A specific deficit in context processing in the unaffected siblings of patients with schizophrenia.
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.
MacDonald
Angus W
AW
Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA. macdo046@umn.edu
Pogue-Geile
Michael F
MF
Johnson
Melissa K
MK
Carter
Cameron S
CS
D000328:Adult; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D011930:Reaction Time; D012559:Schizophrenia / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D035781:Siblings