(PS2-74) Examining in Vivo Kappa Opioid Receptor Availability, Hoarding Behaviors, and Suicide Risk in Psychiatric Subjects: Results from a Pilot Study Using [11C]EKAP PET

Introduction: Hoarding disorder (HD) is associated with impulsivity, self-control difficulties, depression, exposure to early life stress, and executive dysfunction. Recent studies have highlighted the risk of impulsive suicide attempts (SA) in HD, reporting SA rates of 24%, and an emerging neurobiological model of hoarding implicates emotion dysregulation in HD pathology. The endogenous opioid system has been virtually unexplored in HD, despite relevance to emotion dysregulation, obsessive-compulsive disorder, compulsive behavior, and pre-clinical work showing that opioid antagonists decrease food hoarding behavior. The opioid system plays a role in impulsivity and suicide risk, and kappa opioid receptors (KOR) are implicated in stress, depressed mood, and cognition. Using [¹¹C]EKAP positron emission tomography (PET), this pilot study examined KOR availability in vivo in psychiatric subjects with hoarding behaviors (HB).  

Methods: 7 subjects with HB (i.e., impulsive buying/spending; M age=36.0, SD=12.8; 42.9% F), 6 psychiatric comparison controls (PCC; M age=37.3, SD=10.5; 50.0% F), and 7 healthy controls ([HC]; M age=34.0, SD=10.7; 42.9% F) participated in an [¹¹C]EKAP PET scan and comprehensive clinical assessment. Volume of distribution (VT: ratio of parent radioligand concentration in tissue relative to that in blood) in grey matter regions was the outcome measure. Hoarding behaviors (impulsive buying/spending), were measured by the Barratt Impulsivity Scale (BIS).

Results: Groups did not differ in age or biological sex. In cingulo-opercular regions implicated in HD, KOR availability differed across groups, F(2, 17)=6.82, p=.007, np²=0.45. HB showed 27% lower KOR availability relative to PCC (p=.006; M_diff=-8.40, 95% CI [-14.10, -2.69]) and HC (p=.005; M_diff = -8.43, 95% CI [-13.91, -2.95]). PCC and HC did not differ significantly. There were negative correlations between KOR availability, impulsivity (r=-.56, p=.045) and impulsive buying (r=-.80, p=.001) in all psychiatric subjects. 71.4% of HB reported a past suicide attempt, relative to 33.3% of PCC. In all psychiatric subjects, there was 18.8% lower KOR availability in subjects with a past SA, (t(11)=1.62, p=.125, d=0.92), although the difference was not statistically significant.

Discussion: The findings show preliminary evidence for KOR dysfunction in HB. Specifically, in cingulo-opercular regions implicated in HD, we found 27% lower KOR availability in HB relative to PCC and HC. The difference observed between HB and PCC suggests a unique relationship between HB and KOR in these brain areas. Relatedly, we observed preliminary evidence for relationships between KOR availability, HB, suicide attempt history, and endophenotypic correlates of suicide risk (e.g., impulsivity) in brain areas implicated in HD pathophysiology. Descriptive findings showed that individuals reporting HB were qualitatively more likely to have a suicide attempt history (71.4%) relative to PCC (33.3%). Certain limitations must be considered; HB was not assessed for full criteria HD. However, results highlight the relevance of the endogenous opioid system in HB and risk-related behaviors, providing a foundation for further exploration of HD’s pathophysiology.