Abstract
Background
Functional neuroimaging and electrophysiologic studies have found disturbed frontotemporal
interaction in schizophrenia. We sought to determine whether abnormalities of frontotemporal
connectivity are trait markers of genetic risk for schizophrenia.
Methods
We investigated 64 schizophrenia patients, 79 of their clinically unaffected siblings,
and 88 unrelated normal controls with an auditory oddball electroencephalogram (EEG)
evoked potential paradigm. We measured: 1) frontotemporal event-related EEG-coherence
(i.e. a measure of functional connectivity); and 2) we performed structural equation
modeling of the effective connectivity between the frontal P300 and temporoparietal
P300-amplitude.
Results
Schizophrenic patients and their siblings showed a reduction of frontotemporal coherence.
At peak activation during the P300 time-window, a negative (“inhibitory”) frontotemporal
path coefficient was found in normal controls, whereas a positive coefficient was
seen in schizophrenic patients with siblings being intermediate. Intra-class correlations
between sib-pairs and relative risk estimates of the applied connectivity measures
were non-significant. Topographic correlation matrix analyses suggested that the altered
functional and effective frontotemporal connectivity indirectly reflect regional abnormalities
of increased activation variance.
Conclusions
Impaired interaction of the frontotemporal macro-circuit indirectly reflects genetically
determined abnormalities of frontal and temporoparietal microcircuits. The reasons
why frontotemporal connectivity appears to be a poor predictor of genetic risk for
schizophrenia are discussed.
Keywords
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Article info
Publication history
Accepted:
May 9,
2003
Received in revised form:
April 25,
2003
Received:
December 17,
2002
Identification
Copyright
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
