Decreased nociceptin receptors are related to resilience and recovery in college women who have experienced sexual violence: therapeutic implications for PTSD

OBJECTIVE: 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. statistical analyses Comparisons between the sexual violence and healthy control groups on the demographic variables and baseline scan parameters injected t-tests. primary analyses conducted were correlational in all subjects sexual the diagnostic criteria for Normality of the were using tests prior to product explore between regional [ 11 C]NOP-1A V T and other rating scales, HAM-A, a linear mixed model a interaction A two-tailed probability p selected it unclear whether factors such as the phase of menstrual cycle, hormonal contraceptive use, and nicotine use the correlational findings observed in this study. No studies have examined the effects of menstrual cycle phases on NOP receptor expression in brain regions such as the midbrain and cerebellum. However, recent investigations in the spinal cord trigeminal neurons and hypothalamus (a unique brain region, which regulates the synthesis of sex steroids) suggest that the progesterone to estrogen ratio, which fluctuates during the menstrual cycle influences NOP receptor expression and binding. These studies have reported increases in NOP in the hypothalamic nuclei following both estrogen and estrogen + progesterone treatment; and decreases in NOP in the trigeminal neurons during the proestrous (high estrogen/low progesterone) compared to diestrous (low estrogen/high progesterone) phase of the rodent menstrual cycle 58). It is unclear as to whether, and how menstrual cycle phase may have influenced [ 11 C]NOP-1A V T measurements in the midbrain and cerebellum in this imaging study. A retrospective evaluation of the phase of menstrual cycle based on the subjects’ self-reported last menstrual period before the scan shows that the majority of women with a history of sexual violence were scanned either in the luteal phase or when on a hormone-based contraceptive (n = 16/18, This is reassuring as it suggests relative stability in estrogen and progesterone levels at the time of the PET scan in women who experienced sexual violence, despite higher levels in luteal phase (n = 5), and lower levels on hormonal contraceptives (n