**Major Depressive Disorder**
Depression is a mental state of low mood. There are several subtypes of depression, but major depressive disorder is the one that's usually intended. It is expected to be the number one cause of disease burden worldwide by 2030.
**DSM 5 Criteria - Major Depressive Disorder**
The term major depressive disorder was first used in the 1970s, and the disorder was added to the Diagnostic and Statistical Manual of Mental Disorders, known as the DSM, in the 1980s. Today we have the DSM-5, which lays out 9 criteria on which the diagnosis is based. They include a low mood most of the day on most days and anhedonia, which means a loss of pleasure or interest in previously enjoyable activities. These two are considered core symptoms, and one of them must be present for a diagnosis of major depressive disorder.
The other criteria include significant weight loss or weight gain, insomnia or hypersomnia (meaning not sleeping enough or sleeping too much), fatigue or a loss of energy nearly every day, psychomotor retardation (which means a slowing down of thoughts and physical movements that is noticed by others), inappropriate guilt or feeling worthless, a reduction in the ability to concentrate, and recurrent thoughts of death. A total of five or more over a period of at least two weeks leading to significant clinical distress or impaired functioning need to be present for the diagnosis, and the symptoms cannot be the result of substance abuse or another condition.
**Depression Causes & Risk Factors**
Major depressive disorder is thought to be caused by multiple factors, including genetic and environmental factors. Some studies have suggested that 40% of the difference in risk between individuals can be accounted for by genetics. There is a high concordance rate of depression in monozygotic twins, and overall, this means a family history is considered a risk factor.
Environmental factors can include stressful life events and childhood abuse, which also correlates with the severity of the depression, as well as a diagnosis of another medical condition or substance abuse. However, as we mentioned, they cannot be the direct cause. Based on these factors, there's the diathesis-stress model represented by these two cups. It states that the stressful event on a pre-existing vulnerability means an increased likelihood of developing depression. So, from two people experiencing the same stress, one may develop depression while the other may not, visualized as the contents of the cup spilling over.
**Depression Pathophysiology**
Taking this a step further, the exact mechanisms underlying major depressive disorder are not entirely known, but theories include the monoamine theory, which suggests that a lack of monoamine neurotransmitters like serotonin, dopamine, and norepinephrine is the cause. There is evidence to support this; however, lower serotonin levels in healthy individuals do not cause depression, and antidepressants instantly replenish neurotransmitter levels, but the effects are not felt for several weeks.
Other theories include abnormalities in the hypothalamic-pituitary axis, as people with depression have demonstrated elevated cortisol levels and less dexamethasone suppression. There is also thought to be a link between thyroid hormone and growth hormone levels with depression. Immune system abnormalities may also be involved, including excessive cytokine release. This is suggested by the improvement of symptoms on non-steroidal anti-inflammatory drugs and normalization of cytokine levels after treatment. This may also explain closer links with immune-related diseases like asthma.
**Depression Epidemiology**
The lifetime risk of developing major depressive disorder is around 12 percent, or approximately one in eight. It is nearly twice as common in females as it is in males, which may be explained by different psychosocial stressors and hormonal differences, but the exact cause is not clear. The mean age of onset is 40; however, depression is becoming increasingly prevalent in younger people.
We have already mentioned the clinical depression diagnosis criteria for the diagnosis via the DSM-5, and there is also a set of criteria known as the ICD-11, primarily used in Europe. The severity of depression can be gauged using scoring systems like the Patient Health Questionnaire-9. It's also important to note that the presence of other disorders is more likely in patients with depression. This includes anxiety and substance misuse, especially alcohol. Others can include an association with ADHD, PTSD, and the presence of chronic pain.
**Depression Treatment**
The treatment for major depressive disorder can vary, with combinations being thought to be the most effective. This usually involves lifestyle modification, including exercise, healthier diets, limiting alcohol use and smoking, stopping drug use, and developing a regular schedule.
Then there is psychotherapy, also called talking therapy, examples of which include cognitive behavioural therapy or interpersonal therapy. They are often the first line and have been shown to be effective. It is the treatment of choice for patients under the age of 18, according to the NICE guidelines. Pharmacological therapy is used in patients with moderate or severe depression or in patients who have mild depression that is not responding to other interventions.
The medications include selective serotonin reuptake inhibitors like sertraline, citalopram, or fluoxetine, which are usually first line. Serotonin norepinephrine reuptake inhibitors like duloxetine and venlafaxine can also be used, especially in patients with associated pain disorders. Atypical antidepressants, with metazepine in particular, aid in increasing appetite and regulating sleep.
Then we have tricyclic antidepressants like amitriptyline and monoamine oxidase inhibitors like phenelzine; these are used less commonly due to the high incidence of side effects. There's also some evidence to suggest that vitamin D supplementation can help depressive symptoms in those who are vitamin D deficient, and COX-2 inhibitors like celecoxib have also been found to be effective, according to some studies.
Electroconvulsive therapy is the most effective therapy for major depressive disorder. It involves electrically inducing seizures to relieve the disorder. It's been estimated to be effective in around 50 percent of patients with treatment-resistant major depressive disorder and is normally administered with a muscle relaxant under general anaesthesia. However, around 50 percent of patients who do respond will relapse within 12 months.