AN INTEGRATIVE MODEL OF CHILDHOOD AND ADOLESCENT DEPRESSION

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An integrative model of depression in children and adolescents is presented, taking into account the complex interplay among genetic, neurobiological, cognitive and environmental factors in concert with developmental challenges and gender influences in the onset and maintenance of depression (see Figure 1; also see [7]). According to the model, genetic factors and early-life experiences influence temperamental characteristics and the neurobiological substrate (physiological stress reactivity, in particular). Early adverse experiences (e.g., poor-parenting practices and family disruption) also interfere with the development of secure and nurturing parent-child relationships. These adverse experiences alone or in interaction with temperament are internalized in the form of maladaptive conceptions about the self and interpersonal relationships. Family dysfunction and/or
temperament also are likely to have an impact on coping styles. Maladaptive conceptions of the self and interpersonal relationships, ineffective coping methods and neurobiological vulnerability, in turn, may create difficulties in interpersonal relationships, resulting in depression, or may augment vulnerability to depression under stressful situations. Sensitivity to stress may be highest during developmental transitions marked by maturational changes (e.g., the onset of puberty) or social-contextual changes (e.g., school transitions), thereby
intensifying the association between prior vulnerability and depression. Girls may be particularly at risk during this period due to gender-related distinctive characteristics that make them more vulnerable to the effects of transitions (i.e., a tendency toward negative selfevaluation, high investment in maintaining close relationships, and less adaptive responses to stress) as well as increased exposure to stress (e.g., increased parent-child conflict due to social expectations for gender-related roles).

Depression is likely to further compromise development by interfering with the achievement of key developmental tasks (e.g., academic achievement, negotiating changes in family relationships, and establishing peer networks), resulting in the generation of additional stress, and perhaps even contributing to compromised neurobiological development and sensitization to future stress, depression and other psychopathology.

These dynamic processes may account, in part, for why early-onset depression tends to be recurrent throughout the lifespan and is also accompanied by other psychiatric problems and significant disability.

ASSESSMENT OF DEPRESSION IN CHILDREN AND ADOLESCENTS

The assessment of depression in children and adolescents should include a careful evaluation of depressive symptoms, as well as assessment of other co-occurring psychiatric disorders and associated academic and psychosocial problems. It is also important to identify specific strengths of the child in addition to a medical evaluation. In order to reduce the variability in diagnosis across clinicians, a number of standardized tools have been developed to assess depression and comorbid disorders in youngsters (for reviews, see [278, 279]).
Overall, these instruments have demonstrated good inter-rater reliability for depressive symptoms, especially for children over 6 years. Test-retest reliability, however, has been less favorable since depressive symptoms tend to be unstable in younger age groups. In addition to standard diagnostic assessments, several ratings scales are available for assessing depressive symptoms in youngsters [278]. Because of their low specificity, these scales are not helpful for diagnosing clinical depression but they are useful to screen for depressive symptoms, to assess severity and to monitor clinical response to treatment. It is also important to note that many of these instruments were developed for the adult population, and the language of adult measures may be too sophisticated for youngsters [278]. This is particularly relevant for self-report measures that are completed independently. The contexts in which adults and youngsters function also are different. For example, items that reflect impairment in work and sexual domains will be less relevant for children than those that address school
performance. Moreover, a more thorough assessment may be warranted to assess symptoms found to typify depression in youngsters since maturational differences have been documented in the characteristics of depressive symptoms [25, 27, 30, 31]. A key issue in assessing psychopathology in youngsters is the selection of informants and the problems of integrating reports from different sources of information [280, 281]. For
example, cognitive and linguistic abilities in reporting internal feelings and perceptions vary markedly across development. Even though older children and adolescents are capable of reporting on their emotional states, they have limited cognitive ability to reflect on their functional states in the context of prior history and in comparison with their peers. Therefore, other sources of information, particularly from parents and teachers, are essential in the determination of psychopathology. The agreement among informants in reporting depressive
symptoms, however, is generally low [281]. One potential source of these discrepancies is the characteristics of the rater. For example, mothers who are depressed appear to overestimate the level of their children’s depressive symptoms [282]. Discrepancies also may result from true differences in behavior observed in different settings [280]. At present, there are no clear guidelines on how best to integrate data from different informants. It is generally accepted that children offer a better account of internal symptoms, such as depressed mood and
suicidal ideation, whereas parents and teachers are more aware of overt behaviors. Further investigation, especially focusing on the predictive validity of data from different informants, is necessary in clarifying these  issues.

TREATMENT AND PREVENTION OF DEPRESSION IN CHILDREN
AND ADOLESCENTS

Pharmacological Interventions

In adults, a number of antidepressant medications have shown efficacy not only in alleviating depressive symptoms and improving function but also in reducing relapse rates . In contrast, randomized clinical trials of these agents in children and adolescents showed only limited efficacy. Tricyclic antidepressants did not show efficacy in the treatment of pediatric depression , and moreover, these agents were considerably more lethal when overdosed in youngsters than in adults . Selective serotonin re-uptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) showed limited efficacy in pediatric depression. A number of methodological issues need to be considered in interpreting these findings, including modest sample sizes, limited number of trials, heterogeneity of samples and methods across sites, and
higher placebo response in younger patients. Fluoxetine is the best-studied antidepressant in pediatric depression, and in multiple trials, fluoxetine showed efficacy in relatively large samples of children and adolescents . These three studies were conducted at a single or limited number of sites by investigators with significant clinical and research experience in pharmacologic treatment of pediatric depression, thereby reducing the variance in depression ratings across raters and sites. Furthermore, these investigations either had an extended evaluation or placebo washout phase, potentially reducing the placebo response rate. In addition to short-term efficacy, in a well-designed randomized controlled trial, continuation treatment with fluoxetine was found to reduce the risk of relapse of depression.

The most troublesome issue related to pediatric use of antidepressants has been warnings about increases in suicidal ideation and behavior in children, adolescents and young adults, although no suicides were reported . No compelling data are available to indicate whether the net result of treatment of depression with these compounds in youth is an overall increase or decrease in the hazard of completed suicide . Until further evidence is  available, clinicians should carefully weigh the risks and benefits of antidepressant treatment in each individual patient, and to monitor patients closely after treatment is instituted, particularly during periods of initial treatment and dose titration. In addition to expanding the clinical trials of newer antidepressant drugs in children and adolescents, future investigations should attempt identify predictors of clinical response and adverse events so that more specific and safe treatment strategies can be implemented for specific subgroups of patients.

Psychosocial Interventions

Psychosocial approaches have shown promise in the treatment of pediatric depression. Of the various psychosocial interventions, cognitive-behavioral therapy (CBT) has received the most empirical attention in children and adolescents. Randomized controlled trials of CBT have been conducted in both clinical and community samples, targeting depressive symptoms or clinical depression . Although CBT programs for pediatric depression broadly target cognitive distortions and behavioral skill deficits, specific CBT manuals vary substantially in the extent to which they emphasize cognitive vs. behavioral strategies, employ techniques drawn from other therapeutic interventions (e.g., family therapy), utilize a group vs. individual approach, or require meeting with the youth alone or involve parents in some components of the treatment  . The programs also differ in the number and overall structure of the sessions. In addition to CBT, interpersonal psychotherapy has shown efficacy in adolescent depression  . Interpersonal psychotherapy for adolescents (IPT-A) focuses more strongly on reducing interpersonal stress and developing more adaptive responses to interpersonal difficulties  . IPT-A also appears to target cognitive processes . There is limited evidence for the efficacy of family therapy in adolescent depression . Despite the demonstrated efficacy of psychosocial interventions for pediatric depression, CBT in particular, dissemination of these therapeutic interventions in clinical settings has not been successful . Effect sizes for psychotherapeutic interventions in mental health clinics are significantly lower than those seen in randomized efficacy trials . A number of factors might explain this discrepancy to this gap, including the characteristics of youth and families enrolled research studies versus those seen in community care , and the resources available for training and supervision in controlled trials versus practice settings  . There is also a lack of understanding of which core components of empiricallybased treatments need to be disseminated because very few studies measured the core processes of treatment and evaluated whether the changes in these processes accounted for intervention outcomes . In order to bridge the gap between laboratory and clinical settings, a dramatic shift is necessary both in research and policy.

 

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