Oxytocin Administration Increases Proactive Control in Men with Overweight or Obesity: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.

OBJECTIVE: Preclinical and clinical evidence suggests that oxytocin administration decreases food intake and weight. The mechanisms underlying the anorexigenic effects of oxytocin in humans are unknown but critical to study to consider oxytocin as a neurohormonal weight loss treatment. Complementing ongoing research into metabolic and food motivation mechanisms of oxytocin, this study hypothesized that in humans, oxytocin improves cognitive control over behavior. METHODS: In a randomized, double-blind, placebo-controlled crossover study of 24-IU single-dose intranasal oxytocin, 10 men with overweight or obesity completed a stop-signal task assessing ability and strategy to suppress behavioral impulses, in which they performed a choice-reaction task (go task) but had to withhold their response when prompted (stop task). It was hypothesized that oxytocin would improve suppression of behavioral impulses. RESULTS: After receiving oxytocin, compared with placebo, participants showed increased reaction times in the go task (mean [M] = 936 milliseconds vs. 833 millseconds; P = 0.012; 95% CI: 29 to 178) and displayed fewer stop errors (M = 36.41% vs. 41.15%; P = 0.049; 95% CI: -9.43% to -0.03%). CONCLUSIONS: Oxytocin triggers increased proactive control over behavior. Future studies need to further characterize the impact of oxytocin on cognitive control and investigate its potential role in the anorexigenic effects of oxytocin in human obesity.

Effects of Intranasal Oxytocin on the Blood Oxygenation Level-Dependent Signal in Food Motivation and Cognitive Control Pathways in Overweight and Obese Men.

Recent research indicates that the hypothalamic neuropeptide hormone oxytocin is a key central nervous system factor in the regulation of food intake and weight. However, the mechanisms underlying the anorexigenic effects of oxytocin in humans are unknown and critical to study to consider oxytocin as a neurohormonal weight loss treatment. We performed a randomized, double-blind, placebo-controlled crossover study with single-dose intranasal oxytocin (24 IU) in ten overweight or obese, otherwise healthy men. Following oxytocin/placebo administration, participants completed an established functional magnetic resonance imaging food motivation paradigm. We hypothesized that oxytocin would reduce the blood oxygenation level-dependent (BOLD) signal to high-calorie food vs non-food visual stimuli in the ventral tegmental area (VTA), the origin of the mesolimbic dopaminergic reward system. Following oxytocin administration, compared to placebo, participants showed bilateral VTA hypoactivation to high-calorie food stimuli. A secondary exploratory whole-brain analysis revealed hypoactivation in additional hedonic (orbitofrontal cortex, insula, globus pallidus, putamen, hippocampus, and amygdala) and homeostatic (hypothalamus) food motivation and hyperactivation in cognitive control (anterior cingulate and frontopolar cortex) brain regions following oxytocin administration vs placebo. Oxytocin administration reduces the BOLD signal in reward-related food motivation brain regions, providing a potential neurobiological mechanism for the anorexigenic oxytocin effects in humans. Furthermore, our data indicate that oxytocin administration reduces activation in homeostatic and increases activation in cognitive control brain regions critically involved in regulating food intake and resolving affective conflict, respectively. Future studies are required to link these changes in brain activation to oxytocin effects on food intake and weight.