The unmet needs in diagnosis and treatment of mood disorders in children and adolescentsAre child-, adolescent-, and adult-onset depression one and the same disorder?
Introduction
The existence of major depressive disorder (MDD) in children and adolescents was controversial before the late 1970s (Puig-Antich and Gittleman 1982). Research over the past 2 decades, however, has clearly demonstrated that children are capable of experiencing episodes of depression that meet standard DSM-IV criteria for MDD Birmaher et al 1996b, Ryan et al 1987. In addition, MDD in children and adolescents is common, recurrent, and associated with significant morbidity and mortality (Birmaher et al 1996b). Epidemiologic studies estimate the prevalence of depression is 2% in children (Kashani et al 1983) and 5 to 8% in adolescents (Lewinsohn et al 1994). Within 5 years of the onset of MDD, 70% of depressed children and adolescents will experience a recurrence Kovacs et al 1984, Rao et al 1995. In addition, early-onset episodes of depression are associated with significant and persistent functional impairment (Puig-Antich et al 1993). Longitudinal follow-up studies estimate that 20 to 25% of depressed adolescents will develop a substance-abuse disorder (Birmaher et al 1996b), and as many as 5 to 10% will complete suicide within 15 years of their initial episode of MDD Rao et al 1993, Weissman et al 1999.
Despite similarities in the clinical picture and longitudinal course of MDD in children, adolescents, and adults (Kovacs 1996), there are notable differences in the neurobiological correlates and treatment response of depressed patients in these different age cohorts that warrant careful consideration. Most notably, depressed children and adolescents do not show evidence of hypercortisolemia as is frequently reported in adults Kaufman and Ryan 1999, Ryan and Dahl 1993, and depressed children and adolescents fail to respond to tricyclic antidepressants Hazell et al 1995, Keller et al in press.
There are many precedents in medicine in which earlier and later onset forms of disease represent illnesses with distinct neurobiological mechanisms despite similarity in clinical picture (Childs and Scriver 1986). A classic example is the comparison of juvenile- to adult-onset diabetes (Geller and Luby 1997). Nonetheless, there are alternate plausible explanations for the discrepant findings in child, adolescent, and adult studies.
This article is divided into three sections. The first section reviews extant data on the neurobiological correlates and treatment response of depressed children and adolescents. The second section discusses alternate explanations for the discrepancies in research findings across the life cycle. The differences are proposed to be due to 1) developmental factors, 2) stage of illness factors (e.g., number of episodes, total duration of illness), or 3) heterogeneity in clinical outcome (e.g., recurrent unipolar course vs. new-onset bipolar disorder). Because available data preclude definitive conclusions regarding the merits of these alternate hypotheses, the last section delineates directions for future research. Unfortunately, an answer to the question posed in the title of this article will require further systematic investigation.
Section snippets
Neurobiological correlates and treatment response of depression across the life cycle
As stated previously, there are significant inconsistencies in the neurobiological correlates and treatment response of depression in children, adolescents, and adults. There are also a few similarities. In this review, the similarities will be discussed first, followed by a discussion of the discrepancies in research findings across the life cycle. The data showing inconsistencies in research findings fall into two categories: research suggesting children and adolescents differ from one
Summary
Although there are some similarities in the neurobiological correlates and treatment response of depressed children, adolescents, and adults, the differences far outnumber the similarities. Both children and adolescents differ from depressed adults on measures of basal cortisol secretion, corticotropin stimulation post-CRH infusion, response to several serotonergic probes, immunity indices, and efficacy of TCA medications. Given the consistent inconsistencies in research findings across the
Reasons for discrepancies in research findings across the life cycle
There are at least three sets of factors that could contribute to the discrepant findings reported in studies of children, adolescents, and adults with depression. These include 1) developmental factors, 2) stage of illness factors, and 3) heterogeneity in clinical outcome. These alternate explanations are discussed further in the remainder of this section.
Directions for future research
The pattern of findings observed in the neruobiological correlates and treatment response of depressed children, adolescents, and adults is not entirely consistent nor easily understood (e.g., DST nonsuppression, normal basal cortisol secretion, normal corticotropin post-CRH infusion). The incorporation of central measures in neurobiological studies of early-onset affective disorders will allow for more direct examinations of similarities, differences, and potential developmental changes in the
Conclusion
Depression in children and adolescents is common, recurrent, and associated with significant morbidity and mortality. Over the past 15 years, we have learned that we cannot extrapolate down from what we know about depression in adults. There are many differences in the neurobiological correlates and treatment response of depressed children, adolescents, and adults. We currently do not know if child-, adolescent-, and adult-onset MDD are one and the same disorder. Systematic longitudinal
Acknowledgements
The preparation of this manuscript was supported by the Connecticut and Massachusetts Mental Illness Research Clinical Center (MIRECC), which is funded by a grant from the U.S. Department of Veterans Affairs (Director: Bruce J. Rounsaville, M.D.).
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