Sex differences in neural responses to emotional facial expressions are associated with lifetime depression and mania risk

Manan Arora; Michele A Bertocci; Maya C Schumer; Alexander S Skeba; Genna Bebko; Richelle S Stiffler; Tyler J Brady; Yvette Afriyie-Agyemang; Haris A Aslam; Simona Graur; Osasumwen Benjamin; Yiming Wang; Mary L Phillips

doi:10.1016/j.jad.2024.05.042

Sex differences in neural responses to emotional facial expressions are associated with lifetime depression and mania risk

J Affect Disord. 2024 May 10:359:33-40. doi: 10.1016/j.jad.2024.05.042. Online ahead of print.

Authors

Affiliations

¹ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: aroram2@upmc.edu.
² Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: bertoccima@upmc.edu.
³ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: schumerm@upmc.edu.
⁴ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: skebaas@upmc.edu.
⁵ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: bebkog@upmc.edu.
⁶ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: stifflerrs@upmc.edu.
⁷ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: bradyt7@upmc.edu.
⁸ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: afriyieagyemangy@upmc.edu.
⁹ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: aslamha@upmc.edu.
¹⁰ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: graurs@upmc.edu.
¹¹ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: benjaminoe@upmc.edu.
¹² Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: wangy40@upmc.edu.
¹³ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: phillipsml@upmc.edu.

PMID: 38735582
DOI: 10.1016/j.jad.2024.05.042

Abstract

Introduction: No studies systematically examined sex differences in neural mechanisms underlying depression and mania/hypomania risk.

Method: 80 females and 35 males, n = 115(age21.6±1.90) were scanned using 3TfMRI during an implicit emotional-faces task. We examined neural activation to all emotional faces versus baseline, using an anatomical region-of-interest mask comprising regions supporting emotion and salience processing. Sex was a covariate. Extracted parameter estimates(FWE < 0.05,k > 15), age, IQ and their sex interactions were independent variables(IV) in two penalized regression models: dependent variable either MOODS-SR-lifetime, depressive or manic domain score as measures of mania and depression risk. Subsequent Poisson regression models included the non-zero variables identified in the penalized regression models. We tested each model in 2 independent samples. Test sample-I,n = 108(21.6 ± 2.09 years,males/females = 33/75); Test sample-II,n = 93(23.7 ± 2.9 years,males/females = 31/62).

Results: Poisson regression models yielded significant relationships with depression and mania risk: Positive correlations were found between right fusiform activity and depression(beta = 0.610) and mania(beta = 0.690) risk. There was a significant interaction between sex and right fusiform activity(beta = -0.609) related to depression risk, where females had a positive relationship than; and a significant interaction(beta = 0.743) between sex and left precuneus activity related to mania risk, with a more negative relationship in females than males. All findings were replicated in the test samples(qs < 0.05,FDR).

Limitations: No longitudinal follow-up.

Conclusion: Greater visual attention to emotional faces might underlie greater depression and mania risk, and confer greater vulnerability to depression in females, because of heightened visual attention to emotional faces. Females have a more negative relationship between mania risk and left precuneus activity, suggesting heightened empathy might be associated with reduced mania/hypomania risk in females more than males.

Keywords: Bipolar disorder; Depression; Mania; Neural markers; Risk; Sex differences.