Review
Childhood and adolescent depression: Why do children and adults respond differently to antidepressant drugs?

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Abstract

Childhood and adolescent depression is an increasingly problematic diagnosis for young people due to a lack of effective treatments for this age group. The symptoms of adult depression can be treated effectively with multiple classes of antidepressant drugs which have been developed over the years using animal and human studies. But many of the antidepressants used to treat adult depression cannot be used for pediatric depression because of a lack of efficacy and/or side effects. The reason that children and adolescents respond differently to antidepressant treatment than adults is poorly understood. In order to better understand the etiology of pediatric depression and treatments that are effective for this age group, the differences between adults, children and adolescents needed to be elucidated. Much of the understanding of adult depression has come from studies using adult animals, therefore studies using juvenile animals would likely help us to better understand childhood and adolescent depression. Recent studies have shown both neurochemical and behavioral differences between adult and juvenile animals after antidepressant treatment. Juvenile animals have differences compared to adult animals in the maturation of the serotonergic and noradrenergic systems, and in dose of antidepressant drug needed to achieve similar brain levels. Differences after administration of antidepressant drug have also been reported for adrenergic receptor regulation, a physiologic hypothermic response, as well as behavioral differences in two animal models of depression. The differences between adults and juveniles not only in the human response to antidepressants but also with animals studies warrant a specific distinction between the study of pediatric and adult depression and the manner in which new treatments are pursued.

Section snippets

Adult depression

Depression describes a transient mood state experienced by virtually all individuals at some time in their life, generally in response to stressful life events as well as a serious clinical disorder. Major depressive disorder (MDD, American Psychiatric Association's DSM-IV manual) is a debilitating and serious mental illness that affects approximately 2–5% of the population worldwide, with a lifetime prevalence of around 15%. This disorder significantly interferes with the ability of the

Childhood and adolescent depression

Major depressive disorder not only affects adults but also commonly diagnosed in the pediatric population. Although the clinical symptoms of adolescent and childhood depression vary with developmental age, overall they are similar to those seen in adults. It is one of the most common mental health disorders in this population, with a prevalence in children of up to 2.5% (Birmaher et al., 1996) and during adolescence somewhere between 4 and 8%, with a 25% prevalence by the end of adolescence (

Differences between adult and juvenile animals

One approach to address this need of developing better therapies for pediatric depression is to determine the response of juvenile animals to antidepressant administration and compare to the response of adult animals. Because the brains of juvenile animals are not yet mature, it is necessary to have some understanding of the roles that maturation of the various neurotransmitter systems, particularly those for norepinephrine and serotonin, play in the response of juvenile animals to

Receptor regulation by antidepressant drugs

Because the adrenergic nervous system is not fully developed until late adolescence, the mechanisms regulating receptor density similarly may not yet be mature in young mammals, and thus the response to antidepressants that increase norepinephrine levels may be different in juveniles as compared to adults. Thus, it is of interest to compare the effects of desipramine treatment on cortical alpha-2 and beta-adrenergic receptors in juvenile and adult rats (Deupree et al., 2007). Desipramine was

Effect of desipramine administration on hypothermia

Another indication that the adrenergic nervous system is not fully developed until late adolescence is the lack of a hypothermic response of juvenile rats to acute desipramine administration. In adult rats, acute administration of desipramine results in a significant decrease in body (rectal) temperature. This effect may be a result of the increased synaptic norepinephrine activating the alpha-2A adrenergic receptor, because directly stimulating this receptor with an agonist produces

Animals models of depression and antidepressant drug action

A significant hindrance to basic research related to pediatric depression is the lack of juvenile animal models of study pediatric depression and antidepressant drug action in juveniles. Although there are some studies in which juvenile animals are subjected to various types of manipulations or stressors and then evaluated for depression-like behavior as an adult, studies on juvenile animals themselves are rare indeed. Using the two best accepted adult models, learned helplessness and the

Conclusion

Basic research directed toward the understanding of the differences in responses of juvenile and adult animals to drug administration must take into account several factors. First are the developmental aspects of the systems under study, particularly in terms of the signal transduction pathway (pharmacodynamics). Second are the difference in the pharmacokinetics, including differences in dose administered and the half-life of the agent. The antidepressant-like effects of desipramine, but not

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