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Am J Psychiatry 1995; 152:1286-1290
Copyright © 1995 by American Psychiatric Association
Diagnostic accuracy and linkage analysis: how useful are schizophrenia spectrum phenotypes?
SV Faraone, WS Kremen, MJ Lyons, JR Pepple, LJ Seidman and MT Tsuang
Harvard Medical School Department of Psychiatry, Massachusetts Mental Health Center, Boston, USA.
OBJECTIVE: Numerous studies suggest that the nonschizophrenic relatives of
schizophrenic patients exhibit psychiatric and other features that
discriminate them from normal comparison subjects. These features have been
put forth as "spectrum" phenotypes that may be variant manifestations of
the schizophrenia genotype. However, most of these studies do not address a
key measurement question: does the diagnostic accuracy of these spectrum
classifications warrant their use in genetic linkage studies of
schizophrenia? METHOD: The authors reviewed 30 studies of putative
indicators of the schizophrenic genotype: schizotypal personality disorder,
eye tracking dysfunction, attentional impairment, auditory evoked
potentials, neurological signs, neuropsychological impairment, and allusive
thinking. RESULTS: Although each of 42 measures of these indicators
discriminated the relatives of schizophrenic patients from the normal
comparison subjects, a diagnostic accuracy analysis suggested that only six
of these would improve the informativeness of genetic linkage data.
CONCLUSIONS: Many proposed spectrum phenotypes for schizophrenia may not be
useful for linkage analysis because of high false positive rates (poor
specificity). Future work aimed at describing and developing phenotypes for
linkage analysis should assess the diagnostic accuracy of proposed
measures.
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