3 - (SYM 50) Kappa Opioid Receptor as a Novel Biomarker for Suicide Risk in Trauma-related Psychopathology: Preliminary Results from an [11C]EKAP PET Imaging Study

Trauma-related psychopathology (TRP; including PTSD, borderline personality disorder [BPD]) is a substantial source of public health burden, associated with alarmingly high morbidity and mortality rates, and increased risk for suicide behavior (SB) including ideation (SI), attempt (SA), and death by suicide. Critically, limited effective pharmacotherapeutic treatments exist for TRP. Kappa opioid receptors (KOR) have been implicated as a potential novel treatment target for TRP and SB, though the role of KOR in TRP has not been directly investigated. This study examined relationships between KOR availability, TRP, and SB in vivo for the first time using [¹¹C]EKAP PET.

Individuals with TRP (PTSD or BPD; N=20,10 with history of SA,10 without [NSA]), and psychiatrically healthy adults ([HA] N=16) were recruited from the community. Participants completed 1 MRI and PET scan, psychiatric, and cognitive assessments. Analyses included a frontolimbic circuit of regions relevant to TRP.

Groups did not differ significantly on age, sex, or smoking status. ANOVA analyses revealed significant group differences in KOR availability (V_T; p=.002, TRP 29% lower than HA). TRP individuals with a history of SA had significantly lower KOR availability relative to TRP-NSA (p< .001; 23% difference), and HA (p< .001; 30% difference). KOR availability was negatively correlated with endophenotypic risk factors for SB, including fearlessness about one’s own death (r’s=-.51-.58, p’s=.01-.03), pain tolerance (r’s=-.45-.63, p’s= .01-.04), loneliness (r’s=-.44-.50, .02-.04), emotion dysregulation, and sleep difficulty (r’s=-.45-.63, p’s=.001-.04). In the TRP-SA group, KOR availability was negatively associated with depressive symptom severity (r’s=.68-.84, p’s=.005-.03), and thwarted belongingness (r’s=.72-.82, p’s=.01-.02). KOR availability was not associated with scan-day SI and did not differ as a function of recency/lethality of reported SA.

Results support a relationship between KOR, TRP, and SB. Individuals with TRP had lower frontolimbic KOR availability than HA, and those with a history of SA had significantly lower KOR availability relative to TRP-NSA and HA. Further, KOR availability was negatively associated with endophenotypic correlates of suicide risk and predictors of functional outcome in TRP (e.g., loneliness, emotion dysregulation). KOR did not differ as a function of SA recency, implicating KOR as a potential trait marker of suicide risk in this population. Additional evaluation of KOR targets for TRP treatment is warranted.