Evidence that altered amygdala activity in schizophrenia is related to clinical state and not genetic risk.
OBJECTIVE
Although amygdala dysfunction is reported in schizophrenia, it is unknown whether this deficit represents a heritable phenotype that is related to risk for schizophrenia or whether it is related to disease state. The purpose of the present study was to examine amygdala response to threatening faces among healthy siblings of schizophrenia patients in whom a subtler heritable deficit might be observed.


METHODS
Participants were 34 schizophrenia patients, 29 unaffected siblings, and 20 healthy comparison subjects. Blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was conducted during an implicit facial information processing task. The N-back working memory task, which has been shown to elicit prefrontal cortex abnormalities in unaffected siblings of schizophrenia patients, was employed as a positive experimental control.


RESULTS
Schizophrenia patients demonstrated a deficit in amygdala reactivity to negative face stimuli and an alteration, correlated with neuroleptic drug dosage, in the functional coupling between the amygdala and subgenual cingulate. In contrast, unaffected siblings showed a pattern that was not statistically different from that of healthy comparison subjects. During the N-back working memory task, both schizophrenia patients and their unaffected siblings demonstrated a pattern of inefficient prefrontal cortex engagement, which is consistent with earlier evidence that this pattern is related to genetic risk for schizophrenia.


CONCLUSIONS
These data suggest that the pathophysiological mechanism underlying the inability of individuals with schizophrenia to normally engage the amygdala in processing fearful and angry facial representations is more likely a phenomenon related to the disease state, specifically to treatment.
Rasetti
Roberta
R
Genes, Cognition, and Psychosis Program, IRP, NIMH, NIH, Rm. 4S-235, 10 Center Dr., Bethesda, MD 20892, USA.
Mattay
Venkata S
VS
Wiedholz
Lisa M
LM
Kolachana
Bhaskar S
BS
Hariri
Ahmad R
AR
Callicott
Joseph H
JH
Meyer-Lindenberg
Andreas
A
Weinberger
Daniel R
DR
D000328:Adult; D000679:Amygdala / Q000503:physiopathology*; D000786:Anger; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D004292:Dominance, Cerebral / Q000502:physiology; D005149:Facial Expression; D005239:Fear / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term; D009415:Nerve Net / Q000503:physiopathology; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood*; D010364:Pattern Recognition, Visual / Q000502:physiology; D010641:Phenotype; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*
D010100:Oxygen