Pediatric Depression

Pediatric depression in the form of childhood and adolescent major depressive disorder (MDD) is a relatively common psychiatric condition that can continue episodically into adulthood. 

Childhood depression seems to be evident at earlier ages in successive cohorts and often occurs with comorbid psychiatric disorders, increased risk for suicide, substance abuse, and behavior problems. Children and adolescents with depression frequently have poor psychosocial, academic, and family functioning. (See Etiology.) 

The degree to which adverse childhood events, biologic processes, and genetic predispositions trigger depressive episodes remains the topic of some debate. However, the final common pathways to depression involve neurochemical changes in the brain. (See Pathophysiology and Etiology.) 

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) uses the same basic criteria to diagnose depression in adults and children. (See Presentation.) 

The choice of initial acute therapy depends on the following factors: 

• Severity 

• Number of prior episodes 

• Chronicity 

• Subtype 

• Patient age 

• Contextual issues – family conflict, academic problems, exposure to negative life events 

• Ability to adhere to treatment recommendations 

• Previous response to treatment 

• Patient's and family’s motivation for treatment 

In mild cases, psychosocial interventions and psychotherapies are often recommended as first-line treatments, whereas in moderate to severe cases, medication in addition to psychotherapeutic intervention is often recommended. (See Treatment.) 

Cognitive-behavioral therapy (CBT) as well as interpersonal therapy (IPT) have both been shown in multiple randomized clinical trials to be effective in the treatment of MDD in children and adolescents. For moderate-to-severe depression, both psychotherapy and psychopharmacologic treatment are recommended. Hospitalization should be considered for severely depressed patients for whom an effective safety plan and supervision cannot be provided at home and for those patients and families unable or unlikely to adhere to treatment recommendations. ^[2] (See Treatment and Medication.) 

Go to the Medscape article on depression for complete information on this topic.

The pathophysiology of depression is complex, multifactorial, and incompletely understood. Differences in clinical presentation, etiological factors, subjective diagnostic criteria, and the methodological challenges inherent in studying behavior have made research in this area difficult. However, as available evidence grows, it seems increasingly evident that there is not a single pathophysiologic pathway to exhibiting the signs and symptoms of depression. Indeed, there is enough diversity in genetic, psychosocial, anatomical, neurochemical, and developmental factors in individuals presenting with clinical depression that it has been suggested that major depressive disorder (MDD) is the final common pathway of a variety of physiologic anomalies rather than a discrete disorder of its own. ^{[2, 3]}   

Stress response 

The hypothalamic–pituitary–adrenal axis is activated in response to perceived stress, including psychological stress. Dysregulation of this axis, with abnormalities in negative feedback and CRH production, have been noted in pediatric depression. ^[4] In contrast, this finding has not been commonly observed in adult depression, except in those with significant trauma exposures. ^[3] This may be explained in part by the greater contribution from childhood adversity noted in pediatric-age depressive disorders. ^[2]  

Brain changes 

A variety of neuroimaging and post-mortem studies of depression agree that there are subtle yet significant anatomical and functional differences in the brains of depressed individuals. Unfortunately, there has been little consensus between studies on what exactly these changes are. Differences in the prefrontal cortex, ^[5]  total cerebral volume, lateral ventricle size, ^[6] reduced hippocampal volume, altered anterofrontal perfusion, ^[7]  and other changes have been inconsistently observed in youth with depression. 

These inconsistencies between studies reflect the difficulty of detecting subtle brain changes and correlating these changes between different imaging techniques. This is made even more difficult given the heterogeneity in what is currently categorized as major depression. Further complicating interpretation of these results is understanding how an observed neuroimaging difference correlates to a specific functional outcome and determining the correct etiology of observed changes. Determining the etiology of neuroimaging changes can be especially difficult given the comorbidities, such as trauma and anxiety, often present in depressed individuals. ^[8]  

Despite these difficulties, decreased volume and abnormal function of the left subgenual cingulate cortex has been identified in a variety of functional, structural, and post-mortum studies in depressed patients. ^[3] This has further been verified by more recent meta-analyses of neuroimaging data, including an analysis by Gray et al in 2020 ^[9] that found decreased size and increased activity of the subgenual cingulate to be a convergent finding between studies. This analysis also identified decreased size and increased activity in the left hippocampus and right amygdala, and decreased activity in the right putamen as weakly convergent abnormalities.  

Monoamine abnormalities 

The monoaminergic system includes serotonergic, noradrenergic, and dopaminergic neurons projecting from the midbrain and brainstem to significant portions of the entire brain. This system is involved in the regulation of a variety of brain functions that are altered in depression including mood, attention, sleep, appetite, cognition, and reward processing. This system has long been implicated in the pathophysiology of depression and remains the primary target of known pharmacologic interventions. ^[8]  

Monoamine deficiency as part of the pathophysiology of depression is supported by numerous studies over the years. These studies have observed that tryptophan deficiency in individuals with a family history of depression can induce symptoms of depression, ^[3]  that individuals with depression have lower monoamine oxidase (MAO) B activity, ^[10]  that these individuals exhibit decreases in certain serotonergic and dopaminergic receptors, ^[11] and that pharmacologic compounds that block reuptake of monoamines or inhibit MAO generally have antidepressant effects.  

Deficiency in monoamines, however, has not been sufficient to explain the entirety of the pathophysiology of depression. For example, other studies have shown that tryptophan deficiency does not cause depression in individuals without a family history of depression and that reserpine, which depletes around 95% of the brain’s monoamine supply, only causes depressive symptoms in around 5% of patients. In addition, SSRI medication leads to an almost immediate increase in synaptic serotonin activity, however, improvement in depressive symptoms typically does not occur for 3–5 weeks after starting an SSRI. For these reasons, monoamine deficiency is considered only part of the complex pathophysiology of depression. ^[8]  

Circuit dysfunction 

Integration of neuroimaging and neurochemical findings remains an ongoing area of research, however, there has been a shift in regarding depression as strictly a neurochemical or a neuroanatomical abnormality. Rather, an integrated model where a pathway of brain areas becomes dysregulated and eventually leads to persistent affective changes is increasingly adopted. In this circuit model, areas of the limbic system involved in affect regulation, such as the prefrontal and orbitofrontal cortices, anterior cingulate, basal ganglia, and thalamus, make up a neurologic circuit. Many of the brain areas involved in this circuit are either connected by or regulated by monoamine tracts. The circuit as a whole is affected by developmental experiences that exploit potential genetic vulnerabilities and lead to epigenetic, functional, and anatomic changes to the circuit. These changes result in affect deregulation and persistent depressive symptoms. ^[12]  

Biologic versus nonbiologic causes 

Both family history and psychosocial stressors, especially childhood adversity, are identified risk factors for the development of depression. While the relative contributions of these factors to the development of depression in a specific individual may vary, the final common pathways to depression involve neurochemical changes in the brain. (See Pathophysiology.)  

Genetic predispositions 

Major depression has been shown to be a familial disorder across a variety of family, twin, and adoption studies. ^[3]  Keeping in mind that depression is a multifactorial illness, genetic factors have been suggested to account for about 30–40% of this risk ^[13] with the remaining risk attributed predominantly to psychosocial stress. In pediatrics, around 40–60% of children and adolescents with a depressed parent will develop the disorder, most commonly initially presenting in adolescence. ^[2]  

Early life adversity 

Psychosocial stress is a well-established risk factor for the development of depressive disorders and can take a variety of forms. From interpersonal traumas and family relationship issues to societal issues such as poverty, discrimination, and acculturation stress, these events and circumstances can contribute to depression risk in all ages. In particular, early childhood adversity occurring prior to age 13 is an inciting factor in the majority (around 57%) of individuals with early onset (prepubertal) depression and remains a strong contributor in about 30% of those with later-onset depression. ^[14] While these associations are strongest with severe forms of child maltreatment such as abuse and neglect, less malignant stressors like interpersonal loss, household dysfunction, and economic hardship can add to the cumulative risk of depression. Several studies have noted that depression risk and severity correlate with the number and severity of adverse events in a dose response fashion. ^[15]  

Temperament and parent–child relationship effects 

In addition to childhood adversity, child temperament and parenting style can have potentially depressogenic potential. Child traits that increase risk for depression include underdeveloped self-understanding, underdeveloped mentalization, negative affectivity, and negative attributional style. Features of parent–child interaction and attachment can also contribute to depression risk. These features may include obvious issues such as emotional abuse, unsupportive parenting, and insecure attachment, or may be subtle such as diminished reward effort, dysfunctional interpersonal processes, impaired self-regulation, learned helplessness, or passive parenting styles. ^[2]  

Adults with depression report low paternal involvement and high maternal overprotection during early childhood. Troubled relationships with parents, siblings, and peers are common in children and adolescents with affective illness. ^[16] A child who is affectively ill often has a parent who is affectively ill. It is not uncommon for children to report abuse and/or neglect by the parent or parents who are affectively ill. 

Hammen et al reported a significant temporal association between maternal and child stress and depression. ^[17] They found that children with substantial stress exposure who also had a symptomatic mother were significantly more depressed than children who were exposed to comparable levels of stress only. 

Cohort effect 

Klerman and Gershon reported a progressive increase in the lifetime cases of major depression over the last 70 years. They found high rates of affective disorders among relatives, with a younger age of onset in successive cohorts. ^[18]  

Electronic media and screen time 

Increased time spent using electronic devices (eg, cell phones, tablets, computers, etc.) may have played a role in the increased rates of depression and suicide observed between 2010 and 2015, especially among girls, according to one study. Researchers found that adolescents who spent more time on new media (including social media) were more likely to report mental health issues, and adolescents who spent more time on nonscreen activities (in-person social interaction, sports/exercise, homework, print media, and attending religious services) were less likely. Although the study demonstrates a correlation between long hours of daily screen time and symptoms of alienation, it does not prove that one causes the other. ^[19]  

 A study by Boers et al in 2019 found an increase in 4-year depressive symptom severity for every hour increase in screen time. This correlation was strongest for social media screen time, but also was found with computer use and watching television. ^[20]  

Occurrence in the United States 

Reported US prevalence rates for depression in children and adolescents vary. Differences may be due to different populations sampled and variable criteria used. Studies have demonstrated that the occurrence of depression is not rare and is encountered regularly in pediatric and psychiatric practice. 

According to the Centers for Disease Control and Prevention (CDC), 4.4% (approximately 2.7 million) of children aged 3–17 years in 2016–2019 received a diagnosis for depression. ^{[21, 22]}  

The 2022 American Academy of Child and Adolescent Psychiatry (AACAP) Clinical Practice Guideline ^[2] reported lifetime prevalence of major depressive disorder in adolescents to be 11% with a past-year prevalence of 7.5%. Major depressive disorder (MDD) prevalence increased across adolescence with greater increases in female youth compared to male youth. Rates of depression in prepubertal children are lower, with a prevalence of preschool-age depression less than 2% 

International occurrence 

A meta-analysis completed by Polanczyk et al in 2015 estimated the worldwide prevalence of depressive disorders in children and adolescents to be 2.6%. ^[23]  

According to Jablensky, the World Health Organization (WHO) collaborative study on the assessment of depressive disorders examined depressive patients in Canada, Iran, Japan, and Switzerland and found considerable similarity in depressive symptomatology across cultures. ^[24]  

Age-related demographics 

Evidence suggests that the presentation of some symptoms may change with age. Symptoms such as somatic complaints, irritability, and social withdrawal are more common in children, whereas psychomotor retardation, hypersomnia, and delusions are less common prior to puberty than they are in adolescence and adulthood. ^{[25, 26, 27, 28]}  

Gender-related demographics 

A 2012 report by the Substance Abuse and Mental Health Services Administration (SAMHSA) indicates that gender differences in depression rates emerge at 12–17 years. The report states that girls aged 12–17 years are 3 times more likely than boys aged 12–17 years to have had a major depressive episode in the last year. ^[29]  

During adolescence, the increase of the overall rates of depression and the onset of new cases of depression peak. The rates of depression increase dramatically for both sexes, and the rate of depression in females grows to 3 times the prevalence rate for males. No sex differences are noted for depression symptom severity or recurrence. 

Race- and culture-related demographics 

Cultural norms associated with differing racial and ethnic groups can affect the experience and reporting of symptoms of depression. In some cultures, for example, depression may be experienced largely in somatic terms, in place of sadness or guilt. Several studies point toward the role of culture in childhood and adolescent depression. For example, the stress of acculturation was found to have a role in the increased incidence of depressive symptoms and suicidal ideation among Hispanic youths. ^[30]  

In an epidemiologic study of youths aged 12–17 years in Los Angeles County in 1998, Siegel et al found that Hispanic youths reported more symptoms of depression, independent of socioeconomic status, when compared with White, African American, or Asian American adolescents, using the Children’s Depression Inventory (CDI). ^[31] This study also found significant effects of social class on depression. As income decreased, the average level of depression increased. 

Studies have shown that both Black and Hispanic adolescents receive fewer mental health services in general and are less likely to receive minimally adequate pharmacotherapy for depression compared to Whites. This finding remained significant regardless of socioeconomic status. Hispanic children are 50% more likely to be admitted to the hospital for mental health reasons compared to White children. ^[32]  

More extensive studies of ethnic subpopulations of adolescents who are depressed are needed. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) states that a symptom should not be dismissed because it is part of a cultural norm. ^[1] Likewise, culturally distinctive experiences (eg, fear of being hexed or bewitched; experience of visitations from the dead) should be distinguished from actual hallucinations or delusions that may be part of a major depressive episode with psychotic features. 

A 2014 World Health Organization (WHO) report, “Health for the World’s Adolescents: A Second Chance in the Second Decade,” states that depression is the most frequent cause worldwide of illness and disability in persons aged 10–19 years, with the rate being highest in females. ^{[33, 34]} The report also states that as many as half of all mental disorders arise by age 14 years but are usually not recognized. Suicide is listed as the third leading cause of death among adolescents, behind road injuries and HIV/AIDS. 

Episode duration 

The median duration of a major depressive disorder (MDD) episode has been estimated at 1 to 2 months in community samples and 8 months in clinical samples. The average duration of persistent depressive disorder is estimated to be 3–4 years in both community and clinical samples. ^[2]  

Risk of future depression 

According to the American Academy of Child and Adolescent Psychiatry 2022 practice guideline for depressive disorders in childhood and adolescence, MDD is highly recurrent. An estimated 20% to 60% of cases will reoccur within 1–2 years after remission and 70% will reoccur within 5 years. Cases with higher comorbidity, prior reoccurrence, persistent subsyndromal symptoms, negative cognitive style, family dysfunction, and ongoing adversity are more likely to reoccur. Around 10% of cases become chronic. ^[2]  

Risk of suicide 

There were 41,149 deaths from suicide in 2013. In 2015, the CDC reported suicide as the third leading cause of death among persons aged 10–14 years and the second among persons aged 15–34 years. ^[35]  

Because mood disorders, such as depression, substantially increase the risk of suicide, suicidal behavior is a matter of serious concern for clinicians who deal with the mental health problems of children and adolescents. The incidence of suicide attempts reaches a peak during the mid-adolescent years, and the mortality rate from suicide increases steadily through the teenage years, with suicide being the third leading cause of death in that age group. 

Risk factors for completed suicide include the presence of a major mood disorder, recent life stressor, occurrence of command auditory hallucinations, use of substances, and evidence of specific plans and an attempt to prevent discovery, as well as patient perception of failure of the issues that precipitated suicidal thinking to change. This lack of action tends to escalate the patients’ sense of hopelessness. 

Around 30% of adolescents with MDD report suicidality of some form in the past year. Roughly 10% of adolescents with MDD report attempting suicide. ^[2]  

The Clinical Trial Registration Information–Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study noted that a history of nonsuicidal self injury (NSSI) can be predictive of future NSSI and suicide attempts in adolescents with treatment-resistant depression. ^[36]  

Another study noted a significant NSSI rate (3000 in 10,000) among Native American youths aged 10–14 years, specifically the White Mountain Apache tribe. Females reported a higher rate of NSSI than males; severe substance abuse was also noted among both boys and girls. While NSSI is largely unaddressed among the White Mountain Apache Tribe and likely other reservation communities, it is important to recognize that this mental health issue could serve as a precursor to suicide in this population. ^[37]  

Educating parents about children’s emotional problems is very important. Education is known to result in better compliance with treatment and to improve parents’ understanding toward their children. Patients should be educated in a manner congruent with individual development, level of impairment, and clinician judgment. 

The clinician should instruct parents and others in the homes of depressed youths to remove firearms or other lethal weapons from their homes to decrease the risk of suicide. Household medications also should not be accessible to depressed youths. Clinicians should help youth and families develop working safety plans for worsening symptoms. ^{[38, 39]}