Oxytocin and Anorexia Nervosa
Anorexia nervosa (AN) is an intractable illness that is difficult to treat. The identification of neural correlates and novel agents to transform treatment has become priority avenues for research. Oxytocin (OT) is a neuropeptide whose emerging sphere of influence on mammalian behaviour and demonstrated impact on psychiatric illness suggest it may have potential in AN. Abnormal postprandial serum oxytocin dynamics in women with anorexia nervosa, even after recovery. Higher oxytocin secretion in response to a meal, which may reflect attenuated central signaling of satiety, was associated with higher levels of disordered eating psychopathology in women with active and weight-recovered anorexia nervosa, independent of cortisol and leptin levels. Oxytocin has appetite-regulating functions, and dysregulation in anorexia nervosa may contribute to symptoms of disordered eating. A study administering oxytocin to humans will be an important step in further defining the role of this hormone in appetite and food intake.
Oxytocin is a nine-amino acid peptide hormone with a range of physiological effects, including modulation of food intake in animals . Produced in the supraoptic and paraventricular nuclei of the hypothalamus, oxytocin is stored and released into the peripheral circulation via the posterior pituitary gland. There are central projections of oxytocin neurons to regions throughout the brain, and receptors have been identified in areas involved in food motivation, including the hypothalamus, amygdala, hippocampus, frontal cortex, and insula. Most data suggest that oxytocin acts as an anorexigenic hormone, inhibiting food intake, although there are conflicting studies and few data defining the role of oxytocin in food motivation pathways in humans. There is evidence that leptin, a key anorexigenic hormone produced by fat cells, signals via oxytocin neurons
In anorexia nervosa, a psychiatric illness characterized by severe restriction of food intake, comorbid anxiety and depression, low body weight, hypercortisolemia, and hypoleptinemia, nocturnal serum oxytocin levels are low compared with controls. Postprandial oxytocin secretion, however, has not been studied in anorexia nervosa. There is evidence that activation of oxytocinergic appetite pathways in the brain results in inhibition of peripheral oxytocin secretion, as measured in the serum. Response to food intake, peripheral oxytocin levels in weight-recovered women with anorexia nervosa would be low, representing an increase in central signaling of satiety as a trait feature of this eating disorder. In contrast postprandial peripheral oxytocin secretion in women with active anorexia nervosa would be relatively high, reflecting a lower satiety signal in the starved state. Using a food-related functional magnetic resonance imaging (fMRI) paradigm, we recently demonstrated hypoactivation of regions of the brain involved in food motivation in women with active and, to a lesser extent, weight-recovered anorexia nervosa compared with healthy women. In these same subjects, we expected that abnormal postprandial oxytocin secretion in women with anorexia nervosa, even after recovery, would be associated with hypoactivation of food motivation neurocircuitry and disordered eating psychopathology. Hypothalamic-pituitary-adrenal axis activation and subsequent hypercortisolemia is seen in anorexia nervosa, and there is overlap between brain regions involved in the stress response and food motivation pathways (for example, the hypothalamus, amygdala, hippocampus, and insula)
There’s no doubt that certain combinations of foods trigger responses in the neuroendocrine system, so it’s not unreasonable to say that those emotional connections to food are caused by neurotransmitters. However, it is impossible to point to one peptide and say, “this is what is causing your craving for chocolate.” The neuroendocrine system is highly interrelated, so we have to look not only at a specific peptide, but also to its relationship to other peptides. As it turns out, oxytocin and vasopressin are no different.
Oxytocin and vasopressin are very similar to each other. Both are only nine amino acids long, and between the two peptides, only two of the amino acids are different. They both act in both the peripheral and central nervous systems. In the peripheral nervous system, oxytocin is one of the hormones responsible for inducing uterine contractions during birth, release of milk into the collecting ducts in new mothers, and is elevated during orgasm in both men and women. Vasopressin is important for kidney function and blood pressure regulation. It helps to regulate how much water is released from the body as urine, and can increase blood pressure. In the Central Nervous System, oxytocin has been shown to have very important functions related to memory, mother-infant bonding, pair bonding, and trust. Vasopressin also plays a role in memory and partner preference, as well as aggression and circadian rhythm. In many cases, oxytocin and vasopressin seem to be reciprocal to one another: Oxytocin disrupts memory, while vasopressin enhances it.
In people with anorexia nervosa, the concentration of oxytocin in the brain is reduced, and peripheral nervous system responses are reduced or impaired. Vasopressin, on the other hand, is elevated. In patients with bulimia, oxytocin levels are normal, but vasopressin is elevated. These reduced and elevated hormonal profiles are most likely to be the result of restricted eating and starvation rather than the cause of them. But the elevated levels of vasopressin may play a role in recovery. If vasopressin is important during the formation and retrieval of memories, it could be contributing to the difficulty many patients have in changing their old routines of restriction.
Oxytocin secretion is substantially associated with abnormal activation of food motivation neurocircuitry in active anorexia nervosa (a state characteristic) as well as in those who have recovered weight (a trait characteristic). Specifically, oxytocin secretion is associated with trait differences in activation of the hypothalamus and insula and state differences in activation of numerous food motivation regions, including the hypothalamus, amygdala, and insula. Importantly, the hypothalamus is central to integration of feeding signals, and the insula integrates interoceptive signaling. A lack of interoceptive awareness, or ability to recognize one’s internal state, has been reported in anorexia nervosa . Insular hypoactivation in anorexia nervosa and hypothesized that an insular defect in this disorder may result in abnormal processing of internal signals, including those involving food motivation. The hypothesis suggests that due to failure in integration of incoming emotional, visceral, and homeostatic cues, insular dysfunction may result in an inability to appropriately identify the state of hunger vs. satiety. One possibility raised by our data is that insular dysfunction in anorexia nervosa may reflect impaired oxytocin signaling pathways. Interestingly, oxytocin administration resulted in increased insular activation and functional connectivity to the amygdala in prior fMRI studies of healthy individuals. Association between oxytocin secretion and both state and trait differences in activation of food motivation regions suggests that inherent abnormalities in oxytocin pathways may contribute to underlying deficits that increase susceptibility to developing and sustaining active anorexia nervosa.
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