Abstract Disclosure: M. Wronski: None. F. Plessow: None. M. Rogers: None. D.L. Kahn: None. E.R. Golden: None. M. Slattery: None. J.J. Thomas: None. L.M. Holsen: None. K.T. Eddy: None. M. Misra: None. E.A. Lawson: None. Background: Preclinical and clinical evidence suggests that the hypothalamic neuropeptide oxytocin (OXT) impacts inhibitory control and reward processing. In male adults with overweight or obesity, we showed that exogeneous OXT increases inhibitory control and neural activation in associated brain regions while attenuating activation in reward-related brain regions. Low-weight eating disorders (LWEDs) are characterized by decreased endogenous OXT levels, altered inhibitory control over behavior, and reduced responsiveness to rewards. However, links between these characteristics are unknown in LWEDs. Here, we examined associations between endogenous OXT levels and performance in behavioral tasks requiring inhibitory control and reward-based decision-making in individuals with a LWED compared to healthy controls (HC). Methods: In 58 females with a LWED and 39 female HC (aged 11-23 years), we measured serum OXT concentrations fasting and 30, 60, and 120 minutes after a 400-kcal standardized meal and calculated OXT area under the curve (AUC) as a composite measure. After the meal (following the 60-minute blood draw), participants completed a Go/NoGo Task to assess inhibitory control over behavior and a monetary Delay Discounting Task to assess reward-based decision-making. We analyzed associations between OXT AUC and behavioral outcomes across groups using robust linear models with main effects of group (LWED vs. HC) and OXT AUC, the interaction effect of group*OXT AUC, and covariates age and body mass index (BMI) z score. Results: Per study design, individuals with a LWED had a lower BMI z score (t=10.90, p<0.001, d=2.00), whereas groups did not differ in OXT AUC (t=1.20, p=0.232, d=0.24). For the Go/NoGo Task, we observed a group effect on NoGo error rate (higher values indicating lower inhibitory control; NoGo error rate: adj. mean [std. error] LWED 35.6 [2.7] % > HC 26.6 [3.4] %) as well as an interaction effect of group*OXT AUC, independent of age and BMI z score (t=2.73, p=0.008, d=0.72). Follow-up simple main effects analysis within each group revealed a significant negative relationship of OXT AUC and NoGo error rate in individuals with a LWED (t=-2.42, p=0.022, d=0.85), while this relationship emerged as nonsignificant but trend-level positive in HC (t=1.73, p=0.099, d=0.74). We did not detect group (t=0.69, p=0.493, d=0.17) or group*OXT interaction (t<0.01, p=0.996, d<0.01) effects on delay discounting rate. Conclusions: In females with a LWED, lower OXT exposure around a meal correlated with lower inhibitory control over behavior. In HC, however, our data yielded a trend of opposite directionality. Links between OXT exposure and reward-related decision-making were absent across groups. Our findings indicate potential relevance and mechanistic involvement of OXT in inhibitory control in LWEDs that warrants further causal investigations. Presentation: 6/3/2024
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