Global Prefrontal and Fronto-Amygdala Dysconnectivity in Bipolar I Disorder with Psychosis History
Open accessAbstract
Background Pathophysiological models of bipolar disorder postulate that mood dysregulation arises from fronto-limbic dysfunction, marked by reduced prefrontal cortex (PFC) inhibitory control. This might occur due to both disruptions within PFC networks and abnormal inhibition over subcortical structures involved in emotional processing. However, no study has examined global PFC dysconnectivity in bipolar disorder and tested whether regions with within-PFC dysconnectivity also exhibit fronto-limbic connectivity deficits. Furthermore, no study has investigated whether such connectivity disruptions differ for bipolar patients with psychosis history, who might exhibit a more severe clinical course.Methods We collected resting-state functional magnetic resonance imaging at 3T in 68 remitted bipolar I patients (34 with psychosis history) and 51 demographically matched healthy participants. We employed a recently developed global brain connectivity method, restricted to PFC (rGBC). We also independently tested connectivity between anatomically defined amygdala and PFC.Results Bipolar patients exhibited reduced medial prefrontal cortex (mPFC) rGBC, increased amygdala-mPFC connectivity, and reduced connectivity between amygdala and dorsolateral PFC. All effects were driven by psychosis history. Moreover, the magnitude of observed effects was significantly associated with lifetime psychotic symptom severity.Conclusions This convergence between rGBC, seed-based amygdala findings, and symptom severity analyses highlights that mPFC, a core emotion regulation region, exhibits both within-PFC dysconnectivity and connectivity abnormalities with limbic structures in bipolar illness. Furthermore, lateral PFC dysconnectivity in patients with psychosis history converges with published work in schizophrenia, indicating possible shared risk factors. Observed dysconnectivity in remitted patients suggests a bipolar trait characteristic and might constitute a risk factor for phasic features of the disorder.
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Mood disorders including major depressive disorder and bipolar disorder are associated with enhanced activity and connectivity of default network structures with key regions of the limbic and/or salience networks.
“For example, mood disorders including major depressive disorder and bipolar disorder are associated with enhanced activity and connectivity of DN structures with key regions of the limbic and/or salience networks.147,148,215–219”
From The default network and self-generated thought: component processes, dynamic control, and clinical relevance (2014) · cites this paper as [219]
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- Authors
- Anticevic, A., Brumbaugh, M. S., Winkler, A. M., Lombardo, L. E., Barrett, J., Corlett, P. R., Kober, H., Gruber, J., Repovs, G., Cole, M. W., Krystal, J. H., Pearlson, G. D., & Glahn, D. C.
- Affiliations
- Yale University (US)
- Hartford Hospital (US)
- Washington University in St. Louis (US)
- Corresponding author
- Anticevic, Alan
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 73
- Issue
- 6
- Pages
- 565-573
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3549314
- OpenAlex
- W2030041890
- Cited by
- 263
- References
- 68
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 7 · 2023: 12 · 2022: 14 · 2021: 43 · 2020: 20 · 2019: 13 · 2018: 23 · 2017: 17 · 2016: 29 · 2015: 21 · 2014: 26 · 2013: 19 · 2012: 3
- FWCI
- 15.71
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Repository of the University of Ljubljana (University of Ljubljana) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ORBi (University of Liège) (submittedVersion, other-oa)
- ScholarWorks @ UTRGV (The University of Texas Rio Grande Valley) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institute of Mental Health (R01MH080912, R01MH078143)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Keywords
- bipolar I disorder, amygdala, medial prefrontal cortex, dorsolateral prefrontal cortex, global brain connectivity, emotion regulation, resting-state functional connectivity, psychotic symptom severity
- MeSH terms
- Adult, Amygdala, Bipolar Disorder, Female, Humans, Male, Neural Pathways, Psychotic Disorders, Severity of Illness Index, Case-Control Studies, Prefrontal Cortex, Functional Neuroimaging
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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