Decreased Nociceptin Receptors Are Related to Resilience and Recovery in College Women Who Have Experienced Sexual Violence: Therapeutic Implications for Posttraumatic Stress Disorder

Abstract

Post-traumatic stress disorder (PTSD) is a stress disorder that develops in only some individuals following a traumatic event. Data suggest that a substantial fraction of women recover after sexual violence. Thus, the investigation of stress and anti-stress neuropeptides in this sample has the potential to inform the neurochemistry of resilience following trauma. Nociceptin is an anti-stress neuropeptide in the brain that promotes resilience in animal models of PTSD. METHODS: [ 11 C]NOP-1A PET was used to measure the in vivo binding to nociceptin receptors in 18 college women who had experienced sexual violence irrespective of whether they met DSM-5 diagnostic criteria for PTSD. [ 11 C]NOP-1A data from 18 healthy controls was also included to provide a contrast with the sexual violence group. [ 11 C]NOP-1A total distribution volume (V T) in the regions of interest were measured with kinetic analysis using the arterial input function. The relationships between regional V T and Clinician-Administered PTSD Scale total symptom and subscale severity were examined using correlational analyses. RESULTS: No differences in [ 11 C]NOP-1A V T were noted between the sexual violence and control groups. V T in the midbrain and cerebellum were positively correlated with PTSD total symptom severity in the past month prior to PET. Intrusion/re-experiencing and avoidance subscale symptoms drove this relationship. Stratification of subjects by a DSM-5 PTSD diagnosis and contrasting their V T with that in controls showed no group differences. CONCLUSION: Decreased midbrain and cerebellum nociceptin receptors are associated with less severe PTSD symptoms. Medications that target nociceptin should be explored to prevent and treat PTSD.

Modulation of the NOP receptor signaling affects resilience to acute stress

“…On the contrary, its blockage prevented this phenomenon, contributing to increased resilience to stress. These findings are in agreement with recent studies that showed an association between increased NOP receptor signaling and vulnerability to stress (Der-Avakian et al, 2017; Narendran et al, 2019). Furthermore, depression is a gateway to drug addiction (Gómez-Coronado et al, 2018).…”

“…This pivotal study, for the first time, linked the overexpression of the endogenous N/OFQ system with a depressive-related phenotype. Recently, midbrain and cerebellum NOP receptor binding, measured by positron emission tomography, was positively correlated with post-traumatic stress disorder (PTSD) symptoms in women who have experienced sexual violence (Narendran et al, 2019). This study reinforces the view that lower NOP receptor signaling is related to resilience and recovery in PTSD.…”

Harnessing the Neurobiology of Resilience to Protect the Mental Well-Being of Healthcare Workers During the COVID-19 Pandemic

“…Other peptides which have been shown to influence resilience and stress responses, though at a much more preliminary level of evidence, include the endogenous opioid family of enkephalins ( Nam et al, 2019 ), orexin ( Staton et al, 2018 ; Summers et al, 2020 ), nociceptin ( Narendran et al, 2019 ), somatostatin ( Stengel and Tache, 2017 ), and galanin ( Sciolino et al, 2015 ). These peptides have been shown to enhance resilience in animal models during experimental stress-inducing procedures, and to influence other molecules of key importance in brain resilience, such as BDNF.…”

Links Between the Neurobiology of Oxytocin and Human Musicality

“…Of the many endogenous opioids, β-endorphin—which may be raised by social music-making—has been implicated in resilience, stress, and PTSD (Bali et al, 2015 ) as has the neuropeptide nociceptin (Tollefson et al, 2017 ; Narendran et al, 2019 ). Nociceptin receptor polymorphisms have been linked to the severity of PTSD, but unlike β-endorphin, no relationship to music has been examined.…”