Objective: The authors investigated impaired
differentiation of limbic-prefrontal
systems by autonomic arousal in
schizophrenia. It was predicted that paranoid
patients would be distinguished by
a disjunction of hyperarousal but reduced
amygdala and medial prefrontal
activity relative to both healthy comparison
subjects and patients with nonparanoid
schizophrenia.
Method: Pictures depicting facial expressions
of fear were presented to 27 schizophrenia
patients (13 paranoid, 14 nonparanoid)
and 22 matched healthy
comparison subjects in an implicit perception
task to evoke limbic activity. Simultaneous
functional magnetic resonance
imaging and skin conductance arousal recordings
were acquired during presentation
of faces expressing fear or neutral
emotion. Responses to fear stimuli were
further examined by contrasting those
that were associated with a skin conductance
response (“with arousal”) and those
that were not (“without arousal”).
Results: In the comparison subjects,
arousal dissociated amygdala/medial prefrontal
(“visceral”) networks and hippocampus/
lateral prefrontal (“context”)
networks for fear perception. Excessive
arousal responses were elicited in the
schizophrenia subjects, but there was an
associated reduction in amygdala/medial
prefrontal activity. This disjunction was
pronounced in paranoid patients relative
to both healthy subjects and nonparanoid
patients. Paranoid patients also showed a
relatively greater prefrontal deficit for
“without-arousal” responses.
Conclusions: This is the first study to reveal
a functional disconnection in autonomic
and central systems for processing
threat-related signals in patients with
paranoid schizophrenia. Paranoid cognition
may reflect an internally generated
cycle of misattribution regarding incoming
fear signals due to a breakdown in the
regulation of these systems.