Literature review on depressive disorders

Depression is one of the most prevailing medical disorders. Depression has been recognized as a distinct pathological entity from early Egyptian times (Reus, 2000).

Depression is the most common psychiatric disorders. Each year, more than 100 million people worldwide develop clinical depression (Bjornlund, 2010). During a lifetime, it is estimated that between 8% and 20% of the general population will experience at least one clinically significant episode of depression (Kessler et al., 1994).

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Major depression causes the fourth-highest burden of disease among all medical diseases. It is expected to rise to second place, preceded only by cardiovascular disease by 2020 (Thompson, 2007).

Depressive disorder has significant potential morbidity and mortality. Suicide is the second leading cause of death in persons aged 20-35 years. Depressive disorder is a major factor in around 50% of these deaths (Semple et al., 2005).

A suicide attempt among patients with major depressive disorder is associated with the presence and severity of depressive symptoms. Lack of partner, previous suicide attempts and time spent in depression are risk factors of suicide attempts. Reducing the time of depression is a likely preventive measure of suicide (Sokero et al., 2005).

Depression is a medically significant condition that needs to be diagnosed and properly treated. It is a severe disorder, tend to recur, and it costs the individual and society (Stefanis & Stefanis, 2002).

Epidemiology of Depressive Disorders

Prevalence and Incidence

Studies show substantial variability in the lifetime rates of depression. Lifetime rates are ranging from under 5 percent to 30 percent, but it is widely accepted that the lifetime prevalence is between 10 percent and 20 percent. The 6-month prevalence rate is considered to be between 2 percent and 5 percent based on surveys in several countries (Young et al., 2010).

A cross- sectional WHO world health survey carried out in 60 countries covering all regions of the world showed a 1-year prevalence of depressive episode of 3.2 percent, with a 95 percent confidence interval of 3.0 percent to 3.5 percent (Moussavi et al., 2007). The life time prevalence of depression for adults varied from 3 percent in Japan to 16.9 percent in the US, with most countries in the range between 8 percent and 12 percent (Andrade et al., 2003).

The prevalence of major depressive disorder is estimated to be about 2 percent in children (Birmaher et al., 1996). Estimates of the point prevalence of MDD in adolescence is range from 0.4 percent to 8.3 percent. Lifetime prevalence rates across adolescence range is from 15 percent to 20 percent (Roberts & Bishop, 2005).

In Dubai the prevalence of depressive disorders were 13.7% among women mostly neurotic depression (Ghubash et al., 1992).

About 12-20% of persons experiencing an acute episode develop a chronic depressive syndrome, and up to 15% of patients who have depression for more than one month commit suicide (Reus, 2000).

Risk Factors
Genetics

There is now substantial evidence that the genetic factors are of major importance as risk factors for vulnerability to major depression. Traditional estimates have put the heritability about 40 % (Joyce, 2003). Genetic influences are most marked in patients with more severe forms of depressive

disorder and ‘biological’ symptoms. The morbid risk in first-degree relatives is increased in all studies. This elevation is independent of the effects of environment or upbringing. In fewer severe forms of depression, genetic factors are fewer significant and environmental factors relatively more important (Souery et al., 1997).

Gender

Major depressive disorder is the twofold greater prevalence in women than in men independent of country or culture. The reasons for the difference are hypothesized to involve hormonal differences, the effects of childbirth, and differing on psychosocial stressors for women and for men (Sadock & Sadock, 2007).

Age

Major depressive disorder occurs in all cultures and affects all age groups. Depression is common in Childhood and late adult. The mean age of onset is generally in the 30s (Dunner, 2008).

Early-onset depression is associated with a higher female to a male ratio than late-onset depression. The incidence of major depressive disorder in old age is lower in both sexes. However, first incidence and prevalence of minor depressive disorder shows the opposite trend (Rihmer & Angst, 2009).

Personality

In younger people, mild depression tends to affect anxious or dependent personalities with poor tolerance of stress. Severe depressive illness in middle age tends to affect hard-working, conventional people with high standards and obsessional traits. Obsessional personalities can find it, particularly difficult to adapt to stress or life changes, as in work or relationships, and this can ‘come out’ as depression (Gill, 2007).

Childhood experiences

Early theorizing suggested that the loss of a parent in childhood increased the later risk for major depression. However, many studies have examined this issue; they have inconsistently found it to be a risk factor for

adult depression (Tennant, 1988). Childhood sexual abuse has been established as a risk factor for adult major depression (Joyce, 2003).

Marital status

Rates of depressive illness is lower in the married man than in the single, widowed, or divorced. The protective effects of marriage are less marked in women. Young married women with children have high rates of depression; single women have low rates (Gill, 2007). However, those in a poor marriage with deficient intimacy are at increased risk of depression (Weissman, 1987).

Social classes and occupation

People of low socio-economic status (i.e. low levels of income, employment, and education) are at higher risk of depression (Semple et al., 2005).

While job satisfaction can enhance mental well-being, the workplace can also be a source of stress and depression. However, the consequences of unemployment probably have far changed on mental health. The economic hardship to the unemployed and their families with depression due to long-term unemployment hindering job seeking and re-employment chances, exacerbated by loss of confidence and perceived loss of skills (Strandh, 2001).

Depression is more common in urban than a rural district (Gill, 2007).

Physical illness

Having a chronic or severe physical illness is associated with an increased risk for depression. This suggests that the stress associated with a serious or chronic physical illness may act by bringing out an individual’s lifetime vulnerability to depression (Joyce, 2003).

Etiology of Depressive Disorders

The etiology of major depressive disorder is unknown (Dunner, 2008). Multiple etiologic factors genetic, biochemical, psychodynamics, and socio-environmental may interact in complex ways to cause major depressive disorder (Loosen & Shelton, 2011).

GENETIC MODELS OF DEPRESSION

There is evidence to suggest a genetic basis for the major depression disorder. Occurrences of major depressive episodes are clearly cluster in families. This degree of increased risk is about three to five times that of the normal population.

Twin and adoption study is consistent with a genetic contribution to major depressive disorders. However, studies suggest that other factors also are important (Schiffer, 2008). Actually, it is the tendency to become depressed in response to life events that are inherited (Hirschfield & Weissman, 2002). Moreover, family and twin studies show a clear genetic component of life events themselves (Kendler & Karkowski, 1997).

ENDOCRINE MODELS OF DEPRESSION

Neuroendocrine abnormalities that reflect the neurovegetative signs and symptoms of depression include: first, increased cortisol and corticotrophin-releasing hormone (CRH) secretion, second, an increase in adrenal size, third, a decreased inhibitory response of glucocorticoids to dexamethasone, and fourth, a blunted response of thyroid-stimulating hormone (TSH) level to infusion of thyroid-releasing hormone (TRH). Antidepressant treatment leads to normalization of these pituitary-adrenal abnormalities (Reus, 2008).

Thyroid hormone may potentiate both the speed and the efficacy of antidepressant medication (Altshuler et al., 2001). Furthermore, there also evidence that patient resistant to other treatments may respond to addition of thyroid hormone (Joffe & Marriott, 2000).

NEUROCHEMICAL MODELS OF DEPRESSION

The most famous hypotheses generated to account for the actual mechanism of the mood disorder focus on regulatory disturbances in the monoamine neurotransmitter systems, particularly that involving norepinephrine and serotonin (5-hydroxytryptamine). It has also been hypothesized that depression is associated with an alteration in the acetylcholine-adrenergic balance and characterized by a relative cholinergic dominance. In addition, there are suggestions that dopamine is functionally decreased in some cases of major depression.

Original reports suggesting that patients with endogenous depression experienced either decreased noradrenergic or serotonergic activity now appear to be overly simplistic. All the monoamine neurotransmitter systems are interrelated and subject to compensatory adaptation to perturbation over time (Reus, 2000).

CELLULAR MODELS OF DEPRESSION

Most current hypotheses of neurotransmitter function in altered mood states have focused on changes in receptor sensitivity and second messenger

systems. With a few exceptions long-term antidepressant treatment is associated with reduced postsynaptic I?-adrenergic receptor sensitivity and enhanced postsynaptic serotonergic and cyclic adenosine monophosphate activity (Reus, 2000).

A number of intracellular changes which involve alterations in cellular second messenger systems and ion channels are postulated to occur in depression. Intracellular changes may involve changes in guanine triphosphate binding proteins, G-proteins on the receptor, cyclic adenosine monophosphate (cAMP) regulation, reduced protein kinase activity and brain derived neurotrophic factor (BDNF). Antidepressants as well as ECT increase BDNF and BDNF have been found to increase functioning of serotonin (Kay & Tasman, 2006).

NEUROIMAGING MODELS OF DEPRESSION

Recent rapid advances in neuroimaging methodology have attempted to relate the phenomenological abnormalities seen in depression to

changes in brain structure and function (Fu et al., 2003). There is increasing evidence that depression may be associated with structural brain pathology. Magnetic resonance imaging (MRI) has revealed decreased volume in cortical regions, particularly the frontal cortex, but also in subcortical structures, such as the hippocampus, amygdala, caudate, and putamen (Sheline & Minyun, 2002).

The most widely replicated Positron emission tomography (PET) scanning (PET) finding in depression is decreased anterior brain metabolism, which is generally more pronounced on the left side. In addition, increased glucose metabolism has been observed in several limbic regions (Thase, 2009).

Neuroimaging has also helped in the further investigation of the neurochemical deficits in depression. The largest study to date using PET found a marked global reduction in brain 5-HT2 receptor binding (22-27%) in various regions (Sheline & Minyun, 2002).

There is an increasing literature using neuroimaging to understand suicidality, particularly in depression. Mann (2005) cites several imaging studies suggesting decreased serotonin function in suicidal individuals and decreased activity in associated areas of the dorsal system involved in emotion regulation, such as the anterior cingulate. A number of regions more speci¬?c to suicidality are also highlighted, particularly those that seem to be involved in impulsivity and aggression, such as the right lateral temporal cortex, right frontopolar cortex, and right ventrolateral prefrontal cortex (Goethals et al., 2005). This literature has as well found structural abnormalities in relevant regions of the dorsal system, particularly the orbitofrontal cortex, which has speci¬?cally been linked to potential decision making de¬?cits that could lead to suicidality. Thus, such data potentially suggest clinically important subtype differentiation in brain function for this symptom (Ingram, 2009).

PSYCHOSOCIAL FACTORS

Stressful life events more often precede first, rather than subsequent, episodes of mood disorders. Some clinicians believe that life events play the primary or principal role in depression; others suggest that life events have only a limited role in the onset and timing of depression. Data indicate that the life event sometimes associated with development of depression is losing a parent before age 11. The loss of a spouse is the environmental stressor most often

associated with the onset of an episode of depression.

Another risk factor is unemployment; persons out of work are three times more likely to report symptoms of an episode of major depression than those who are employed (Sadock & Sadock, 2007).

PSYCHOLOGICAL FACTORS
PSYCHODYNAMIC THEORIES OF DEPRESSION

Psychoanalytic theory as postulated by both Freud and Abraham emphasized the connection between mourning and melancholia. The melancholic patient experiences a loss of self esteem with associated helplessness, prominent guilt and self deprecation. According to the theory, these symptoms result from internally directed anger or aggression turned against the self, leading to a depressive experience (Kay & Tasman, 2006).

Melanie Klein understood depression as involving the expression of aggression toward loved ones. Edward Bibring regarded depression as a phenomenon that sets in when a person becomes aware of the discrepancy between extraordinarily high ideals and the inability to meet those goals. Edith Jacobson saw the state of depression as similar to a powerless, helpless child victimized by a tormenting parent.

Silvano Arieti observed that many depressed people have lived their lives for someone else (a principle, an ideal, or an institution, as well as an individual) rather than for themselves. Heinz Kohut’s conceptualization of depression, derived from his self-psychological theory, rests on the assumption that the developing self has specific needs that must be met by parents to give the child a positive sense of self-esteem and self-cohesion. When others do not meet these needs, there is a massive loss of self-esteem that presents as depression. John Bowlby believed that damaged early attachments and traumatic separation in childhood predispose to depression. Adult losses are said to revive the traumatic childhood loss and so precipitate adult depressive episodes (Sadock & Sadock, 2007).

Interpersonal Theory (IPT)

Interpersonal theory focuses on difficulties in current interpersonal functioning. In IPT, depression is held to relate to one or more of four functional areas: grief, interpersonal role disputes, role transitions, and interpersonal deficits.

In IPT, the reciprocal relationship between one’s mood and interpersonal events is investigated. Stressful life events may overwhelm coping ability and produce a depressed mood, which then contributes to ongoing interpersonal difficulties. Once this relationship is identified, modifying it becomes the focus of treatment (Grunze et al., 2008).

THE COGNITIVE MODEL

Cognitive theories of depression hypothesize that particular negative ways of thinking increase individuals’ probability of developing and maintaining depression when they experience stressful life events. According to these theories, individuals that possess specific maladaptive cognitive patterns are vulnerable to depression because they tend to develop negative information processing about themselves and their experiences (Sanderson & McGinn, 2001).

Behavioral Models

Martin Seligman developed the theory of learned helplessness as he was searching for an animal model of depression. In this formulation, individuals in stressful situations in which they are unable to prevent or alter an aversive stimulus (i.e., physical or psychic pain) withdraw and make no further attempts to escape even when opportunities to improve the situation become available (Reus, 2000).

Clinical Features of Depressive Disorders

Depressed mood is the most characteristic symptom, occurring in over 90% of patients. The patient usually describes himself or herself as feeling sad, low, empty, hopeless, gloomy, or down in the dumps. The physician often observes changes in the patient’s posture, speech, faces, dress, and grooming consistent with the patient’s self-report. A small percentage of patients does not report a depressed mood, usually referred to as masked depression. Similarly, some children and adolescents do not exhibit a sad demeanor, presenting instead as irritable or odd (Loose & Shelton, 2008).

Anhedonia manifests with a lack of interest in formerly pleasurable activities; sports and hobbies, etc. no longer arouse patients, and if they force themselves to partake, they take no pleasure in such activities. Libido is routinely lost and there is no pleasure in sexual activity (Moore, 2008).

Depressed individuals frequently report cognitive changes that include impaired attention, concentration, and decision making (Woo & Keatinge, 2008).

Sleep may be increased or decreased. Insomnia is one of the major manifestations of depressive illness and is characterized more by multiple awakenings, especially in the early hours of the morning than by difficulty falling asleep. Young depressive patients, especially those with bipolar tendencies, typically complain of hypersomnia, sleeping as long as 12 to 15 hours a day. Obviously, such patients will have difficulty getting up in the morning.

Although decreased sexual desire occurs in both men and women, women are more likely to complain of infrequent menses or cessation of menses. Decrease or loss of libido in men often results in erectile failure (Dunner, 2008).

Appetite can be decreased or increased with or without weight loss or gain; the most typical pattern is a decrease in appetite with weight loss (Faravelli et al., 2005).

Psychomotor disturbances include, on the one hand, agitation and on the other, retardation. Agitation, usually accompanied by anxiety, irritability and restlessness, is a common symptom of depression. In contrast, retardation, manifested as slowing of bodily movements, mask-like facial expression, lengthening of reaction time to stimuli, increased speech paucity. The extreme form of retardation is an inability to move or to be mentally and emotionally activated (stupor) (Stefanis & Stefanis, 2002).

The attitude and outlook of these patients may become profoundly negative and pessimistic. They have no hope for themselves or for the future. Self-esteem sinks and the workings of conscience become prominent. Patients see themselves as worthless, as having never done anything of value. Rather they see their sins multiply before them (Moore & Jefferson, 2004).

Suicidal ideation is almost always present. At times this may be merely passive and patients may wish aloud that they might die of some disease or accident. Conversely, it may be active, and patients may consider hanging or shooting themselves, jumping from bridges, or overdosing on their

medications. Often the risk of suicide greatest as patients begin to recover. Still seeing themselves worthless and hopeless sinners, these patients, now with some relief from fatigue, may find themselves with enough energy to carry out their suicidal plans.

The overall suicide rate in major depressive disorder is about 4 percent; among those with depressive episodes severe enough to prompt hospitalization, however, the rate rises to about 9 percent (Moore, 2008). Up to 15 percent of untreated or unsatisfactorily treated patients give up hope of ever recovering and kill themselves (Akiskal, 2009).

Proximal risk factors for suicide include agitation, current suicidal intent or plan, severe depression and/or anhedonia, instability (e.g., alcohol abuse or decline in health), recent loss, and availability of a lethal agent. Distal risk factors include a current suicidal intent with a plan, personal or family history of suicide, aggressive or impulsive behavioral pattern, poor response to treatment for depression, poor treatment alliance, a history of abuse or trauma, and/or substance or alcohol abuse (Hawton & Harriss, 2007).

Paranoid symptoms can occur among patients with major depression. There are usually exaggerated ideas of reference associated with notions of worthlessness. Characteristic delusions of patients with depression are those of a hypochondriacal or nihilistic type. Hallucinations may also occur in major depression. These commonly involve accusatory voices or visions of deceased relatives associated with feelings of guilt (North & Yutzy, 2010).

Adolescent-onset depression often takes on a more chronic course associated with dysthymic symptoms. In adolescence, MDD appears to be associated with greater fatigue, worthlessness and more prominent vegetative signs. The sequelae of depression in children and adolescents are sometimes characterized by disruption in school performance, social withdrawal, increased behavioral disruption and substance abuse (Kay & Tasman, 2006).

Among the elderly, agitation and hypochondriacal concerns are common, and indeed the patient may deny feeling depressed at all. Memory and concentration may be so impaired in demented elderly. In the past, this has been called a “pseudodementia,” presumably to distinguish it from other kinds of dementia. However, a better, more recent term is “dementia syndrome of depression” (Moore & Jefferson, 2004).

Elderly people are more likely than younger adults to have a depressive illness that goes undetected and thus untreated, which may contribute to the high risk

of suicide among older patients. The suicide rate of this population is higher than for any other age group, and the attempts are serious: One out of four succeeds, compared with one out of two hundred for young adults (Bjornlund, 2010).

Diagnosis and Classification of Depressive Disorders

Depression conceives a variety of psychic and somatic syndromes, and the diagnosis is derived from diligent clinical observation (Grunze et al., 2008).

Depression as a term in popular use is mostly considered to be synonymous with low mood or grief. Depression mental (and medical) disorder, however, is different, and besides low mood, is characterized by a variety of additional symptoms (Grunze et al., 2008).

Depressive disorders are defined by clinically derived standard diagnostic criteria of emotional, behavioral, cognitive, and somatic symptoms, and associated with functional impairment. They are assessed through structured clinical interviews and observation. The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 2000) and International Classification of Diseases 10 (ICD-10; World Health Organization, 1992) use the same criteria to diagnose depressive disorders in children, adolescents, and adults (Roberts & Bishop, 2005).

The term affect usually refers to the outward and changeable manifestation of a person’s emotional tone, whereas mood is a more enduring emotional orientation that colors the person’s psychology (American Psychiatric Association, 1984).

Subtypes of Depressive Disorders:
Major Depressive Disorder (MDD)

According to DSM-IV-TR, a major depressive disorder occurs without a history of a manic, mixed, or hypomanic episode. A major depressive episode must last at least 2 weeks. Typically, a person with a diagnosis of a major depressive episode also experiences at least four symptoms from a list that includes changes in appetite and weight, changes in sleep and activity, lack of energy, feelings of guilt, problems thinking and making decisions, and recurring thoughts of death or suicide (Sadock & Sadock, 2007). Table 1.1.1 shows DSM-IV-TR criteria for major depressive episode.

Unipolar and Bipolar Depression

When a person develops an episode of mania they are conventionally identified as suffering from bipolar disorder. Patients with depressive episodes only are diagnosed as having unipolar depression (Baldwin & Birtwistle, 2002).

Melancholic Depression

Individuals with melancholic depression experience a loss of pleasure in all or almost all activities or are nonreactive to usually pleasurable activities (American Psychiatric Association, 2000). In addition, according to the DSM-IV-TR, the individual must display three or more symptoms from a list of six, such as worsening depression in the morning, early morning awakening, significant weight loss or anorexia, and the perception that one’s mood is qualitatively different from that experienced in other contexts. Melancholic depression is considered a severe form of affective illness (Woo & Keatinge, 2008).

Self-belittlement, an exaggerated sense of guilt, a feeling that life is pointless and that one has failed in everything are very often accompanied by severe recurrent suicidal thoughts and thoughts about death. However, the risk of suicide usually first becomes prominent when the patient is in the process of

improvement and the psychomotor inhibition decreases while, at the same time, expectations about the capacity to cope with the psychosocial situation are still very negative (Wasserman, 2001).

Table 1.1.1 DSM-IV-TR criteria for major depressive episode

Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.

Note: Do not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations.

depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful). Note: In children and adolescents, can be irritable mood.

markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others)

significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. Note: In children, consider failure to make expected weight gains.

insomnia or hypersomnia nearly every day

psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down)

fatigue or loss of energy nearly every day

feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick)

diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others)

recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide

The symptoms do not meet criteria for a mixed episode.

The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism).

The symptoms are not better accounted for by bereavement, i.e., after the loss of a loved one. The symptoms persist for longer than two months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.

Source. Reprinted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000.

Masked Depression

About 50% of major depressive episodes are unrecognized because depressed mood is less obvious than other symptoms of the disorder. Alexithymia, or inability to express emotions in words, can focus a patient’s attention on physical symptoms of depression, such as insomnia, low energy,

and difficulty concentrating, without any awareness of feeling depressed. Common masked presentations of major depression include marital and family conflicts, absenteeism from work, poor school performance, social withdrawal, loss of a sense of humor, and lack of motivation (Joska & Stein, 2008).

Seasonal depression

Seasonal depression is a condition in which depressed mood accompanied by lethargy, excessive sleep, increased appetite, and irritability recurs each winter. It was believed to respond exclusively to light treatment. However, recent studies indicate it can be just as effectively managed with standard methods of treatment, such as medication (Gill, 2007).

Psychotic Depression

The term psychotic depression (or delusional depression) refers to a major depressive episode accompanied by psychotic features (i.e., delusions and/or hallucinations). Most studies report that 16%-54% of depressed patients have psychotic symptoms. Delusions occur without hallucinations in one-half to two-thirds of the adults with psychotic depression, whereas hallucinations are unaccompanied by delusions in 3%-25% of patients. Half of all psychotically depressed patients experience more than one kind of delusion (Dubovsky & Thomas, 1992).

Dysthymic Disorder

Dysthymia refers to symptoms of mild depression, which have persisted for at least two years. Symptoms fluctuate more than in major depression, and they are ‘typical’ including insomnia, lack of appetite, or poor concentration (Bech, 2003).

Double Depression

Double depression characterized by the development of MDD superimposed upon a mild, chronic dysthymic disorder (DD). Individuals with double depression often demonstrate poor interepisode recovery. Furthermore,

25% of the depressed individuals manifest double depression (First &Tasman, 2006).

Table 1.1.2 shows DSM-IV-TR criteria for dysthymic disorder.

Table 1.1.2 DSM-IV-TR diagnostic criteria for dysthymic disorder

Depressed mood for most of the day, for more days than not, as indicated either by subjective account or observation by others, for at least 2 years. Note: In children and adolescents, mood can be irritable and duration must be at least 1 year.

Presence, while depressed, of two (or more) of the following:

poor appetite or overeating

insomnia or hypersomnia

low energy or fatigue

low self-esteem

poor concentration or difficulty making decisions

feelings of hopelessness

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