PhD Scientific Days 2026

Poster Session 2.K - Mental Health Sciences

Genes, Brain, and Environment: Comparing Polygenic Models of Environmental Sensitivity and Amygdala Functional Connectivity

Name of the presenter

Nagy, Bernadett

Institute/workplace of the presenter

Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary

Authors

Bernadett Nagy^1,2,3, Kinga Gecse^1,2,3, Dóra Török^1,2,3, Gyöngyi Kökönyei^1,2,3,4, Miklós Emri⁵, Csaba Sándor Aranyi⁵, Gabriella Juhász^1,2,3, György Bagdy^1,2,3
1: Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary
2: Center of Pharmacology and Drug Research & Development, Semmelweis University, Budapest, Hungary
3: NAP3.0-SE Neuropsychopharmacology Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary
4: Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
5: Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

Text of the abstract

Introduction: Understanding the genetic basis of environmental sensitivity is crucial for uncovering the biological pathways of psychiatric phenotypes. Different approaches to polygenic risk score (PRS) calculations may use different aspects of the sensitivity. Life-event-based models and family-based designs such as monozygotic (MZ) twin differences offer complementary perspectives, yet their overlap and neurobiological relevance remain unclear.
Aims: We aimed to determine if PRSs based on life events and on MZ twin differences reflect the same aspects of environmental sensitivity, and to examine whether they have shared neural mechanisms, focusing on amygdala connectivity.
Methods: We analyzed 232 healthy participants (71 male, 160 female). We constructed PRSs using two approaches: (1) a life-event-based model capturing negative (PRSstress) and positive (PRSvantage) effects, and (2) an MZ twin differences model estimating genetic risk for depression (PRSdep_largest) and subjective wellbeing (PRSwellbeing). We tested statistical correlations between PRSs, and we used functional magnetic resonance imaging (fMRI) to assess functional connectivity of the amygdala in relation to PRSs.
Result: PRSs from the two approaches were not significantly correlated. fMRI analyses showed no association between negative PRSs and amygdala connectivity. In contrast, PRSvantage was linked to connectivity between the left amygdala and the precentral gyrus (right: p=0,002; left: p=0,009) and the right postcentral gyrus (p=0,01) and between the right amygdala and the right postcentral gyrus (p=0,0004) and the right precentral gyrus (p=0,048). PRSwellbeing was associated with connectivity between the right amygdala and the left anterior cingulate cortex (p=1,2E-7).
Conclusion: Life-event-based and MZ twin-based PRSs capture distinct genetic dimensions of environmental sensitivity. However, their convergence in amygdala connectivity with motor and regulatory regions suggests shared mechanisms of adaptive responsivity. These findings support linking emotional processing to action readiness and top-down regulation, indicating that positive PRSs may reflect protective pathways involving better emotional regulation and behavioral integration.
Funding: NKFIH K143391; SE250+; 2017-1.2.1-NKP-2017-00002; NAP2022-I-4/2022; TKP2021-EGA-25