Depression and Anxiety Disorders

Daphne J. Korczak

Suneeta Monga

Depression and anxiety disorders are highly prevalent among adolescents and young adults (AYAs): 75% of all lifetime cases will have started by age 24 years.¹ Social withdrawal, substance use, poor academic performance, decreased concentration, fatigue, and other somatic complaints may all indicate a new onset of a mental health issue. AYAs, collectively referred to as youth in this chapter, may also have limited awareness of the severity or functional impact of their symptoms, because of symptom chronicity or reluctance to acknowledge a mental health problem. Thus, clinicians working with youth must have a high index of suspicion for mental health disorders among this population. This chapter reviews the most frequently encountered mood and anxiety disorders of adolescence and young adulthood, and discusses the key causes, assessments, and diagnoses of, and treatments for, these conditions.

DEPRESSION IN YOUTH

Epidemiology

According to the WHO, depression is a leading cause of disability globally.
Clinically significant depressive illness occurs in about 5% to 8% of adolescents in the US, Canada, and Europe.
Depressive symptoms are widely reported in community studies of youth. In one community survey of 9,863 adolescents in the US,² 18% of participants in early-middle adolescence reported depressive symptoms.
About 25% to 50% of depressed youth have comorbid anxiety disorders; about 10% to 15% of anxious youth have depression.
Gender: By mid-adolescence, the female predominance noted in adult samples is established: twice as many girls as boys are affected.
Age of Onset: Although the mean age of onset of a first depressive episode is mid-20s, this age is decreasing with each generation; the prevalence of the pre-adult age of onset of major depressive disorder (MDD) is increasing. Many children experience subsyndromal and syndromal symptoms for years before coming to medical attention. Early identification of depression is important for healthy psychosocial and cognitive development and improved illness outcomes among youth.
Onset of depression in adolescence is more likely to remain undetected for a longer period of time than onset in young adult or adulthood.
Clinicians treating youth with depression play a critical role in altering lifelong developmental trajectories.

Course of Illness

Onset of depression in adolescence is associated with a more severe course of illness than onset in young adulthood or adulthood.³,⁴ Affected adolescents are at greater risk of more depressive episodes, more severe episodes, increased suicidality, increased likelihood of dropping out of high school, poorer academic, occupational, and social outcomes, and greater psychiatric comorbidity than those who first experience depression as young adults or adults.

About 60% to 70% of those who have a depressive episode in adolescence will have a recurrence within 5 years.
Increased risk of recurrence is associated with greater episode severity, chronicity of symptoms, incomplete recovery, presence of dysthymia, comorbid anxiety, persistence of stressful life events, and parental history of depression.
Early in the course of depression, a psychosocial stressor is frequently present and identified as a precipitant for the depressive episode. In contrast, depressive episodes later in adulthood may occur without any discernible precipitating stressful event.

Risk Factors

A number of biological, psychosocial, and social factors have been associated with increased risk of depression among youth (Table 69.1).

Biological

Children of parents with a history of depression are at increased risk of developing depression.

Twin-study estimates of the heritability of MDD range from 0.36 to 0.70.⁵,⁶
Family studies⁷,⁸ estimate a 10% to 25% risk of MDD in first-degree relatives of MDD probands, two- to three times higher than that in controls.
Youth with depression are more likely than adults to have a family history of depression in a first-degree relative.
Offspring of parents with early-onset depression have about a four to five times higher risk of developing MDD (25% to 40% risk of MDD) than controls.
An adopted person’s risk of developing depression is increased if his or her biological parent had depression.

TABLE 69.1 Risk Factors for Depression among Youth

Biological Factors

Female sex
Older age
Parent/family history of depression
Comorbid chronic illness (e.g., diabetes, anxiety disorder, ADHD)
Past history of depression
Comorbid learning disorders
Genetics (presence of specific serotonin-transporter gene variants)
Certain medications (e.g., prednisone, isotretinoin [Accutane])
Substance use

Psychosocial Risk Factors

Family or peer conflict (e.g., bullying)
Childhood neglect or abuse (physical, emotional, sexual)
Poverty
Recent loss, e.g., death of a loved one, break up of romantic relationship
Academic difficulties or failure of the child
Discrimination and social exclusion
Poor (e.g., conflictual) home-school relationships
Poor-quality (e.g., high conflict, low community support) neighborhoods

Psychological

Psychological factors that may contribute to the development of depression include:

a tendency to respond to stress with unpleasant emotions, although many people with depression do not have strong emotional responses before the onset of depression
a tendency to interpret emotionally neutral events as negative.

The experience of depressive illness during adolescence and young adulthood disrupts normative developmental growth of personality characteristics.

Social

A number of social factors also are risk factors for development of depression among youth:

Bullying
Poverty
Poor physical health
Perceived discrimination within the household (i.e., the perception of having less access to material and emotional supports than other children in the home)
Increased daily-life stresses (e.g., excessive work or chores, academic difficulties)
Early-life stress, such as childhood abuse and neglect. Evidence indicates that early-life stress can induce persistent changes in the responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to stress later in life that is associated with depression (see below).

Causality

The origin of depression is multifactorial: neurobiological, pathophysiological, psychological, and social factors contribute to the genesis of MDD.

Neurobiological. Abnormalities of several brain structures are found in people with MDD, including the hippocampus, the hypothalamus, the amygdala, and the nucleus accumbens. Both structural and functional abnormalities have been described. Several neurotransmitter systems (serotonin, norepinephrine, dopamine) have also been implicated in the dysfunction reported in individuals with MDD, forming the basis for the use of the medication in treatment, as described below.
Pathophysiological. Possible underlying pathological processes causing depression include dysfunction of the HPA axis, increased proinflammatory cytokines, and oxidative stress.
Psychological. Numerous psychological theories about the basis of depression have been proposed. Both cognitive and interpersonal theories have led to specific treatment modalities for depressed youth (see treatment for depression). Other psychodynamic formulations of depression consider early developmental theories as a basis for understanding distress.⁹ It is important that clinicians using psychotherapeutic treatment modalities are well versed in the psychological theories pertaining to the basis of depression and the treatment modality that they intend to employ.

ASSESSMENT

In contrast to the transitory aspects of a normal depressed mood in youth, depressive illness is characterized by the persistence of depressed mood and associated features. Pessimism, reduced ability to experience pleasure, and decreased energy and motivation are also frequently present. Experiences of helplessness, hopelessness, or worthlessness may occur. Together with associated depressive symptoms, the condition interferes with the ability to function at school, at home, and with friends.

Important Elements in the Assessment of Depression

Interviews and Collateral Information

Individual clinical interview of the youth and interviews with the parents or guardians (whenever possible) to obtain collateral information are essential in order to assess symptoms and their functional impact. This should include depressive symptoms, assessment of suicidality and self-harm behaviors, elucidation of precipitating stressors (e.g., breakup of a romantic relationship, bullying, new disclosure of homosexuality), and presence of additional symptoms (psychotic, anxious) or behaviors (substance use) required to ascertain an accurate diagnostic impression.

Youth must be made aware of the limits of confidentiality in this interview when disclosures may have a potential impact on the safety of the patient or others. Youth may downplay or misunderstand the basis of these symptoms and attribute them to problems with nerves, imbalance, or being physically unfit. Sleep disturbance and loss of energy are the most uniformly reported of depressive symptoms. Sadness may be denied at first, but later elicited through clinical interview or inferred from facial expression.

Assessment of Illness Characteristics

The severity of the current depressive episode (mild, moderate, or severe), the presence of associated illness specifiers (e.g., presence of psychotic features), and the nature of the overarching mood disorder (bipolar or unipolar) must be determined.

Consideration of Cultural Background

Cultural background may affect the type and intensity of affective expression.¹⁰ Symptoms of depression share many similarities across cultures, but culture may affect the symptoms emphasized and the idioms used to describe distress.¹⁰ For example, poor eye contact may be a symptom of emotional distress in cultures that stress individual autonomy, but may be a sign of respect in cultures that stress deference. In addition, patients may report symptoms of considerable suffering, but their restrained expression of distress may strain the credibility of the report. Conversely, they may describe symptoms in a highly expressive manner that seems exaggerated. In some cultures, somatic symptoms may constitute the presenting complaint.

Screening Tools for Depression

A number of self-report and clinician-administered instruments have been evaluated and validated for use in the screening and
monitoring of depressive symptoms among youth. Self-report measures, in particular, have wide appeal because of their ease of administration, patient acceptability, and ability to translate symptom dimensions into quantifiable scores for evaluation. Although these instruments may be helpful supplementary tools for screening and monitoring depressive symptoms, they are not diagnostic instruments and cannot substitute for clinical assessment of depression. Although some measures have been validated in non-English-speaking youth, clinicians must be aware of individual cultural differences, intellectual or cognitive impairments, and comorbidity of depression with psychiatric and other chronic illnesses that may be pertinent and limit the generalizability of the measure’s utility for their patient.

Commonly used depression-specific measures, with demonstrated reliability and validity in the populations outlined below, include (but are not limited to) the following:

Beck Depression Inventory-II

Beck Depression Inventory-II (BDI -II) is a 21-item self-report instrument that takes 10 to 15 minutes to complete by individuals 13 years of age and older. Each question is scored from 0 to 3. Higher scores indicate more severe depressive symptoms.

Children’s Depression Inventory

Children’s Depression Inventory (CDI-2) is a 28-item scale derived from the BDI used to assess depressive symptoms in children and adolescents. Questions from the BDI were modified to make them more appropriate for younger ages. The CDI-2 is a self-report measure that takes 15 to 20 minutes to complete by patients 7 to 17 years of age. Each item is scored from 0 to 3. In addition, two-scale (emotional problems and functional problems) and four-subscale scores can be computed. Higher scores indicate more severe depressive symptoms.

Children’s Depression Rating Scale—Revised

This rating scale is a 17-item interviewer-administered instrument used to determine the presence and severity of depressive symptoms in children and adolescents. Each of the items is scored on a seven-point rating scale.

Patient Health Questionnaire

This questionnaire consists of nine self-report items that takes the adolescent or young adult about 5 to 10 minutes to complete. Originally developed for adults over 18 years of age, psychometric validity data also support its use among adolescent patients in primary care and pediatric hospital settings.

DEPRESSIVE DISORDERS AND THE DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL DISORDERS, FIFTH EDITION (DSM-5)

Major Depressive Episode¹¹

Five (or more) of the following nine symptoms must be present during the same two-week period.
Symptoms must either be newly present or have clearly worsened when compared with those present before the person’s current episode.
Symptoms must persist for most of the day, nearly every day, for at least two consecutive weeks.
At least one of the symptoms must be either (1) depressed mood or (2) loss of interest or pleasure.

Depressed mood, as indicated by either subjective or objective report, most of the day, nearly every day. For adolescents, the mood may be irritable.
Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day
Significant weight loss when not dieting, weight gain, or change in appetite
Insomnia or hypersomnia nearly every day
Psychomotor agitation or retardation nearly every day, observable by others, not merely subjective feelings of restlessness or of 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
Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, suicide attempt, or a specific plan for committing suicide Note: symptoms must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. The episode cannot be attributable to the physiological effects of a substance or to another medical condition. All of these criteria must be met to represent a major depressive episode.

Adjustment Disorder

See Chapter 34.

Persistent Depression (Dysthymia)¹¹

Depressed mood that occurs for most of the day, for more days than not, for at least 2 years (or one year for adolescents). Youth whose depressed mood resolves consistently during the summer months, for example, do not have a persistent depressive disorder.
At least two of six associated depressive neurovegetative or cognitive symptoms must be present.
At times, the patient may have also experienced a major depressive episode.
People with this disorder often describe years of feeling sad. Some youth may be unable to remember a time when they did not feel this way or attribute the experience to part of their personality.
Youth with persistent depressive symptoms are at high risk of developing comorbid psychiatric illness, including substance use disorders and personality disorders. As a result, they may require treatment for these in addition to management of their depressive disorder.

Bipolar Depression¹¹

Bipolar depression is differentiated from unipolar depressive illnesses by the presence of one or more periods of hypomania or mania during the course of illness. That is, bipolar depression refers to a Major Depressive Episode that occurs within the context of bipolar disorder.
Youth with bipolar disorder, despite having suffered a hypomanic or manic episode in their lifetime, frequently experience much of the illness’ morbidity as the result of either syndromal or subsyndromal depressive symptoms.
A Major Depressive Episode in adolescence or young adulthood may be the index mood episode of bipolar disorder; the mean age of onset of the first mood episode is about 18 years of age.
The presence of psychotic features, profound psychomotor retardation, or a family history of bipolar disorder should alert the clinician to the possibility of bipolar depression.
Clinicians considering the diagnosis of bipolar depression should request psychiatric consultation to assess the potential of an underlying bipolar diathesis and obtain management suggestions because treatment algorithms are substantially different from those for unipolar depressive illness.

Youth with depressive disorders may also suffer from comorbid psychiatric illness (particularly, substance use, attention deficit hyperactivity disorder [ADHD], conduct and anxiety disorders). These disorders must also be identified to ensure safe and appropriate recommendations for treatment are made.

TREATMENT

General Considerations

Ensure Safety

The single most important consideration in determining a treatment plan for depressed youth is to assess for the risk for suicide and ensure safety. Care providers must first decide whether the patient should be hospitalized or can be safely managed as an outpatient before proceeding with other treatment recommendations.

Provide Psychoeducation

Communication of the diagnosis of depression, eliciting patient and family conceptualizations of the illness, and the provision of psychoeducation about the symptoms, course, and treatments available for depression are key components to undertake before determining a treatment plan.

Identify and Address Stressors and Psychiatric Comorbidity

Additional components of a comprehensive treatment plan include discussing stressors that may be perpetuating depressive symptoms (e.g., ongoing family or peer conflict), and screening for and addressing comorbid psychiatric illness (e.g., substance use or anxiety disorders), as appropriate. It may be necessary to involve parents and/or guardians in order to address these factors.

Mild Depression

For youth with mild depression, addressing perpetuating factors, providing active support, scheduling regular visits, and monitoring symptoms may help alleviate symptoms.
Providing active, supportive strategies (e.g., encouraging involvement in enjoyable activities, ensuring sound sleep-hygiene routines, promoting routine physical activity, advocating for patients when they are having difficulties with academics or bullying at school) may relieve symptoms in as many as 20% of depressed youth.¹²
Patients who do not respond to these strategies should begin a depression-specific treatment.

Moderate to Severe Depression

Youth with moderate or severe depression should be referred to a specialist for assessment and management recommendations.
Once assessed, primary care physicians may undertake management plans alone or in collaboration with a mental health specialist.
Youth with moderate to severe symptoms are less likely to experience symptom remission without psychotherapy, medication, or combination treatment.

Psychotherapy

Cognitive Behavioral Therapy

Cognitive behavioral therapy (CBT) is a manualized treatment modality that can be delivered either individually or in groups, and administered in primary care settings. CBT is based on the cognitive theory of depression, which describes how people’s perceptions of, or spontaneous thoughts about, situations influence their emotional, behavioral (and often physiological) reactions. Perceptions are often distorted when people are depressed, and a stream of seemingly spontaneous negative thoughts, called automatic thoughts may be experienced. Depressive automatic thoughts fall into one of three categories: negative thoughts about the self, the world or environment, and the future.

CBT is an effective stand-alone treatment for depression in adolescents and a first-line treatment for depression of mild to moderate severity.¹³
The combination of CBT and pharmacotherapy is reportedly more efficacious than either treatment modality alone for the treatment of adolescent depression.¹⁴
The largest randomized placebo-controlled study to date, the Treatment for Adolescents with Depression Study,¹⁴ compared placebo, CBT alone, fluoxetine alone, and combination fluoxetine plus CBT. Adolescent participants in the medication arms demonstrated significantly greater improvement in their depressive symptoms than those in either the CBT-alone or placebo arms. In this investigator-initiated study, patients with more severe and persistent depression benefited equally from medication alone or from combined medication and CBT. Another study,¹² however, found that the addition of CBT to antidepressant medication and routine specialist care did not further reduce depressive symptoms for more severely depressed adolescents.

CBT has been adapted for the treatment of depression by focusing on correcting cognitive distortions such as depressive negative self-cognitions (e.g., “I am worthless,” “nobody likes me”), utilizing mood diaries to monitor symptoms, and expanding the behavioral component to include behavioral activation strategies (e.g., exercise, participation in group activities).

Interpersonal Therapy

Interpersonal therapy (IPT) is based on the interpersonal theory of depression, which suggests that people who are prone to depression are more likely to seek excessive reassurance in relationships. This support-seeking behavior tends to elicit support-giving behavior, which reinforces the depressive symptoms. The model further posits that this style of interpersonal communication may also occur more commonly in people with deficient social skills. People who excessively seek reassurance and may have poor social skills are theorized to have more interpersonal difficulties, including rejection, within their relationships, which further increases their depressive symptoms. As IPT was originally developed for the treatment of depression in adults, much of the evidence for its effectiveness comes from studies of adult populations, including young adults.

IPT has since been adapted for administration in adolescents (interpersonal therapy for adolescents [IPT-A]).
The central tenet of IPT is that depressive symptoms and interpersonal relationships are intertwined.
Connections are made between the person’s depressive symptoms and the practical life events that either precipitate or follow from the onset of the illness.
Patients must be assessed as having one of four relational areas as a central theme to inform the therapy: role transitions (e.g., graduation, moving away to school), grief, role disputes (having conflictual relationships with important people in their lives), or interpersonal deficits (difficulty forming relationships with peers).
Similar to CBT, IPT and IPT-A are structured, short-term, manualized therapies.
In contrast to CBT for the treatment of adolescent depression, data supporting the efficacy of IPT-A is more limited.
Comparison of the use of IPT-A to medication or in combination with medication to examine its comparative benefit has not been studied.

Nonspecific Psychotherapies

CBT and IPT (or IPT-A) are psychotherapies that may be indicated specifically for treatment of depressive symptoms among youth.
Youth with depression may also have comorbid psychiatric conditions or symptoms that are functionally impairing and highly problematic in their lives. The clinician may wish to consider using a psychotherapeutic modality that specifically targets these concerns, despite its lack of specificity for depressive symptoms, based on the difficulties that are the most distressing or impairing for the patient. For example, youth with highly conflictual family relationships may benefit from family therapy; those struggling with ongoing themes of past trauma may require a trauma-focused therapy. Motivational interviewing may address comorbid substance use; Dialectical Behavior Therapy may be required to address persistent thoughts and urges to engage in self-harm or suicidal behavior. Although these psychotherapies are not specific for the treatment of depression, the amelioration of the potentially perpetuating stressor or symptom may have nonspecific benefits in improving depressive symptoms.

Medication

Antidepressant medications are classified on the basis of their specific relation to brain neurotransmitters. Selective serotonin reuptake inhibitors (SSRIs) are a class of medications that include fluoxetine, sertraline, citalopram, escitalopram, fluvoxamine, and paroxetine (Table 69.2). SSRIs inhibit serotonin transporters, blocking reuptake and increasing the concentration of the serotonin neurotransmitter within the synapse. Within the broader class of SSRIs, specific medications may also influence other neurotransmitter systems (e.g., dopamine, norepinephrine), affecting the effectiveness and adverse effects of various SSRIs.

Laboratory Investigations

Laboratory investigations may be necessary to