▪ Mood Disorders Background Information
Childhood mood disorders have the potential for severely impacting development. Although described in adults (as melancholia and mania) since antiquity, the recognition of mood disorders in children is a much more recent historical phenomena and one that continues to be controversial in some ways.
Studies of childhood depression began to appear in the 1980s. Until that time, it was assumed, largely for theoretical reasons, that children either did not develop depressive disorders or that they presented in other ways (so-called “masked” depression). Although childhood depression can, at times, present in ways somewhat different than adults, it became clear that many of the symptoms are similar and that childhood depression is frequent, is a major source of suffering, and can be associated with suicide (see Chapter 24).
Similarly, although bipolar disorder in adults has been recognized since antiquity and was classically described by Kraepelin in the late 19th century, it was assumed for many years that children and adolescents did not experience it. However, work with adults suggested that, as with depression, symptoms often begin in childhood. Although bipolar disorder manifests itself somewhat differently in children, it clearly is observed. Differences from adults include manic periods that are shorter and more frequently interspersed with periods of subsyndromal mania, hypomania, or depression. As a result, case detection and treatment are frequently delayed as is diagnostic recognition of the condition.
DEPRESSIVE DISORDERS
Definition and Clinical Description
In children and adolescents, the hallmarks of depressive disorder include chronic, pervasive, and all-encompassing sadness; lack of pleasure in life and activities; and sometimes irritability. Depressive disorders differ from transient feelings of low mood based on their degree of pervasiveness, association with impairment, and lack of responsiveness to the usual activities that would make youth feel less depressed. The Diagnostic and Statistical Manual (DSM-IV-TR) recognizes several specifically defined depressive disorders as well as a not otherwise specified (NOS) category and mood associations with other conditions (e.g., medical conditions and substance abuse). Some of the relevant clinical features of these conditions are provided in Table 11.1.
TABLE 11.1 DEPRESSIVE DISORDERS IN CHILDHOOD AND ADOLESCENCE: AN OVERVIEW OF CLINICAL AND DIAGNOSTIC FEATURES1 | ||||||||||||||||||||||||||||||||||||||
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By definition, history of a manic, mixed, or hypomanic episode is an exclusionary criterion (in these cases, a bipolar diagnosis, discussed subsequently, is appropriate). It is possible to use various specifiers for severity (mild, moderate, severe), for the presence or absence of psychotic features, and for remission status (partial or full) for the most recent episode. Various other specifiers less relevant to children can also be made. For major depressive disorder, a child or adolescent must exhibit at least one major depressive episode (a period of 2 weeks of depressed or irritable mood or loss of interest or pleasure in activities). By definition, several additional symptoms of depression (e.g., weight loss or gain, loss of appetite, sleep problems, feelings of guilt or worthless, suicidal ideas or attempts, loss of energy, agitation, difficulties concentrating) must be present. Some modification of these criteria is made for children (e.g., failure to gain anticipated weight or irritability rather than depression).
For dysthymic disorder, a depressed or irritable mood must be present for at least 1 year and be associated with at least two depressive symptoms, such as appetite (under- or overeating) or sleep (insomnia or hypersomnia) disturbances, lack of energy, low self-esteem, difficulties with concentration or decision making, or hopeless feelings. By definition, the child or adolescent cannot be free of these symptoms for more than 2 months at a time. For a diagnosis of depressive disorder NOS, there must be a period of at least 2 weeks of depressed or irritable mood with some symptoms of major depressive disorder also present. Thus, the “subthreshold”
depression NOS is comparatively mild, but dysthymic disorder is somewhat more serious based on its chronicity and greater number of symptoms. In this group, the most severe condition is major depression in which multiple other symptoms are present; these may include withdrawal from social activities, suicidal thoughts, changes in need for sleep, feelings of guilt or worthlessness, lowered motivation or trouble concentrating, and decreased interest in food. Psychotic symptoms can be present in major depression, and the content of hallucinations or delusions usually has a marked depressive “flavor” (although sometimes paranoid thinking is observed); psychotic symptoms are less common in children. Major depression is often preceded by dysthymic disorder. The association with mania is another important consideration.
depression NOS is comparatively mild, but dysthymic disorder is somewhat more serious based on its chronicity and greater number of symptoms. In this group, the most severe condition is major depression in which multiple other symptoms are present; these may include withdrawal from social activities, suicidal thoughts, changes in need for sleep, feelings of guilt or worthlessness, lowered motivation or trouble concentrating, and decreased interest in food. Psychotic symptoms can be present in major depression, and the content of hallucinations or delusions usually has a marked depressive “flavor” (although sometimes paranoid thinking is observed); psychotic symptoms are less common in children. Major depression is often preceded by dysthymic disorder. The association with mania is another important consideration.
Other conditions with significant depressive aspects include adjustment disorders with depressed mood (e.g., after stress). Mood disorders can also be associated with general medical conditions (e.g., hypothyroidism). Various other conditions associated with depression can be diagnosed but are more common in adults.
There are some differences with the International Classification of Diseases (ICD-10)approach to the diagnosis of depressive disorders. The ICD 10 does not include criteria specific to children such as irritability and failure to make expected weight gain. Other differences include symptom thresholds and duration requirements. On balance, the DSM-IV-TR approach is somewhat more inclusive and likely more appropriate for children.
One of the great complications in understanding depression is the complex relationships depression has with other conditions. Anxiety disorders are very frequently observed in association with (often preceding) depression. Depression is also associated with attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) as well as with substance abuse problems and has a strong familial basis. The nature of this comorbidity remains somewhat poorly understood. It might, for example, relate to commonalities in the various conditions or might reflect the fact that our nosology is attempting overly fine-grained distinctions.
Epidemiology and Demographics
The prevalence of depressive disorders ranges from about 1% to 2% in childhood to somewhere between 4% and 8% of adolescents. By the end of adolescence, about 20% individuals will have been depressed. Starting in adolescence, female predominance emerges (female: male ratio, 3:1), possibly as a result of differential effects of hormones in the central nervous system (CNS), higher rates of anxiety disorder in girls, or an interaction of genetic and other risk factors.
Recent work has underscored the potential for depression to exist even in young children, although in this age group, either irritability or sadness may be prominent. Before puberty, depression is strongly associated with a range of other problems, including psychosocial adversity, chronic family fighting, parental substance abuse, or criminality. Prepubertal depression also increases the risk of adult antisocial disorder. In some cases, familial transmission is striking with associations to other disorders such as anxiety and bipolar disorders.
Etiology
Genetic factors are a major risk factor for depressive disorders. Studies in twins show a heritability of about 40% to 65% with higher concordance rates in identical twins. Early onset (before puberty) may be more mediated by environmental factors. Depressive disorders are also strongly related to anxiety symptoms, and there is some suggestion that anxiety symptoms might increase the risk by making individuals more susceptible perhaps via specific genetic factors.
Cognitive factors have also been implicated in the pathogenesis. In contrast to individuals without depression, those with depression tend to develop cognitive biases associated with depressive symptoms (e.g., in response to stressors). These distortions are seen in both children and adolescents, but they often persist in the adolescent group even after the depressive episode
itself has passed. Neuropsychological differences have also been identified in relation to specific memory and affective tasks.
itself has passed. Neuropsychological differences have also been identified in relation to specific memory and affective tasks.
Case Study: Depressive Disorder
Tommy was a 12-year-old boy who had exhibited difficulties in school over the past year. He was seen in the emergency department (ED) and complained of chronic depression, difficulties with sleeping and attention, lack of energy, and social isolation. He was overtly depressed with a sad mood. He cried easily and talked about his difficulties in school, which seemed related to his mood problems. He recently had been refusing to go to school. The visit to the ED was precipitated when his mother found Tommy’s diary open on his computer and saw that he was having thoughts of suicide (planning to jump in front of a train on tracks near their house). There was a strong family history of depression and anxiety problems. His mother herself had been treated for many years with a selective serotonin reuptake inhibitor (SSRI), and as an adolescent, she had one episode of suicidal ideation that led to hospital admission.
After the initial assessment, Tommy agreed to a no suicide contract, and both his parents and evaluator were comfortable with the arrangements the family had made to ensure his safety. Rapid follow-up was arranged, and he was enrolled in a partial hospital program quickly. A combination of an SSRI and cognitive behavior therapy led to remission of his symptoms, and he began attending school more regularly and transitioned into a less intense outpatient treatment program. At the time of last followup (age 15 years), he remained on medications but was free of depression and had returned to his previous levels of social and academic achievement in school.
Studies of twins have also shown the importance of environmental factors. Indeed, shared environmental effects appear at least as strong as genetic ones. So, for example, having a depressed mother might provide not only a genetic risk but also a model for depression. Families in which depression exists without a strong family history are more likely to have had various forms of psychosocial adversity. Similarly, child neglect and abuse increase the risk for depression as does loss of a parent or significant other (particularly if a strong family history of mood disorder exists). On the other hand, protective factors include good connections to family, community, and school; engagement with supportive peers; and appropriate parental expectations and supervision. Studies of the noradrenergic and serotonergic neurotransmission systems have noted some differences in children with depression. Sleep complaints are very frequent in early-onset depression but somewhat surprisingly are not strongly correlated with sleep patterns observed in sleep laboratories. There is some suggestion of differences in cortisol secretion in adolescents.
Neuroimaging studies have noted several potential areas of difference. For example, depressed adolescents exhibit differences in several brain areas, including the prefrontal cortex, as well as changes in the pituitary and amygdale. In one study by Thomas and colleagues (2001), differences were found in amygdala activation for depressed and anxious children.
Differential Diagnosis and Evaluation
Assessment of childhood and adolescent depression begins with the comprehensive evaluation of the child and often separate interviews with the parents. The focus is on both the depression and other comorbid diagnoses. As noted previously, symptoms must meet certain requirements in terms of duration and number and must be a source of impairment (e.g., on school performance or peer relationships). The focus on impairment is essential in differentiating normative
mood changes from a clinical disorder. As noted previously, the DSM-IV-TR allows irritable mood (rather than depression per se) to qualify for this diagnosis in children; when irritability is the presenting symptom, the clinician should be alert to the potential for depressive disorders to present in this fashion and alert to the possibility that the child or adolescent has relatively little awareness of the impact of his or her irritability on others. Similarly, the parents may not initially believe the child to be depressed and may view irritability as a sign of normal adolescent “storm and drung” (although the latter is not, in fact, necessarily normative; see Chapter 2). The adolescent may have somewhat greater insight given the increased cognitive capacities in this age group. Difficulties in school may result from chronic fatigue and difficulties with concentration and memory. Similarly, weight loss or failure to gain expected weight may be seen (excessive weight gain is more typical in adults). The individual may complain of feeling isolated or worthless. Adolescents are more likely than younger children to exhibit psychotic features or suicide attempts, but the latter is possible at any age (see Chapter 24). Given the complexities in how depression may present, it is common for the initial complaint to be one focused on school work or behavior change or substance abuse; sometimes a suicide attempt or expression of suicidal thoughts is what prompts parents or teachers to seek evaluation.
mood changes from a clinical disorder. As noted previously, the DSM-IV-TR allows irritable mood (rather than depression per se) to qualify for this diagnosis in children; when irritability is the presenting symptom, the clinician should be alert to the potential for depressive disorders to present in this fashion and alert to the possibility that the child or adolescent has relatively little awareness of the impact of his or her irritability on others. Similarly, the parents may not initially believe the child to be depressed and may view irritability as a sign of normal adolescent “storm and drung” (although the latter is not, in fact, necessarily normative; see Chapter 2). The adolescent may have somewhat greater insight given the increased cognitive capacities in this age group. Difficulties in school may result from chronic fatigue and difficulties with concentration and memory. Similarly, weight loss or failure to gain expected weight may be seen (excessive weight gain is more typical in adults). The individual may complain of feeling isolated or worthless. Adolescents are more likely than younger children to exhibit psychotic features or suicide attempts, but the latter is possible at any age (see Chapter 24). Given the complexities in how depression may present, it is common for the initial complaint to be one focused on school work or behavior change or substance abuse; sometimes a suicide attempt or expression of suicidal thoughts is what prompts parents or teachers to seek evaluation.
Comorbidity is frequent and is a complication for assessment. As many as half of depressed youth may have at least two comorbid conditions, and a single comorbid condition is even more frequent. For example, it is common for an anxiety disorder to precede depression and to be comorbid with it. Other frequent conditions include substance abuse, attentional disorders, and conduct problems. The presence of comorbid conditions can have important implications for treatment and thus their presence is an important aspect of the initial assessment. The clinician should also be alert to the possibility that children and adolescents with bipolar disorder may present with a depressive episode. Accordingly, careful inquire about manic or hypomanic symptomatology should be conducted, and the clinician following the child over time should be aware of the potential for bipolar disorder to develop after an initial period of depression. In taking a history, the clinician should be alert to the importance of potential stressors (e.g., for adjustment disorder with depressed mood), Similarly, bereavement can result in depressive symptoms. Substance use and withdrawal can also be associated with irritability or feelings of depression (substance-induced mood disorder can be diagnosed, but again the clinician should be alert to the possibility that the child has essentially been self-medicating depression). The role of routine laboratory tests is relatively limited with the exception of symptoms that suggest hypothyroidism, which should prompt testing. Features that suggest substance abuse or the presence of a general medical condition might prompt other laboratory studies. A host of other medical problems can include a significant component of depression (e.g., seizure disorders, infections, other endocrinologic conditions, and autoimmune disorders, among others). Children with infections such as mononucleosis may also complain of chronic fatigue, difficulties concentrating, and mood problems suggestive of depression. Finally, a variety of medications (including antibiotics, steroids, oral contraceptives, and others) can be associated with symptoms suggestive of depression. When depression can be reasonably attributed to any of these conditions, a diagnosis of mood disorder associated with a general medical condition is made.
The task of the clinician is complicated by the considerable symptom overlap between depressive disorders and a range of other conditions including eating problems associated with eating or feeding disorders (see Chapter 14); sleep problems associated with stress or other psychiatric conditions (see Chapter 20); and mood and self-esteem problems that are frequent in children with developmental, learning, or attention-deficits disorders.
Several rating scales and checklists are available. These include Children’s Depression Rating Scale-Revised (CDRS-R), a clinician-administered assessment of various symptom areas; this scale can be used at baseline and then for monitoring treatment efficacy.
Treatment
Effective treatments are available, including both pharmacologic and psychotherapeutic methods. These are used alone and in combination. In addition to medications, cognitive behavior
therapy (CBT) and interpersonal therapy (IPT) have been shown to be useful (see Chapters 22 and 23). Treatment studies in prepubertal children have been more limited than those in somewhat older children. Several studies have now questioned the effectiveness of the tricyclic antidepressants (TCAs) relative to placebo, although other studies using the selective serotonin reuptake inhibitor (SSRI) antidepressants have indicated benefit. Fluoxetine has been the most intensively studied agent in this class. There is some suggestion of age-related differences in response to the various available antidepressants in older individuals, and the differences in children and adolescents may be a manifestation of these developmental effects, with adolescents responding more favorably to these agents. In the Treatment of Adolescents with Depression Study (TADS), fluoxetine was more effective than either placebo or CBT. Interestingly, in that study, combined treatments were, overall, most effective. Although the SSRIs appear to be of greater benefit than placebo, the overall effect size is not high, reflecting a robust placebo response rate. Other SSRIs have been studied as well, although less extensively, and show benefit, although effect sizes are relatively small. Children appear to respond less well than adolescents. Side effects and adverse events are a source of concern. In a meta review conducted by the Food and Drug Administration, there were higher rates of suicide-related adverse events, mostly early on in treatment. Although the risk-to-benefit ratio appears to be acceptable, caution and careful monitoring, particularly early in treatment, are indicated. Other adverse effects include agitation and restlessness, sleep and gastrointestinal problems, and some risk for increased bruising. If combinations of serotonergic agents are used, there is an increased potential for serotonin syndrome, a potentially life-threatening toxic condition caused by excess CNS serotonin with autonomic, cognitive, and other effects. There is also some risk of eliciting mania. Some work in adults has suggested poorer response to the SSRIs if the short serotonin transporter variant is present. One of the potential advantages of agents such as fluoxetine is the potential for targeting anxiety, which may precede depression.
therapy (CBT) and interpersonal therapy (IPT) have been shown to be useful (see Chapters 22 and 23). Treatment studies in prepubertal children have been more limited than those in somewhat older children. Several studies have now questioned the effectiveness of the tricyclic antidepressants (TCAs) relative to placebo, although other studies using the selective serotonin reuptake inhibitor (SSRI) antidepressants have indicated benefit. Fluoxetine has been the most intensively studied agent in this class. There is some suggestion of age-related differences in response to the various available antidepressants in older individuals, and the differences in children and adolescents may be a manifestation of these developmental effects, with adolescents responding more favorably to these agents. In the Treatment of Adolescents with Depression Study (TADS), fluoxetine was more effective than either placebo or CBT. Interestingly, in that study, combined treatments were, overall, most effective. Although the SSRIs appear to be of greater benefit than placebo, the overall effect size is not high, reflecting a robust placebo response rate. Other SSRIs have been studied as well, although less extensively, and show benefit, although effect sizes are relatively small. Children appear to respond less well than adolescents. Side effects and adverse events are a source of concern. In a meta review conducted by the Food and Drug Administration, there were higher rates of suicide-related adverse events, mostly early on in treatment. Although the risk-to-benefit ratio appears to be acceptable, caution and careful monitoring, particularly early in treatment, are indicated. Other adverse effects include agitation and restlessness, sleep and gastrointestinal problems, and some risk for increased bruising. If combinations of serotonergic agents are used, there is an increased potential for serotonin syndrome, a potentially life-threatening toxic condition caused by excess CNS serotonin with autonomic, cognitive, and other effects. There is also some risk of eliciting mania. Some work in adults has suggested poorer response to the SSRIs if the short serotonin transporter variant is present. One of the potential advantages of agents such as fluoxetine is the potential for targeting anxiety, which may precede depression.
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