Major depressive disorder

Major depressive disorder, also known as endogenous depression or unipolar depression, is a mood disorder characterized by symptoms such as: profound sadness, decreased vital drive, loss of interest in normal activities, negative and pessimistic thoughts, disturbances in cognitive function, and vegetative symptoms such as altered sleep and appetite (Otte et al., 2016). It is a very common disorder, with twice the incidence in women, and is particularly prevalent. The World Health Organization (WHO) ranks major depression as one of the most disabling disorders in the world, with a very high social cost. In fact, in addition to psychiatric problems, major depressive disorder is associated with an increased risk of developing diabetes, heart disease, and stroke (Whooley et al., 2013). Major depressive disorder was added in 1980 to the DSM-III, the Statistical and Diagnostic Manual of Mental Disorders, which is now in its fifth edition (DSM-5).

Major depressive disorder is a debilitating psychiatric disorder characterized by the presence of at least one depressive episode lasting at least two weeks.

Major depressive disorder is characterized by a severe decline in mood, a reduction in interests and pleasurable activities, changes in thought content and cognition, and vegetative problems such as changes in sleep and appetite.

In fact, patients remain in a state of deep sadness, hopelessness, and apathy throughout the day, with continuous brooding, decreased attention, and negative thoughts about themselves, their future, and the social context around them (Otte et al., 2016).


Major depressive disorder occurs predominantly in women, with a ratio of approximately 2:1 to men (Seedat et al., 2009), and affects approximately 6% of the world’s population (Bromet et al., 2011). It is also estimated that one in six people will experience at least one episode of major depression in their lifetime (ibidem).

The average age of onset is 25 years, and the peak incidence is between late adolescence and the age of 40. In Western countries, there is also a modest decrease in the intensity and symptoms of depression with increasing age. The incidence then increases with age (Kessler et al., 2013).

Course of the disorder

The course of major depression varies considerably from case to case. In some cases there is a complete remission, in others the disorder tends to become chronic. In general, greater symptom severity, other psychiatric comorbidities, and the presence of childhood trauma make the course of recovery more complex (Phenninx et al., 2010). On average, a depressive episode lasts between 13 and 30 weeks, and approximately 70-90% of patients outgrow the episode within the first year after onset (Spijker et al., 2002).

After remission of a depressive disorder, it is possible for some symptoms and difficulties in daily life to remain (Ormel et al., 2010), thus reducing patients’ quality of life (Ormel, J. et al., 2004). In addition, the likelihood of relapse is high. It is estimated that 80% of patients with a history of major depressive disorder will develop at least one second depressive episode in their lifetime (Vos et al., 2004).


Major depressive disorder is a serious illness that requires appropriate treatment. In fact, major depression is one of the psychiatric disorders with the highest suicide rate (Chesney, E et al., 2014). In addition, the presence of depression not only affects mental health, but also physical health.

Studies have shown that patients with major depression have an increased risk of developing other conditions such as diabetes mellitus, heart disease, stroke, hypertension, obesity, cancer, cognitive disorders, and Alzheimer’s disease (Penninx et al., 2013Haapakoski, R. et al., 2015).

Symptoms of depression

The symptoms of major depression are varied, multiple, and can present in very different ways. In general, the typical aspects of this disorder are an altered mood (deep sadness) and loss of interest in normal daily activities. The main symptoms of depression include

  • Depressed mood (e.g., feeling sad, empty, hopeless)
  • Loss of interest and pleasure in doing things.
  • Significant weight loss or gain.
  • Psychomotor agitation or slowness.
  • Chronic fatigue or loss of energy.
  • Excessive or inappropriate feelings of worthlessness or guilt.
  • Increased difficulty thinking or concentrating, or pathological indecisiveness.
  • Recurrent thoughts of death, recurrent suicidal thoughts, or suicide attempts.

Depressed mood

Among the affective symptoms, the central one in major depression is a deep sadness that is almost always present throughout the day and is insensitive to any positive events. Pathological sadness is different from ordinary sadness. In fact, non-pathological sadness is situational, tied to specific moments, and does not permeate the individual’s entire life.

People who suffer from major depression, on the other hand, complain of deep daily sadness and a sense of hopelessness that does not change in the face of pleasant and joyful events.

Negative thoughts

Major depressive disorder, in addition to affecting the area of emotions and mood, has important applications to the content of thoughts that are negative and catastrophic. In fact, depressed patients tend to have a low opinion of themselves and their abilities.

They also show negative expectations and thoughts about others and their environment, as well as negative expectations about their future (Clark & Beck, 2010).

In general, the negative content of thoughts worsens as mood deteriorates, leading to the presence of delusional ideations (delusions of incurability, guilt, doom, etc.) or suicidal ideations or actions. (Disner et al., 2011Walker et al., 2015).

Cognitive functional disorders

In addition to alterations in thought content, people with major depression may have difficulties with cognitive processes. Very common in depressed patients is rumination (Sheline et al., 2009), which is the tendency to constantly think about one’s symptoms, condition, and negative content about one’s future (Hui Xia et al, 2020Cooney, R. E. et al., 2010). 

In addition, patients may complain of difficulties with concentration, memory, and decision making (Pan et al., 2019; Maier, S. U. et al., 2015).

Behavioral symptoms of depression

The most prominent behavioral symptoms include a reduction in daily activities. Loss of pleasure in doing anything (anhedonia), loss of interest (apathy) combined with the feeling of chronic fatigue lead the subject to gradually reduce all daily activities, reduce social contacts, thus closing himself off from the world and life.

The gradual and steady reduction of daily activities leads to perceived (“I am no longer able to do my own thing”) and actual disability. Other behavioral aspects typical of major depression are the progressive disappearance of actions aimed at one’s own well-being and self-care.

People with this disorder generally find it distressing to take care of their physical appearance and personal hygiene. In addition, there is a progressive and gradual abandonment of all social activities, with worsening feelings of loneliness and worthlessness, resulting in a worsening clinical picture.

Physical symptoms of depression

Major depressive disorder also manifests itself somatically. Some patients may somatize the sadness by manifesting more somatic symptoms (chronic fatigue, widespread pain, gastrointestinal problems). In some cases, patients may deny the mood disorder by worrying only about physical symptoms, even to the point of manifesting true hypochondriacal delusions.

In addition to somatic manifestations, a depressive disorder may be manifested by an altered sleep-wake rhythm, increased or decreased nighttime sleep, changes in eating habits (with increased or decreased appetite), decreased sexual desire, and other problems related to the sexual sphere. In very severe cases, a general slowing of the patient’s motor skills (psychomotor slowing) may be observed (Kapfhammer, 2006).

Causes of major depression

Among the causes of major depressive disorder, we find having experienced adverse life events in adolescence or adulthood (Goodyer, I. M. et al., 2000). These events are indeed correlated with an increased likelihood of developing major depression. For example, disadvantaged socioeconomic conditions, poverty, and poor schooling are considered risk factors for depression (Lorant, V. et al., 2003). Growing up with a depressed parent also increases the risk of developing depression. In general, however, major sources of stress increase the risk of developing major depression (Kessler, 1997). Some of the major causes include

  • Trauma or abuse
  • Death or loss of a significant other
  • Divorce and separation
  • Unemployment or financial insecurity
  • Social isolation
  • Workplace or school bullying
  • Serious or chronic illness

More recently, studies have shown how adverse life events during childhood can influence the development of depressive disorders in adulthood. These stressful events include physical or sexual violence, parental neglect, exposure to domestic violence, or early separation from a parental figure due to death or spousal separation (Li et al., 2016).

Genetic factors

Compared to bipolar disorder, which has been shown to have a very important genetic component, the influence of familiarity is more modest but present in major depression (Geschwind, D. H., & Flint, J. 2015). Twin studies have confirmed a higher likelihood of developing a depressive disorder for those who have a twin with the same disorder (Jansen, R., 2016).

In major depression, however, it seems that adverse life events and psychological traits that are not only acquired but also learned during development have a greater influence than genetic susceptibility (Flint, J et al., 2014). Thus, the relationship between predisposing genetic factors and adverse life events seems to be crucial (Klengel, T., & Binder, E. B.; 2015). However, further studies are planned to further investigate the genetic component underlying depressive disorders (Hyman, S., 2014).

Psychological vulnerability

The causes of depression also include individual variables. While it is true that all stressful situations can lead to depression, it is also true that not everyone who experiences stressful situations becomes ill. Psychological vulnerabilities include: low self-esteem and self-efficacy, tendency to self-criticism, inability to meet one’s own needs, and poor adaptability to life changes.

In addition, the transition through certain life stages can be particularly delicate. The transition from adolescence to adulthood, retirement, and the birth of a child are all sensitive times that can increase stress levels and lead to the development of a depressive disorder.

Diagnosing major depression

According to the DSM-5, at least 5 of the following symptoms are required for a diagnosis of major depression

  • Depressed mood (e.g., feeling sad, empty, hopeless)
  • Loss of interest and pleasure in doing things.
  • Significant weight loss or gain.
  • Psychomotor agitation or slowness.
  • Chronic fatigue or loss of energy.
  • Excessive or inappropriate feelings of worthlessness or guilt.
  • Increased difficulty thinking or concentrating, or pathological indecisiveness.
  • Recurrent thoughts of death, recurrent suicidal thoughts, or suicide attempts.
  • At least one of the above symptoms must be depressed mood or loss of interest in activities.

Treatment of depression

The treatment of depression involves integrated pharmacological and non-pharmacological interventions (NICE, 2009). In fact, research has shown that in most cases, pharmacological treatment combined with psychotherapeutic treatment promotes the best clinical outcomes (Cuijpers et al, 2009).

Pharmacological treatment for depression

There are various pharmacological therapies that are used, and the right medication is always highly individualized. Therefore, it is essential to be followed by a psychiatrist. The drugs used to treat depression are diverse and act on different receptors and biological substrates.

Among the drugs used are tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine and serotonin reuptake inhibitors (NSRIs), and other types of drugs (for a review on this topic, see Paris, 2004). Neuroleptic drugs may also be used, especially when the symptoms of depression are particularly severe and result in psychotic symptoms (Dubovsky et al., 2020).

Psychotherapy for depression

In the field of psychotherapy, many interventions are aimed at improving and treating depression through non-pharmacological strategies. Over the years, it is mainly cognitive behavioral interventions that have had more efficacy studies (Zhang et al., 2019).

Cognitive behavioral psychotherapy

Cognitive behavioral psychotherapy focuses on the underlying thoughts, emotions, situations, and conditions that triggered or perpetuated the depressive disorder. It teaches patients to identify dysfunctional negative thoughts that support depression and provides skills to change these thoughts and replace them with more realistic and positive thoughts.

Behavioral activation

Behavioral activation therapy aims to increase the frequency with which patients engage in activities that are pleasurable or meaningful to them. Avoidance processes, which are often present in patients with depression, are also identified and modified.

Psychodynamic psychotherapy

Psychodynamic therapy helps patients explore and understand how emotions, thoughts, and early life experiences created psychological patterns that led to the development of a depressive disorder. Identifying these patterns contributes to greater self-awareness and provides patients with the opportunity to change these patterns.

Problem solving

Problem solving helps patients develop new skills and creative ways to deal with problems, identify how to overcome possible obstacles to achieving their goals, and make more effective decisions.

Interpersonal therapy

Interpersonal therapy helps patients identify and resolve interpersonal and social problems, including interpersonal conflicts, role transitions, and diminished or impoverished relationships.

Mindfulness-Based therapies

Also known as third-generation psychotherapies, such as acceptance and commitment therapy, mindfulness-based therapies use mindfulness as a therapeutic tool. Mindfulness comes from contemplative practices, primarily Buddhism, and is a form of meditation in which the practitioner pays attention to his or her thoughts, emotions, and sounds or physical sensations in a nonjudgmental way.

Hospitalization for depression

Hospitalization for depression can take place in hospital wards and is always indicated in severe cases or when the disorder seems resistant to outpatient treatment. During inpatient hospitalization, clinical monitoring and the daily presence of psychiatrists and other mental health professionals make it possible to plan an intensive therapeutic-rehabilitative intervention.


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