Paediatric mood disorders
David Brent
Boris Birmaher
In this chapter, we describe the nosology and epidemiology of paediatric unipolar and bipolar disorders, risk factors and predictors of course, and the evidence base for pharmacological and psychosocial treatments. We conclude this chapter by suggesting areas for future research.
Clinical picture
Mood disorders may be classified on three dimensions: (a) severity; (b) course; and (c) presence or absence of mania/hypomania.(1) Depressed children and adolescents may not describe their mood as sad, but instead as, ‘grouchy’, ‘bored’, ‘having no fun’, or ‘empty’.(2) The most severe depressive condition is major depression, which requires at least 2 weeks of a depressed, sad, bored, or anhedonic mood for most of the time, and four additional depressive symptoms involving impairment in concentration, suicidal thoughts, difficulty making decisions, impaired sleep and appetite, guilt, and a decreased sense of self-worth (Box 9.2.7.1). Patients with depressive symptoms, but whose clinical picture is below the threshold for major depression (so-called minor depression or depression NOS) can still show significant impairment.(3) Dysthymic disorder is more chronic and intermittent than major depression, with periods of depression interspersed with normal mood, but with duration of at least 1 year (Box 9.2.7.2). Adjustment disorder with depressed
mood is a milder and self-limited disturbance of mood that follows a significant life stressor (Box 9.2.7.3).
mood is a milder and self-limited disturbance of mood that follows a significant life stressor (Box 9.2.7.3).
Box 9.2.7.1 Criteria for the diagnosis of a 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.
1 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.
2 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).
3 Significant weight loss when not dieting or weight gain (e.g. a change of more than 5 per cent 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.
4 Insomnia or hypersomnia nearly every day.
5 Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down).
6 Fatigue or loss of energy nearly every day.
7 Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional nearly every day (not merely self-reproach or guilt about being sick).
8 Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).
9 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 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 2 months or are characterized by marked functional impairment morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.
(Modified from APA (2000), Diagnostic and statistical manual of mental disorders (4th edn), American Psychiatric Association Press, Washington, DC.)
Box 9.2.7.2 Criteria for the diagnosis of 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:
1 poor appetite or overeating
2 insomnia or hypersomnia
3 low energy or fatigue
4 low self-esteem
5 poor concentration or difficulty making decisions
6 feelings of hopelessness
During the 2-year period (1 year for children or adolescents) of the disturbance, the person has never been without the symptoms in Criteria A and B for more than 2 months at a time.
No Major Depressive Episode (see p. 356)(1) has been present during the first 2 years of the disturbance (1 year for children and adolescents); that is the disturbance is not better accounted for by chronic Major Depressive Disorder, or Major Depressive Disorder, In Partial Remission. Note: There may have been a previous Major Depressive Episode provided there was a full remission (no significant signs or symptoms for 2 months) before development of the dysthymic disorder. In addition, after the initial 2 years (1 year in children or adolescents) of dysthymic disorder, there may be superimposed episodes of Major Depressive Disorder, in which case both diagnoses may be given when the criteria are met for a Major Depressive Episode.
There has never been a Manic Episode (see p. 362),(1) a Mixed Episode (see p. 365),(1) or a Hypomanic Episode (see p. 368),(1) and criteria have never been met for Cyclothymic Disorder.
The disturbance does not occur exclusively during the course of a chronic Psychotic Disorder, such as Schizophrenia or Delusional Disorder.
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 cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
(Modified from APA (2000), Diagnostic and statistical manual of mental disorders (4th edn), American Psychiatric Association Press, Washington, DC.)
The presence of clinically significant manic or hypomanic symptomatology suggests bipolar spectrum disorder. The symptomatology of mania can be thought of as the mirror image of depression, with mood characterized by elation or grandiosity. Mania is associated
with clear impairment, whereas hypomania, while associated with a change in functioning, does not always result in impairment per se. Bipolar individuals, especially in the paediatric age group, frequently do not show the classic distinct alternating manic and depressive periods found in adult bipolar patients. Instead they may either experience depression and manic symptoms simultaneously, so-called mixed episodes, or alternations of mania and depression that may occur within a month, a week, or even a day, e.g. rapid cycling.(4) Common symptoms of paediatric bipolar disorder are pressure of speech, increased energy, and decreased need for sleep. Risk-taking behaviour showing poor judgement (e.g. gambling, hypersexuality, excessive spending) and joking and excessive humour are very specific for paediatric bipolar disorder, but less common in paediatric samples. While irritability is a common symptom of paediatric bipolar disorder, it is very non-specific and is commonly found in many other conditions, such as depression, oppositional defiant disorder, and attention deficit disorder. The DSM-IV requires a relatively long duration of mania (7 days) and hypomania (4 days) in order to meet criteria. Many paediatric patients may show the same symptom pattern but have very rapid cycling and therefore, do not meet these criteria. If altered function is present, such patients should receive a diagnosis of Bipolar Disorder NOS. Bipolar NOS is a common diagnosis for children with manic symptoms because very often, paediatric bipolar illness does not fulfil the duration criteria for mania, in part due to the frequency of rapid cycling conform to the classic adult patterns of distinct patterns of mania and depression.(4) However, in children and adolescents, Bipolar disorder NOS does not appear to be different from Bipolar I or II with regard to impairment, rate of comorbid disorders, response to treatment, or family history of bipolar disorder, and many patients with BP-NOS upon longitudinal follow-up go on to develop BP-I or BP-II disorders.(4) Individuals who have had a history of full mania plus major depression receive a diagnosis of Bipolar I disorder, those with hypomania plus major depression receive a diagnosis of Bipolar II disorder, and those with hypomania and dysthymia receive a diagnosis of cyclothymic disorder (see Boxes 9.2.7.4 and 9.2.7.5).
with clear impairment, whereas hypomania, while associated with a change in functioning, does not always result in impairment per se. Bipolar individuals, especially in the paediatric age group, frequently do not show the classic distinct alternating manic and depressive periods found in adult bipolar patients. Instead they may either experience depression and manic symptoms simultaneously, so-called mixed episodes, or alternations of mania and depression that may occur within a month, a week, or even a day, e.g. rapid cycling.(4) Common symptoms of paediatric bipolar disorder are pressure of speech, increased energy, and decreased need for sleep. Risk-taking behaviour showing poor judgement (e.g. gambling, hypersexuality, excessive spending) and joking and excessive humour are very specific for paediatric bipolar disorder, but less common in paediatric samples. While irritability is a common symptom of paediatric bipolar disorder, it is very non-specific and is commonly found in many other conditions, such as depression, oppositional defiant disorder, and attention deficit disorder. The DSM-IV requires a relatively long duration of mania (7 days) and hypomania (4 days) in order to meet criteria. Many paediatric patients may show the same symptom pattern but have very rapid cycling and therefore, do not meet these criteria. If altered function is present, such patients should receive a diagnosis of Bipolar Disorder NOS. Bipolar NOS is a common diagnosis for children with manic symptoms because very often, paediatric bipolar illness does not fulfil the duration criteria for mania, in part due to the frequency of rapid cycling conform to the classic adult patterns of distinct patterns of mania and depression.(4) However, in children and adolescents, Bipolar disorder NOS does not appear to be different from Bipolar I or II with regard to impairment, rate of comorbid disorders, response to treatment, or family history of bipolar disorder, and many patients with BP-NOS upon longitudinal follow-up go on to develop BP-I or BP-II disorders.(4) Individuals who have had a history of full mania plus major depression receive a diagnosis of Bipolar I disorder, those with hypomania plus major depression receive a diagnosis of Bipolar II disorder, and those with hypomania and dysthymia receive a diagnosis of cyclothymic disorder (see Boxes 9.2.7.4 and 9.2.7.5).
Box 9.2.7.3 Criteria for the diagnosis of adjustment disorder with depressed mood
The development of emotional or behavioural symptoms in response to an identifiable stressor(s) occurring within 3 months of the onset of the stressor(s).
These symptoms or behaviours are clinically significant as evidenced by either of the following:
1 marked distress that is in excess of what would be expected from exposure to the stressor
2 significant impairment in social or occupational (academic) functioning
The stress-related disturbance does not meet the criteria for another specific Axis I disorder and is not merely an exacerbation of a pre-existing Axis I or Axis II disorder.
The symptoms do not represent bereavement.
Once the stressor (or its consequences) has terminated, the symptoms do not persist for more than an additional 6 months.
(Modified from APA (2000), Diagnostic and statistical manual of mental disorders (4th edn), American Psychiatric Association Press, Washington, DC.)
While some in the field continue to raise questions about the validity of the diagnosis of paediatric bipolar disorder, the convergent evidence from longitudinal and high-risk studies is that there it is the essentially an earlier manifestation of the same illness as is found in adults, is highly familial, and shows a chronic and consistent course.(4, 5)
Differential diagnosis
Attention deficit hyperactive disorder (ADHD) and disruptive disorders
Patients with ADHD, oppositional disorder, and conduct disorder are often irritable, show a low frustration tolerance, and can become demoralized due to school failure and peer rejection. However, in the absence of true depression, their mood will be restored as soon as the source of their frustration has been remedied. While both ADHD and depression are associated with poor concentration, the age of onset of ADHD is usually earlier than in mood disorders. Patients with ADHD have other accompanying difficulties such as hyperactivity and impulsivity that are part of the depressive picture. Conversely, depressed patients will show changes in sleep, energy level, appetite, mood, and self-worth that are not part of the picture of ADHD. The symptoms of ADHD, such as poor concentration, hyperactivity, and impulsivity can also be seen in bipolar disorder but patients with ADHD rarely have concomitant hypersexuality, grandiosity, and decreased need for sleep.(4, 5) However, hypersexuality may also be seen in victims of sexual abuse, but in contrast with the hypersexuality of bipolar disorder, is not accompanied by clinically significant grandiosity, pressure of speech, increased energy, and diminished need for sleep. Often, the diagnostic difficulty is not simply distinguishing between disruptive and mood disorders, but in the proper attribution of shared symptoms in patients with comorbidity, as is very often the case. When patients have both mood disorder and ADHD, usually the ADHD antedates the mood disorder. A diagnosis of a mood disorder can only be made when the shared symptoms, such as impaired concentration become worse in association with depressed or manic mood.
Anxiety disorders
Patients with anxiety disorder may also become quite dysphoric, but when the anxiogenic situation is removed, normal mood frequently ensues. Anxiety is a frequent antecedent of paediatric depression and bipolar disorder.(5, 6) Symptoms that are shared between disorders, such as difficulty with sleep, or impaired concentration, are attributed to the mood disorder only if they become worse with the onset of a depressed or manic mood state. Panic disorder is often comorbid with paediatric bipolar disorder.(5) However, it is important to distinguish between the symptoms of panic disorder, that are prominently somatic and associated with thoughts and feelings of dread, and rapid cycling and a mixed state, which are marked with mood instability and the presence of simultaneous, or rapidly alternating depressive and manic symptoms.
Box 9.2.7.4 Criteria for the diagnosis of bipolar disorder
There has previously been at least one Major Depressive Episode (see p. 356),(1) Manic Episode (see p. 362),(1) or Mixed Episode (see p. 365).(1)
The mood episodes in Criteria A and B are not better accounted for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified.
Past or current history of a Manic Episode is characterized by:
A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary).
During the period of mood disturbance, three (or more of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:
1 inflated self-esteem or grandiosity
2 decreased need for sleep (e.g. feels rested after only 3 h of sleep)
3 more talkative than usual or pressure to keep talking
4 flight of ideas or subjective experience that thoughts are racing
5 distractibility (i.e. attention to easily drawn to unimportant or irrelevant external stimuli)
6 increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation
7 excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g. engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.
The symptoms are not due to the direct physiological effects of a substance (e.g. a drug of abuse, a medication, or other treatment) or a general medical condition (e.g. hyperthyroidism).
Note: Manic-like episodes that are clearly caused by somatic antidepressant treatment (e.g. medication, electroconvulsive therapy, light therapy, should not count toward a diagnosis of Bipolar I disorder.
(Modified from APA (2000), Diagnostic and statistical manual of mental disorders (4th edn), American Psychiatric Association Press, Washington, DC.)
Box 9.2.7.5 Criteria for the diagnosis of cyclothymic disorder
For at least 2 years, the presence of numerous periods with hypomanic symptoms (see p. 368)(1) and numerous periods with depressive symptoms that do not meet criteria for a Major Depressive Episode. Note: In children and adolescents, the duration must be at least 1 year.
During the above 2-year period (1 year in children and adolescents), the person has not been without the symptoms in Criterion A for more than 2 months at a time.
No Major Depressive Episode (p. 356),(1) Manic Episode (p. 362),(1) or Mixed Episode (see p. 365)(1) has been present during the first 2 years of the disturbance.
Note: After the initial 2 years (1 year in children and adolescents) of Cyclothymic Disorder, there may be superimposed Manic or Mixed Episodes (in which case both Bipolar I disorder and Cyclothymic Disorder may be diagnosed) or Major Depressive Episodes (in which case both Bipolar II disorder and Cyclothymic Disorder may be diagnosed).
The symptoms in Criterion A are not better accounted for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified.
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. hyperthyroidism).
The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
(Modified from APA (2000), Diagnostic and statistical manual of mental disorders (4th edn), American Psychiatric Association Press, Washington, DC.)
Substance abuse
The use of marijuana, alcohol, or opiates can mimic the symptoms of depression, such as difficulty with concentration, motivation, low energy, and dysphoria. Amphetamine and cocaine abuse can mimic mania. Depressed and bipolar patients are at greatly increased risk of abusing substances, so that the presence of substance abuse does not rule out a mood disorder or vice versa, but in fact, should raise the suspicion of possible comorbidity.
Eating disorder
Patients with a restricting eating disorder who are nutritionally compromised may show symptoms that overlap with depression, including decreased appetite, low energy, and sad mood. Often the sadness is found in patients with anorexia who are being forced to gain or maintain weight against their will. A diagnosis of depression, unless there is a clear historical precedent that antedates the eating disorder, should only be made when the nutritional status of the patient has been normalized. Bulimic disordered patients often have difficulties with impulse control that need to be differentiated from bipolar disorder.
Borderline personality disorder
Although there is evidence that borderline personality disorder can be reliably diagnosed in adolescents,(7) diagnostic convention requires that this diagnosis only be applied for adults. Still, there is general agreement that many adolescents, particularly those with mood disorders, have ‘borderline features’, such as mood lability, impulsivity, suicidal thoughts and behaviour, chaotic interpersonal relationships, and risky behaviour that has a high likelihood of resulting in personal harm. Others have argued that borderline personality disorder is really a form of bipolar spectrum disorder, although family studies have not confirmed this.(5) Instead, the high degree of overlap between personality disorder and bipolar disorder suggests that care be taken in not attributing symptoms that more appropriately are associated with a lifelong personality style to bipolar disorder. Conversely, in the presence of a clear and unremitting paediatric mood disorder, personality disorder should not be diagnosed.
Psychosis
Although rare in childhood, incipient schizophrenia can present with sad and detached mood, sleep disturbance, and social withdrawal. Psychotic symptoms that evolve in schizophrenia are more likely to be mood-incongruent. In contrast, psychosis in depression and bipolar disorder is more often, but not always, mood-congruent.(2, 5) This is a diagnosis that often can only be made upon careful longitudinal follow-up. Since psychosis is often seen in youth with mood disorders, and schizophrenia is rare at this age group, any child or adolescents with psychosis needs to be carefully assessed for the presence of a mood disorder, particularly bipolar illness.
Comorbidity
Comorbidity is the rule, rather than the exception.(8) Anxiety disorder frequently antedates paediatric depression and bipolar disorder, with common precursors being social phobia and panic disorder, respectively. ADHD is frequently comorbid with both conditions. Substance abuse is often a complication of mood disorder, although this condition in turn lengthens episodes and increases the risk for recurrence.
Medical comorbidity
Medications used to treat epilepsy, inflammatory bowel disease, and rheumatic and allergic disease can have profound effects on mood. Corticosteroids can induce depression or mania. Phenobarbital is associated with depression, as is use of interferon.(9) Moreover, systemic aspects of the diseases themselves may increase the risk for depression, in epilepsy, asthma, diabetes, and thyroid illness. Oral contraceptives can also result in mood changes.
Descriptive epidemiology
The point prevalence of major depression in around 1-2 per cent in prepubertal samples, and between 3-8 per cent in adolescent samples.(10) The prevalence of bipolar disorder is around 1 per cent in paediatric populations, although the rate of ‘soft’ bipolar disorder, which has some, but not all of the core features of bipolar disorder, has been reported to be as high as 5 per cent in some adolescent samples.(11) The male to female ratio is around 1:1 for prepubertal depression, but increases to around 1:3 for depression after puberty. In contrast, the males and females have similar risk for bipolar disorder, regardless of pubertal status. The increased rate of depression after puberty is accounted for almost entirely by the increased risk in females, and may be related to changes in estradiol and testosterone associated with puberty.(12) Prepubertal major depression is an admixture of two subtypes: one is highly familial, with a high risk for recurrence and for eventual paediatric mania, and the second with comorbid with disruptive disorders, a low risk for depressive recurrence, an association with parental criminality, substance abuse, and family discord, and a course more similar to conduct disorder than to mood disorder.(13) A clear clinical syndrome of depression has been reported in children as young as aged 3, particularly in those young children with a family history of mood disorders.(14)
Course
Paediatric mood disorders tend to be both chronic and recurrent. While prepubertal depression comorbid with conduct disorder is likely not to be recurrent, studies of child-onset depression with a family history of depression show high rates of recurrence, with risks of recurrence of 40 per cent in 2 years, and over 70 per cent within 5 years.(2) The average length of a depressive episode is around 4-6 months in community samples, and 6-8 months in clinical samples.(15) The duration of dysthymic disorder is much longer, on average, around 5 years, according to one careful longitudinal study.(2) In patients with comorbid dysthymic disorder and depression, so-called double depression, the risk for prolonged episodes and recurrence are both very high.(2) Longer episodes are also predicted by comorbidity with substance abuse, conduct disorder, or anxiety disorder, family conflict, and parental depression.(10, 16)
Paediatric bipolar disorder does not often present with ‘classic’ periods of alternating depression and mania. Instead, such patients frequently present with either a mixed state, e.g. simultaneous occurrence of depression and mania, or rapid cycling, with brief and alternating periods of depression and mania.(4) In comparing the course of paediatric and adult bipolar patients, paediatric bipolar patients have many more episodes per year, and spend less time in remission.(4) Consistent with these longitudinal observations are findings from adult pedigrees that age of onset in bipolar disorder appears to be familial, and that earlier age of onset is associated with higher rates of drug abuse, alcohol abuse, rapid cycling, and suicide attempts.(17) Much of the impairment in paediatric bipolar disorder is associated with depressive symptoms that often never completely remit. As noted above, the adult criteria requiring 1 week and 4 days for mania and hypomania, respectively, may be overly stringent, insofar as a fairly high proportion (25 per cent) of patients below those criteria, so-called bipolar NOS, go on in longitudinal follow-up to develop clear Bipolar I or II disorder and 20 per cent of those with BP-II go on to develop BP-I within 2 years of follow-up.(4) A longer period to recovery is predicted by longer duration of mood disorder, rapid cycling or mixed episode, psychosis, and lower SES.(4)
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