Connection between Depression and Diabetes

Depression- Diagnosis, Etiology, and Epidemiology

Depression is a commonly occurring, recurring disorder which can directly affect the quality of life, medical morbidity, and mortality. Major depression is ranked as the fourth leading cause of disability. Depression is a chronic mental disorder that can negatively impact the quality of life of the affected individual, taking away the ability to live a fulfilling life and decreasing the capacity to complete basic tasks (Fekadu et al., 2017). As a disease, it is growing worldwide and is projected to be the leading disease burden by 2030.

The causes of depression are many-fold. Gender is a significant factor, with women twice as affected as men suggesting that biological differences may be an important precedent for incidence (Albert, 2015). Stress is another factor that is becoming more prominent. Anxiety and depression are interconnected by two mechanisms - hypothalamic-pituitary-adrenocortical (HPA) axis and sympathetic adrenomedullary (SAM) system (Khan and Khan, 2017). Genetics and hereditary account for some of the reported cases. Research shows that the risk of genetic inheritance is 40% if the parent suffers from depression. Physical illness is an understated reason for the development of mental diseases notably for chronic, long-standing diseases like diabetes.

Prevalence

Depression is a global phenomenon, and according to a 2012 World Health Organization (WHO) survey, affects 350 million people worldwide. Of these, nearly half live in the South-East Asia region and Western Pacific region, reflecting the higher population density in those areas.  A 2015 survey has shown that 4.4% of the global population suffers from varying levels of depression. Recent figures suggest that women are consistently more affected than men, accounting for 9.5% of all reported cases against men, who account for 5.8% cases. Prevalence rates also vary according to the age of the patient. The age group of 55-74 years is most affected. Although adolescents below the age of 15 years are also affected, the prevalence is much lower ("Depression and other," 2017). Between 2005 and 2015, people suffering from depression rose by 18.4%, this reflects the worryingly increasing trend of increased depression. An outpatient meta-analysis survey examined 83 cross-sectional studies that involved a total of 41, 344 individuals. The average showed that around 27% of all individuals suffered from depression. The study also showed that distress associated with outpatients in developing countries was more significant than outpatients in developed countries (Wang et al., 2017).

Assessment

The DSM-5 diagnostic criteria are essential markers to recognize depressive symptoms (Sadock et al., 2015). Out of the given symptoms, the individuals must be experiencing five or more of the symptoms during the two-week assessment period, and at least one of the signs should be a loss of interest or depressed mood ("American Psychiatric Association," 2013). The criteria cover a large swathe of symptoms like a depressed mood for most of the day, a markedly diminished interest in daily activities, significant weight loss when not undergoing any therapy for the same, slowing down of thought and reduced physical action, fatigue or loss of energy, a feeling of worthlessness often accompanying recurrent thoughts about death, and in extreme cases, thoughts of suicide or attempts at suicide (APA, 2013). The 2017 iteration of DSM-5 also specifies two new criteria. These are 'with mixed features' which allows for the presence of manic symptoms that do not yet fulfill the criteria for manic episodes and 'with anxious distress' which refers to patients with anxiety that the current therapy will not help them. This may affect the prognosis (Shelton, 2018).

Like DSM-5 criteria, ICD-10 is another set of standards that can help diagnose depression. ICD-10 uses ten rules that divide depression into mild, moderate or severe. To be considered as depression, at least 2 of the three symptoms should be present  loss of interest and ability to enjoy, depressive mood or increase in fatigability. Like DSM-5, the signs should be present for two weeks or more.

 Screening

Screening is another method to detect depressive symptoms on a large scale. Testing is generally recommended in scenarios where many individuals need to be identified for depression. Examples of the most reliable and utilized screening methods used in practice for the evaluation or detection depression include tools such as the Hamilton Rating Scale for Depression (HAM-D), The Beck Depression Inventory (BDI) or the Patient Health Questionaries' (PHQ)-2 or PHQ-9. The HAM-D is often used to monitor and evaluate a change in response to pharmacological and other interventions with a focus on somatic symptomology (Sadock et al., 2015). The BDI notably the BDI-II focuses on the cognitive, behavioral and somatic symptom dimensions of depression with coverage for the most recent two weeks. The PHQ-9 and PHQ-2, offer psychologists concise, self-administered tools for assessing depression. The PHQ-9 and PHQ-2 incorporate DSM-5 depression criteria with other leading major depressive symptoms into a brief self-report instruments that are commonly used for screening and diagnosis, as well as selecting and monitoring treatment (American Psychological Association, 2018). Screening can also be conducted for specific target groups, where depression onset can be anticipated. These include patients with chronic diseases. Life-event stressors can also serve as precursors to depression. Examples include loss of a loved one, humiliation, physical or emotional abuse.

Novel approaches have also been used to diagnose depression. Transcriptomics determines the change in gene expression based on different factors like drugs, disease or hormones (Bilello, 2016). Metabolic phenotyping analyses different metabolites and detects a difference in their appearance under disease conditions. The metabolic phenotyping method can help identify the pathophysiologic processes underlying a psychiatric condition. Neurotransmitters like dopamine and norepinephrine are specifically targeted. Proteomics analyses the entire protein complement expressed by a cell, tissue or an organ and identifies the protein signatures associated with an evolving situation (Bilello, 2016). The proteomics process is still in its infancy, however. Although new biomarkers can potentially be discovered using this method, there is a lack of empirical biomarkers for neuropsychiatric diseases.

Case Scenario

Depression and diabetes form a nexus that is being studied intensely in recent times. The rate of depression is 2-3 times higher among people with diabetes compared to non-diabetic individuals. The current paper constructs a complexly integrated case study including major depressive disorder and diabetes.

Presenting problem:  The current case is that of Ms. A, a 33-year-old single, white, female patient who was seen regularly by her primary physician for her Type 2 Diabetes Mellitus (T2DM) for the past two years. The patient was referred to a mental health provider by her physician as she complained of being in a "sad mood" in general with a reduced interest in daily activities for the past 3-4 months. Ms. A, reports that approximately four months ago, the patient started developing a feeling of laziness which used to last almost an entire day. The patient recently began to feel less active, gradually stopped exercising and gained more weight. The patient also stopped socializing and felt a general feeling of sadness during the same period and reported that she kept forgetting things, becoming irritable and frustrated. She also stated that her daily activities and work-related activities suffered the most as she could not concentrate on anything to get the work done. Ms. A reports no anxiousness or restlessness associated with her general tired or sad mood but does confess that she is a little worried about her health, finances and personal life and wants to "get it together" for the sake of it. She states "I feel like I'm stuck and going nowhere in life. I'm not getting any younger.  There are so many things in life I want to do." She reports her friends tend to complain that she does not participate in fun or group activities like before. She also reported her family has noticed she does not come around as much recently and has not been tending to her garden or attending church as often. Patient confirms that she has difficulty in falling asleep and wakes up with a feeling of tiredness.

Past Medical History:  Ms. A denies any surgical or psychiatric problems. Ms. A was first diagnosed with T2DM about two years ago when she visited her physician with complaints of frequent micturition and increased hunger and thirst. Fasting and postprandial glucose levels were evaluated and compared to glycated hemoglobin levels which revealed poorly controlled T2DM. Following this diagnosis, she has prescribed an oral hypoglycemic agent and was educated regarding the methods of routine self-monitoring of blood glucose levels. She reported that she was advised on certain lifestyle modifications which she has been unable to adhere to for the past several months, of which has also contributed to her increased weight. The patient is mildly obese with a Body Mass Index (BMI) of 30.2 kg/m2 which she reports has increased from a BMI of 24 over last six months. Currently, her most recent self-reported fasting and post-prandial blood sugar levels were measured to be 140 mg/dl and 200 mg/dl respectively which these levels reveal that she has insufficient control over her diabetic levels.

Additionally, her most recent glycated hemoglobin levels (HbA1C) measured at 7%, which revealed that the patient had poor control over her blood sugar levels. The patient is currently taking an oral hypoglycemic agent but does not monitor her glucose levels regularly. She reports she takes her medication "most" of the time.

Drug/Alcohol History:          Ms. A reports she has been a lifelong non-smoker. Denies use of illegal drugs and reports drinking 3-4 beers a month on weekends with friends for most of her adult life.

Suicidal/Homicidal Ideation:  She denies any suicidal or homicidal ideation. She denies any history of abuse.

Family and Social History:  Ms. A has never been married and denies any current relationships. She currently lives alone in her home which she rents. She reports having a few close friends. Denies having children or ever being pregnant. Patient revealed that her father suffers from T2DM and hypertension and is presently on medication for each of these medical conditions. Her mother suffers from T2DM which is well-controlled with the help of oral hypoglycemic agents along with dietary and lifestyle changes. The patient reported no history of mental health problems in the family.

Employment History:  She reports she that she has worked at the same supermarket as a cashier in her hometown since she graduated high school.

Education:  Ms. A reports graduating from high school and being an average student. Denies attending college but she would like to start classes to become a medical assistant

Criminal/Legal Trouble:  Denies any criminal or legal trouble.

Developmental History:  No significant abnormalities noted.

Spiritual Assessment:  Ms. A has been a practicing Catholic her entire life and was attending mass weekly up until the past few months.

Cultural Assessment:  Ms. A considers herself American.

Financial Assessment:  Patient reports having grown up in a low socioeconomic household and states that she "still lives paycheck-to-paycheck" and struggles to make more money to aid her financial stability.

Coping Skills:  She reports a moderate amount of stress in her life over the past year due to finances, her uncontrolled diabetes and lack of having a meaningful romantic personal relationship and states she worries she will never find someone to spend her life with,

Interests and Abilities:  Ms. A reports she likes to garden and has a huge flower and vegetable garden. Reports she enjoys spending time with her family and friend until recently. Reports she would like to travel more if she had the finances to do so.

Mental Status Exam (MSE)

Ms. A is a 33-year-old calm appearing white female who appears to be her stated age. She was polite and cooperative during the interview process. Her eye contact was poor at times with the interviewer, and she looks down at the ground for most of the interview. Her appearance is somewhat unkempt; she is dressed in baggy sweatpants and a sweatshirt that appear to have stains and holes in them, she does not appear to be wearing any makeup, and her hair is pulled up and appears to be unbrushed. Her mood is sad, and her affect is flattened. Her speech is slow, monotonous in rhythm and she answers questions providing very little information and often her responses are very brief in context.  Her thought processes were negative. She did not show any loose associations or problems with abstract thinking. Her thought content was normal and did not demonstrate any paranoia, aggressiveness, or obsessive thinking. No psychotic thinking was demonstrated. She has full insight regarding her depressive symptoms and how they are affecting her life as well of potential causes such as her current poor health status, financial instability, desire to improve her life with a better career and longing for meaningful romantic relationship. She is oriented to person and place and time. She had normal impulse control and demonstrated normal judgment during the exam.

Summary and Synthesis

In summary, Ms. A is a middle-aged female, suffering from Type 2 Diabetes Mellitus and depressive symptoms. Current laboratory results show that the fasting and post-prandial blood levels are both above average, indicating that her diabetes not well controlled at this time. Furthermore, the patient's weight has gradually increased over the last few months, suggesting she has not been adhering to the recommended dietary modifications. Ms. A's depressive symptoms are currently impairing her social and occupational functioning within her daily life.

Various methods and screening tests may be used for diagnosing the state and levels of depression that Ms. A suffers. DSM-5 is an all-encompassing criterion that can diagnose a wide variety of depressive symptoms. According to the requirements, MS. A suffers from a lack of enjoyment, loss of interest and inability to mix socially. These symptoms validate depressive symptoms according to DSM-5 diagnostic criteria.

Further validation of symptoms of depression, in this case, was performed with the help of Beck's Depression Inventory II and the Patient Health Questionnaire (PHQ)-9. While Beck's scale is a 21-question containing self-reporting inventory, the latter includes nine questions. Beck's Scale considers not only mental symptoms such as tiredness, irritability, and other feelings such as guilt but also includes physical symptoms such as fatigue, weight loss, and reduced sexual activity. Ms. A scored a total of 21 on the Beck's Depression Inventory II, indicative of depression of moderate severity. The PHQ-9 score of 10 in Ms. A's test also corroborates the results of Beck's Depression Inventory II, indicative of depression of moderate severity.

Research

Through research of available literature, it is evident that depression is deeply related to pre-existing diabetes. One explanation is that poor self-care behaviors can predispose to both diabetes and depression, as is seen in this scenario. Another reason is that depression can be seen coincident with diabetes as both share a similar lifestyle and environmental factors. These include reduced physical activity, economic and social deprivation. The stress in the patient's life that revolves around her poorly controlled diabetes, personal life, or other reasons such as her socioeconomic condition can be the stressors that activate the HPA axis in the patient, thereby affecting the glucocorticoid production (Moulton et al., 2015).

A recent study conducted by Budescu et al., (2016), showed that there are not any common genetic factors to account for the positive association between depression and type 1 or 2 diabetes. However, different environmental factors (epigenetic factors) may activate common pathways that promote T2DM and depression in the end. One crucial factor is a low socioeconomic status that increases the odds for T2DM but also appears to be a cause for depression. The other common causes of T2DM and depression are poor sleep, lack of physical exercises and diet. Taking into consideration these factors, a key candidate for a common pathway could be the activation and disturbance of the stress system. Chronic stress activates the hypothalamus  pituitary  adrenal axis (HPA-axis) and the sympathetic nervous system (SNS), increasing the production of cortisol in the adrenal cortex and the production of adrenaline and noradrenaline in the adrenal medulla. Chronic hypercortisolemia and prolonged SNS activation promote insulin resistance, visceral obesity and lead to metabolic syndrome and T2DM .

On the other hand, chronic stress has behavioral consequences: noradrenaline, cortisol, and other hormones activate the fear system determining anxiety, anorexia or hyperphagia; the same mediators cause tachyphylaxis of the reward system, which produces depression and cravings for food, other substances or stress. Excess cortisol disturbs neurogenesis in the hippocampus, a region involved in depression as well as in T2DM .  Moreover, chronic stress induces immune dysfunction directly or through the HPA axis or SNS, increasing the production of inflammatory cytokines. High amounts of inflammatory cytokines interact with the normal functioning of the pancreatic ??-cells, induce insulin resistance, and thus, promote the appearance of T2DM (B??descu et al., 2016).

Many new studies suggest that inflammatory responses are also involved in the pathophysiology of depression. Proinflammatory cytokines have been found to interact with many of the pathophysiological domains that characterize depression, including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, and behavior (B??descu et al., 2016).  Fifty percent of the patients treated with interferon Alfa develop depression and patients with depression had statistically higher blood levels of cytokines like tumor necrosis factor and interleukin 6 than those without depression. These correlations suggested that stress (through the chronic impairment of HPA axis and SNS) and inflammation both promote depression and T2DM, giving a feasible common link between them (B??descu et al., 2016).

In conclusion, the patient presented in this case scenario would greatly benefit from a combined treatment modality that includes pharmacological management with an anti-depressant medication(s) and psychotherapy. The patient will also need to value the importance of adhering to recommendations from her primary care physician such as lifestyle modifications, daily blood glucose monitoring and medication compliance thus serving to achieve optimal control of her T2DM as well as her depression.  The diabetes-depression nexus is still obscure and requires to be understood by studying various biomarkers to identify ideal treatment protocols. The inflammatory pathways influence both insulin resistance and the development of depression. Therefore, by gaining control over the blood sugar levels, it can be deduced that the symptoms of depression also can be controlled.

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