Depressive and Bipolar Disorders
BACKGROUND
Although described in adults since antiquity, depressive disorders were only recognized in children beginning 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 present in ways somewhat different from that in adults, it became clear that many of the symptoms are similar and that childhood depression is a frequent and impairing disorder.
Similarly, bipolar disorder or mania was first recognized in adults in ancient Greece and described by Kraepelin in the late 19th century, but it was assumed for many years that children could not experience it. Now there is recognition that, as with depression, children can suffer from bipolar disorders. Even more so, in most adults with bipolar disorder, the origins of the disorder can be traced to childhood or adolescence.
DEPRESSIVE DISORDERS
Diagnosis, Definition, and Clinical Features
In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (American Psychiatric Association, 2013), depressive disorders are separated from bipolar disorder and listed in separate chapters. In children and adolescents, the hallmarks of depressive disorder include chronic, pervasive, and all-encompassing sadness, lack of pleasure in enjoyable activities, and sometimes irritability. Depressive disorders differ from transient feelings of low mood based on their degree of pervasiveness and association with impairment in daily life or important areas of functioning. DSM-5 currently recognizes several specific depressive disorders as well as an unspecified depressive disorder and depressive disorders due to medical conditions and substance abuse. Some of the relevant clinical features of these conditions are provided in Table 14.1.
Depressive disorders exist on a continuum classified based on the number and severity of symptoms and the degree of associated functional impairment. It is also possible to use 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. For major
depressive disorder, a child or adolescent must exhibit one of two cardinal symptoms: (1) sad or irritable mood or (2) lack of interest and pleasure for at least 2 weeks. Youth must also have four or more other symptoms such as social withdrawal, difficulty concentrating, insomnia or hypersomnia, feelings of worthlessness, and thoughts of death or suicidal ideations.
depressive disorder, a child or adolescent must exhibit one of two cardinal symptoms: (1) sad or irritable mood or (2) lack of interest and pleasure for at least 2 weeks. Youth must also have four or more other symptoms such as social withdrawal, difficulty concentrating, insomnia or hypersomnia, feelings of worthlessness, and thoughts of death or suicidal ideations.
TABLE 14.1 Depressive Disorders in Childhood and Adolescence: An Overview of Clinical and Diagnostic Features | ||||
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For persistent depressive disorder, which is also called dysthymia, 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 (undereating or overeating) or sleep (insomnia or hypersomnia)
disturbances, lack of energy, low self-esteem, difficulties with concentration or decision making, or hopeless feelings. To meet criteria for dysthymia, the child or adolescent cannot be free of these symptoms for more than 2 months at a time. Milder versions of depressive disorder and subclinical forms of depression can still lead to considerable distress and impairment (Wesselhoeft et al., 2019). Other conditions with significant depressive aspects include adjustment disorders with depressed mood (e.g., after stress) and depressive disorders associated with general medical conditions (e.g., hypothyroidism). Various other conditions associated with depression can be diagnosed but are more common in adults.
disturbances, lack of energy, low self-esteem, difficulties with concentration or decision making, or hopeless feelings. To meet criteria for dysthymia, the child or adolescent cannot be free of these symptoms for more than 2 months at a time. Milder versions of depressive disorder and subclinical forms of depression can still lead to considerable distress and impairment (Wesselhoeft et al., 2019). Other conditions with significant depressive aspects include adjustment disorders with depressed mood (e.g., after stress) and depressive disorders associated with general medical conditions (e.g., hypothyroidism). Various other conditions associated with depression can be diagnosed but are more common in adults.
A new childhood disorder was introduced in the DSM-5 chapter on depressive disorder: disruptive mood dysregulation disorder (DMDD) (Roy et al., 2014). This disorder was included in the DSM-5 to recognize the cardinal mood feature of pediatric irritability and to address concerns about over-diagnosis of bipolar disorder based on chronic irritability. DMDD is diagnosed based on chronic and severe irritability, manifested in frequent temper outbursts with angry or depressed mood between outbursts. Temper outbursts typically occur in response to frustration or provocation and can be associated with verbal and physical aggression. DMDD is common among children seeking mental health services and the 1-year prevalence rates are estimated to be between 2% and 5%. DMDD is also highly comorbid with other childhood disorders, most notably attention deficit hyperactivity disorder (ADHD) and anxiety. Frequent temper outbursts are also a symptom in oppositional defiant disorder (ODD), and the differential diagnosis of DMDD requires the presence of persistent disruption of mood between outbursts. In addition, diagnosis of DMDD requires severe impairment in at least one setting and moderate impairment in the second setting. DMDD is considered a more severe disorder than ODD, although some diagnostic confusion between the two disorders remains as diagnosis of ODD has three specifiers—mild, moderate, and severe—based on the presence of symptoms in one, two, or three and more settings, respectively (Stringaris et al., 2018).
One of the great complications in understanding and diagnosing depression (and other mood disorders) in children and adolescents is the complex relationships among various forms of psychopathology. Anxiety disorders are very frequently observed in association with (often preceding) depression. Depression is also associated with ADHD and conduct disorder (CD) as well as with substance abuse problems and has a strong familial basis. The nature of these comorbidities 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 (Angold et al., 1999).
Epidemiology and Demographics
The yearly prevalence of depressive disorders ranges from about 1% to 2% in childhood to between 4% and 8% of adolescents. The lifetime prevalence of depression by the end of teenage years can be as high as 20%. Starting in adolescence, female predominance emerges (female: male ratio 3:1), possibly as a result of differential effects of hormones in the changes in the brain circuitry involved in emotion regulation as well as higher rates of other internalizing disorders such as anxiety disorder in girls during adolescence (Avenevoli et al., 2015).
Recent work has underscored the potential for depression in young children, although in this age group, either irritability or sadness may be prominent (Donohue et al., 2019). Before puberty, depression is strongly associated with a range of other problems, including psychosocial adversity, chronic family fighting, parental substance abuse, or criminality. In some cases, familial transmission is striking with associations to other disorders such as anxiety and bipolar disorders (Shanahan et al., 2011).
Etiology and Pathogenesis
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 of developing depression, perhaps via specific genetic factors (Brent, 2018).
(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 of developing depression, perhaps via specific genetic factors (Brent, 2018).
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 including negative view of self, future, and the world (Beck et al., 1979). These cognitive distortions and biases can exacerbate reactions to stressful life events and predict onset of exacerbation of depressive symptoms. These cognitive distortions have been identified in both children and adolescents, and they often persist even after the depressive episode has passed, posing risk for recurrence of depression. Ruminative cognitive style, which involves repetitive and passive focus on upsetting events, has been particularly strongly associated with depression in adolescence and adulthood (Nolen-Hoeksema, 1991).
Studies of twins have also shown the importance of environmental factors. Indeed, shared environmental effects appear at least as strong as genetic ones (Goodyer, 2015). 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 the loss of a parent or significant other (particularly if a strong family history of mood disorder exists) (LeMoult et al., 2020). On the other hand, protective factors include good connections to family, community, and school; engagement with supportive peers; and appropriate parental expectations and supervision.
Neuroimaging studies have shown consistent differences in the structure and function of brain regions and networks in emotional processing. For example, depressed adolescents were found to have dysfunctional connectivity in the attentional networks leading to greater attention to negative emotional cues and decreased activity in prefrontal cognitive networks that inhibit subcortical regions such as the amygdala that are involved in negative emotions (Miller et al., 2015). There are also consistent findings of abnormal neural processing of reward in children and adolescents with depression, namely, reduced striatal signal during reward processing (Keren et al., 2018). These neuroimaging results were found to be associated with concurrent symptoms of sadness and low positive affect as well as with the risk of developing depressive disorder later in life (Toenders et al., 2019). Studies of the noradrenergic and serotonergic neurotransmission systems have noted some differences in children with depression. Further, there is some suggestion of differences in cortisol secretion in adolescents (Brent, 2018).
Differential Diagnosis and Assessment
Assessment of childhood and adolescent depression begins with a 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-5 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 their 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 stress” (although the latter is not, in fact, necessarily normative; see Chapters 3 and 11). The adolescent may have greater insight into the nuances of their emotional experiences and interpersonal situations that might be linked to the experience and expression of sadness and anger. Difficulties in school are often associated with depression in children and adolescents and 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). Children may complain of feeling bored or worthless. Adolescents are more likely than younger children to exhibit some of the more serious features of depression including psychotic features or suicide attempts, but the latter is possible at any age (see Chapter 27). Given the complexities of how depression may present, it is common for the initial complaint to be one focused on school work, behavior change, or substance abuse; sometimes a suicide attempt or expression of suicidal thoughts is what prompts parents or teachers to seek evaluation (Box 14.1).
be seen (excessive weight gain is more typical in adults). Children may complain of feeling bored or worthless. Adolescents are more likely than younger children to exhibit some of the more serious features of depression including psychotic features or suicide attempts, but the latter is possible at any age (see Chapter 27). Given the complexities of how depression may present, it is common for the initial complaint to be one focused on school work, behavior change, or substance abuse; sometimes a suicide attempt or expression of suicidal thoughts is what prompts parents or teachers to seek evaluation (Box 14.1).
BOX 14.1 Case Study: Depressive Disorder
Liam is a 12-year-old boy who had exhibited difficulties in school over the past year. He was seen in the emergency department 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 emergency department was precipitated when his mother found Liam’s diary open on his computer and saw that he was writing about 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, and as an adolescent, she had one episode of suicidal ideation that led to hospital admission.
After the initial assessment, Liam agreed to a no-suicide contract, and both his parents and emergency department clinician were comfortable with the arrangements the family had made to ensure his safety. Rapid follow-up was arranged with the local community mental health clinic, and he was enrolled in a partial hospital program quickly. A combination of a selective serotonin reuptake inhibitor 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 follow-up (age 15 years), he remained on medications but was free of depression symptoms and had returned to the expected levels of social and academic achievement in school.
Reprinted with permission from Volkmar, F. R., & Martin, A. (2011). Essentials of Lewis’s child and adolescent psychiatry (1st ed., p. 142). Lippincott Williams & Wilkins/Wolters Kluwer.
Comorbidity is frequent and complicates 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 inquiry 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 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.
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 disorders (see Chapter 17); sleep problems associated with stress or other psychiatric conditions (see Chapter 21); and mood and self-esteem problems that are frequent in children with developmental, learning, or attention deficit disorders (see Chapters 7, 9, and 10).
Several rating scales and checklists are available. These include Children’s Depression Rating Scale-Revised (CDRS-R) (Poznanski & Mokros, 1996), a clinician-administered assessment of various symptom areas. The CDRS-R can be used at baseline and then for monitoring treatment efficacy. The Children Depression Inventory is another popular scale that has parent-rated and child self-report forms that provide cutoff scores for severity of depression based on a large standardization sample (Kovacs, 1992).
Treatment
Current guidelines for treatment of depression in children and adolescents are informed by four large clinical trials: the Treatment of Adolescents with Depression Study (TADS [N = 439]) (March, 2004), Treatment of Resistant Depression in Adolescents (TORDIA [N = 334]) (Brent et al., 2008), Adolescent Depression Antidepressants and Psychotherapy Trial (ADAPT [N = 208]) (Goodyer et al., 2008), and Improving Mood with Psychoanalytic and Cognitive Therapies (IMPACT [N = 465]) (Goodyer et al., 2017). Recent reviews summarize well-established approaches to assessment and treatment (especially psychotherapy) of adolescent depression (Goodyer & Wilkinson, 2019) as well as approaches to treatment-resistant depression (Dwyer et al., 2020). All treatment approaches emphasize psychoeducation, family engagements, and careful assessment of high-risk behavior of harm to self or others. Children with mild forms of depression can benefit from brief evidence-based psychotherapy and supportive counseling. Moderate to severe depression can require more intensive services and combinations of psychotherapy with medication.
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