Technology Enhanced Adolescent Mental Health (TEAM) (TEAM)

Leveraging Biomarkers and New Technologies to Reduce Self-Injury and Substance Abuse Risk Among Highly Vulnerable Adolescents

Adolescent nonsuicidal self-injury (NSSI) and alcohol misuse, alone and especially in combination, portend significant functional impairment in adulthood (e.g., relationship dysfunction, depression, suicidality). Although psychosocial interventions for NSSI and substance use are effective for some, they are also expensive and require highly trained clinicians. Treatment is therefore often unavailable to disadvantaged adolescents and those who live rurally. Thus, lower-cost alternative treatments are needed. We will evaluate the efficacy of noninvasive transcutaneous vagus nerve stimulation (tVNS), an effective treatment for depression, in reducing risk for NSSI and substance misuse among vulnerable adolescents.

The overarching goals of the proposed project are threefold. AIM 1: Evaluate the clinical efficacy of tVNS in reducing NSSI and alcohol misuse among vulnerable adolescents. We hypothesize that self-administered tVNS, delivered in 25-minute sessions, will reduce self-reported NSSI and alcohol use, improve adolescents' self-reported emotion regulation, and yield improvements in sympathetic and parasympathetic nervous system markers of emotion regulation and vulnerability to NSSI and alcohol misuse. AIM 2: Evaluate treatment adherence compared with traditional psychosocial interventions of similar duration. We hypothesize that adolescents will demonstrate greater treatment adherence than observed in traditional psychosocial interventions of similar duration, and rate tVNS as acceptable, unobtrusive, and favorable to face-to-face treatment. AIM 3: Evaluate maltreatment effects on tVNS. We hypothesize that tVNS will be effective for those with histories of maltreatment. Although rarely used to date among adolescents, tVNS alters neural and emotional responses to sad stimuli, and among adults, reduces suicide risk up to five years later. At present, it is being evaluated as a treatment for alcohol misuse in a NIH-funded clinical trial. This suggests potential for treating NSSI, alcohol misuse, post-traumatic stress symptoms (PTSS), and other disorders of emotion dysregulation. As outlined above, we will test the efficacy of tVNS in altering behavioral, emotional, and autonomic nervous system risk for NSSI and alcohol misuse, evaluate adherence and acceptability of tVNS among adolescents, and determine if maltreatment histories moderate treatment response.

Participants will be evaluated on the maintenance of any such treatment effects 3 months post intervention.

Participants will complete a 2-3 minute survey daily in which they are to report on different feelings and emotions such as happiness, sadness, and anger.

Adherence of participants' self-administered daily 25-minute tVNS sessions will be measured from participants' tVNS phone app. They will also report on acceptability, obtrusiveness, and favorability of tVNS.

Inclusion Criteria: Have used alcohol Have engaged in ≥ 3 episodes of NSSI in the past 6 months or ≥ 5 lifetime (1 of these 5 must be in the past year) Own a smartphone (iPhone or Android) Exclusion Criteria: Autism Schizophrenia Have a cardiac pacemaker, implanted defibrillator, or implanted or metallic electronic device Pregnant or breastfeeding Have a history of seizures or epilepsy Temperomandibular Joint Disorder Bell's Palsy Impaired cranial nerve function or facial pain

Aaronson ST, Sears P, Ruvuna F, Bunker M, Conway CR, Dougherty DD, Reimherr FW, Schwartz TL, Zajecka JM. A 5-Year Observational Study of Patients With Treatment-Resistant Depression Treated With Vagus Nerve Stimulation or Treatment as Usual: Comparison of Response, Remission, and Suicidality. Am J Psychiatry. 2017 Jul 1;174(7):640-648. doi: 10.1176/appi.ajp.2017.16010034. Epub 2017 Mar 31. Erratum In: Am J Psychiatry. 2017 Sep 1;174(9):907.

Achenbach, T.M. (1991). Manual for the youth self-report and 1991 profile. Burlington, VT: University of Vermont Department of Psychiatry.

American Foundation for Suicide Prevention. (2021). Project 2025: A nationwide initiative to reduce the annual rate of suicide in the U.S. by 20 percent by 2025. Retrieved on 6/23/2021 from https://project2025.afsp.org/

Anestis MD, Pennings SM, Lavender JM, Tull MT, Gratz KL. Low distress tolerance as an indirect risk factor for suicidal behavior: considering the explanatory role of non-suicidal self-injury. Compr Psychiatry. 2013 Oct;54(7):996-1002. doi: 10.1016/j.comppsych.2013.04.005. Epub 2013 May 16.

Beauchaine T. Vagal tone, development, and Gray's motivational theory: toward an integrated model of autonomic nervous system functioning in psychopathology. Dev Psychopathol. 2001 Spring;13(2):183-214. doi: 10.1017/s0954579401002012.

Beauchaine TP. Future Directions in Emotion Dysregulation and Youth Psychopathology. J Clin Child Adolesc Psychol. 2015;44(5):875-96. doi: 10.1080/15374416.2015.1038827. Epub 2015 May 27.

Beauchaine TP, Thayer JF. Heart rate variability as a transdiagnostic biomarker of psychopathology. Int J Psychophysiol. 2015 Nov;98(2 Pt 2):338-350. doi: 10.1016/j.ijpsycho.2015.08.004. Epub 2015 Aug 11.

Beauchaine TP, Cicchetti D. Emotion dysregulation and emerging psychopathology: A transdiagnostic, transdisciplinary perspective. Dev Psychopathol. 2019 Aug;31(3):799-804. doi: 10.1017/S0954579419000671. No abstract available.

Beauchaine TP, Hinshaw SP, Bridge JA. Nonsuicidal Self-Injury and Suicidal Behaviors in Girls: The Case for Targeted Prevention in Preadolescence. Clin Psychol Sci. 2019 Jul;7(4):643-667. doi: 10.1177/2167702618818474. Epub 2019 Jan 28.

Beauchaine TP, Bell Z, Knapton E, McDonough-Caplan H, Shader T, Zisner A. Respiratory sinus arrhythmia reactivity across empirically based structural dimensions of psychopathology: A meta-analysis. Psychophysiology. 2019 May;56(5):e13329. doi: 10.1111/psyp.13329. Epub 2019 Jan 23.

Beauchaine TP, Sauder CL, Derbidge CM, Uyeji LL. Self-injuring adolescent girls exhibit insular cortex volumetric abnormalities that are similar to those seen in adults with borderline personality disorder. Dev Psychopathol. 2019 Oct;31(4):1203-1212. doi: 10.1017/S0954579418000822.

Beauchaine, T. P., & Crowell, S. E. (Eds.) (2020). The Oxford handbook of emotion dysregulation. NY: Oxford University Press.

Behavioral Tech. (2021). DBT training and certification. Retrieved on 6/23/2021 from https://behavioraltech.org/re sources/faqs/training-faqs/

Bell Z, Shader T, Webster-Stratton C, Reid MJ, Beauchaine TP. Improvements in Negative Parenting Mediate Changes in Children's Autonomic Responding Following a Preschool Intervention for ADHD. Clin Psychol Sci. 2018;6(1):134-144. doi: 10.1177/2167702617727559. Epub 2017 Sep 26.

Berman, A. H., Bergman, H., Palmstierna, T., & Schlyter, F. (2002). Drug use disorders identification test. https://www.emcdda.europa.eu/system/files/attachments/12173/DUDIT-English-version.pdf

Bernstein DP, Stein JA, Newcomb MD, Walker E, Pogge D, Ahluvalia T, Stokes J, Handelsman L, Medrano M, Desmond D, Zule W. Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse Negl. 2003 Feb;27(2):169-90. doi: 10.1016/s0145-2134(02)00541-0.

Berntson GG, Cacioppo JT, Quigley KS. Autonomic determinism: the modes of autonomic control, the doctrine of autonomic space, and the laws of autonomic constraint. Psychol Rev. 1991 Oct;98(4):459-87. doi: 10.1037/0033-295x.98.4.459.

Bertrand K, Richer I, Brunelle N, Beaudoin I, Lemieux A, Menard JM. Substance abuse treatment for adolescents: how are family factors related to substance use change? J Psychoactive Drugs. 2013 Jan-Mar;45(1):28-38. doi: 10.1080/02791072.2013.763560.

Borges U, Pfannenstiel M, Tsukahara J, Laborde S, Klatt S, Raab M. Transcutaneous vagus nerve stimulation via tragus or cymba conchae: Are its psychophysiological effects dependent on the stimulation area? Int J Psychophysiol. 2021 Mar;161:64-75. doi: 10.1016/j.ijpsycho.2021.01.003. Epub 2021 Jan 11.

Brausch AM, Woods SE. Emotion Regulation Deficits and Nonsuicidal Self-Injury Prospectively Predict Suicide Ideation in Adolescents. Suicide Life Threat Behav. 2019 Jun;49(3):868-880. doi: 10.1111/sltb.12478. Epub 2018 Jun 14.

Brenner SL, Beauchaine TP. Pre-ejection period reactivity and psychiatric comorbidity prospectively predict substance use initiation among middle-schoolers: a pilot study. Psychophysiology. 2011 Nov;48(11):1588-1596. doi: 10.1111/j.1469-8986.2011.01230.x. Epub 2011 Jul 5.

Brent D. Nonsuicidal self-injury as a predictor of suicidal behavior in depressed adolescents. Am J Psychiatry. 2011 May;168(5):452-4. doi: 10.1176/appi.ajp.2011.11020215. No abstract available.

Brent DA, McMakin DL, Kennard BD, Goldstein TR, Mayes TL, Douaihy AB. Protecting adolescents from self-harm: a critical review of intervention studies. J Am Acad Child Adolesc Psychiatry. 2013 Dec;52(12):1260-71. doi: 10.1016/j.jaac.2013.09.009. Epub 2013 Sep 29.

Bresin K, Mekawi Y. Different Ways to Drown Out the Pain: A Meta-Analysis of the Association Between Nonsuicidal Self-Injury and Alcohol Use. Arch Suicide Res. 2022 Apr-Jun;26(2):348-369. doi: 10.1080/13811118.2020.1802378. Epub 2020 Aug 11.

Bretherton B, Atkinson L, Murray A, Clancy J, Deuchars S, Deuchars J. Effects of transcutaneous vagus nerve stimulation in individuals aged 55 years or above: potential benefits of daily stimulation. Aging (Albany NY). 2019 Jul 30;11(14):4836-4857. doi: 10.18632/aging.102074.

Burger AM, Van Diest I, Van der Does W, Korbee JN, Waziri N, Brosschot JF, Verkuil B. The effect of transcutaneous vagus nerve stimulation on fear generalization and subsequent fear extinction. Neurobiol Learn Mem. 2019 May;161:192-201. doi: 10.1016/j.nlm.2019.04.006. Epub 2019 Apr 12.

Burger AM, Van der Does W, Thayer JF, Brosschot JF, Verkuil B. Transcutaneous vagus nerve stimulation reduces spontaneous but not induced negative thought intrusions in high worriers. Biol Psychol. 2019 Mar;142:80-89. doi: 10.1016/j.biopsycho.2019.01.014. Epub 2019 Jan 30.

Centers for Disease Control. (2006). CDC injury fact book. Atlanta, GA: National Center for Injury Prevention Control.

Centers for Disease Control (2020). Suicide rates in the United States continue to increase. Retrieved on 9/8/2020 from https://www.cdc.gov/nchs/products/databriefs/db309.htm#fig2

Centers for Disease Control and Prevention (2021). Youth Risk Behavior Surveillance System (YRBSS) results. Downloaded on 6/22/2021 from https://www.cdc.gov/healthyyouth/data/yrbs/results.htm

Clark DB, Thatcher DL, Martin CS. Child abuse and other traumatic experiences, alcohol use disorders, and health problems in adolescence and young adulthood. J Pediatr Psychol. 2010 Jun;35(5):499-510. doi: 10.1093/jpepsy/jsp117. Epub 2009 Dec 4.

ClinicalTrials.gov. (2021). A study of new treatment for excessive alcohol users by electric stimulation of nerves around the ear. Retrieved on 6/24/2021 from https://clinicaltrials.gov/ct2/show/NCT04106739

Cohen JR, Thomsen KN, Tu KM, Thakur H, McNeil S, Menon SV. Cardiac autonomic functioning and post-traumatic stress: A preliminary study in youth at-risk for PTSD. Psychiatry Res. 2020 Feb;284:112684. doi: 10.1016/j.psychres.2019.112684. Epub 2019 Nov 7.

Cooper ML, Frone MR, Russell M, Mudar P. Drinking to regulate positive and negative emotions: a motivational model of alcohol use. J Pers Soc Psychol. 1995 Nov;69(5):990-1005. doi: 10.1037//0022-3514.69.5.990.

Crowell SE, Beauchaine TP, McCauley E, Smith CJ, Stevens AL, Sylvers P. Psychological, autonomic, and serotonergic correlates of parasuicide among adolescent girls. Dev Psychopathol. 2005 Fall;17(4):1105-27. doi: 10.1017/s0954579405050522.

Crowell SE, Beauchaine TP, McCauley E, Smith CJ, Vasilev CA, Stevens AL. Parent-child interactions, peripheral serotonin, and self-inflicted injury in adolescents. J Consult Clin Psychol. 2008 Feb;76(1):15-21. doi: 10.1037/0022-006X.76.1.15.

Crowell SE, Beauchaine TP, Linehan MM. A biosocial developmental model of borderline personality: Elaborating and extending Linehan's theory. Psychol Bull. 2009 May;135(3):495-510. doi: 10.1037/a0015616.

Crowell SE, Baucom BR, McCauley E, Potapova NV, Fitelson M, Barth H, Smith CJ, Beauchaine TP. Mechanisms of contextual risk for adolescent self-injury: invalidation and conflict escalation in mother-child interactions. J Clin Child Adolesc Psychol. 2013;42(4):467-80. doi: 10.1080/15374416.2013.785360. Epub 2013 Apr 14.

Crowell SE, Butner JE, Wiltshire TJ, Munion AK, Yaptangco M, Beauchaine TP. Evaluating Emotional and Biological Sensitivity to Maternal Behavior among Self-injuring and Depressed Adolescent Girls Using Nonlinear Dynamics. Clin Psychol Sci. 2017 Mar 1;5(2):272-285. doi: 10.1177/2167702617692861. Epub 2017 Mar 13.

Donovan JE, Molina BS. Childhood risk factors for early-onset drinking. J Stud Alcohol Drugs. 2011 Sep;72(5):741-51. doi: 10.15288/jsad.2011.72.741.

Dvorak RD, Sargent EM, Kilwein TM, Stevenson BL, Kuvaas NJ, Williams TJ. Alcohol use and alcohol-related consequences: associations with emotion regulation difficulties. Am J Drug Alcohol Abuse. 2014 Mar;40(2):125-30. doi: 10.3109/00952990.2013.877920.

Fang J, Rong P, Hong Y, Fan Y, Liu J, Wang H, Zhang G, Chen X, Shi S, Wang L, Liu R, Hwang J, Li Z, Tao J, Wang Y, Zhu B, Kong J. Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder. Biol Psychiatry. 2016 Feb 15;79(4):266-73. doi: 10.1016/j.biopsych.2015.03.025. Epub 2015 Apr 2.

Fang J, Egorova N, Rong P, Liu J, Hong Y, Fan Y, Wang X, Wang H, Yu Y, Ma Y, Xu C, Li S, Zhao J, Luo M, Zhu B, Kong J. Early cortical biomarkers of longitudinal transcutaneous vagus nerve stimulation treatment success in depression. Neuroimage Clin. 2016 Dec 18;14:105-111. doi: 10.1016/j.nicl.2016.12.016. eCollection 2017.

Foley, J. O., & DuBois, F. S. (1937). Quantitative studies of the vagus nerve in the cat. I. The ratio of sensory to motor fibers. Journal of Comparative Neurology, 67, 49-67.

Ford JD, Steinberg KL, Hawke J, Levine J, Zhang W. Randomized trial comparison of emotion regulation and relational psychotherapies for PTSD with girls involved in delinquency. J Clin Child Adolesc Psychol. 2012;41(1):27-37. doi: 10.1080/15374416.2012.632343.

Ford JD, Gomez JM. The relationship of psychological trauma and dissociative and posttraumatic stress disorders to nonsuicidal self-injury and suicidality: a review. J Trauma Dissociation. 2015;16(3):232-71. doi: 10.1080/15299732.2015.989563. Epub 2015 Mar 11.

Fox HC, Hong KA, Sinha R. Difficulties in emotion regulation and impulse control in recently abstinent alcoholics compared with social drinkers. Addict Behav. 2008 Feb;33(2):388-94. doi: 10.1016/j.addbeh.2007.10.002. Epub 2007 Oct 16.

Gadow, K. D., & Sprafkin, J. (2013). Child and Adolescent Symptom Inventory-5. Stony Brook, NY: Checkmate Plus.

George MS, Rush AJ, Marangell LB, Sackeim HA, Brannan SK, Davis SM, Howland R, Kling MA, Moreno F, Rittberg B, Dunner D, Schwartz T, Carpenter L, Burke M, Ninan P, Goodnick P. A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression. Biol Psychiatry. 2005 Sep 1;58(5):364-73. doi: 10.1016/j.biopsych.2005.07.028.

Goldin PR, McRae K, Ramel W, Gross JJ. The neural bases of emotion regulation: reappraisal and suppression of negative emotion. Biol Psychiatry. 2008 Mar 15;63(6):577-86. doi: 10.1016/j.biopsych.2007.05.031. Epub 2007 Sep 21.

Graham JW. Missing data analysis: making it work in the real world. Annu Rev Psychol. 2009;60:549-76. doi: 10.1146/annurev.psych.58.110405.085530.

Gratz, K. L. & Roemer, L. (2004). Multidimensional assessment of emotion regulation and dysregulation: Development, factor structure, and initial validation of the Difficulties in Emotion Regulation Scale. Journal of Psychopathology and Behavioral Assessment, 26, 41-54.

Grossman P, van Beek J, Wientjes C. A comparison of three quantification methods for estimation of respiratory sinus arrhythmia. Psychophysiology. 1990 Nov;27(6):702-14. doi: 10.1111/j.1469-8986.1990.tb03198.x.

Haag K, Hiller R, Peyk P, Michael T, Meiser-Stedman R, Fearon P, Ehlers A, Halligan SL. A Longitudinal Examination of Heart-Rate and Heart Rate Variability as Risk Markers for Child Posttraumatic Stress Symptoms in an Acute Injury Sample. J Abnorm Child Psychol. 2019 Nov;47(11):1811-1820. doi: 10.1007/s10802-019-00553-2.

He W, Jing X, Wang X, Rong P, Li L, Shi H, Shang H, Wang Y, Zhang J, Zhu B. Transcutaneous auricular vagus nerve stimulation as a complementary therapy for pediatric epilepsy: a pilot trial. Epilepsy Behav. 2013 Sep;28(3):343-6. doi: 10.1016/j.yebeh.2013.02.001. Epub 2013 Jun 29.

Hewig, J., Hagemann, D., Seifert, J., Gollwitzer, M., Naumann, E., & Bartussek, D. (2005). A revised film set for the induction of basic emotions. Cognition and Emotion, 19(7), 1095-1109. doi:10.1080/ 02699930541000084

Humeniuk R, Ali R, Babor TF, Farrell M, Formigoni ML, Jittiwutikarn J, de Lacerda RB, Ling W, Marsden J, Monteiro M, Nhiwatiwa S, Pal H, Poznyak V, Simon S. Validation of the Alcohol, Smoking And Substance Involvement Screening Test (ASSIST). Addiction. 2008 Jun;103(6):1039-47. doi: 10.1111/j.1360-0443.2007.02114.x. Epub 2008 Mar 28.

Hutcherson CA, Goldin PR, Ochsner KN, Gabrieli JD, Barrett LF, Gross JJ. Attention and emotion: does rating emotion alter neural responses to amusing and sad films? Neuroimage. 2005 Sep;27(3):656-68. doi: 10.1016/j.neuroimage.2005.04.028.

Johnson RL, Wilson CG. A review of vagus nerve stimulation as a therapeutic intervention. J Inflamm Res. 2018 May 16;11:203-213. doi: 10.2147/JIR.S163248. eCollection 2018.

Jongkees BJ, Immink MA, Finisguerra A, Colzato LS. Transcutaneous Vagus Nerve Stimulation (tVNS) Enhances Response Selection During Sequential Action. Front Psychol. 2018 Jul 6;9:1159. doi: 10.3389/fpsyg.2018.01159. eCollection 2018.

Kapetanovic, S., Gurdal, S., Ander, B., & Sorbring, E. (2021). Reported changes in adolescent psychosocial functioning during the COVID-19 outbreak. Adolescents, 1, 10-20. doi:10.3390/adolescents1010002

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 Jan;38(1):9-26. doi: 10.1111/acer.12270. Epub 2013 Oct 11.

Klonsky ED. The functions of deliberate self-injury: a review of the evidence. Clin Psychol Rev. 2007 Mar;27(2):226-39. doi: 10.1016/j.cpr.2006.08.002. Epub 2006 Oct 2.

Klonsky ED. The functions of self-injury in young adults who cut themselves: clarifying the evidence for affect-regulation. Psychiatry Res. 2009 Apr 30;166(2-3):260-8. doi: 10.1016/j.psychres.2008.02.008. Epub 2009 Mar 10.

Klonsky ED, Glenn CR, Styer DM, Olino TM, Washburn JJ. The functions of nonsuicidal self-injury: converging evidence for a two-factor structure. Child Adolesc Psychiatry Ment Health. 2015 Sep 28;9:44. doi: 10.1186/s13034-015-0073-4. eCollection 2015.

Koenig J, Parzer P, Haigis N, Liebemann J, Jung T, Resch F, Kaess M. Effects of acute transcutaneous vagus nerve stimulation on emotion recognition in adolescent depression. Psychol Med. 2021 Feb;51(3):511-520. doi: 10.1017/S0033291719003490. Epub 2019 Dec 10.

Kong J, Fang J, Park J, Li S, Rong P. Treating Depression with Transcutaneous Auricular Vagus Nerve Stimulation: State of the Art and Future Perspectives. Front Psychiatry. 2018 Feb 5;9:20. doi: 10.3389/fpsyt.2018.00020. eCollection 2018.

Kuntsche E, Knibbe R, Gmel G, Engels R. Why do young people drink? A review of drinking motives. Clin Psychol Rev. 2005 Nov;25(7):841-61. doi: 10.1016/j.cpr.2005.06.002.

Linehan, M. M., Comtois, K. A., & Ward-Ciesielski, E. F. (2012). Assessing and managing risk with suicidal individuals. Cognitive and Behavioral Practice,19(2), 218-232.

Liu J, Fang J, Wang Z, Rong P, Hong Y, Fan Y, Wang X, Park J, Jin Y, Liu C, Zhu B, Kong J. Transcutaneous vagus nerve stimulation modulates amygdala functional connectivity in patients with depression. J Affect Disord. 2016 Nov 15;205:319-326. doi: 10.1016/j.jad.2016.08.003. Epub 2016 Aug 11.

Marangell LB, Rush AJ, George MS, Sackeim HA, Johnson CR, Husain MM, Nahas Z, Lisanby SH. Vagus nerve stimulation (VNS) for major depressive episodes: one year outcomes. Biol Psychiatry. 2002 Feb 15;51(4):280-7. doi: 10.1016/s0006-3223(01)01343-9.

McDonough-Caplan H, Klein DN, Beauchaine TP. Comorbidity and continuity of depression and conduct problems from elementary school to adolescence. J Abnorm Psychol. 2018 Apr;127(3):326-337. doi: 10.1037/abn0000339. Epub 2018 Feb 26.

Miller JC, Horvath SM. Impedance cardiography. Psychophysiology. 1978 Jan;15(1):80-91. doi: 10.1111/j.1469-8986.1978.tb01340.x. No abstract available.

Moran P, Coffey C, Romaniuk H, Degenhardt L, Borschmann R, Patton GC. Substance use in adulthood following adolescent self-harm: a population-based cohort study. Acta Psychiatr Scand. 2015 Jan;131(1):61-8. doi: 10.1111/acps.12306. Epub 2014 Jun 23.

Muller HHO, Moeller S, Lucke C, Lam AP, Braun N, Philipsen A. Vagus Nerve Stimulation (VNS) and Other Augmentation Strategies for Therapy-Resistant Depression (TRD): Review of the Evidence and Clinical Advice for Use. Front Neurosci. 2018 Apr 10;12:239. doi: 10.3389/fnins.2018.00239. eCollection 2018.

National Institute of Mental Health. (2021). NIMH Strategic Plan for Research. Retrieved on 6/21/2021 from https://iamhrf.org/sites/iamhrf.org/files/uploads/publication/files/nimh_strategicplanforresearch.pdf

National Institute on Alcohol Abuse and Alcoholism. (2021). NIAAA Strategic Plan. Downloaded on 6/21/2021 from https://www.niaaa.nih.gov/strategic-plan.

Neumann A, van Lier PA, Gratz KL, Koot HM. Multidimensional assessment of emotion regulation difficulties in adolescents using the Difficulties in Emotion Regulation Scale. Assessment. 2010 Mar;17(1):138-49. doi: 10.1177/1073191109349579. Epub 2009 Nov 14.

McManama O'Brien KH, Becker SJ, Spirito A, Simon V, Prinstein MJ. Differentiating adolescent suicide attempters from ideators: examining the interaction between depression severity and alcohol use. Suicide Life Threat Behav. 2014 Feb;44(1):23-33. doi: 10.1111/sltb.12050. Epub 2013 Jul 25.

Oetzel, B. K., & Scherer, D. G. (2003). Therapeutic engagement with adolescents in psychotherapy. Psychotherapy: Theory, Research, Practice, Training, 40, 215-225. doi:10.1037/0033-3204.40.3.215

O'Reardon JP, Cristancho P, Peshek AD. Vagus Nerve Stimulation (VNS) and Treatment of Depression: To the Brainstem and Beyond. Psychiatry (Edgmont). 2006 May;3(5):54-63.

Patrick ME, Schulenberg JE, O'Malley PM, Johnston LD, Bachman JG. Adolescents' reported reasons for alcohol and marijuana use as predictors of substance use and problems in adulthood. J Stud Alcohol Drugs. 2011 Jan;72(1):106-16. doi: 10.15288/jsad.2011.72.106.

Penry JK, Dean JC. Prevention of intractable partial seizures by intermittent vagal stimulation in humans: preliminary results. Epilepsia. 1990;31 Suppl 2:S40-3. doi: 10.1111/j.1528-1157.1990.tb05848.x.

Perepletchikova F, Nathanson D, Axelrod SR, Merrill C, Walker A, Grossman M, Rebeta J, Scahill L, Kaufman J, Flye B, Mauer E, Walkup J. Randomized Clinical Trial of Dialectical Behavior Therapy for Preadolescent Children With Disruptive Mood Dysregulation Disorder: Feasibility and Outcomes. J Am Acad Child Adolesc Psychiatry. 2017 Oct;56(10):832-840. doi: 10.1016/j.jaac.2017.07.789. Epub 2017 Aug 10.

Porges SW. Orienting in a defensive world: mammalian modifications of our evolutionary heritage. A Polyvagal Theory. Psychophysiology. 1995 Jul;32(4):301-18. doi: 10.1111/j.1469-8986.1995.tb01213.x.

Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011 Dec;168(12):1266-77. doi: 10.1176/appi.ajp.2011.10111704.

Prechtl JC, Powley TL. The fiber composition of the abdominal vagus of the rat. Anat Embryol (Berl). 1990;181(2):101-15. doi: 10.1007/BF00198950.

Quintana DS, McGregor IS, Guastella AJ, Malhi GS, Kemp AH. A meta-analysis on the impact of alcohol dependence on short-term resting-state heart rate variability: implications for cardiovascular risk. Alcohol Clin Exp Res. 2013 Jan;37 Suppl 1:E23-9. doi: 10.1111/j.1530-0277.2012.01913.x. Epub 2012 Jul 26.

Redgrave J, Day D, Leung H, Laud PJ, Ali A, Lindert R, Majid A. Safety and tolerability of Transcutaneous Vagus Nerve stimulation in humans; a systematic review. Brain Stimul. 2018 Nov-Dec;11(6):1225-1238. doi: 10.1016/j.brs.2018.08.010. Epub 2018 Aug 23.

Reynolds, W. M. (1987). Suicidal Ideation Questionnaire-Junior. Odessa, FL: Psychological Assessment Resources.

Reynolds, W. M. (1988). Suicidal Ideation Questionnaire: Professional manual. Odessa, FL: Psychological Assessment Resources.

Reynolds SK, Lindenboim N, Comtois KA, Murray A, Linehan MM. Risky assessments: participant suicidality and distress associated with research assessments in a treatment study of suicidal behavior. Suicide Life Threat Behav. 2006 Feb;36(1):19-34. doi: 10.1521/suli.2006.36.1.19.

Rong PJ, Fang JL, Wang LP, Meng H, Liu J, Ma YG, Ben H, Li L, Liu RP, Huang ZX, Zhao YF, Li X, Zhu B, Kong J. Transcutaneous vagus nerve stimulation for the treatment of depression: a study protocol for a double blinded randomized clinical trial. BMC Complement Altern Med. 2012 Dec 14;12:255. doi: 10.1186/1472-6882-12-255.

Rong P, Liu J, Wang L, Liu R, Fang J, Zhao J, Zhao Y, Wang H, Vangel M, Sun S, Ben H, Park J, Li S, Meng H, Zhu B, Kong J. Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: A nonrandomized controlled pilot study. J Affect Disord. 2016 May;195:172-9. doi: 10.1016/j.jad.2016.02.031. Epub 2016 Feb 10.

Sauder CL, Derbidge CM, Beauchaine TP. Neural responses to monetary incentives among self-injuring adolescent girls. Dev Psychopathol. 2016 Feb;28(1):277-91. doi: 10.1017/S0954579415000449. Epub 2015 Jun 8. Erratum In: Dev Psychopathol. 2018 Oct;30(4):1543.

Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption--II. Addiction. 1993 Jun;88(6):791-804. doi: 10.1111/j.1360-0443.1993.tb02093.x.

Sayette MA. The effects of alcohol on emotion in social drinkers. Behav Res Ther. 2017 Jan;88:76-89. doi: 10.1016/j.brat.2016.06.005.

Schmitz WM Jr, Allen MH, Feldman BN, Gutin NJ, Jahn DR, Kleespies PM, Quinnett P, Simpson S. Preventing suicide through improved training in suicide risk assessment and care: an American Association of Suicidology Task Force report addressing serious gaps in U.S. mental health training. Suicide Life Threat Behav. 2012 Jun;42(3):292-304. doi: 10.1111/j.1943-278X.2012.00090.x. Epub 2012 Apr 11.

Naeger S. Emergency Department Visits Involving Underage Alcohol Misuse: 2010 to 2013. 2017 May 16. In: The CBHSQ Report. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2013-. Available from http://www.ncbi.nlm.nih.gov/books/NBK436366/

Swannell SV, Martin GE, Page A, Hasking P, St John NJ. Prevalence of nonsuicidal self-injury in nonclinical samples: systematic review, meta-analysis and meta-regression. Suicide Life Threat Behav. 2014 Jun;44(3):273-303. doi: 10.1111/sltb.12070. Epub 2014 Jan 15.

Thayer JF, Lane RD. Claude Bernard and the heart-brain connection: further elaboration of a model of neurovisceral integration. Neurosci Biobehav Rev. 2009 Feb;33(2):81-8. doi: 10.1016/j.neubiorev.2008.08.004. Epub 2008 Aug 13.

Tuisku V, Kiviruusu O, Pelkonen M, Karlsson L, Strandholm T, Marttunen M. Depressed adolescents as young adults - predictors of suicide attempt and non-suicidal self-injury during an 8-year follow-up. J Affect Disord. 2014 Jan;152-154:313-9. doi: 10.1016/j.jad.2013.09.031. Epub 2013 Oct 5.

Valentine SE, Bankoff SM, Poulin RM, Reidler EB, Pantalone DW. The use of dialectical behavior therapy skills training as stand-alone treatment: a systematic review of the treatment outcome literature. J Clin Psychol. 2015 Jan;71(1):1-20. doi: 10.1002/jclp.22114. Epub 2014 Jul 14.

van den Bosch LM, Verheul R, Schippers GM, van den Brink W. Dialectical Behavior Therapy of borderline patients with and without substance use problems. Implementation and long-term effects. Addict Behav. 2002 Nov-Dec;27(6):911-23. doi: 10.1016/s0306-4603(02)00293-9.

Verma N, Mudge JD, Kasole M, Chen RC, Blanz SL, Trevathan JK, Lovett EG, Williams JC, Ludwig KA. Auricular Vagus Neuromodulation-A Systematic Review on Quality of Evidence and Clinical Effects. Front Neurosci. 2021 Apr 30;15:664740. doi: 10.3389/fnins.2021.664740. eCollection 2021.

Wang Z, Fang J, Liu J, Rong P, Jorgenson K, Park J, Lang C, Hong Y, Zhu B, Kong J. Frequency-dependent functional connectivity of the nucleus accumbens during continuous transcutaneous vagus nerve stimulation in major depressive disorder. J Psychiatr Res. 2018 Jul;102:123-131. doi: 10.1016/j.jpsychires.2017.12.018. Epub 2017 Dec 28.

Weissman DG, Bitran D, Miller AB, Schaefer JD, Sheridan MA, McLaughlin KA. Difficulties with emotion regulation as a transdiagnostic mechanism linking child maltreatment with the emergence of psychopathology. Dev Psychopathol. 2019 Aug;31(3):899-915. doi: 10.1017/S0954579419000348. Epub 2019 Apr 8.

Williams F, Hasking P. Emotion regulation, coping and alcohol use as moderators in the relationship between non-suicidal self-injury and psychological distress. Prev Sci. 2010 Mar;11(1):33-41. doi: 10.1007/s11121-009-0147-8.

Wittbrodt MT, Gurel NZ, Nye JA, Ladd S, Shandhi MMH, Huang M, Shah AJ, Pearce BD, Alam ZS, Rapaport MH, Murrah N, Ko YA, Haffer AA, Shallenberger LH, Vaccarino V, Inan OT, Bremner JD. Non-invasive vagal nerve stimulation decreases brain activity during trauma scripts. Brain Stimul. 2020 Sep-Oct;13(5):1333-1348. doi: 10.1016/j.brs.2020.07.002. Epub 2020 Jul 10.

Wolff JC, Thompson E, Thomas SA, Nesi J, Bettis AH, Ransford B, Scopelliti K, Frazier EA, Liu RT. Emotion dysregulation and non-suicidal self-injury: A systematic review and meta-analysis. Eur Psychiatry. 2019 Jun;59:25-36. doi: 10.1016/j.eurpsy.2019.03.004. Epub 2019 Apr 12.

Zalewski M, Lewis JK, Martin CG. Identifying novel applications of dialectical behavior therapy: considering emotion regulation and parenting. Curr Opin Psychol. 2018 Jun;21:122-126. doi: 10.1016/j.copsyc.2018.02.013. Epub 2018 Mar 1.