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Leptin & Cortisol in Eating Disorders (aka My Research Paper)

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Eating disorders can leave harmful effects on survivors, prior to the destruction that takes place while the disorder is in full effect. In the midst of an eating disorder, one can suffer from digestive issues, fatigue, and dry skin, among other symptoms (“Anorexia nervosa – medical complications”, 2015). An in-depth look at the most common eating disorder - anorexia nervosa - reveals a physiological effect beyond a thin stature and restricted food intake: potentially serious hormonal imbalances in levels of leptin and cortisol.

Anorexia Nervosa Explained

The most prevalent of all eating disorders, anorexia nervosa is one characterized by weight loss or inadequate weight gain, difficulty maintaining a proper weight, body image distortion, and sometimes exercise addiction (“Anorexia: Overview and Statistics”). A collection of studies in the International Journal of Eating Disorders found a prevalence rate of up to about 1% among young females for strictly defined anorexia nervosa (Wijbrand, 2003, p. 385). The vast majority of these studies found significantly higher prevalence rates for partial syndromes of anorexia, meaning that the full set of diagnostic criteria for AN was not met, but rather a smaller handful of signs of the disorder. While a mere 1% of the world’s population can seem a small number, and while most medical professionals do classify anorexia nervosa as a rare mental illness when compared with others, the incidence rates are rising rapidly in the 15-19 year-old female age group (Smink, 2012, p. 408).

Survivors of anorexia nervosa can likely vividly remember the signs and symptoms associated, though during the disorder, one probably would have denied anything unusual at all. What typically begins with an innocent decrease in calories/overall food intake in pursuit of weight loss often progresses into a restriction or elimination of at least one entire food group (i.e. carbohydrates or fats). From there, specific food rituals, like excessive chewing and/or organization of foods and eating patterns develop. Concerns about eating in public and/or social gatherings promote withdrawal and isolation. Other mechanisms of avoiding meals include random excuses to exclude oneself and denial of hunger, as well as consistent over-exercising (“Warning Signs and Symptoms”).

Psychologically, a preoccupation with food often clouds one’s mind with thoughts of how to consume the least amount possible, how to “burn off” calories consumed, fear of eating or gaining fat, etc. Additionally, denial of one’s low body weight, extreme influence of one’s weight or physical shape on emotional and mental state, and body dysmorphia – fixation on a perceived flaw or imperfection in one’s physical appearance, body shape, or specific feature – become mentally and socially consuming (Phillips). Flexibility with daily life occurrences like eating and making social plans diminishes as one seeks control and relies on specific, strict dietary patterns, and isolation and withdrawal often result (“Warning Signs and Symptoms”).

DSM-5 diagnostic criteria include restriction of energy intake to amounts far lower than recommended, intense fear of weight gain despite one’s current weight, and a disturbance in one’s own perception of body shape and consequent extreme self-evaluation and denial of the disorder (“Anorexia: Overview and Statistics”). Atypical anorexia occurs when one shows some or all symptoms of AN but is not underweight, despite weight loss.

A main consequence of prolonged AN is a disruption of the body’s ability to regulate hormones. Two hormones most significantly affected include leptin and cortisol, which involve maintenance of appetite and satiation and management of stress levels, respectively. At first, this disruption might not manifest itself obviously, but if not treated, can over time lead to inability to regain a healthy amount of weight and/or damage and even loss of cognition.

Leptin

Leptin is a hormone directly tied to and secreted by body fat. Sometimes called the “satiety hormone”, leptin’s main function is signaling to the brain that energy is present in the body, so appetite can decrease (What Is Leptin?). Specifically, leptin “travels from fat to the bloodstream and binds with the hypothalamus region of the brain, which is involved in regulating appetite” (Tara, 2016, p. 42). Therefore, a higher level of circulating leptin in the blood typically equals a lower appetite (assuming no metabolic issues like obesity or diabetes are present) (Margetic, 2002, p. 1409-1410).

A study published in the International Journal of Eating Disorders compared the plasma leptin levels of patients with anorexia nervosa to that of normal control women without the disorder. Each individual’s level of various hormones including leptin was measured, as well as menstrual score, percent body fat, and eating behavior score. Researchers found a significant relationship between leptin levels and body fat mass, eating behavior score, and menstrual status. Eating behavior score was defined on a scale of one to five based on the patient’s 48-hour diet history prior to blood testing – a lower score was given to patients with lower calorie intake and a higher score to those with extreme caloric intake. Menstrual score on a scale of one to three was based on regularity of the menstrual cycle for the three months prior to blood testing – amenorrhea for at least three months was given a score of one while a regular cycle was given a score of three. Overall, lower leptin levels (observed mostly in the patients with AN) were seen paired with lower body fat mass, eating behavior score, and menstrual score. This signified that symptoms of AN, mainly decreased caloric intake and excessive exercise leading to extreme weight loss, lower the body’s leptin levels, and consequently, menstrual regulation (Nakai, 1999, p. 32).

The same study also pointed out that leptin has been linked to reproductive function. Though it does not play a direct role in the initiation of puberty and the reproductive cycle, leptin does act in a permissive fashion, as “a metabolic gate to allow pubertal maturation to proceed” (Nakai, 1999, p. 34). In another study, both male and female mice with mutations resulting in leptin deficiency were observed to be infertile, and only achieved proper sexual development when provided with leptin. Mice with low leptin levels displayed “morphological and biochemical abnormalities”, like low sperm counts and underweight, underdeveloped reproductive organs (Elias, 2012, p. 842). Similarly, the pituitary contents of luteinizing hormone and follicular stimulating hormone, two main hormones that regulate ovulation, were low in leptin-deficient mice (Elias, 2012, p. 843) (Martin, 2013).

Researchers for the Journal of Clinical Endocrinology and Metabolism found that during the weight restoration phase of AN treatment, leptin levels reached what was considered “normal” (that of healthy individuals without AN), but patients were still significantly underweight. This helps explain why some suffering from AN struggle in gaining weight even after recovering from the disorder – leptin levels have increased, so appetite has decreased. Leptin levels likely increase at a faster rate than weight gain does, which represents potential difficulty some might face in the treatment and full weight-restoration process (Mantzoros, 1997, p. 1850).

A study published in the research journal PLOS ONE found results that agreed with that of the previous study. These researchers found that in previously high-severity AN patients, now weight-restored patients, an increase in leptin levels was correlated with an increased incidence of psychological disturbances like depression, anxiety, and stress. Researchers are unsure of the causes and mechanisms behind this occurrence, but it is possible that the reality of weight gain could have shocked and upset patients who weren’t mentally recovered and prepared for the changes in physical appearance that weight gain brings (Stroe-Kunold, 2016, p. 10).

Current research surrounding hormone restoration, especially that for leptin levels, rests on the side of the more overweight and obese who likely suffer from leptin resistance, rather than deficiency – explaining how to regulate leptin in speeding up metabolism and increasing the body’s rate of burning fat as a source of energy and decreasing appetite. This is not the desired mechanism in restoring hormone levels for those with AN, as a fat-burning metabolism and decreased appetite will likely worsen the existing weight issue.

It is clear that leptin levels are low in those with anorexia nervosa. Low leptin levels should display an increased appetite and amount of food consumed, but the opposite is seen in those with AN, probably due to a preoccupation with the nutrition facts of foods, body weight and appearance, and overall fear and anxiety surrounding food (“Warning Signs and Symptoms”). During the weight restoration and treatment phase, leptin levels have been seen to increase in patients with AN in a linear fashion with weight and BMI – a good sign. However, to maintain this weight, reshaping the mindset of one with AN is just as important, if not more so. Without a positive relationship with food and an understanding of its essential role in everyday life, a patient with AN who gains weight and restores leptin could lose the weight after a period of time due to leptin’s function in decreasing appetite. 

Cortisol

A steroid hormone that helps regulate metabolism, prevent inflammation, enhance memory, and control electrolyte balance and blood pressure, cortisol is the body’s main hormone when it comes to handling to stress. When the body experiences stressful situations, cortisol secretion increases to respond to the stress-inducing situation (Cortisol, 2017). Stress arises not only when the body is under harmful physical attack, but also when it is unable to mentally and/or emotionally cope with certain situations, and this is usually when disorders like depression and anxiety develop.

AN induces stress on the body not only by forcing the individual into a nutrient-deficit, but also by altering the neurological systems within the brain, specifically those that regulate enjoyment of food and emotional sensitivity. Psychologically, the brains of patients with AN show enhanced feelings of pleasure and reward when starvation is chosen over eating, which helps explain the difficulty these patients find in gaining weight. “Disturbed interoceptive awareness of satiety and hunger” play a significant role in preventing patients with AN from recognizing bodily cues to eat. Additionally, these patients tend to feel high levels of anxiety in situations involving food, and therefore turn to starvation as a coping mechanism to decrease the anxiety (Kaye, 2014, p. 1-2).

Patients with AN show abnormalities in CT scans similar to patients with Cushing’s syndrome – ventricular enlargement in the brain and cerebral atrophy (Kellner, 1983, p. 191). This particular study found that the degree of cortisol secretion and ventricular size shared a strong linear relationship. A significant increase in cortisol can increase brain ventricular size, eventually leading to a condition called “normal pressure hydrocephalus”, in which the cerebrospinal fluid does not drain, but rather builds up and causes further expansion of the ventricles. The resulting pressure on the brain from the ventricles typically results in symptoms like compromised memory and cognition, also known as dementia (Lava, 2016). Methods to prevent NPH, specifically that caused by AN, includes reaching and maintaining a healthy weight and exercise routine (Lava, 2016).

Of the several harmful consequences an eating disorder can cause, the hormonal disruptions – specifically leptin and cortisol – can be the most physically detrimental. In the recovery phase, survivors can find the weight-gain process challenging because leptin levels tend to increase at a faster rate than actual weight gain. Increasing cortisol levels during AN, if not treated in time, can cause brain alterations similar to that which occurs during Cushing’s syndrome. Though these changes are often difficult to deal with, they can be prevented and treated by increasing awareness of the damaging effects of AN, and decreasing negative stigmas surrounding AN. As society becomes more aware of eating disorders and proper prevention and treatment methods, these hormonal disturbances can become less and less prevalent.

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