Dysregulation of Arousal and Amygdala-Prefrontal Systems in Paranoid Schizophrenia
Abstract
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.
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This shift in sympathovagal balance can intensify symptoms of hypervigilance and paranoia.
“This in turn can intensify symptoms of hypervigilance and paranoia69.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [69]
In paranoid schizophrenia patients with persistently high arousal states, lack of engagement between amygdala-prefrontal brain regions may lead to preservation and exacerbation of arousal responses and a shift in sympathovagal balance influencing the heart.
“In a group of paranoid SCZ patients (DSM IV criteria), with persistently high arousal states, the lack of engagement between these brain regions may lead to preservation and exacerbation of arousal responses and a shift in sympathovagal balance influencing the heart28,69.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [69]
The relationship between HRV and symptoms may be mediated by reduced activity in the amygdala-prefrontal circuits that have been described in schizophrenia.
“It is postulated that the relationship with HRV may be mediated by the reduced activity in the amygdala–prefrontal circuits that have been described in SCZ69.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [69]
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- Authors
- Williams, L. M., Das, P., Harris, A. W. F., Liddell, B. B., Brammer, M. J., Olivieri, G., Skerrett, D., Phillips, M. L., David, A. S., Peduto, A., & Gordon, E.
- Affiliations
- The University of Sydney (AU)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2004-03-01
- Volume
- 161
- Issue
- 3
- Pages
- 480-489
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2137483563
- Cited by
- 337
- References
- 33
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 8 · 2023: 5 · 2022: 5 · 2021: 10 · 2020: 13 · 2019: 8 · 2018: 8 · 2017: 9 · 2016: 23 · 2015: 20 · 2014: 6 · 2013: 14 · 2012: 30
- FWCI
- 15.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
- Keywords
- paranoid schizophrenia, autonomic arousal, skin conductance, amygdala, medial prefrontal cortex, fear perception, hyperarousal, threat processing, functional disconnection
- MeSH terms
- Adult, Amygdala, Arousal, Autonomic Nervous System, Facial Expression, Fear, Female, Galvanic Skin Response, Hippocampus, Humans, Image Enhancement, Magnetic Resonance Imaging, Male, Nerve Net, Oxygen, Pattern Recognition, Visual, Psychiatric Status Rating Scales, Reference Values, Schizophrenia, Paranoid, Social Perception, Prefrontal Cortex
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