Abstract
Adolescents engaging in non-suicidal self-injury (NSSI) have been reported to show altered autonomic nervous system (ANS) function, indexed by decreased heart rate variability (HRV) and increased heart rate (HR). Preliminary findings in adolescents with borderline personality disorder (BPD) traits suggest, that improvement in ANS function is longitudinally associated with clinical improvement and that ANS activity predicts clinical outcome. Existing studies, however, are limited by small sample sizes and short follow-ups. N = 227 help-seeking adolescents with NSSI disorder who presented to an early intervention service for BPD participated in baseline and two yearly follow-up assessments (NFU1 = 81, NFU2 = 37), including comprehensive clinical diagnostics as well as recordings of resting electrocardiography. Associations between HR, HRV and clinical outcomes of interest (i.e., NSSI frequency, depression severity, number of BPD criteria and global functioning) were examined using structural equation modelling. While multivariate models showed no evidence for an association between HRV or HR and any of the clinical outcomes, there was evidence from models including cross-lagged effects, that HRV and HR predicted depression severity, number of BPD criteria (HRV only) and global functioning at subsequent assessments. This effect was not observed for NSSI frequency. Improvements in ANS function, indexed by an increase in HRV and decrease in HR, seem to precede the improvement of clinical symptoms in adolescents engaging in NSSI. Findings have clinical implications, suggesting that targeting ANS function as adjuvant treatment in adolescents engaging in NSSI is warranted, and routine monitoring of ANS function my guide clinical decision making.
Similar content being viewed by others
Data availability
Due to the nature of this research project, participants did not provide consent for their data to be shared publicly, so supporting data is not publicly available. However, anonymized data can be made available upon request from the corresponding author.
References
Clarke S, Allerhand LA, Berk MS. Recent advances in understanding and managing self-harm in adolescents. F1000Res. 2019;8:F1000 Faculty Rev-1794. https://doi.org/10.12688/f1000research.19868.1.
Kaess M, Hooley JM, Klimes-Dougan B, Koenig J, Plener PL, Reichl C, et al. Advancing a temporal framework for understanding the biology of nonsuicidal self- injury: An expert review. Neurosci Biobehav Rev. 2021;130:228–39. https://doi.org/10.1016/j.neubiorev.2021.08.022.
Koenig J, Rinnewitz L, Parzer P, Resch F, Thayer JF, Kaess M. Resting cardiac function in adolescent non-suicidal self-injury: The impact of borderline personality disorder symptoms and psychosocial functioning. Psychiatry Res. 2017;248:117–20. https://doi.org/10.1016/j.psychres.2016.12.024.
Weise S, Parzer P, Zimmermann R, Fürer L, Resch F, Kaess M, et al. Emotion dysregulation and resting-state autonomic function in adolescent borderline personality disorder-A multimodal assessment approach. Personal Disord. 2020;11:46–53. https://doi.org/10.1037/per0000367.
Koenig J, Weise S, Rinnewitz L, Parzer P, Resch F, Kaess M. Longitudinal covariance of resting-state cardiac function and borderline personality disorder symptoms in adolescent non-suicidal self-injury. World J Biol Psychiatry. 2018;19:152–7. https://doi.org/10.1080/15622975.2017.1342046.
Weise S, Parzer P, Fürer L, Zimmermann R, Schmeck K, Resch F, et al. Autonomic nervous system activity and dialectical behavioral therapy outcome in adolescent borderline personality pathology. World J Biol Psychiatry. 2021;22:535–45. https://doi.org/10.1080/15622975.2020.1858155.
Sigrist C, Reichl C, Schmidt SJ, Brunner R, Kaess M, Koenig J. Cardiac autonomic functioning and clinical outcome in adolescent borderline personality disorder over two years. Prog Neuropsychopharmacol Biol Psychiatry. 2021;111:110336. https://doi.org/10.1016/j.pnpbp.2021.110336.
Galin S, Keren H. The predictive potential of heart rate variability for depression. Neuroscience. 2024;546:88–103. https://doi.org/10.1016/j.neuroscience.2024.03.013.
Pizzoli SFM, Marzorati C, Gatti D, Monzani D, Mazzocco K, Pravettoni G. A meta-analysis on heart rate variability biofeedback and depressive symptoms. Sci Rep. 2021;11:6650. https://doi.org/10.1038/s41598-021-86149-7.
Austelle CW, O’Leary GH, Thompson S, Gruber E, Kahn A, Manett AJ, et al. A comprehensive review of vagus nerve stimulation for depression. Neuromodulation. 2022;25:309–15. https://doi.org/10.1111/ner.13528.
Huang M, Shah A, Su S, Goldberg J, Lampert RJ, Levantsevych OM, et al. Association of depressive symptoms and heart rate variability in Vietnam War–Era Twins: A longitudinal twin difference Study. JAMA Psychiatry. 2018;75:7. https://doi.org/10.1001/jamapsychiatry.2018.0747.
von den Driesch L, Koenig J, Reichl C, Sigrist C, Sele S, Kaess M. Predicting urges for non-suicidal self-injury using cardiac autonomic indices in outpatient adolescents: A pilot ecological momentary assessment study. J Affect Disord. 2026;394:120578. https://doi.org/10.1016/j.jad.2025.120578.
Kaess M, Ghinea D, Fischer-Waldschmidt G, Resch F. Die Ambulanz für Risikoverhalten und Selbstschädigung (AtR!Sk) – ein Pionierkonzept der ambulanten Früherkennung und Frühintervention von Borderline-Persönlichkeitsstörungen. Prax Kinderpsychol Kinderpsychiatr. 2017;66:404–22. https://doi.org/10.13109/prkk.2017.66.6.404.
General Assembly of the World Medical Association. World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. J Am Coll Dent. 2014;81:14–18.
Cavelti M, Blaha Y, Lerch S, Hertel C, Berger T, Reichl C, et al. The evaluation of a stepped care approach for early intervention of borderline personality disorder. Borderline Personal Disord Emot Dysregul. 2024;11:12. https://doi.org/10.1186/s40479-024-00256-1.
Fischer G, Ameis N, Parzer P, Plener PL, Groschwitz R, Vonderlin E, et al. The German version of the self-injurious thoughts and behaviors interview (SITBI-G): A tool to assess non-suicidal self-injury and suicidal behavior disorder. BMC Psychiatry. 2014;14:265. https://doi.org/10.1186/s12888-014-0265-0.
First MB, Gibbon M, Spitzer RL, Williams JBW, Benjamin L Structured Clinical Interview for DSM-IV Axis II Personality Disorders, (SCID-II). American Psychiatric Press; 1997. https://cir.nii.ac.jp/crid/1370004237531794560.
Barkmann C, Schulte-Markwort M, Brähler E Klinisch-psychiatrische Ratingskalen für das Kindes- und Jugendalter. Hogrefe Verlag; 2010.
Shaffer D, Gould MS, Brasic J, Ambrosini P, Fisher P, Bird H, et al. A Children’s Global Assessment Scale (CGAS). Arch Gen Psychiatry. 1983;40:1228. https://doi.org/10.1001/archpsyc.1983.01790100074010.
Jennings JR, Kamarck T, Stewart C, Eddy M, Johnson P. Alternate cardiovascular baseline assessment techniques: Vanilla or resting baseline. Psychophysiology. 1992;29:742–50. https://doi.org/10.1111/j.1469-8986.1992.tb02052.x.
Quintana DS, Alvares GA, Heathers JAJ. Guidelines for reporting articles on psychiatry and heart rate variability (GRAPH): Recommendations to advance research communication. Transl Psychiatry. 2016;6:e803. https://doi.org/10.1038/tp.2016.73.
Laborde S, Mosley E, Mertgen A. A unifying conceptual framework of factors associated to cardiac vagal control. Heliyon. 2018;4:12. https://doi.org/10.1016/j.heliyon.2018.e01002.
Tarvainen MP, Niskanen J-P, Lipponen JA, Ranta-aho PO, Karjalainen PA. Kubios HRV – Heart rate variability analysis software. Comput Methods Programs Biomed. 2014;113:210–20. https://doi.org/10.1016/j.cmpb.2013.07.024.
García Martínez CA, Otero Quintana A, Vila XA, Lado Touriño MJ, Rodríguez-Liñares L, Rodríguez Presedo JM, Méndez Penín AJ. Heart Rate Variability Analysis with the R package RHRV. Springer Cham. 2017. https://doi.org/10.1007/978-3-319-65355-6.
Sterne JA, Davey Smith G. Sifting the evidence-what’s wrong with significance tests?. BMJ (Clinical Research Ed.). 2001;322:226–31.
Muthén LK, Muthén BO Mplus User’s Guide. Eighth Edition. Muthén & Muthén; 1998.
Jandackova VK, Britton A, Malik M, Steptoe A. Heart rate variability and depressive symptoms: A cross-lagged analysis over a 10-year period in the Whitehall II study. Psychol Med. 2016;46:10. https://doi.org/10.1017/S003329171600060X. Scopus.
Fagioli S, Watanabe DK, Koenig J, Free M, Fazio RH, Vasey MW, et al. Heart rate variability predicts therapy outcome in anxiety disorders: the role of inhibitory learning. Appl Psychophysiol Biofeedback. 2025;50:235–45. https://doi.org/10.1007/s10484-025-09686-1.
Hage, B, Sinacore, J, Heilman, K, Porges, SW, & Halaris, A (2017). Heart rate variability predicts treatment outcome in major depression. J Psychiatry Brain Sci, 2. https://doi.org/10.20900/jpbs.20170017
Karpyak VM, Romanowicz M, Schmidt JE, Lewis KA, Bostwick JM. Characteristics of heart rate variability in alcohol-dependent subjects and nondependent chronic alcohol users. Alcohol: Clin Exp Res. 2014;38:1. https://doi.org/10.1111/acer.12270.
Carney RM, Freedland KE, Stein PK, Skala JA, Hoffman P, Jaffe AS. Change in heart rate and heart rate variability during treatment for depression in patients with coronary heart disease. Psychosom Med. 2000;62:639–47. https://doi.org/10.1097/00006842-200009000-00007.
Moccia L, Bartolucci G, Pepe M, Marcelli I, Grisoni F, Brugnami A, et al. Heart rate variability as a potential predictor of response to intranasal esketamine in patients with treatment-resistant depression: a preliminary report. J Clin Med. 2024;13:4767. https://doi.org/10.3390/jcm13164767.
Neyer S, Witthöft M, Cropley M, Pawelzik M, Lugo RG, Sütterlin S. Reduction of depressive symptoms during inpatient treatment is not associated with changes in heart rate variability. PLoS ONE. 2021;16:e0248686. https://doi.org/10.1371/journal.pone.0248686.
Geiss L, Beck B, Stemmler M, Hillemacher T, Hösl KM. Heart rate variability during inpatient treatment of depression. J Mood Anxiety Disord. 2024;6:100059. https://doi.org/10.1016/j.xjmad.2024.100059.
Balint EM, Daniele V, Langgartner D, Reber SO, Rothermund E, Gündel H, et al. Heart rate variability predicts outcome of short-term psychotherapy at the workplace. Psychophysiology. 2023;60:e14150. https://doi.org/10.1111/psyp.14150.
Choi KW, Jeon HJ. Heart rate variability for the prediction of treatment response in major depressive disorder. Front Psychiatry. 2020;11:607. https://doi.org/10.3389/fpsyt.2020.00607.
Koenig J. Neurovisceral regulatory circuits of affective resilience in youth: Principal outline of a dynamic model of neurovisceral integration in development. Psychophysiology. 2020;57:e13568. https://doi.org/10.1111/psyp.13568.
Beauchaine TP, Thayer JF. Heart rate variability as a transdiagnostic biomarker of psychopathology. Int J Psychophysiol. 2015;98:338–50. https://doi.org/10.1016/j.ijpsycho.2015.08.004.
Deutz MHF, Geeraerts SB, Belsky J, Deković M, van Baar AL, Prinzie P, et al. General psychopathology and dysregulation profile in a longitudinal community sample: Stability, antecedents and outcomes. Child Psychiatry Hum Dev. 2020;51:114–26. https://doi.org/10.1007/s10578-019-00916-2.
Routledge FS, Campbell TS, McFetridge-Durdle JA, Bacon SL. Improvements in heart rate variability with exercise therapy. Can J Cardiol. 2010;26:303–12.
Young HA, Benton D. Heart-rate variability: A biomarker to study the influence of nutrition on physiological and psychological health?. Behav Pharmacol. 2018;29:140–51. https://doi.org/10.1097/FBP.0000000000000383.
Koenig J, Vöckel J. Transcutaneous auricular vagus nerve stimulation in adolescent treatment resistant depression-a case report. J Pediatr. 2024;271:114078. https://doi.org/10.1016/j.jpeds.2024.114078.
Swiss National Advisory Commission on Biomedical Ethics Human research with minors: Ethical considerations. Swiss Confederation; 2008. https://www.nek-cne.admin.ch.
van Dijk W, Faber MJ, Tanke MAC, Jeurissen PPT, Westert GP. Medicalisation and overdiagnosis: What society does to medicine. Int J Health Policy Manag. 2016;5:619–22. https://doi.org/10.15171/ijhpm.2016.121.
Crowell SE, Kaufman EA. Development of self-inflicted injury: Comorbidities and continuities with borderline and antisocial personality traits. Dev Psychopathol. 2016;28:1071–88. https://doi.org/10.1017/S0954579416000705.
Caldwell YT, Steffen PR. Adding HRV biofeedback to psychotherapy increases heart rate variability and improves the treatment of major depressive disorder. Int J Psychophysiol. 2018;131:96–101. https://doi.org/10.1016/j.ijpsycho.2018.01.001.
Dufey M, González T, Bravo T, Fernández AM, Riquelme P, Ramos V. What the heart brings to therapy: A systematic review on heart rate variability contributions to psychotherapy research. J Psychopathol Clin Psychol. 2023;28:245–62.
Acknowledgements
This research was conducted at the University of Heidelberg, Department of Child and Adolescent Psychiatry. The outpatient clinic for risk-taking and self-harm behavior (AtR!Sk) and AtR!Sk-Bio are funded by the Dietmar Hopp Stiftung. We wish to thank Saskia Höper, Felix Birmanns, Nebile Guezel, Anna-Sophia Roesch, Änne Homann, Pelin Kilavuz, Iris Siljak and Henriette Thater for their help in recruiting participants and conducting the neurobiological assessments. We thank Gloria Fischer-Waldschmidt, Denisa Ghinea, Alexandra Edinger, Sindy Weise, Natascha Schmitt, Ines Baumann, Annika Beckmann and Monika Schwarz for their continuous help in recruiting patients and conducting the clinical interviews.
Funding
Open Access funding enabled and organized by Projekt DEAL.
Author information
Authors and Affiliations
Contributions
JK: project funding, project supervision, drafted the manuscript, revised the manuscript, approved the final version submitted. IMML: revised the manuscript, approved the final version submitted. NH: drafted the manuscript, revised the manuscript, approved the final version submitted. SS: statistical analyses, prepared figures, approved the final version submitted. MK: project funding, project supervision, revised the manuscript, approved the final version submitted
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Koenig, J., Mürner-Lavanchy, I.M., Hedinger, N. et al. Improvements in resting-state autonomic function precede clinical improvement in adolescent non-suicidal self-injury. Transl Psychiatry (2026). https://doi.org/10.1038/s41398-026-04012-7
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41398-026-04012-7
