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Peer-reviewedCC BYBiological psychiatry. Cognitive neuroscience and neuroimaging

Amygdala Functional Hyperconnectivity: A Multiple Symptom Subdomain Marker of the Bipolar Risk to Disorder Spectrum

  • Maya C. Schumer1,2
  • Michele A. Bertocci3
  • Satish Iyengar3,4
  • Haris A. Aslam3
  • Simona Graur3
  • Genna Bebko3
  • Richelle S. Stiffler3
  • Osasumwen Benjamin3
  • Yiming Wang3
  • Henry W. Chase3
  • Mary L. Phillips3
4 affiliations
  1. 1Psychotic Disorders Division, McLean Hospital, 115 Mill St, Belmont, MA, 02478, USA
  2. 2Department of Psychiatry, Harvard Medical School, 22 Shattuck St, Boston, MA, 02115, USA
  3. 3Department of Psychiatry, University of Pittsburgh School of Medicine, 121 Meyran Ave, Pittsburgh, PA, 15213, USA
  4. 4Department of Statistics, University of Pittsburgh, Pittsburgh, PA, 15213, USA
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Abstract

BACKGROUND: Identifying reproducible neural markers of bipolar disorder (BD) risk is critical for early detection and differentiation from unipolar/major depression. We previously demonstrated that interamygdala functional connectivity (FC) and bilateral ventrolateral prefrontal cortex-right dorsolateral prefrontal cortex (vlPFC-dlPFC) FC were positively associated with both mania/hypomania and depression risk and mania/hypomania risk, respectively, as measured by the Mood Spectrum Self-Report (MOODS-SR) mood subdomains, and this was replicated in 3 independent samples. We tested whether these neural markers also generalized to the MOODS-SR cognition and energy subdomains and whether they are elevated in individuals with BD versus individuals at risk. METHODS: Three independent young adult samples without BD (n = 299/ages 18-30 years) completed a functional magnetic resonance imaging approach emotion-processing task (discovery n = 114/age = 21.60 ± 1.91 years; test sample 1 n = 103/21.57 ± 2.09 years; test sample 2 n = 82/23.43 ± 2.86 years), and a fourth sample with BD (n = 32/25.11 ± 3.73 years) completed the same protocol. Poisson loglinear models were used to test whether previously identified neural markers of MOODS-SR mood subdomains were also associated with manic and depressive cognition and energy subdomains. One-way analyses of variance were used to compare neural variables showing significant relationships with subdomain scores between low-risk, high-risk, and BD groups. RESULTS: = 3.56, p = .03) and was higher in BD versus low-risk and in high-risk versus low-risk groups (ps = .033). CONCLUSIONS: Interamygdala FC emerged as a robust cross-dimensional correlate of BD risk, linking subsyndromal risk to syndromal BD, whereas vlPFC-dlPFC FC was specific to mania risk. Findings support a multidimensional circuit-based model of BD risk supporting early identification and prevention.

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Cite

BibTeXRIS
BibTeX
@article{schumer2026amygdala,
  title = {{Amygdala Functional Hyperconnectivity: A Multiple Symptom Subdomain Marker of the Bipolar Risk to Disorder Spectrum}},
  author = {Maya C. Schumer and Michele A. Bertocci and Satish Iyengar and Haris A. Aslam and Simona Graur and Genna Bebko and Richelle S. Stiffler and Osasumwen Benjamin and Yiming Wang and Henry W. Chase and Mary L. Phillips},
  journal = {Biological psychiatry. Cognitive neuroscience and neuroimaging},
  year = {2026},
  month = jul,
  doi = {10.1016/j.bpsc.2026.07.007},
  url = {https://doi.org/10.1016/j.bpsc.2026.07.007},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Amygdala Functional Hyperconnectivity: A Multiple Symptom Subdomain Marker of the Bipolar Risk to Disorder Spectrum
AU  - Maya C. Schumer
AU  - Michele A. Bertocci
AU  - Satish Iyengar
AU  - Haris A. Aslam
AU  - Simona Graur
AU  - Genna Bebko
AU  - Richelle S. Stiffler
AU  - Osasumwen Benjamin
AU  - Yiming Wang
AU  - Henry W. Chase
AU  - Mary L. Phillips
PY  - 2026
DA  - 2026/07/29
JO  - Biological psychiatry. Cognitive neuroscience and neuroimaging
DO  - 10.1016/j.bpsc.2026.07.007
UR  - https://doi.org/10.1016/j.bpsc.2026.07.007
AB  - BACKGROUND: Identifying reproducible neural markers of bipolar disorder (BD) risk is critical for early detection and differentiation from unipolar/major depression. We previously demonstrated that interamygdala functional connectivity (FC) and bilateral ventrolateral prefrontal cortex-right dorsolateral prefrontal cortex (vlPFC-dlPFC) FC were positively associated with both mania/hypomania and depression risk and mania/hypomania risk, respectively, as measured by the Mood Spectrum Self-Report (MOODS-SR) mood subdomains, and this was replicated in 3 independent samples. We tested whether these neural markers also generalized to the MOODS-SR cognition and energy subdomains and whether they are elevated in individuals with BD versus individuals at risk. METHODS: Three independent young adult samples without BD (n = 299/ages 18-30 years) completed a functional magnetic resonance imaging approach emotion-processing task (discovery n = 114/age = 21.60 ± 1.91 years; test sample 1 n = 103/21.57 ± 2.09 years; test sample 2 n = 82/23.43 ± 2.86 years), and a fourth sample with BD (n = 32/25.11 ± 3.73 years) completed the same protocol. Poisson loglinear models were used to test whether previously identified neural markers of MOODS-SR mood subdomains were also associated with manic and depressive cognition and energy subdomains. One-way analyses of variance were used to compare neural variables showing significant relationships with subdomain scores between low-risk, high-risk, and BD groups. RESULTS: = 3.56, p = .03) and was higher in BD versus low-risk and in high-risk versus low-risk groups (ps = .033). CONCLUSIONS: Interamygdala FC emerged as a robust cross-dimensional correlate of BD risk, linking subsyndromal risk to syndromal BD, whereas vlPFC-dlPFC FC was specific to mania risk. Findings support a multidimensional circuit-based model of BD risk supporting early identification and prevention.
SN  - 2451-9022
SN  - 2451-9030
ER  -