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  Vol. 60 No. 1, January 2003 TABLE OF CONTENTS
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A Specific Deficit in Context Processing in the Unaffected Siblings of Patients With Schizophrenia

Angus W. MacDonald III, PhD; Michael F. Pogue-Geile, PhD; Melissa K. Johnson, BA; Cameron S. Carter, MD

Arch Gen Psychiatry. 2003;60:57-65.

Background  Understanding the biological basis of complex, heritable illnesses such as schizophrenia is facilitated by sensitive and functionally specific measures of intermediate processes. Context processing is a theoretically motivated construct associated with executive function. Impairments in this process have been associated with dysfunction of the prefrontal cortex. In the present study, we evaluated whether a specific deficit in context processing could be associated with the unexpressed genetic liability to schizophrenia.

Methods  Twenty-four patients with schizophrenia, 24 unaffected siblings and 36 control subjects completed a version of the AX task with (1) a condition that required context processing and (2) an expectancy condition in which intact context processing could lead to errors.

Results  Patients and unaffected siblings performed relatively worse in the context processing condition, whereas controls performed relatively worse in the expectancy condition. A double dissociation between siblings and controls (F = 9.5, P<.005) constituted strong evidence of a specific deficit in context processing associated with a familial or genetic liability to schizophrenia. Preliminary evidence of high diagnostic efficiency was also noted (specificity, 38%; and sensitivity, 100%).

Conclusions  Context processing deficits have been associated with dorsolateral prefrontal cortex dysfunctions in schizophrenia. Such a dysfunction may occur even when genetic liability to schizophrenia is unexpressed clinically. The present method of demonstrating a double dissociation may be a useful approach to exploring endophenotypes related to specific cognitive and neural processes that can be measured in ways sensitive to subtle group differences.


From the Departments of Psychology (Drs MacDonald, Pogue-Geile, and Carter) and Psychiatry (Drs MacDonald and Carter and Ms Johnson), University of Pittsburgh, Pittsburgh, Pa. Dr MacDonald is now with the Departments of Psychology and Psychiatry, University of Minnesota, Minneapolis.



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Imaging Genetic Liability to Schizophrenia: Systematic Review of fMRI Studies of Patients' Nonpsychotic Relatives
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Genetic Heterogeneity, Modifier Genes, and Quantitative Phenotypes in Psychiatric Illness: Searching for a Framework
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Focus 2006;4:423.
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Factors Mediating Cognitive Deficits and Psychopathology Among Siblings of Individuals With Schizophrenia
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Cognitive Deficits in Unaffected First-Degree Relatives of Schizophrenia Patients: A Meta-analytic Review of Putative Endophenotypes
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Am. J. Psychiatry 2005;162:2322-2329.
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Specificity of Prefrontal Dysfunction and Context Processing Deficits to Schizophrenia in Never-Medicated Patients With First-Episode Psychosis
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Am. J. Psychiatry 2005;162:475-484.
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