The initial episode of major depression in clinically referred children and adolescents heralds a bifurcated clinical course. The indications are that among those who recover from that episode (i.e., >90%), around 20-30% continue to remain free of major depression episodes for up to 20 years. However, for about 70-80% of youths with childhood-onset depression, the initial episode of depression is the gateway to repeated depressions as the years go by. The typical episode of major depression in clinically referred youngsters lasts about 6-9 months; the interepisode intervals are variable but usually last several years. However, the occurrence of repeated episodes across the developmentally important phases of late childhood and adolescence has obvious negative implications for functioning. Whereas depression in community samples of adolescents and young adults typically reflects less severe forms of MDD, up to about one-third of such affected individuals report related functional impairment in their daily activities.7
Thus, the bulk of the evidence suggests that the occurrence of an initial episode of MDD in clinically referred children and adolescents signals a chronic condition for the vast majority. This course is characterized by depression episodes of variable lengths and longer periods of interepisode, mostly symptom-free, intervals. The most notable part of the literature on the course and outcome of depression is the relative consistency of findings on rates of remission and recurrence across the age span and across episodes of depression.2,3,5 This parallelism was illustrated by contrasting the findings of two methodologically similar follow-up studies of clinically referred samples: the Pittsburgh Longitudinal Study of Childhood Depression, which followed young patients from ages 8 to 13 years across more than 20 years into adulthood, and the NIMH Collaborative Study of Depression, which enrolled adult patients in their mid-30s, on average, and likewise followed them for several decades. However, because JOD signals a chronologically earlier onset of this chronic condition, adults with JOD will have spent more of their life in depression episodes than comparably aged peers whose depression first occurred in adulthood.
In the search for predictors of recovery from and recurrence of JOD, none of the traditional demographic or clinical variables has consistently emerged as a valid and reliable indicator of the outcomes in question. Furthermore, neither uncontrolled treatment, monitored during naturalistic follow-up of youths with MDD, nor receipt of state-of-the-art interventions in randomized clinical trials, appear to lead to clear-cut positive effects on rates of remission or recurrence in pediatric MDD. Once again, the findings on clinically referred youths echo the results from studies of adult patients, exemplified by the NIMH Collaborative Study of Depression.
In light ofthese findings, what research directions should be pursued? Given the overwhelming evidence that MDD episodes prognosticate extremely high rates of recovery in a variety of samples, even without treatment, it is not clear whether and how further studies of recovery and its predictors would advance the field. With regard to recurrence and its predictors, one very important issue concerns the bifurcated clinical course after the first MDD episode: in what ways do youths with a single episode of MDD (about 20-30%) differ from those who continue to experience a chronic course of repeated mood episodes? Given the methodological challenges of a new study that could answer this question, archival data could possibly be used to identify some of the critical dimensions or variables.
However, the evidence regarding the clinical course of MDD across the age span clearly suggests that research should be directed to a better understanding of how initial or subsequent episodes of MDD can be prevented or, in the case of children, at least delayed. Such a research direction involves a focus on risk factors or risk mechanisms that precede the onset of clinical depression and/or persist subsequent to an episode and serve to sensitize the affected individual to further spells of depression. This chapter illustrates one such approach to risk research that has focused on the role of mood repair and associated autonomic nervous system processes as playing a key role in depression. Studies of these variables among youths and adults already affected by depression and young offspringat high risk for depression (owing to depression in their parents or siblings), offer initial evidence that a combination of impaired mood repair and atypical CVC activity may be one risk factor for depression, one that also affects its course. Importantly, these constructs are developmentally mediated, which may enable early identification of high-risk cases. Additionally, the indications are that both mood repair and CVC can be modified, the former by various behavioral or cognitive strategies103 and the latter by means of meditation techniques,104 although other creative approaches are most likely needed to intervene with young children. Finally, there is ongoing interest in the identification of other constructs, which have both physiological and behavioral or psychosocial concomitants that may represent additional risk factors (or vulnerabilities) for depression in youths.29 By eventually integrating the results of such initiatives, successful ways to prevent or forestall JOD may emerge.