1 Major Depression
Although in the past there was some doubt as to whether prepubertal children experience depression similar to that seen in adults, this view has been dispelled through the use of structured interviews and rating scales. Major depression is characterized by dysphoria (which in children may present as irritability) and an obvious loss of interest and pleasure in usual activities. Diagnostic symptoms also include a significant weight change secondary to decreased or increased food intake, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue or loss of energy on most days, feelings of worthlessness and excessive guilt, diminished ability to concentrate, and recurrent thoughts of death. A melancholic subtype of depression, characterized by marked anhedonia and early morning awakening, has been described in adolescents.
Epidemiology.

The prevalence of depression varies based on sampling and measurement: Studies in childhood report rates of 0.4–2.5% and in adolescence, 0.4–8.3%. The lifetime prevalence of depression starting in adolescence is 15–20%, underscoring the fact that depression is a common disorder. At least twice as many girls as boys meet criteria for depression during adolescence; prepubertal depression is equally common among the sexes. Depression is undertreated across the life span, despite available and effective treatments shown to counter the high cost of lost productivity (e.g., school failure in adolescence) associated with ongoing depression.

Etiology.
Many factors contribute to causing depression. However, there is strong evidence of a genetic basis for major depressive disorders across the life span. Individuals at high genetic risk appear to be more sensitive to the effects of adverse environmental conditions. Twin studies have shown a 76% concordance for depression among monozygotic twins reared together and 67% for monozygotic twins reared apart compared with 19% for dizygotic twins reared together. There is also an increased rate of depression (3–6 times greater) in first-degree relatives of patients suffering from a major affective disorder. Low functional levels of norepinephrine and serotonin are thought to be important genetic markers for depression and low urinary levels of 3-methoxyhydroxyphenylglycol and 5-hydroxyindoleacetic acid have been described in depressed patients. Positron emission tomography scans reveal altered metabolic activity in specific brain regions associated with mood, sleep, and appetite regulation. Neuroimaging data are reinforced by the fact that antidepressants that block presynaptic reuptake of serotonin are highly effective in treating depression. The development of hopelessness and helplessness secondary to an actual loss or the perception of loss suggests that cognitive factors play a role in the onset and maintenance of depression. Numerous studies confirm that adverse life events clearly play a role in causing depression, and there is even research on the pathophysiology linking experience and mood.

Clinical Manifestations.
Depressive symptoms vary according to age and developmental level. Spitz described the anaclitic depression of infancy, and Bowlby observed that separation from a primary caregiver after 6–7 mo of age first leads to strong protest (e.g., crying and searching). Eventually, abandoned infants become withdrawn and apathetic, exhibiting hypotonia, lethargy, and an obviously sad facial expression. These infants often cry silently and, when picked up, may cling to a stranger, though they are usually inconsolable.
The clinical picture of depression in children somewhat parallels that of adults, except that children are more likely to present with separation anxiety, phobias, somatic complaints, and behavioral problems. Instead of reporting sadness, children may behave irritably. The hallmark of psychotic depression in children is the occurrence of hallucinations; delusions are more common in adolescents and adults.
The symptoms of a major depressive episode usually develop over a period of many days or weeks. The duration of each episode of depression is variable, though symptoms often persist for 7–9 mo without treatment; 6–10% of episodes are more protracted. Several longitudinal studies show that children and adolescents who are depressed are at risk for the development of later episodes of depression. Other studies have shown that, within 2 yr of the first depressive episode, 40% of children who have had a major depressive disorder experience a relapse. For children, like adults, depression should be considered a chronic disease marked by periods of normal mood. However, 20–40% of teenagers hospitalized with major depression develop a manic episode within 3–4 yr of discharge. Three predictors of later mania in depressed adolescents are (1) a depressive symptom cluster characterized by rapid onset, psychomotor retardation, and mood-congruent psychotic features; (2) a family history of bipolar illness or other affective illness; and (3) induction of hypomania by antidepressant medication. The picture of depression is further complicated by the fact that co-morbidity commonly occurs: 20–50% of depressed children have two or more diagnoses, including an anxiety disorder (30–80%), a disruptive behavior disorder (10–80%), dysthymic disorder (30–80%), or substance abuse disorder (20–30%).

Diagnosis.
The Children's Depression Inventory, Children's Depression Scale, Depression Self-Rating Scale, and the Center for Epidemiological Studies Depression Scale for Children have all been shown to be helpful to clinicians in diagnosing depression in children and adolescents. However, clinical interview with the child and multiple adults familiar with the child
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remains the gold standard. There are no biologic tests specific for depression, though various biologic markers have been studied. For instance, during major depressive episodes, some children have been shown to hyposecrete growth hormone in response to insulin-induced hypoglycemia, whereas others produce higher growth hormone peaks during sleep. However, no test has sufficient sensitivity or specificity to assist in diagnostic assessment.

Treatment.
Both psychotherapy and pharmacotherapy are effective in treating depression in childhood and adolescence. Psychotherapy is especially important for patients with multiple diagnoses or precipitants related to family disruption or conflict. Cognitive behavioral therapy (12–16 wk) has been most well studied and is effective in about 70% of cases of adolescent depression. Rigorous studies have also shown that selective serotonin reuptake inhibitors (SSRIs) reduce depressive symptoms in about 70% of cases. However, only 1 of 12 controlled studies of tricyclic antidepressants (TCAs) have demonstrated efficacy, and these agents, which have a narrow therapeutic window and serious side effects, are rarely indicated for depression in childhood. Furthermore, because depression is strongly associated with suicidal ideation and attempts and TCAs are deadly in overdose, the pediatrician should avoid using these drugs for depression.