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Major depressive disorder MDD , also known simply as depression , is a mental disorder characterized by at least two weeks of low mood that is present across most situations. The cause is believed to be a combination of genetic , environmental, and psychological factors. Typically, people are treated with counseling and antidepressant medication. Major depression significantly affects a person's family and personal relationships, work or school life, sleeping and eating habits, and general health.

A person having a major depressive episode usually exhibits a very low mood, which pervades all aspects of life, and an inability to experience pleasure in activities that were formerly enjoyed. Depressed people may be preoccupied with, or ruminate over, thoughts and feelings of worthlessness, inappropriate guilt or regret, helplessness, hopelessness, and self-hatred. These symptoms include delusions or, less commonly, hallucinations , usually unpleasant.

Insomnia is common among the depressed. In the typical pattern, a person wakes very early and cannot get back to sleep. A depressed person may report multiple physical symptoms such as fatigue , headaches, or digestive problems; physical complaints are the most common presenting problem in developing countries, according to the World Health Organization 's criteria for depression.

Depressed children may often display an irritable mood rather than a depressed one, [22] and show varying symptoms depending on age and situation. They may be described as clingy, demanding, dependent, or insecure. Major depression frequently co-occurs with other psychiatric problems. The —92 National Comorbidity Survey US reports that half of those with major depression also have lifetime anxiety and its associated disorders such as generalized anxiety disorder. Depression and pain often co-occur.

The diagnosis of depression is often delayed or missed, and the outcome can worsen if the depression is noticed but completely misunderstood. Depression is also associated with a 1. People with major depression are less likely to follow medical recommendations for treating and preventing cardiovascular disorders , which further increases their risk of medical complications.

The cause of major depressive disorder is unknown. The biopsychosocial model proposes that biological, psychological, and social factors all play a role in causing depression. The preexisting vulnerability can be either genetic , [42] [43] implying an interaction between nature and nurture , or schematic , resulting from views of the world learned in childhood.

Childhood abuse , either physical, sexual or psychological, are all risk factors for depression, among other psychiatric issues that co-occur such as anxiety and drug abuse. Childhood trauma also correlates with severity of depression, lack of response to treatment and length of illness.

However, some are more susceptible to developing mental illness such as depression after trauma, and various genes have been suggested to control susceptibility.

The 5-HTTLPR , or serotonin transporter promoter gene 's short allele has been associated with increased risk of depression. However, since the s, results have been inconsistent, with three recent reviews finding an effect and two finding none. A study found 44 areas within the chromosomes that were linked to MDD. Therapies associated with depression include interferons , beta-blockers , isotretinoin , contraceptives , [54] cardiac agents, anticonvulsants , antimigraine drugs , antipsychotics , and hormonal agents such as gonadotropin-releasing hormone agonist.

The pathophysiology of depression is not yet understood, but the current theories center around monoaminergic systems, the circadian rhythm , immunological dysfunction, HPA axis dysfunction and structural or functional abnormalities of emotional circuits. The monoamine theory, derived from the efficacy of monoaminergic drugs in treating depression, was the dominant theory until recently. The theory postulates that insufficient activity of monoamine neurotransmitters is the primary cause of depression.

Evidence for the monoamine theory comes from multiple areas. Firstly, acute depletion of tryptophan , a necessary precursor of serotonin , a monoamine, can cause depression in those in remission or relatives of depressed patients; this suggests that decreased serotonergic neurotransmission is important in depression. Third, decreased size of the locus coeruleus , decreased activity of tyrosine hydroxylase , increased density of alpha-2 adrenergic receptor , and evidence from rat models suggest decreased adrenergic neurotransmission in depression.

Further countering the monoamine hypothesis is the fact that rats with lesions of the dorsal raphe are not more depressive that controls, the finding of increased jugular 5-HIAA in depressed patients that normalized with SSRI treatment, and the preference for carbohydrates in depressed patients.

Immune system abnormalities have been observed, including increased levels of cytokines involved in generating sickness behavior which shares overlap with depression. HPA axis abnormalities have been suggested in depression given the association of CRHR1 with depression and the increased frequency of dexamethasone test non-suppression in depressed patients. Theories unifying neuroimaging findings have been proposed. The first model proposed is the "Limbic Cortical Model", which involves hyperactivity of the ventral paralimbic regions and hypoactivity of frontal regulatory regions in emotional processing.

A diagnostic assessment may be conducted by a suitably trained general practitioner , or by a psychiatrist or psychologist , [20] who records the person's current circumstances, biographical history, current symptoms, and family history. The broad clinical aim is to formulate the relevant biological, psychological, and social factors that may be impacting on the individual's mood. The assessor may also discuss the person's current ways of regulating mood healthy or otherwise such as alcohol and drug use.

The assessment also includes a mental state examination , which is an assessment of the person's current mood and thought content, in particular the presence of themes of hopelessness or pessimism , self-harm or suicide, and an absence of positive thoughts or plans.

Primary-care physicians and other non-psychiatrist physicians have more difficulty with underrecognition and undertreatment of depression compared to psychiatric physicians , in part because of the physical symptoms that often accompany depression, in addition to many potential patient, provider, and system barriers. A review found that non-psychiatrist physicians miss about two-thirds of cases, though this has improved somewhat in more recent studies.

Before diagnosing a major depressive disorder, in general a doctor performs a medical examination and selected investigations to rule out other causes of symptoms. These include blood tests measuring TSH and thyroxine to exclude hypothyroidism ; basic electrolytes and serum calcium to rule out a metabolic disturbance ; and a full blood count including ESR to rule out a systemic infection or chronic disease.

Testosterone levels may be evaluated to diagnose hypogonadism , a cause of depression in men. Subjective cognitive complaints appear in older depressed people, but they can also be indicative of the onset of a dementing disorder , such as Alzheimer's disease.

No biological tests confirm major depression. There are several potential biomarkers, including brain-derived neurotrophic factor and various functional MRI fMRI techniques. One study developed a decision tree model of interpreting a series of fMRI scans taken during various activities. However, much more research is needed before these tests can be used clinically. At least one of these must be present to make a diagnosis of major depressive episode. The category Depressive Disorder Not Otherwise Specified is diagnosed if the depressive episode's manifestation does not meet the criteria for a major depressive episode.

The ICD system does not use the term major depressive disorder but lists very similar criteria for the diagnosis of a depressive episode mild, moderate or severe ; the term recurrent may be added if there have been multiple episodes without mania. A major depressive episode is characterized by the presence of a severely depressed mood that persists for at least two weeks. An episode with psychotic features—commonly referred to as psychotic depression —is automatically rated as severe.

If the patient has had an episode of mania or markedly elevated mood , a diagnosis of bipolar disorder is made instead. DSM-IV-TR excludes cases where the symptoms are a result of bereavement , although it is possible for normal bereavement to evolve into a depressive episode if the mood persists and the characteristic features of a major depressive episode develop.

In , the United States Preventive Services Task Force USPSTF recommended screening in the adult populations with evidence that it increases the detection of people with depression and with proper treatment improves outcomes. A Cochrane review from found screening programs do not significantly improve detection rates, treatment, or outcome. To confirm major depressive disorder as the most likely diagnosis, other potential diagnoses must be considered, including dysthymia, adjustment disorder with depressed mood, or bipolar disorder.

Dysthymia is a chronic, milder mood disturbance in which a person reports a low mood almost daily over a span of at least two years. The symptoms are not as severe as those for major depression, although people with dysthymia are vulnerable to secondary episodes of major depression sometimes referred to as double depression.

Although depression is currently categorized as a separate disorder, there is ongoing debate because individuals diagnosed with major depression often experience some hypomanic symptoms, indicating a mood disorder continuum. Other disorders need to be ruled out before diagnosing major depressive disorder.

They include depressions due to physical illness, medications , and substance abuse. Depression due to physical illness is diagnosed as a mood disorder due to a general medical condition. This condition is determined based on history, laboratory findings, or physical examination.

When the depression is caused by a medication, drug of abuse, or exposure to a toxin , it is then diagnosed as a specific mood disorder previously called substance-induced mood disorder in the DSM-IV-TR. Behavioral interventions, such as interpersonal therapy and cognitive-behavioral therapy , are effective at preventing new onset depression.

However, an earlier meta-analysis found preventive programs with a competence-enhancing component to be superior to behavior-oriented programs overall, and found behavioral programs to be particularly unhelpful for older people, for whom social support programs were uniquely beneficial. In addition, the programs that best prevented depression comprised more than eight sessions, each lasting between 60 and 90 minutes, were provided by a combination of lay and professional workers, had a high-quality research design, reported attrition rates , and had a well-defined intervention.

The Netherlands mental health care system provides preventive interventions, such as the "Coping with Depression" course CWD for people with sub-threshold depression. The three most common treatments for depression are psychotherapy, medication, and electroconvulsive therapy. Psychotherapy is the treatment of choice over medication for people under The UK National Institute for Health and Care Excellence NICE guidelines indicate that antidepressants should not be used for the initial treatment of mild depression, because the risk-benefit ratio is poor.

The guidelines recommend that antidepressants treatment in combination with psychosocial interventions should be considered for:. The guidelines further note that antidepressant treatment should be continued for at least six months to reduce the risk of relapse , and that SSRIs are better tolerated than tricyclic antidepressants. American Psychiatric Association treatment guidelines recommend that initial treatment should be individually tailored based on factors including severity of symptoms, co-existing disorders, prior treatment experience, and patient preference.

Options may include pharmacotherapy, psychotherapy, exercise, electroconvulsive therapy ECT , transcranial magnetic stimulation TMS or light therapy. Antidepressant medication is recommended as an initial treatment choice in people with mild, moderate, or severe major depression, and should be given to all patients with severe depression unless ECT is planned.

Treatment options are much more limited in developing countries, where access to mental health staff, medication, and psychotherapy is often difficult. Development of mental health services is minimal in many countries; depression is viewed as a phenomenon of the developed world despite evidence to the contrary, and not as an inherently life-threatening condition.

Physical exercise is recommended for management of mild depression, [] and has a moderate effect on symptoms. There is a small amount of evidence that skipping a night's sleep may improve depressive symptoms, with the effects usually showing up within a day. This effect is usually temporary. Besides sleepiness, this method can cause a side effect of mania or hypomania. In observational studies, smoking cessation has benefits in depression as large as or larger than those of medications.

Besides exercise, sleep and diet may play a role in depression, and interventions in these areas may be an effective add-on to conventional methods. Psychotherapy can be delivered to individuals, groups, or families by mental health professionals. A review found that cognitive behavioral therapy appears to be similar to antidepressant medication in terms of effect. Psychotherapy has been shown to be effective in older people. Cognitive behavioral therapy CBT currently has the most research evidence for the treatment of depression in children and adolescents, and CBT and interpersonal psychotherapy IPT are preferred therapies for adolescent depression.

The most-studied form of psychotherapy for depression is CBT, which teaches clients to challenge self-defeating, but enduring ways of thinking cognitions and change counter-productive behaviors. Research beginning in the mids suggested that CBT could perform as well as or better than antidepressants in patients with moderate to severe depression. Cognitive behavioral therapy and occupational programs including modification of work activities and assistance have been shown to be effective in reducing sick days taken by workers with depression.

Several variants of cognitive behavior therapy have been used in those with depression, the most notable being rational emotive behavior therapy , [] and mindfulness-based cognitive therapy.

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