Generalizable links between symptoms of borderline personality disorder and functional connectivity

Golia Shafiei; Arielle S Keller; Maxwell Bertolero; Sheila Shanmugan; Dani S Bassett; Andrew A Chen; Sydney Covitz; Audrey Houghton; Audrey Luo; Kahini Mehta; Taylor Salo; Russell T Shinohara; Damien Fair; Michael N Hallquist; Theodore D Satterthwaite

doi:10.1101/2023.08.03.551534

Generalizable links between symptoms of borderline personality disorder and functional connectivity

bioRxiv [Preprint]. 2023 Aug 21:2023.08.03.551534. doi: 10.1101/2023.08.03.551534.

Authors

Golia Shafiei^{1

2}, Arielle S Keller^{1

2}, Maxwell Bertolero^{1

2}, Sheila Shanmugan^{1

2}, Dani S Bassett^{2

3

4

5

6

7}, Andrew A Chen⁸, Sydney Covitz^{1

2}, Audrey Houghton⁹, Audrey Luo^{1

2}, Kahini Mehta^{1

2}, Taylor Salo^{1

2}, Russell T Shinohara⁸, Damien Fair^{9

10}, Michael N Hallquist¹¹, Theodore D Satterthwaite^{1

2}

Affiliations

¹ Penn Lifespan Informatics and Neuroimaging Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
² Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
³ Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA 19104.
⁴ Department of Physics & Astronomy, College of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104.
⁵ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
⁶ Department of Electrical & Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA 19104.
⁷ Santa Fe Institute, Santa Fe, NM 87501.
⁸ Penn Statistics in Imaging and Visualization Center, Department of Biostatistics,Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
⁹ Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN 55414, USA.
¹⁰ Institute of Child Development, College of Education and Human Development, Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, MN 55414, USA.
¹¹ Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Abstract

Background |: Symptoms of borderline personality disorder (BPD) often manifest in adolescence, yet the underlying relationship between these debilitating symptoms and the development of functional brain networks is not well understood. Here we aimed to investigate how multivariate patterns of functional connectivity are associated with symptoms of BPD in a large sample of young adults and adolescents.

Methods |: We used high-quality functional Magnetic Resonance Imaging (fMRI) data from young adults from the Human Connectome Project: Young Adults (HCP-YA; N = 870, ages 22-37 years, 457 female) and youth from the Human Connectome Project: Development (HCP-D; N = 223, age range 16-21 years, 121 female). A previously validated BPD proxy score was derived from the NEO Five Factor Inventory (NEO-FFI). A ridge regression model with 10-fold cross-validation and nested hyperparameter tuning was trained and tested in HCP-YA to predict BPD scores in unseen data from regional functional connectivity, while controlling for in-scanner motion, age, and sex. The trained model was further tested on data from HCP-D without further tuning. Finally, we tested how the connectivity patterns associated with BPD aligned with age-related changes in connectivity.

Results |: Multivariate functional connectivity patterns significantly predicted out-of-sample BPD proxy scores in unseen data in both young adults (HCP-YA; p_perm = 0.001) and older adolescents (HCP-D; p_perm = 0.001). Predictive capacity of regions was heterogeneous; the most predictive regions were found in functional systems relevant for emotion regulation and executive function, including the ventral attention network. Finally, regional functional connectivity patterns that predicted BPD proxy scores aligned with those associated with development in youth.

Conclusion |: Individual differences in functional connectivity in developmentally-sensitive regions are associated with the symptoms of BPD.

Keywords: BPD; functional connectivity; neurodevelopment; regression analysis; ventral attention network.

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Preprint

Abstract

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