PTSD Study

The goal of this study is to investigate the role of the kappa opioid receptor (KOR) in posttraumatic stress disorder (PTSD), a condition associated with markedly elevated risk for all forms of suicidal behavior [1-3]. Despite awareness of the increased risk associated with PTSD, available pharmacological interventions are often at best partially effective, and rarely reduce suicide risk [4, 5, 6, 7]. Investigation of molecular mechanisms subserving PTSD and suicide risk specifically is an essential next step to both promote development of novel treatments and facilitate risk prevention in this population.

Emerging evidence implicates KOR in PTSD and suicidal behavior. KOR plays critical roles in hyperarousal [8], emotional numbing and dysregulation [9-10], and dissociation [11] – all of which are central to PTSD and related to suicide risk.

This study includes a novel investigation of KOR availability of in individuals with PTSD using positron emission tomography (PET), a brain imaging technique, and radioligand [11C]EKAP which binds selectively to KOR in the brain.

Our Goals

  • Investigate the relationship between KOR availability and PTSD symptom presentation using PET imaging.

  • Evaluate the association between KOR availability, suicide attempt history, and scan day suicide ideation.

  • Evaluate the association between pain tolerance, impulsivity, and executive dysfunction– key presentations associated with suicide risk – and KOR availability.

Citations

  1. Cougle JR, Resnick H, Kilpatrick DG. PTSD, depression, and their comorbidity in relation to suicidality: cross-sectional and prospective analyses of a national probability sample of women. Depress Anxiety. 2009;26(12):1151-1157.

  2. Bernal M, Haro JM, Bernert S, Brugha T, de Graaf R, Bruffaerts R, Lepine JP, de Girolamo G, Vilagut G, Gasquet I, Torres JV, Kovess V, Heider D, Neeleman J, Kessler R, Alonso J, Investigators EM. Risk factors for suicidality in Europe: results from the ESEMED study. J Affect Disord. 2007;101(1-3):27-34.

  3. Conner KR, Bossarte RM, He H, Arora J, Lu N, Tu XM, Katz IR. Posttraumatic stress disorder and suicide in 5.9 million individuals receiving care in the veterans health administration health system. J Affect Disord. 2014;166:1-5.

  4. Bui E. Pharmacological treatments for PTSD: where are we in 2020? European Journal of Psychotraumatology. 2021;12(sup1):1866411.

  5. Kelmendi B, Adams TG, Yarnell S, Southwick S, Abdallah CG, Krystal JH. PTSD: from neurobiology to pharmacological treatments. European journal of psychotraumatology. 2016;7(1):31858.

  6. Krystal JH, Davis LL, Neylan TC, Raskind MA, Schnurr PP, Stein MB, Vessicchio J, Shiner B, Gleason TD, Huang GD. It is time to address the crisis in the pharmacotherapy of posttraumatic stress disorder: a consensus statement of the PTSD Psychopharmacology Working Group. Biological psychiatry. 2017;82(7):e51-e59.

  7. Steckler T, Risbrough V. Pharmacological treatment of PTSD - established and new approaches. Neuropharmacology.2012;62(2):617-627.

  8. Bruchas M, Land B, Chavkin C. The dynorphin/kappa opioid system as a modulator of stress-induced and pro-addictive behaviors. Brain research. 2010;1314:44-55.

  9. Lutz P-E, Kieffer BL. Opioid receptors: distinct roles in mood disorders. Trends in neurosciences. 2013;36(3):195-206.

  10. New AS, Stanley B. An opioid deficit in borderline personality disorder: self-cutting, substance abuse, and social dysfunction: Am Psychiatric Assoc; 2010.

  11. Walsh SL, Strain EC, Abreu ME, Bigelow GE. Enadoline, a selective kappa opioid agonist: comparison with butorphanol and hydromorphone in humans. Psychopharmacology. 2001;157(2):151-162.

This study is possible due to support from the NIMH, AFSP, and National Center for PTSD (NC-PTSD).