Relationship between Depressive Disorder and Eating Disorder

Abstract

Major depressive disorder (MDD) is a mood disorder characterized by intense and persistent feelings of melancholy and disinterest in regular activities for an extended period of time. Anorexia nervosa (AN) is a type of eating disorder categorized by significant weight loss, an intense fear of gaining weight, and a distorted perception of how one views their body shape or weight.

These disorders frequently co occur with one another, in fact, according to a study posted on the National Eating Disorder Association’s website, out of 2400 individuals hospitalized for an eating disorder, 94% had comorbid mood disorders, mostly major depression.

As a result of the inherent comorbidity of these disorders, there is extensive research on the connections between the two. One such connection, is that individuals diagnosed with both MDD and AN have elevated levels of arginine vasopressin (ADH), a hormone (and neuropeptide) responsible for properly conserving water in the kidneys. Research has also proven however, that ADH has anxiogenic effects in the brain, which contrast directly the anxiolytic effects of oxytocin (OXT), a hormone (and neuropeptide) responsible for social bonding and reproduction, that works in tandem with ADH to regulate neurological processes (Inga D. Neumann, Rainer Landgraf, 2012). Due to the close relationship between these two neuropeptides, imbalances of one or the other can occur but can also be balanced out by the other, as is exemplified by the elevated levels of ADH in individuals diagnosed with MDD and the positive effect of oxytocin treatment.

Therefore it can be hypothesized that balancing the elevated levels of ADH by implementing intranasal oxytocin could decrease the negative anxiogenic effects of the ADH in individuals diagnosed with AN, and simultaneously reduce symptoms as well. In order to test this hypothesis, it would be necessary to recruit a sample size of 300 unmedicated females previously diagnosed with AN. 150 participants would be given a dosage of intranasal oxytocin, while the other 150 would be given a placebo. Following this procedure, each participant would be monitored for reactions and/or changes in behavior, and those responses would be recorded and analyzed.

Introduction

Major depressive disorder is classified as a mood disorder while Anorexia nervosa technically falls underneath the umbrella of internalizing disorders. As a result, the brain processes the anxiogenic effects of elevated ADH levels differently. However, since ADH increases anxiety and aggression, the anxiolytic effects of oxytocin can counter these effects, therefore reducing the severity of symptoms. There has already been literature published involving the use of oxytocin to cure MDD, but not as much surrounding AN, despite the two disorders’ inherent comorbidity and the fact that individuals experiencing both disorders reflect a common connection: higher levels of ADH. Therefore one can hypothesize that implementing the same technique with AN patients could positively affect their symptoms.

Major depressive disorder has a complex etiology potentially involving hereditary, familial, cultural, and biological factors. It is characterised by a distinct shift in mood, and deep feelings of sadness or disinterest that don’t go away even when short term stressors or negative occurrences are resolved. Several other factors are also involved in the manifestation of this disorder such as difficulty sleeping, loss of appetite, irritability, exhaustion, and severe MDD could eventually lead to suicidality. In order to be officially diagnosed with MDD, one must experience these symptoms for at least two weeks for a majority of each day. MDD is traditionally treated through medications such as antidepressants or Selective Serotonin Reuptake Inhibitors(SSRIs) and often cognitive behavioral therapy (CBT) as well. (Belmaker, R. H., & Agam, G, 2008). Though proposed but not officially recognized as DSM5 criteria, anxiety symptoms such as unpleasant or irrational worrying, difficulty relaxing, tension, and fear of the future can also be indications of depression (DSM5).

Anorexia nervosa is also very complex and can develop as a result of many different factors including sociocultural influences, parenting style, and genetic predisposition. Apart from significant weight loss, AN symptoms include unhealthy undereating and over exercising, fatigue, irritability, and body dysmorphia. Though more subtle than substance abuse, AN can also be regarded as an addiction. When eating disorder patients lose weight, their brain reward response goes up. For a person without an eating disorder, eating increases the brain reward response but as patients with anorexia have an intense fear of eating and weight gain, eating actually elevates their anxiety, which makes them want to restrict more, and it becomes a vicious cycle. An enhanced dopamine reward system response is an adaptation to starvation, essentially they become addicted to not eating. AN patients also tend to be more angry and irritable as compared to patients with other eating disorders. They also generally deny that they have a problem even after professional diagnosis. AN is mainly treated through cognitive behavioral therapy, although CBT can include a wide array of activities ranging from yoga, to discussion, to art therapy (Guarda, A. S. et al., 2015).

My hypothesis aims to approach AN from a different point of view. Rather than solely focusing on the psychological etiology (ex. disrupted reward system), I want to focus on the combination of psychological and biological factors on order to discover new, more effective treatment options for AN patients. For example, as a result of malnourishment, ADH levels increase and as mentioned earlier, elevated ADH levels contribute to increased anxiety. Since the majority of AN symptoms revolve around anxiety, could this biological reaction to malnourishment also be adding to the severity of AN symptoms? My study is designed to target ADH and balance it with oxytocin treatment which, if effective, could open up a world of AN pharmaceutical treatment that didn’t exist before as any medication taken by individuals with AN before was to treat comorbid disorders, not the AN itself.

Literature Review

ADH and OTX are complex as they function as hormones and neuropeptides in the brain. AVP is important in regulating urine concentration and water content in the kidneys, while oxytocin is often noted for its important role in initiating uterine contractions and milk let down after birth. In the brain, both of these neuropeptides play integral rolls in the regulation of stress and sociability (Baribeau, D. A., & Anagnostou, E, 2015). Homeostasis in the body relies on the balance of OXT and ADH, and there have been some indications that the elevation of ADH specifically can have some negative effects on the body, especially in individuals struggling with MDD or AN.

A study focusing on the levels of ADH in patients with MDD tested the levels of ADH in individuals being treated for depression in inpatient and outpatient facilities. It also tested the ADH levels in melancholic and non-melancholic patients. The study concluded that the levels of ADH were higher in inpatient than outpatient participants, and also higher in melancholic than non-melancholic participants, thus indicating that the levels of ADH are elevated in individuals struggling with MDD. As previously mentioned, ADH has anxiogenic effects, which in turn add to the negative symptoms of MDD (Liesbeth van Londen MD et al., 1997).

Similar findings have also been found in anorexia nervosa patients. For example, one study tested the levels of ADH in the cerebrospinal fluid of women one year after complete AN recovery as compared to a control of healthy women. The results showed a distinct elevation in the ADH levels of AN patients, which indicates that ADH could be related to the pathophysiology of AN. The elevation of ADH in AN patients also occurs as a result of malnutrition, as AN significantly affects the function of all body systems, especially the endocrine system. (Guido K. Frank et al., 2000). It is unclear whether alterations of ADH are a consequence of pathologic eating or malnutrition, however studying the pathology of ADH in AN could introduce new information and treatment ideas for AN.

ADH and OXT are commonly studied in tandem with each other, as they originally evolved from a single genetic source, and are now interactive components of an evolved and integrated system (Carter C. S., 2017). Research also shows that they generally have a reciprocal relationship. For example, in several rodent studies, OXT administered to rats has proven to have an anxiolytic effect while ADH has proven to have an inverse anxiogenic effect (Guido K. Frank et al., 2000). In several other rodent studies, the administration of OXT in rats was shown to facilitate more active stress coping, indicating antidepressive-like effects. Furthermore, there is preclinical and clinical evidence suggesting that OXT is also a contributing factor in the improvement of other depression-related symptoms, such as including sexual dysfunctions, sleep disturbances, and anhedonia (Inga D. Neumann, Rainer Landgraf, 2012).

Studies have also been done in order to test the effect OXT has on individuals with AN. In one Psychoneuroendocrinology study, anorexia nervosa patients and control patients were given intranasal oxytocin and were asked to look at images of different high- and low-caloric foods, weight scales, and thin and overweight people. A visual probe was used to record how quickly the patients identified and processed the images. The group with anorexia nervosa showed significant reductions in the attention they gave toward eating-related stimuli and toward negative body shape stimuli after they were administered intranasal oxytocin (Youl-Ri Kim et al., 2014)

The PLOS study administered oxytocin to the same patients and recorded their reactions to images of negative facial expressions, such as anger and disgust. After taking a dose of oxytocin, patients with anorexia nervosa were less likely to focus on the disgusted and angry faces. They were also less likely to avoid looking at angry faces and simply became vigilant toward them.

Method

Participants

A sample of 300 individuals diagnosed with anorexia nervosa will be recruited for this study. In keeping concordance with the DSM5 criteria, participants will be selected based on official diagnosis of anorexia nervosa. Understanding that other disorders such as depression and anxiety sometimes develop as a result of AN, individuals will not be permitted to partake in this study if they were diagnosed with another disorder before the development of their AN. All subjects will be females between the ages of 17 and 25, in order to eliminate the chance of gender or age biases affecting the data. Additionally, no participant will be accepted if they are taking medication for comorbid disorders as to ensure the independent variable (the oxytocin treatment) remains isolated. The dependent variable will be the shifts in behavior and reactions of participants as a result of receiving intranasal oxytocin or a placebo.

Procedure

The symptoms of all 300 participants will be coded by several researchers and compared to the DSM 5 criteria for AN. The severity, similarities, and differences of the symptoms compared to the criterion for AN will be recorded, in order to have a good understanding of how the disorder presents in each individual. This way, changes in behavior and reactions will be easily trackable later on. Participants will also be asked to fill out an evaluation which asks which symptoms of AN they experience, and how intensely they experience them on a scale of one to five. The purpose of this is to see how severe each participants symptoms are before the administration of the oxytocin, in order to see if the OXT has an effect on the anxiogenic symptoms of AN. All 300 patients will be given the same moderate dose of intranasal oxytocin, and they will be given instructions to take the same dosage once a day, every day. The participants will be asked to return after two weeks, and will be observed and asked to fill out the evaluation once more.

Interpretation of Results/Discussion

Describe the pattern of findings that would support your hypothesis(es), linking those potential outcomes to the original hypotheses, the potential for improving our understanding of the specific disorder(s), and the challenge of understanding comorbidity in general. You do NOT need to get into the specific statistical procedures you would employ to analyze your data.

References

1. Baribeau, D. A., & Anagnostou, E. (2015). Oxytocin and vasopressin: linking pituitary neuropeptides and their receptors to social neurocircuits. Frontiers in neuroscience, 9, 335. doi:10.3389/fnins.2015.00335
2. Belmaker, R. H., & Agam, G. (2008). Major depressive disorder. New England Journal of Medicine, 358(1), 55-68. doi: 10.1056/NEJMra073096
3. Carter C. S. (2017). The Oxytocin-Vasopressin Pathway in the Context of Love and Fear. Frontiers in endocrinology, 8, 356. doi:10.3389/fendo.2017.00356
4. Diagnostic Criteria for Major Depressive Disorder and Depressive Episodes , www.psnpaloalto.com/wp/wp-content/uploads/2010/12/Depression-Diagnostic-Criteria-and-Severity-Rating.pdf.
5. Guarda, A. S., Schreyer, C. C., Boersma, G. J., Tamashiro, K. L., & Moran, T. H. (2015). Anorexia nervosa as a motivated behavior: Relevance of anxiety, stress, fear and learning. Physiology & behavior, 152, 466-472. https://doi.org/10.1016/j.physbeh.2015.04.007
6. Guido K. Frank. Walter H Kaye, Margaret Altemus Catherine G Greeno. (2000). CSF oxytocin and vasopressin levels after recovery from bulimia nervosa and anorexia nervosa, bulimic subtype. Biological Psychiatry. Volume 48, Issue 4, Pages 315-318. https://doi.org/10.1016/S0006-3223(00)00243-2
7. Inga D. Neumann, Rainer Landgraf. (2012). Balance of brain oxytocin and vasopressin: implications for anxiety, depression, and social behaviors. Trends in Neurosciences, Volume 35, Issue 11, , Pages 649-659, ISSN 0166-2236, https://doi.org/10.1016/j.tins.2012.08.004.
8. Kim Y-R, Kim C-H, Park JH, Pyo J, Treasure J (2014) The Impact of Intranasal Oxytocin on Attention to Social Emotional Stimuli in Patients with Anorexia Nervosa: A Double Blind within-Subject Cross-over Experiment. PLoS ONE 9(3): e90721. https://doi.org/10.1371/journal.pone.0090721
9. Liesbeth van Londen MD, Jaap G Goekoop MD, Ph.D, Godfried MJ van Kempen Ph.D, Ank C Frankhuijzen-Sierevogel, Victor M Wiegant Ph.D, Edo A van der Velde & David De Wied MD, Ph.D (1997). Plasma Levels of Arginine Vasopressin Elevated in Patients with Major Depression. Neuropsychopharmacology volume17, pages284–292. doi:10.1016/S0893-133X(97)00054-7
10. Youl-Ri Kim, Chan-Hyung Kim, Valentina Cardi, Jin-Sup Eom, Yoori Seong, Janet Treasure (2014) Intranasal oxytocin attenuates attentional bias for eating and fat shape stimuli in patients with anorexia nervosa. Psychoneuroendocrinology , Volume 44 , 133 - 142 https://doi.org/10.1016/j.psyneuen.2014.02.019 

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