Functional and effective frontotemporal connectivity and genetic risk for schizophrenia.
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.
Winterer
Georg
G
Clinical Brain Disorders Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
Coppola
Richard
R
Egan
Michael F
MF
Goldberg
Terry E
TE
Weinberger
Daniel R
DR
D000328:Adult; D004569:Electroencephalography; D018913:Event-Related Potentials, P300 / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*; D035781:Siblings; D013702:Temporal Lobe / Q000503:physiopathology*