Limbic links to paranoia: increased resting-state functional connectivity between amygdala, hippocampus and orbitofrontal cortex in schizophrenia patients with paranoia

Paranoia is a frequent and highly distressing experience in psychosis. Models of paranoia suggest limbic circuit pathology. Here, we tested whether resting-state functional connectivity (rs-fc) in the limbic circuit was altered in schizophrenia patients with current paranoia. We collected MRI scans...

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Published in:European archives of psychiatry and clinical neuroscience 2022-09, Vol.272 (6), p.1021-1032
Main Authors: Walther, Sebastian, Lefebvre, Stephanie, Conring, Frauke, Gangl, Nicole, Nadesalingam, Niluja, Alexaki, Danai, Wüthrich, Florian, Rüter, Maximilian, Viher, Petra V., Federspiel, Andrea, Wiest, Roland, Stegmayer, Katharina
Format: Article
Language:English
Subjects:
Amygdala
Analysis
Brain
Hippocampus
Hyperactivity
Medical research
Medicine
Medicine & Public Health
Medicine, Experimental
Mental disorders
Neurosciences
Nucleus accumbens
Original Paper
Paranoia
Prefrontal cortex
Psychiatry
Psychosis
Schizoaffective disorder
Schizophrenia
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Summary:Paranoia is a frequent and highly distressing experience in psychosis. Models of paranoia suggest limbic circuit pathology. Here, we tested whether resting-state functional connectivity (rs-fc) in the limbic circuit was altered in schizophrenia patients with current paranoia. We collected MRI scans in 165 subjects including 89 patients with schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, brief psychotic disorder, schizophreniform disorder) and 76 healthy controls. Paranoia was assessed using a Positive And Negative Syndrome Scale composite score. We tested rs-fc between bilateral nucleus accumbens, hippocampus, amygdala and orbitofrontal cortex between groups and as a function of paranoia severity. Patients with paranoia had increased connectivity between hippocampus and amygdala compared to patients without paranoia. Likewise, paranoia severity was linked to increased connectivity between hippocampus and amygdala. Furthermore, paranoia was associated with increased connectivity between orbitofrontal and medial prefrontal cortex. In addition, patients with paranoia had increased functional connectivity within the frontal hubs of the default mode network compared to healthy controls. These results demonstrate that current paranoia is linked to aberrant connectivity within the core limbic circuit and prefrontal cortex reflecting amplified threat processing and impaired emotion regulation. Future studies will need to explore the association between limbic hyperactivity, paranoid ideation and perceived stress.
ISSN:0940-1334
1433-8491
DOI:10.1007/s00406-021-01337-w