Major depressive disorder

Major depressive disorder
Major depressive disorder (also known as clinical depression, major depression, unipolar depression, or unipolar disorder) is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and loss of interest or pleasure in normally enjoyable activities. The term "major depressive disorder" was selected by the American Psychiatric Association to designate this symptom cluster as a mood disorder in the 1980 version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) classification, and has become widely used since. The general term depression is often used to describe the disorder, but as it is also used to describe a more temporarily depressed state of mind, more precise terminology is preferred for the disorder in clinical and research use. Major depression is a disabling condition which adversely affects a person's family, work or school life, sleeping and eating habits, and general health. In the United States, approximately 3.4% of people with major depression commit suicide, and up to 60% of all people who commit suicide have depression or another mood disorder.

The diagnosis of major depressive disorder is based on the patient's self-reported experiences, behavior reported by relatives or friends, and a mental status exam. There is no laboratory test for major depression, although physicians generally request tests for physical conditions that may cause similar symptoms. Major depression is reported about twice as frequently in women as in men, although men are at higher risk for suicide.

The course of the disorder varies widely, from one episode lasting months to a lifelong disorder with recurrent major depressive episodes. Depressed individuals have shorter life expectancies than those without depression, in part because of greater susceptibility to medical illnesses. The understanding of the nature and causes of depression has evolved over the centuries, though many aspects of depression remain incompletely understood and are the subject of discussion and research. Psychological treatments are based on theories of personality, interpersonal communication, and learning theory. Monoamines have been implicated in depression, and most antidepressants work to increase the active levels of at least one.

Symptoms and signs
Major depression is a serious illness that affects a person's family, work or school life, sleeping and eating habits, and general health. Its impact on functioning and well-being has been equated to that of chronic medical conditions such as diabetes.

Depressed people may be preoccupied with, or ruminate over, thoughts and feelings of worthlessness, inappropriate guilt or regret, helplessness, hopelessness, and self hatred. Other symptoms include poor concentration and memory, withdrawal from social situations and activities, reduced sex drive, and thoughts of death or suicide. Depressed children often display an irritable rather than a depressed mood, and show varying symptoms depending on age and situation. Most exhibit a loss of interest in school and a decline in academic performance. The biopsychosocial model proposes that biological, psychological, and social factors all play a role to varying degrees in causing depression. The diathesis–stress model posits that depression results when a preexisting vulnerability, or diathesis, is activated by stressful life events. For example, a prospective, longitudinal study uncovered a moderating effect of the serotonin transporter (5-HTT) gene on stressful life events in predicting depression. A Swedish study estimated the heritability of depression-the degree to which individual differences in occurrence are associated with genetic differences- to be approximately 40 percent for women and 30 percent for men, and evolutionary psychologists have proposed that the genetic basis for depression lies deep in the history of naturally-selected adaptations. A substance-induced mood disorder resembling major depression has been causally linked to long-term drug use or abuse or withdrawal from certain sedative and hypnotic drugs.

Monoamine hypothesis
Most antidepressants increase synaptic levels of serotonin, one of a group of neurotransmitters known as monoamines. Serotonin is hypothesized to help regulate other neurotransmitter systems; decreased serotonin activity may allow these systems to act in unusual and erratic ways. According to this "permissive hypothesis", depression arises when low serotonin levels promote low levels of norepinephrine, another monoamine neurotransmitter. Some antidepressants enhance the levels of norepinephrine directly, whereas others raise the levels of dopamine, a third monoamine neurotransmitter. These observations gave rise to the monoamine hypothesis of depression. Experiments with pharmacological agents that cause depletion of monoamines have shown that this depletion does not cause depression in healthy people nor does it worsen symptoms in depressed patients - although an intact monoamine system is necessary for antidepressants to achieve therapeutic effectiveness.According to an essay published by the Public Library of Science (PLoS), the monoamine hypothesis, already limited, has been further oversimplified when presented to the general public.

Other theories
MRI scans of patients with depression have reported a number of differences in brain structure compared to those without the illness. There may be a link between depression and neurogenesis of the hippocampus, a center for both mood and memory. Drugs may increase serotonin levels in the brain, stimulating neurogenesis and thus increasing the total mass of the hippocampus. Antidepressant treatment increases the blood level of BDNF. Although decreased plasma BDNF levels have been found in many other disorders, there is some evidence that BDNF is involved in the cause of depression and the mechanism of action of antidepressants.

Investigations reveal increased levels of the hormone cortisol and enlarged pituitary and adrenal glands, suggesting disturbances of the endocrine system may play a role in some psychiatric disorders, including major depression. Depression may be related to abnormalities in the circadian rhythm, or biological clock. REM sleep depends on decreased serotonin levels in the brain stem, and is impaired by compounds, such as antidepressants, that increase serotoninergic tone in brain stem structures. Overall, the serotonergic system is least active during sleep and most active during wakefulness. Depressed individuals can exhibit a significant lift in mood after a night of sleep deprivation. Research on the effects of light therapy on treating seasonal affective disorder suggests that light deprivation is related to decreased activity in the serotonergic system and to abnormalities in the sleep cycle, particularly insomnia. Exposure to light also targets the serotonergic system, providing more support for the important role this system may play in depression. Sleep deprivation and light therapy both target the same brain neurotransmitter system and brain areas as antidepressant drugs, and are now used clinically to treat depression. Light therapy, sleep deprivation and sleep time displacement (sleep phase advance therapy) are being used in combination quickly to interrupt a deep depression in hospitalized patients.

The hormone estrogen has been implicated in depressive disorders due to the increase in risk of depressive episodes after puberty, the antenatal period, and reduced rates after menopause. Conversely, the premenstrual and postpartum periods of low estrogen levels are also associated with increased risk. The use of estrogen has been under-researched, and although some small trials show promise in its use to prevent or treat depression, the evidence for its effectiveness is not strong. Estrogen replacement therapy has been shown to be beneficial in improving mood in perimenopause, but it is unclear if it is merely the menopausal symptoms that are being reversed.

Psychological
Various aspects of personality and its development appear to be integral to the occurrence and persistence of depression. Although depressive episodes are strongly correlated with adverse events, a person's characteristic style of coping may be correlated with their resilience. Additionally, low self-esteem and self-defeating or distorted thinking are related to depression. Depression may be less likely to occur, as well as quicker to remit, among those who are religious. It is not always clear which factors are causes or which are effects of depression; however, depressed persons who are able to make corrections in their thinking patterns often show improved mood and self-esteem.

American psychiatrist Aaron T. Beck developed what is now known as a cognitive model of depression in the early 1960s. Depressed individuals often blame themselves for negative events. In a study of hospitalized adolescents with self-reported depression, those who felt responsible for negative events did not take credit for positive outcomes. This tendency is characteristic of a depressive attributional, or pessimistic explanatory style. According to Albert Bandura, a Canadian social psychologist associated with social cognitive theory, depressed individuals have negative beliefs about themselves, based on experiences of failure, observing the failure of social models, a lack of social persuasion that they can succeed, and their own somatic and emotional states including tension and stress. From the classical psychoanalytic perspective of Austrian psychiatrist Sigmund Freud, depression, or melancholia, may be related to interpersonal loss and early life experiences. Existential psychologists have connected depression to the lack of both meaning in the present and a vision of the future. The founder of humanistic psychology, American psychologist Abraham Maslow, suggested that depression could arise when people are unable to self-actualize, or to realize their full potential.

Social
Poverty and social isolation are associated with increased risk of psychiatric problems in general. Child abuse (physical, emotional, sexual, or neglect) is also associated with increased risk of developing depressive disorders later in life. Disturbances in family functioning, such as parental (particularly maternal) depression, severe marital conflict or divorce, death of a parent, or other disturbances in parenting are additional risk factors. In adulthood, stressful life events are strongly associated with the onset of major depressive episodes; a first episode is more likely to be immediately preceded by stressful life events than are recurrent ones.

The relationship between stressful life events and social support has been a matter of some debate; the lack of social support may increase the likelihood that life stress will lead to depression, or the absence of social support may constitute a form of strain that leads to depression directly. There is evidence that neighborhood social disorder, for example, due to crime or illicit drugs, is a risk factor, and that a high neighborhood socioeconomic status, with better amenities, is a protective factor. Adverse conditions at work, particularly demanding jobs with little scope for decision-making, are associated with depression, although diversity and confounding factors make it difficult to confirm that the relationship is causal.

Evolutionary
From the standpoint of evolutionary theory, major depression is hypothesized, in some instances, to increase an individual's ability to reproduce. Evolutionary approaches to depression and evolutionary psychology posit specific mechanisms by which depression may have been genetically incorporated into the human gene pool, accounting for the high heritability and prevalence of depression by proposing that certain components of depression are adaptations, such as the behaviors relating to attachment and social rank. Current behaviors can be explained as adaptations to regulate relationships or resources, although the result may be maladaptive in modern environments.

Drug use
This increased risk may be due in part to the effects of drugs on neurochemistry, such as decreased levels of serotonin and norepinephrine. Alcoholism or excessive alcohol consumption significantly increases the risk of developing this syndrome. Chronic use of benzodiazepines, a class of medication which are commonly used to treat insomnia, anxiety and muscular spasms, also increase the risk. Chronic, severe depression can develop as a result of chronic use of benzodiazepines or as part of a protracted withdrawal syndrome.

Diagnosis
Clinical assessment
Before diagnosing a major depressive disorder, a doctor generally performs a medical examination and selected investigations to rule out other causes of symptoms. Testosterone levels may be evaluated to diagnose hypogonadism, a cause of depression in men. Depression is also a common initial symptom of dementia. Conducted in older depressed people, additional tests such as cognitive testing and brain imaging, can help distinguish depression from dementia. A CT scan can exclude brain pathology in those with psychotic, rapid-onset or otherwise unusual symptoms. No biological tests confirm major depression. Investigations are not generally repeated for a subsequent episode unless there is a medical indication.