Oral Papers: Addiction, Pain, & Transplant I
The demand for solid organ transplantation consistently outpaces the supply of organs available. Therefore, it is necessary to optimize the recovery and survival of recipients following solid organ transplantation. While many patients respond to transplantation with a renewed commitment to their health, others struggle with depression, pain, and treatment adherence. Predicting how patients will respond following transplantation remains a challenge. One strategy has been to conceptualize both psychiatric symptom exacerbation and resilience following transplantation as comparable to what patients experience in response to other life-altering events (Shinozaki 2011, Davydow 2015). It is possible the same genetic factors associated with resilience and post traumatic growth, in contrast to chronic pain, post-traumatic stress and depression, following a life-changing event or trauma (Banerjee 2017, Linnstaedt 2018) could also influence outcomes in transplant recipients.
We are performing a retrospective study investigating the association between potential genetic risk factors and specific clinical outcomes following transplantation. In particular, we will genotype ~850 adults who underwent solid organ transplantation at UNC Hospitals from 4/2014 – 9/2018 for the presence of single nucleotide polymorphisms (SNPs) of genes involved in the hypothalamic-pituitary-adrenal (HPA) axis and neurotransmission. We are simultaneously collecting retrospective clinical outcomes for this same population. We will determine if any of these SNPs are associated with risk for depression, chronic pain, and post-traumatic stress symptoms following organ transplantation. Age and gender will be covariates in the model, and, if feasible, exposure to childhood trauma, pre-transplantation narcotic use, chronic pain and psychiatric diagnoses, and immunosuppression regimen will be controlled for in the model. Published data (Linnstaedt 2018) indicate that in a population of predominantly European Americans who report stress/anxiety and/or a history of trauma, the sample size needed to detect significance (at alpha = 0.05, power = 0.80) is ~450 individuals.
A wide variety of potential risk factors for post-transplantation neuropsychiatric symptoms and treatment non-adherence have been explored. However, very little attention has been paid to potential genetic risk factors (Shinozaki 2011). We will analyze a set of genetic factors that have been associated with depression, chronic pain, and post-traumatic stress in patients following a life-changing or traumatic event to determine if they are associated with adverse outcomes in transplant recipients.
Davydow DS, et al. Posttraumatic stress disorder in organ transplant recipients: a systematic review. Gen Hosp Psychiatry. 2015;37(5):387-98.
Banerjee SB, et al. Genetic approaches for the study of PTSD: Advances and challenges. Neurosci Lett. 2017;649:139-46.
Linnstaedt SD, et al. A Functional riboSNitch in the 3' Untranslated Region of FKBP5 Alters MicroRNA-320a Binding Efficiency and Mediates Vulnerability to Chronic Post-Traumatic Pain. J Neurosci. 2018;38(39):8407-20.
Shinozaki G, et al. Relationship between FKBP5 polymorphisms and depression symptoms among kidney transplant recipients. Depress Anxiety. 2011;28(12):1111-8.