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Neurobiological Mechanisms of Pain Dependent Stress-Regulation in Adolescent Non-Suicidal Self-Injury

English title Neurobiological Mechanisms of Pain Dependent Stress-Regulation in Adolescent Non-Suicidal Self-Injury
Applicant Kaess Michael
Number 182639
Funding scheme Project funding (Div. I-III)
Research institution Universitätsklinik für Kinder- und Jugendpsychiatrie und Psychotherapie Universitäre Psychiatrische Dienste Bern
Institution of higher education University of Berne - BE
Main discipline Neurophysiology and Brain Research
Start/End 01.07.2019 - 30.06.2023
Approved amount 469'153.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Mental Disorders, Psychosomatic Diseases

Keywords (5)

Adolescents; Non-Suicidal Self-Injury ; Stress Regulation; Neurobiology; Pain

Lay Summary (German)

Lead
Nicht-suizidales selbstverletzendes Verhalten (NSSV) ist ein häufiges Phänomen im Jugendalter. Jugendliche ritzen sich häufig um Stress und innere Anspannung abzubauen. Bislang ist unklar, warum der selbstzugefügte Schmerz zu einer Reduktion von Stress beitragen kann. Das Projekt versucht die zugrundeliegenden neurobiologischen Mechanismen aufzudecken.
Lay summary

Inhalt und Ziele des Forschungsprojekts

Etwa 5% der Jugendlichen im Alter zwischen 12 und 17 Jahre verletzen sich regelmäßig selbst. Es wird angenommen, dass NSSV im Jugendalter eine dysfunktionale Strategie der Stressregulation darstellt. Die neurobiologischen Mechanismen, d.h. warum NSSV zu einer Reduktion von Stress führen kann, sind weitgehend unklar.

Im Rahmen der geplanten Studie werden Jugendliche mit und ohne regelmässige Selbstverletzung rekrutiert. Durch ein standardisiertes Interview und leistungsorientierte Aufgaben wird bei allen Jugendlichen zunächst Stress induziert. Im Anschluss an die Stressinduktion wird bei der Hälfte der Teilnehmer durch mechanische Stimulation ein Schmerzreiz gesetzt. Während der Untersuchung wird mittels kurzer Fragebögen und physiologischer Messungen das Stresserleben erfasst. Es wird angenommen, dass das Schmerzerleben bei Jugendlichen mit NSSV zu einer schnelleren Erholung vom Stress führt.

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Das Projekt befasst sich mit Grundlagenforschung. Um NSSV im Jugendalter besser zu verstehen, ist es wichtig die Mechanismen seiner Funktion zu untersuchen. Die Ergebnisse können einen wichtigen Beitrag hinsichtlich der Prävention und Therapie von Selbstverletzung im Jugendalter leisten.

Direct link to Lay Summary Last update: 21.05.2019

Responsible applicant and co-applicants

Abstract

Background: Non-Suicidal Self-Injury (NSSI) has been introduced in the 5th version of the Statistical and Diagnostic Manual of Mental Disorders (DSM-5) under section 3, as a disorder warranting further research. NSSI describes the intentional, self-directed act of injuring one’s own body tissue (i.e., by cutting) without suicidal intent and for purposes not socially sanctioned. NSSI is prevalent in about 17% of non-clinical adolescent samples, with approx. 4% meeting full DSM-5 criteria. In clinical child and adolescent psychiatric samples, the prevalence of NSSI is around 40-50%. NSSI frequently occurs comorbid in the context of various psychiatric conditions, and is considered a key feature of borderline personality disorder (BPD). Adolescents predominantly engage in NSSI to regulate stress and negative affect. We have previously shown that experimentally induced pain in adolescents engaging in NSSI is capable to (momentarily) improve well-being and reduce negative affect. Decreased negative affect following acts of NSSI may promote maintenance of NSSI by rewarding the behavior. NSSI is most frequently performed in the context of intense and acute stress. However, experimental studies have not yet tested whether the experience of pain is capable to provide relief from increased negative affect following acute stress in adolescents engaging in NSSI. While there is preliminary evidence for the mechanistic function of pain in reducing acute stress in adults with BPD, previously no study addressed this link in a within-subject experimental design, assessing subjective and neurobiological measures of stress relief, to provide proof for an ecological-valid psychobiological mechanism of pain experience in adolescent NSSI. Disentangling potential neurobiological mechanisms underlying NSSI, our research focuses on the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS), linking stress- and emotion-regulation. Within two independent studies, providing preliminary data for the present trial, we were able to show that standardized psychosocial stress is associated with a blunted HPA axis and increased negative affect response in adolescents engaging in NSSI compared to controls. This finding highlights inadequate neurobiological support in state of high distress for the regulation of negative affect. In an independent second trial, we were able to show, that experimentally induced pain leads to an enhanced HPA axis and ANS response that contribute to a reduction of negative affect and improvement in momentary well-being in adolescents engaging in NSSI compared to controls. Taken together, these findings highlight that the endogenous stress response systems, mainly the HPA axis and ANS, may be (1) insufficiently triggered by stress and (2) require the experience of pain to efficiently regulate psychological states. These studies form the rational for the present proposal and emphasize a potential mechanism of “pain dependent stress relief” underlying NSSI and its maintenance in adolescents that is to be empirically tested in an experimental within subject design. Aims: The present study aims to test in an experimental trial, if pain compared to a no-pain condition following stress induction specifically alters neurobiological measures and subjective reports of stress experience in adolescents with NSSI compared to a healthy control group. Design: The planed project employs a 2 x 2 factorial design, including a main effect of group (NSSI versus controls) and pain induction (pain versus no-pain), addressing pain-dependent changes in self-reports and neurobiological measures implemented to assess response and recovery following a standardized stressor. Adolescents 12-17 years of age fulfilling DSM-5 diagnostic criteria for NSSI (=5 days with NSSI during the past 12 months) and healthy, age and sex-matched controls (no lifetime NSSI) will be recruited for participation in the study. Based on results from a priori power-analysis derived from own data, 60 adolescents per group (NSSI; controls) will be recruited. All participants will undergo the Trier Social Stress Test (TSST) while their heart rate (ECG), and prefrontal cortex oxygenation (fNIRS) is continuously recorded. Further, repeated blood draws (ACTH and cortisol) as well as self-reports on momentary stress, positive and negative affect as well as dissociation will be obtained to further quantify the subjective experience. Following the TSST, participants from each group will be block randomized to either receive pain induction (stimulus intensity beyond subjective pain threshold) or sham pain induction (stimulus intensity below individual pain threshold). Pain induction is performed repeatedly using a previously evaluated sharp mechanical blade stimulus that has been confirmed as gold standard in studying experimentally induced pain in NSSI within the laboratory setting with respect to its ecological validity. Impact and Importance: The study is capable to uncover a potential fundamental neurobiological mechanism underlying the psychobiological function of NSSI in adolescents. If supported by empirical evidence, findings from the project may lead to new treatment targets in NSSI. More broadly, the project will enhance our understanding of the psychological and neurobiological mechanisms underlying stress-relief following NSSI, the emergence of the behavior and its maintenance.
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