their nonpsychotic biological relatives. Additionally, working memory difficulties have long been documented in schizophrenia patients and have been associated with the genetic liability for the disorder. The present analysis investigated the relationship between prefrontal regional gray matter volumes and two facets of working memory in schizophrenia using a family study. Structural neuroimaging scans provided measurements of rostral middle, superior, and inferior prefrontal cortical gray matter volumes. Participants also completed a spatial working memory task that measured both short-term maintenance and manipulation of material in memory. Both schizophrenia patients and relatives had reduced superior and inferior frontal gray matter volumes. Schizophrenia patients demonstrated a spatial working memory deficit compared to both controls and relatives, with no greater impairment when required to manipulate material. Smaller prefrontal volumes in schizophrenia patients were associated with worse working memory performance. These relationships were absent in the nonpsychotic relatives and controls. Despite normative behavioral performance, nonpsychotic relatives demonstrated abnormalities in brain structure similar to those found in schizophrenia patients. Manipulation abilities were not more impaired than maintenance in schizophrenia patients. Consistent with other neuroimaging research, our results suggest that direct measures of the underlying biology may be more sensitive to the effects of the genetic liability for schizophrenia than behavioral measures.

Original languageEnglish (US)
Pages (from-to)113-121
Number of pages9
JournalSchizophrenia Research
Issue number1-3
StatePublished - Mar 2014

Bibliographical note

Funding Information:
This work was supported by a Thesis Research Grant from the University of Minnesota ; PGS Doctoral Award from the Natural Sciences and Engineering Research Council of Canada ; University of Calgary Start-up, Seed, and Starter Grants ; Canadian Institutes of Health Research Operating Grant and New Investigator Award to VMG; from the Clinical Science Merit Review Program Grant of the Department of Veterans Affairs to SRS; and from the National Institutes of Health ( R24 MH069675 to SRS; R21 MH079262 to AWM; P41 RR008079 and P30 NS057091 to the Center for Magnetic Resonance Imaging at the University of Minnesota). The funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.


  • Family study
  • Gray matter
  • Prefrontal cortex
  • Schizophrenia
  • Working memory


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