Amygdala Hyperactivity at Rest in Paranoid Individuals With Schizophrenia
Abstract
Objective The amygdala's role in threat perception suggests that increased activation of this region may be related to paranoid ideation. However, investigations of amygdala function in paranoid individuals with schizophrenia, compared with both healthy individuals and nonparanoid individuals with schizophrenia, have consistently reported reduced task-related activation. The reliance of blood-oxygen-level-dependent functional MRI on a contrast between events and baseline, and the inability to quantitatively measure this baseline, may account for these counterintuitive findings. The present study tested for differences in baseline levels of amygdala activity in paranoid and nonparanoid individuals with schizophrenia using arterial spin labeling perfusion MRI. Method Resting cerebral blood flow (CBF) and task-related activation of the amygdala were measured in 25 healthy individuals, 16 individuals with schizophrenia who were actively paranoid at the time of scanning, and 16 individuals with schizophrenia who were not paranoid. Results Analysis of relative CBF values extracted from the amygdala bilaterally revealed significantly increased activity in the left amygdala in paranoid patient volunteers compared with healthy comparison subjects and nonparanoid patient volunteers. Increased CBF was also evident in the right amygdala but did not reach the level of statistical significance. Paranoid volunteers also showed significantly decreased task-related activation of the amygdala…
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Overactivation and hyperconnectivity of the amygdala - reflecting amplified detection of salience and threat and insufficient top-down regulation - have been repeatedly linked to paranoia.
“At a neurobiological level of explanation, overactivation and hyperconnectivity of the amygdala – reflecting amplified detection of salience and threat and insufficient top-down regulation – have been repeatedly linked to paranoia (Pinkham et al., 2015; Fan et al., 2021; Pinkham et al., 2022; Walther et al., 2022).”
From A counterweight model for understanding and treating persecutory delusions. (2025) · cites this paper as Pinkham et al., 2015
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Persecutory delusions: a cognitive perspective on understanding and treatment.
Freeman, D. (2016) · The Lancet Psychiatry · doi:10.1016/s2215-0366(16)00066-3 · Cited by 356 · see citing works
Cognitive and neural models of threat appraisal in psychosis: a theoretical integration
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McCutcheon, R., Bloomfield, M. A. P., Dahoun, T., Quinlan, M., Terbeck, S., Mehta, M., & Howes, O. (2018) · Psychological Medicine · doi:10.1017/s0033291717003506 · Cited by 26 · see citing works
Oxytocin increases eye gaze in schizophrenia
Bradley, E. R., Seitz, A., Niles, A. N., Rankin, K. P., Mathalon, D. H., O'Donovan, A., & Woolley, J. D. (2019) · Schizophrenia Research · doi:10.1016/j.schres.2019.07.039 · Cited by 22 · see citing works
A counterweight model for understanding and treating persecutory delusions.
Freeman, D., Isham, L., & Waite, F. (2025) · Psychological Medicine · doi:10.1017/s0033291725001242 · Cited by 15 · see citing works
“…level of explanation, over-activation and hyperconnectivity of the amygdala – reflecting amplified detection of salience and threat and insufficient top-down regulation – have been repeatedly linked to paranoia (Pinkham et al., 2015; Fan et al., 2021; Pinkham et al., 2022; Walther et al., 2022).”
- Authors
- Pinkham, A. E., Liu, P., Lu, H., Kriegsman, M., Simpson, C., & Tamminga, C.
- Affiliations
- The University of Texas at Dallas (US)
- Venue
- American Journal of Psychiatry
- Published
- 2015-08-01
- Volume
- 172
- Issue
- 8
- Pages
- 784-792
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2111198480
- Cited by
- 93
- References
- 7
- Citations by year
- 2026: 1 · 2025: 10 · 2024: 16 · 2023: 9 · 2022: 9 · 2021: 7 · 2020: 5 · 2019: 14 · 2018: 2 · 2017: 8 · 2016: 9 · 2015: 3
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- amygdala hyperactivity, paranoia, schizophrenia, paranoid ideation, resting cerebral blood flow, threat perception
- MeSH terms
- Adult, Amygdala, Cerebrovascular Circulation, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Psychotic Disorders, Schizophrenia, Schizophrenia, Paranoid, Schizophrenic Psychology, Case-Control Studies, Young Adult, Functional Neuroimaging
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