Major depressive disorder

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Major depressive disorder
Classification and external resources

Vincent van Gogh's 1890 painting
Sorrowing old man ('At Eternity's Gate')
ICD-10 F32, F33
ICD-9 296
OMIM 608516
DiseasesDB 3589
MedlinePlus 003213
eMedicine med/532
MeSH D003865

Major depressive disorder (MDD) (also known as recurrent depressive disorder, 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 by loss of interest or pleasure in normally enjoyable activities. This cluster of symptoms (syndrome) was named, described and classified as one of the mood disorders in the 1980 edition of the American Psychiatric Association's diagnostic manual. The term "depression" is ambiguous. It is often used to denote this syndrome but may refer to other mood disorders or to lower mood states lacking clinical significance. Major depressive disorder is a disabling condition that adversely affects a person's family, work or school life, sleeping and eating habits, and general health. In the United States, around 3.4% of people with major depression commit suicide, and up to 60% of people who commit suicide had depression or another mood disorder.[1]

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 examination. There is no laboratory test for major depression, although physicians generally request tests for physical conditions that may cause similar symptoms. The most common time of onset is between the ages of 20 and 30 years, with a later peak between 30 and 40 years.[2]

Typically, patients are treated with antidepressant medication and, in many cases, also receive psychotherapy or counseling, although the effectiveness of medication for mild or moderate cases is questionable. Hospitalization may be necessary in cases with associated self-neglect or a significant risk of harm to self or others. A minority are treated with electroconvulsive therapy (ECT). The course of the disorder varies widely, from one episode lasting weeks 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 and suicide. It is unclear whether or not medications affect the risk of suicide. Current and former patients may be stigmatized.

The understanding of the nature and causes of depression has evolved over the centuries, though this understanding is incomplete and has left many aspects of depression as the subject of discussion and research. Proposed causes include psychological, psycho-social, hereditary, evolutionary and biological factors. Certain types of long-term drug use can both cause and worsen depressive symptoms. Psychological treatments are based on theories of personality, interpersonal communication, and learning. Most biological theories focus on the monoamine chemicals serotonin, norepinephrine and dopamine, which are naturally present in the brain and assist communication between nerve cells.

Symptoms and signs

Major depression significantly affects a person's family and personal relationships, work or school life, sleeping and eating habits, and general health.[3] Its impact on functioning and well-being has been compared to that of chronic medical conditions such as diabetes.[4]

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.[5] In severe cases, depressed people may have symptoms of psychosis. These symptoms include delusions or, less commonly, hallucinations, usually unpleasant.[6] Other symptoms of depression include poor concentration and memory (especially in those with melancholic or psychotic features),[7] withdrawal from social situations and activities, reduced sex drive, and thoughts of death or suicide. Insomnia is common among the depressed. In the typical pattern, a person wakes very early and cannot get back to sleep.[8] Insomnia affects at least 80% of depressed people.[9] Hypersomnia, or oversleeping, can also happen.[8] Some antidepressants may also cause insomnia due to their stimulating effect.[10]

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.[11] Appetite often decreases, with resulting weight loss, although increased appetite and weight gain occasionally occur.[5] Family and friends may notice that the person's behavior is either agitated or lethargic.[8] Older depressed people may have cognitive symptoms of recent onset, such as forgetfulness,[7] and a more noticeable slowing of movements.[12] Depression often coexists with physical disorders common among the elderly, such as stroke, other cardiovascular diseases, Parkinson's disease, and chronic obstructive pulmonary disease.[13]

Depressed children may often display an irritable mood rather than a depressed mood,[5] and show varying symptoms depending on age and situation.[14] Most lose interest in school and show a decline in academic performance. They may be described as clingy, demanding, dependent, or insecure.[8] Diagnosis may be delayed or missed when symptoms are interpreted as normal moodiness.[5] Depression may also coexist with attention-deficit hyperactivity disorder (ADHD), complicating the diagnosis and treatment of both.[15]

Comorbidity

Major depression frequently co-occurs with other psychiatric problems. The 1990–92 National Comorbidity Survey (US) reports that 51% of those with major depression also suffer from lifetime anxiety.[16] Anxiety symptoms can have a major impact on the course of a depressive illness, with delayed recovery, increased risk of relapse, greater disability and increased suicide attempts.[17] American neuroendocrinologist Robert Sapolsky similarly argues that the relationship between stress, anxiety, and depression could be measured and demonstrated biologically.[18] There are increased rates of alcohol and drug abuse and particularly dependence,[19] and around a third of individuals diagnosed with ADHD develop comorbid depression.[20] Post-traumatic stress disorder and depression often co-occur.[3]

Depression and pain often co-occur. This conforms with Seligman's theory of learned helplessness. One or more pain symptoms is present in 65% of depressed patients, and anywhere from five to 85% of patients with pain will be suffering from depression, depending on the setting; there is a lower prevalence in general practice, and higher in specialty clinics. The diagnosis of depression is often delayed or missed, and the outcome worsens. The outcome can also obviously worsen if the depression is noticed but completely misunderstood[21]

Depression is also associated with a 1.5- to 2-fold increased risk of cardiovascular disease, independent of other known risk factors, and is itself linked directly or indirectly to risk factors such as smoking and obesity. People with major depression are less likely to follow medical recommendations for treating cardiovascular disorders, which further increases their risk. In addition, cardiologists may not recognize underlying depression that complicates a cardiovascular problem under their care.[22]

Causes

The biopsychosocial model proposes that biological, psychological, and social factors all play a role in causing depression.[23] The diathesis–stress model specifies that depression results when a preexisting vulnerability, or diathesis, is activated by stressful life events. The preexisting vulnerability can be either genetic,[24][25] implying an interaction between nature and nurture, or schematic, resulting from views of the world learned in childhood.[26]

These interactive models have gained empirical support. For example, researchers in New Zealand took a prospective approach to studying depression, by documenting over time how depression emerged among an initially normal cohort of people. The researchers concluded that variation among the serotonin transporter (5-HTT) gene affects the chances that people who have dealt with very stressful life events will go on to experience depression. To be specific, depression may follow such events, but seems more likely to appear in people with one or two short alleles of the 5-HTT gene.[24] In addition, a Swedish study estimated the heritability of depression—the degree to which individual differences in occurrence are associated with genetic differences—to be around 40% for women and 30% for men,[27] 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 drug abuse, or to withdrawal from certain sedative and hypnotic drugs.[28][29]

Biological

Monoamine hypothesis

Of approx. 30 neurotransmitters that have been identified, researchers have discovered associations between clinical depression and the function of three major neurochemicals. These substances are serotonin, norepinephrine, and dopamine. Antidepressants influence the overall balance of these three neurotransmitters within structures of the brain that regulate emotion, reactions to stress, and the physical drives of sleep, appetite, and sexuality.[30]

Most antidepressant medications increase the levels of one or more of the monoamines — the neurotransmitters serotonin, norepinephrine and dopamine — in the synaptic cleft between neurons in the brain. Some medications affect the monoamine receptors directly.

Serotonin is hypothesized to regulate other neurotransmitter systems; decreased serotonin activity may allow these systems to act in unusual and erratic ways.[31] According to this "permissive hypothesis", depression arises when low serotonin levels promote low levels of norepinephrine, another monoamine neurotransmitter.[32] 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. In its contemporary formulation, the monoamine hypothesis postulates that a deficiency of certain neurotransmitters is responsible for the corresponding features of depression: "Norepinephrine may be related to alertness and energy as well as anxiety, attention, and interest in life; [lack of] serotonin to anxiety, obsessions, and compulsions; and dopamine to attention, motivation, pleasure, and reward, as well as interest in life."[33] The proponents of this theory recommend the choice of an antidepressant with mechanism of action that impacts the most prominent symptoms. Anxious and irritable patients should be treated with SSRIs or norepinephrine reuptake inhibitors, and those experiencing a loss of energy and enjoyment of life with norepinephrine- and dopamine-enhancing drugs.[33]

Besides the clinical observations that drugs that increase the amount of available monoamines are effective antidepressants, recent advances in psychiatric genetics indicate that phenotypic variation in central monoamine function may be marginally associated with vulnerability to depression. Despite these findings, the cause of depression is not simply monoamine deficiency.[34] In the past two decades, research has revealed multiple limitations of the monoamine hypothesis, and its explanatory inadequacy has been highlighted within the psychiatric community.[35] A counterargument is that the mood-enhancing effect of MAO inhibitors and SSRIs takes weeks of treatment to develop, even though the boost in available monoamines occurs within hours. Another counterargument is based on experiments with pharmacological agents that cause depletion of monoamines; while deliberate reduction in the concentration of centrally available monoamines may slightly lower the mood of unmedicated depressed patients, this reduction does not affect the mood of healthy people.[34] The monoamine hypothesis, already limited, has been further oversimplified when presented to the general public as a mass marketing tool, usually phrased as a "chemical imbalance".[36]

In 2003 a gene-environment interaction (GxE) was hypothesized to explain why life stress is a predictor for depressive episodes in some individuals, but not in others, depending on an allelic variation of the serotonin-transporter-linked promoter region (5-HTTLPR);[37] a 2009 meta-analysis showed stressful life events were associated with depression, but found no evidence for an association with the 5-HTTLPR genotype.[38] Another 2009 meta-analysis agreed with the latter finding.[39] A 2010 review of studies in this area found a systematic relationship between the method used to assess environmental adversity and the results of the studies; this review also found that both 2009 meta-analyses were significantly biased toward negative studies, which used self-report measures of adversity.[40]

Other theories

MRI scans of patients with depression have revealed a number of differences in brain structure compared to those who are not depressed. Recent meta-analyses of neuroimaging studies in major depression, reported that compared to controls, depressed patients had increased volume of the lateral ventricles and adrenal gland and smaller volumes of the basal ganglia, thalamus, hippocampus, and frontal lobe (including the orbitofrontal cortex and gyrus rectus).[41][42] Hyperintensities have been associated with patients with a late age of onset, and have led to the development of the theory of vascular depression.[43]

There may be a link between depression and neurogenesis of the hippocampus,[44] a center for both mood and memory. Loss of hippocampal neurons is found in some depressed individuals and correlates with impaired memory and dysthymic mood. Drugs may increase serotonin levels in the brain, stimulating neurogenesis and thus increasing the total mass of the hippocampus. This increase may help to restore mood and memory.[45][46] Similar relationships have been observed between depression and an area of the anterior cingulate cortex implicated in the modulation of emotional behavior.[47] One of the neurotrophins responsible for neurogenesis is brain-derived neurotrophic factor (BDNF). The level of BDNF in the blood plasma of depressed subjects is drastically reduced (more than threefold) as compared to the norm. 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.[48]

There is some evidence that major depression may be caused in part by an overactive hypothalamic-pituitary-adrenal axis (HPA axis) that results in an effect similar to the neuro-endocrine response to stress. 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. Oversecretion of corticotropin-releasing hormone from the hypothalamus is thought to drive this, and is implicated in the cognitive and arousal symptoms.[49]

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.[50] On the converse, the premenstrual and postpartum periods of low estrogen levels are also associated with increased risk.[50] Sudden withdrawal of, fluctuations in or periods of sustained low levels of estrogen have been linked to significant mood lowering. Clinical recovery from depression postpartum, perimenopause, and postmenopause was shown to be effective after levels of estrogen were stabilized or restored.[51][52]

Other research has explored potential roles of molecules necessary for overall cellular functioning: cytokines. The symptoms of major depressive disorder are nearly identical to those of sickness behavior, the response of the body when the immune system is fighting an infection. This raises the possibility that depression can result from a maladaptive manifestation of sickness behavior as a result of abnormalities in circulating cytokines.[53] The involvement of pro-inflammatory cytokines in depression is strongly suggested by a meta-analysis of the clinical literature showing higher blood concentrations of IL-6 and TNF-α in depressed subjects compared to controls.[54] These immunological abnormalities may cause excessive prostaglandin E₂ production and likely excessive COX-2 expression. Abnormalities in how indoleamine 2,3-dioxygenase enyme activates as well as the metabolism of tryptophan-kynurenine may lead to excessive metabolism of tryptophan-kynurenine and lead to increased production of the neurotoxin quinolinic acid, contributing to major depression. NMDA activation leading to excessive glutamatergic neurotransmission, may also contribute.[55]

Finally, some relationships have been reported between specific subtypes of depression and climatic conditions. Thus, the incidence of psychotic depression has been found to increase when the barometric pressure is low, while the incidence of melancholic depression has been found to increase when the temperature and/or sunlight are low.[56]

Psychological

Various aspects of personality and its development appear to be integral to the occurrence and persistence of depression,[57] with negative emotionality as a common precursor.[58] Although depressive episodes are strongly correlated with adverse events, a person's characteristic style of coping may be correlated with his or her resilience.[59] In addition, low self-esteem and self-defeating or distorted thinking are related to depression. Depression is less likely to occur, as well as quicker to remit, among those who are religious.[60][61][62] It is not always clear which factors are causes and which are effects of depression; however, depressed persons who are able to reflect upon and challenge their thinking patterns often show improved mood and self-esteem.[63]

American psychiatrist Aaron T. Beck, following on from the earlier work of George Kelly and Albert Ellis, developed what is now known as a cognitive model of depression in the early 1960s. He proposed that three concepts underlie depression: a triad of negative thoughts composed of cognitive errors about oneself, one's world, and one's future; recurrent patterns of depressive thinking, or schemas; and distorted information processing.[64] From these principles, he developed the structured technique of cognitive behavioral therapy (CBT).[65] According to American psychologist Martin Seligman, depression in humans is similar to learned helplessness in laboratory animals, who remain in unpleasant situations when they are able to escape, but do not because they initially learned they had no control.[66]

Attachment theory, which was developed by English psychiatrist John Bowlby in the 1960s, predicts a relationship between depressive disorder in adulthood and the quality of the earlier bond between the infant and the adult caregiver. In particular, it is thought that "the experiences of early loss, separation and rejection by the parent or caregiver (conveying the message that the child is unlovable) may all lead to insecure internal working models ... Internal cognitive representations of the self as unlovable and of attachment figures as unloving [or] untrustworthy would be consistent with parts of Beck’s cognitive triad".[67] While a wide variety of studies has upheld the basic tenets of attachment theory, research has been inconclusive as to whether self-reported early attachment and later depression are demonstrably related.[67]

Depressed individuals often blame themselves for negative events,[68] and, as shown in a 1993 study of hospitalized adolescents with self-reported depression, those who blame themselves for negative occurrences may not take credit for positive outcomes.[69] This tendency is characteristic of a depressive attributional, or pessimistic explanatory style.[68] 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. These influences may result in a negative self-concept and a lack of self-efficacy; that is, they do not believe they can influence events or achieve personal goals.[70]

An examination of depression in women indicates that vulnerability factors—such as early maternal loss, lack of a confiding relationship, responsibility for the care of several young children at home, and unemployment—can interact with life stressors to increase the risk of depression.[71] For older adults, the factors are often health problems, changes in relationships with a spouse or adult children due to the transition to a care-giving or care-needing role, the death of a significant other, or a change in the availability or quality of social relationships with older friends because of their own health-related life changes.[72]

The understanding of depression has also received contributions from the psychoanalytic and humanistic branches of psychology. From the classical psychoanalytic perspective of Austrian psychiatrist Sigmund Freud, depression, or melancholia, may be related to interpersonal loss[73][74] and early life experiences.[75] Existential therapists have connected depression to the lack of both meaning in the present[76] and a vision of the future.[77][78] The founder of humanistic psychology, American psychologist Abraham Maslow, suggested that depression could arise when people are unable to attain their needs or to self-actualize (to realize their full potential).[79][80]

Social

Poverty and social isolation are associated with increased risk of mental health problems in general.[57] Child abuse (physical, emotional, sexual, or neglect) is also associated with increased risk of developing depressive disorders later in life.[81] Such a link has good face validity given that it is during the years of development that a child is learning how to become a social being. Abuse of the child by the caregiver is bound to distort the developing personality and create a much greater risk for depression and many other debilitating mental and emotional states. 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.[57] In adulthood, stressful life events are strongly associated with the onset of major depressive episodes.[82] In this context, life events connected to social rejection appear to be particularly related to depression.[83][84] Evidence that a first episode of depression is more likely to be immediately preceded by stressful life events than are recurrent ones is consistent with the hypothesis that people may become increasingly sensitized to life stress over successive recurrences of depression.[85][86]

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.[87] 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.[88] 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.[89]

Evolutionary

From the standpoint of evolutionary theory, major depression is hypothesized, in some instances, to increase an individual's reproductive fitness. 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,[90] such as the behaviors relating to attachment and social rank.[91] Current behaviors can be explained as adaptations to regulate relationships or resources, although the result may be maladaptive in modern environments.[92]

From another viewpoint, a counseling therapist may see depression not as a biochemical illness or disorder but as "a species-wide evolved suite of emotional programmes that are mostly activated by a perception, almost always over-negative, of a major decline in personal usefulness, that can sometimes be linked to guilt, shame or perceived rejection".[93] This suite may have manifested in aging hunters in humans' foraging past, who were marginalized by their declining skills, and may continue to appear in alienated members of today's society. The feelings of uselessness generated by such marginalization could in theory prompt support from friends and kin. In addition, in a manner analogous to that in which physical pain has evolved to hinder actions that may cause further injury, "psychic misery" may have evolved to prevent hasty and maladaptive reactions to distressing situations.[94]

Drug and alcohol use

According to the DSM-IV, a diagnosis of mood disorder cannot be made if the cause is believed to be due to "the direct physiological effects of a substance"; when a syndrome resembling major depression is believed to be caused immediately by substance abuse or by an adverse drug reaction, it is referred to as, "substance-induced mood disturbance". Alcoholism or excessive alcohol consumption significantly increases the risk of developing major depression.[95][96][97] Like alcohol, the benzodiazepines are central nervous system depressants; this class of medication is commonly used to treat insomnia, anxiety, and muscular spasms. Similar to alcohol, benzodiazepines increase the risk of developing major depression. This increased risk may be due in part to the effects of drugs on neurochemistry, such as decreased levels of serotonin and norepinephrine.[29] Chronic use of benzodiazepines also can cause or worsen depression,[98][99] or depression may be part of a protracted withdrawal syndrome.[100][101] About a quarter of people recovering from alcoholism experience anxiety and depression which can persist for up to 2 years.[102] Methamphetamine abuse is also commonly associated with depression.[103]

Diagnosis

Clinical assessment

A diagnostic assessment may be conducted by a suitably trained general practitioner, or by a psychiatrist or psychologist,[3] 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 their 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.[3] Specialist mental health services are rare in rural areas, and thus diagnosis and management is left largely to primary-care clinicians.[104] This issue is even more marked in developing countries.[105] The score on a rating scale alone is insufficient to diagnose depression to the satisfaction of the DSM or ICD, but it provides an indication of the severity of symptoms for a time period, so a person who scores above a given cut-off point can be more thoroughly evaluated for a depressive disorder diagnosis.[106] Several rating scales are used for this purpose.[106] Screening programs have been advocated to improve detection of depression, but there is evidence that they do not improve detection rates, treatment, or outcome.[107]

Primary care physicians and other non-psychiatrist physicians have difficulty diagnosing depression, in part because they are trained to recognize and treat physical symptoms, and depression can cause a myriad of physical (psychosomatic) symptoms. Non-psychiatrists miss two-thirds of cases and unnecessarily treat other patients.[108][109]

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.[110] Adverse affective reactions to medications or alcohol misuse are often ruled out, as well. Testosterone levels may be evaluated to diagnose hypogonadism, a cause of depression in men.[111]

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.[112][113] Cognitive testing and brain imaging can help distinguish depression from dementia.[114] A CT scan can exclude brain pathology in those with psychotic, rapid-onset or otherwise unusual symptoms.[115] No biological tests confirm major depression.[116] In general, investigations are not repeated for a subsequent episode unless there is a medical indication.

Biomarkers of depression have been sought to provide an objective method of diagnosis. There are several potential biomarkers, including Brain-Derived Neurotrophic Factor and various functional MRI techniques. One study developed a decision tree model of interpreting a series of fMRI scans taken during various activities. In their subjects, the authors of that study were able to achieve a sensitivity of 80% and a sensitivity of 87%, corresponding to a negative predictive value of 98% and a positive predictive value of 32% (positive and negative likelihood ratios were 6.15, 0.23, respectively). However, much more research is needed before these tests could be used clinically.[117]

DSM-IV-TR and ICD-10 criteria

The most widely used criteria for diagnosing depressive conditions are found in the American Psychiatric Association's revised fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), and the World Health Organization's International Statistical Classification of Diseases and Related Health Problems (ICD-10), which uses the name recurrent depressive disorder.[118] The latter system is typically used in European countries, while the former is used in the US and many other non-European nations,[119] and the authors of both have worked towards conforming one with the other.[120]

Both DSM-IV-TR and ICD-10 mark out typical (main) depressive symptoms. ICD-10 defines three typical depressive symptoms (depressed mood, anhedonia, and reduced energy), two of which should be present to determine depressive disorder diagnosis.[121] According to DSM-IV-TR, there are two main depressive symptoms—depressed mood and anhedonia. At least one of these must be present to make a diagnosis of major depressive episode.[122]

Major depressive disorder is classified as a mood disorder in DSM-IV-TR.[123] The diagnosis hinges on the presence of single or recurrent major depressive episodes.[5] Further qualifiers are used to classify both the episode itself and the course of the disorder. 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-10 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.[124]

Major depressive episode

A major depressive episode is characterized by the presence of a severely depressed mood that persists for at least two weeks.[5] Episodes may be isolated or recurrent and are categorized as mild (few symptoms in excess of minimum criteria), moderate, or severe (marked impact on social or occupational functioning). 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.[125] Depression without mania is sometimes referred to as unipolar because the mood remains at one emotional state or "pole".[126]

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.[127] The criteria have been criticized because they do not take into account any other aspects of the personal and social context in which depression can occur.[128] In addition, some studies have found little empirical support for the DSM-IV cut-off criteria, indicating they are a diagnostic convention imposed on a continuum of depressive symptoms of varying severity and duration:[129] Excluded are a range of related diagnoses, including dysthymia, which involves a chronic but milder mood disturbance;[130] recurrent brief depression, consisting of briefer depressive episodes;[131][132] minor depressive disorder, whereby only some of the symptoms of major depression are present;[133] and adjustment disorder with depressed mood, which denotes low mood resulting from a psychological response to an identifiable event or stressor.[134]

Subtypes

The DSM-IV-TR recognizes five further subtypes of MDD, called specifiers, in addition to noting the length, severity and presence of psychotic features:

  • Melancholic depression is characterized by a loss of pleasure in most or all activities, a failure of reactivity to pleasurable stimuli, a quality of depressed mood more pronounced than that of grief or loss, a worsening of symptoms in the morning hours, early-morning waking, psychomotor retardation, excessive weight loss (not to be confused with anorexia nervosa), or excessive guilt.[135]
  • Atypical depression is characterized by mood reactivity (paradoxical anhedonia) and positivity, significant weight gain or increased appetite (comfort eating), excessive sleep or sleepiness (hypersomnia), a sensation of heaviness in limbs known as leaden paralysis, and significant social impairment as a consequence of hypersensitivity to perceived interpersonal rejection.[136]
  • Catatonic depression is a rare and severe form of major depression involving disturbances of motor behavior and other symptoms. Here the person is mute and almost stuporous, and either remains immobile or exhibits purposeless or even bizarre movements. Catatonic symptoms also occur in schizophrenia or in manic episodes, or may be caused by neuroleptic malignant syndrome.[137]
  • Postpartum depression, or mental and behavioural disorders associated with the puerperium, not elsewhere classified,[138] refers to the intense, sustained and sometimes disabling depression experienced by women after giving birth. Postpartum depression has an incidence rate of 10–15% among new mothers. The DSM-IV mandates that, in order to qualify as postpartum depression, onset occur within one month of delivery. It has been said that postpartum depression can last as long as three months.[139]
  • Seasonal affective disorder (SAD) is a form of depression in which depressive episodes come on in the autumn or winter, and resolve in spring. The diagnosis is made if at least two episodes have occurred in colder months with none at other times, over a two-year period or longer.[140]

Differential diagnoses

To confer 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).[130] Adjustment disorder with depressed mood is a mood disturbance appearing as a psychological response to an identifiable event or stressor, in which the resulting emotional or behavioral symptoms are significant but do not meet the criteria for a major depressive episode.[134] Bipolar disorder, also known as manic–depressive disorder, is a condition in which depressive phases alternate with periods of mania or hypomania. 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.[141]

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 substance abused including a drug of abuse, a medication, or exposure to a toxin, it is then diagnosed as a substance-induced mood disorder.[142] In such cases, a substance is judged to be etiologically related to the mood disturbance.[citation needed]

Schizoaffective disorder is different from major depressive disorder with psychotic features because in the schizoaffective disorder at least two weeks of delusions or hallucinations must occur in the absence of prominent mood symptoms.[citation needed]

Depressive symptoms may be identified during schizophrenia, delusional disorder, and psychotic disorder not otherwise specified, and in such cases those symptoms are considered associated features of these disorders, therefore, a separate diagnosis is not deemed necessary unless the depressive symptoms meet full criteria for a major depressive episode. In that case, a diagnosis of depressive disorder not otherwise specified may be made as well as a diagnosis of schizophrenia.[citation needed]

Some cognitive symptoms of dementia such as disorientation, apathy, difficulty concentrating and memory loss may get confused with a major depressive episode in major depressive disorder. They are especially difficult to determine in elderly patients. In such cases, the premorbid state of the patient may be helpful to differentiate both disorders. In the case of dementia, there tends to be a premorbid history of declining cognitive function. In the case of a major depressive disorder patients tend to exhibit a relatively normal premorbid state and abrupt cognitive decline associated with the depression.[citation needed]

Prevention

Behavioral interventions, such as interpersonal therapy, are effective at preventing new onset depression.[143] Because such interventions appear to be most effective when delivered to individuals or small groups, it has been suggested that they may be able to reach their large target audience most efficiently through the Internet