Recognizing and Treating Depression in Children and Adolescents

Julie A. Dopheide


Am J Health Syst Pharm. 2006;63(3):233-243. 

In This Article

Etiology and Risk Factors

Youth involved in behaviors such as bullying and substance abuse and those with frequent somatic complaints have higher rates of depressive symptoms compared with those not exhibiting such behaviors.[14] High familial loading for a mood disorder (i.e., at least one first-degree and at least one second-degree relative has a mood disorder), a mother's lifetime anxiety disorder, and a behavioral disorder in the child increases the risk of developing a depressive disorder by threefold.[25] Other risk factors for developing depression include genetic predisposition and psychosocial stressors, such as maternal mental illness, lack of paternal communication, unsafe living conditions, physical or sexual abuse, and parental loss through death or divorce.[12,14]

A longitudinal study conducted in New Zealand followed 1265 children from birth to age 21 and monitored factors associated with increased rates of depression and suicidal behavior.[26] As expected, those exposed to sexual abuse, physical abuse, inter-parental violence, parental criminality, and parental use of illicit drugs had higher rates of depression and suicidal thoughts and behavior.[26] Factors associated with resiliency to depression and suicidal behaviors were intact family support systems, positive peer affiliations, and high self-esteem.[26]

Neurobiology of Depression

Magnetic resonance imaging studies have shown measurable brain changes in children and adolescents with depression compared with nondepressed control subjects. The left subgenual prefrontal cortex volume was reduced in young women with adolescent-onset major depression compared with healthy controls.[27] Anterior cingulate cortex glutamatergic concentrations were significantly lower in children with depression compared with age-matched controls.[28] Blunted growth-hormone secretion is associated with an increased risk of depression in youth.[29]

Smaller hippocampal volume was found in depressed women with a history of severe and prolonged abuse in childhood but not in depressed women who had not experienced similar abuse.[30] Another study found smaller amygdala volumes in 20 children and adolescents with major depression compared with 24 healthy controls; hippocampus volumes did not differ between groups.[31] There is increasing evidence of a link among early childhood trauma, depressive illness, and morphological brain changes, further substantiating the biological basis of depression in youth.[28,30]

Neurogenetic studies provide additional evidence for the biological basis of depression. Caspi et al.[32] found that a functional polymorphism in the promoter region of the serotonin transporter (5-HTT) gene moderates the influence of stressful life events on the development of depression. They assessed 1037 children (52% male) for depression and life stressors at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, and 26 years. These children were divided into three groups on the basis of their serotonin-linked promoter region (5-HTTLPR) genotype: those with two copies of the S allele phenotype (S/S homozygotes) (n = 147), those with one copy of the S allele (S/L heterozygotes) (n = 435), and those with two copies of the L allele (L/L homozygotes) (n = 265). The impact of life events on the self-reports of depressive symptoms was significantly stronger among individuals carrying an S allele than among L/L homozygotes (p = 0.02).[32]

Further analysis showed that stressful life events predicted suicidal ideation or attempt among individuals carrying an S allele but not among L/L homozygotes.[32] A separate case-control and family-based study lends support to these earlier findings.[33] Sixty-eight depressed children and 68 age-matched controls found an excess of the S/S genotype (p = 0.025) and of the S allele (p = 0.021) among the children with depressive illness.[33] It seems that depressed and suicidal children are more likely to receive the S allele of the 5-HTTLPR, and this may predispose them to developing depression in association with stressful life events. Polymorphisms in the 5-HTT protein can affect the use of serotonin by the neuron.[32] Serotonin dysregulation is implicated in the pathophysiology of depression in youth, and most effective antidepressants modulate serotonin neurotransmission.[8,12,23]


Suicidal thinking and attempts are common in youth with or without depression, with 19% of 15-19-year olds thinking about suicide and 9% attempting suicide each year.[34] If depressed, 35-50% will attempt suicide, and 2-8% will complete suicide over a decade.[6,34] Longitudinal studies have found that increased rates of suicidal behaviors in youth are associated with a family history of suicide, childhood sexual abuse, personality factors (e.g., high rates of anxiety and novelty seeking), negative peer affiliations, lack of school success, and untreated behavioral disorders and depression.[26,35] Increased suicidality may also be related to developmental factors, such as the lack of coping mechanisms or "black-and-white" thinking, where youth see themselves and their life as "all good" or "all bad." When things seem "all bad," youth turn to suicide because they are unable to conceptualize other options to end their emotional suffering.[9,26] Cognitive restructuring and behavioral interventions toward the development of coping skills and alternatives to suicide are two goals of CBT. CBT is considered a first-line treatment for depression in nonpsychotic youth.[9,26,36]

Completed suicide in youth is considered rare, with an overall 12-month incidence of 0.008% in youth age 15-19 years.[34] Suicide completion rates in youth actually decreased from 1995 to 2005.[5,34] Reasons cited for this reduction include decreased access to firearms and increased recognition and treatment of depression.[5] One study examined regional antidepressant use and national suicide mortality files of children and adolescents in 1990 and compared them with similar data collected in 2000.[37] The study showed that for every 1% increase in selective serotonin-reuptake inhibitor (SSRI) use in 10-19-year olds, there was a decrease of 0.23 completed suicide per 100,000 youth. This study of real-world antidepressant use in youth showed that antidepressants offer a protective effect against suicide completion. This finding conflicts with placebo-controlled clinical trials studying antidepressants in youth, which found increased suicidality early in treatment.[2,37]

Another study analyzed the relationship between antidepressant pharmacy prescription volumes and U.S. suicide rates in all age groups between 1996 and 1998.[38] The annual suicide rate in those three years was 12.32 suicides per 100,000 people.[38] Investigators found that prescriptions for SSRIs and other new-generation antidepressants (nefazodone, mirtazapine, bupropion, and venlafaxine) were associated with a 33% lower suicide rate, or 8.2 suicides per 100,000 people, versus those not receiving antidepressants and those prescribed tricyclic antidepressants.[38] A high number of prescriptions for tricyclic antidepressants in a county was associated with increased suicide rates, although counties with high rates of tricyclic antidepressant prescribing had fewer antidepressant prescriptions.[38] These findings were consistent in children, adults, and the elderly. Similar to previous studies' findings on risk factors of suicide completion, male sex was associated with higher suicide completion rates.[34] Black females were the least likely to complete suicide.[38]

In the United States, females receive more prescriptions for antidepressants compared with males, but males have significantly higher suicide completion rates.[39] This sex difference applies to all ages, including children.[5,34] According to several studies, most suicides and serious nonfatal suicide attempts are committed by individuals with major depression that was untreated at the time of death.[39,40]


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