Prevention of Depression in Children and Adolescents

Abstract

The articles included in this supplement to the American Journal of Preventive Medicine1Garber J. Depression in children and adolescents: linking risk research and prevention.Am J Prev Med. 2006; 31: S104-S125Abstract Full Text Full Text PDF PubMed Scopus (229) Google Scholar, 2Avenevoli S. Merikangas K.R. Implications of high-risk family studies for the prevention of depression.Am J Prev Med. 2006; 31: S126-S135Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar, 3Flannery-Schroeder E.C. Reducing anxiety to prevent depression.Am J Prev Med. 2006; 31: S136-S142Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 4Lynch F.L. Clarke G.N. Estimating the economic burden of depression in children and adolescents.Am J Prev Med. 2006; 31: S143-S151Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar, 5Schmiege S.J. Khoo S.T. Sandler I.N. Ayers T.S. Wolchik S.A. Symptoms of internalizing and externalizing problems: modeling recovery curves after the death of a parent.Am J Prev Med. 2006; 31: S152-S160Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 6Rao U. Links between depression and substance abuse in adolescents: neurobiological mechanisms.Am J Prev Med. 2006; 31: S161-S174Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar, 7O’Connor T.G. Cameron J.L. Translating research findings on early experience to prevention: animal and human evidence on early attachment relationships.Am J Prev Med. 2006; 31: S175-S181Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar were developed from presentations made at a National Institute of Mental Health (NIMH)–supported meeting entitled: Workshop on the Prevention of Depression in Children and Adolescents, held in June 2004. NIMH, in collaboration with the National Institute on Drug Abuse (NIDA), sponsored this meeting to consider extant research on prevention of depression in children and adolescents, and to discuss new opportunities for expanding the empirical base for preventive interventions. In contrast to the state of the science on prevention of aggression and externalizing behaviors in youth,8Barlow J. Parsons J. Group-based parent-training programmes for improving emotional and behavioural adjustment in 0–3 year old children.Cochrane Database Syst Rev. 2003; 2Google Scholar, 9Durlak J.A. Wells A.M. Primary prevention mental health programs for children and adolescents: a meta-analytic review.Am J Community Psychol. 1997; 25: 115-152Crossref PubMed Scopus (621) Google Scholar, 10Greenberg M.T. Domitrovich C. Bumbarger B. The prevention of mental disorders in school-aged children: current state of the field.Prevention and Treatment. 2001; 4: 1-63Google Scholar, 11Webster-Stratton C. Taylor T. Nipping early risk factors in the bud: preventing substance abuse, delinquency, and violence in adolescence through interventions targeted at young children (0–8 years).Prev Sci. 2001; 2: 165-192Crossref PubMed Scopus (362) Google Scholar with few recent exceptions,12Merry S. McDowell H. Hetrick S. Bir J. Muller N. Psychological and/or educational interventions for the prevention of depression in children and adolescents.Cochrane Database Syst Rev. 2004; 2Google Scholar, 13Horowitz J.L. Garber J. The prevention of depressive symptoms in children and adolescents: a meta-analytic review.J Consult Clin Psychol. 2006; 74: 401-415Crossref PubMed Scopus (547) Google Scholar, 14Commission on Adolescent Depression and Bipolar DisorderPrevention of depression and bipolar disorder.in: Evans D.L. Foa E.B. Gur R.E. Treating and preventing adolescent mental health disorders What we know and what we don’t know. Oxford University Press, New York2005: 55-67Google Scholar the evidence base for approaches to prevention of depression and/or anxiety symptoms and disorders in children and adolescents is sparse. Depression in children and adolescents is common, with median estimates of 1% to 2% of prepubertal children and 3% to 4% of adolescents experiencing a clinical depression within a 3- to 12-month period (reviewed in Costello et al.15Costello EJ, Angold A, Egger H. Epidemiology of child and adolescent depression. Review paper for workshop on preventing depression in children and adolescents. Available at: www.nimh.nih.gov/scientificmeetings/pastevents.cfm.Google Scholar), and approximately half of first episodes of depression occurring in adolescence.16Kessler R.C. Wai T.C. Demler O. Walters E.E. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication.Arch Gen Psychiatry. 2005; 62: 617-627Crossref PubMed Scopus (8186) Google Scholar Prior to adolescence, girls and boys have similar rates of depression, but after adolescence, rates of depression onset is higher for girls.17National Institute of Mental Health. Depression. What every woman should know. Bethesda MD: National Institute of Mental Health, National Institutes of Health, U.S. Department of Health and Human Services; 2000. NIH Publication No. 00-3679. Available at www.nimh.nih.gov/publicat/NIMHdepwomenknows.pdf.Google Scholar Depression in youth is associated with significant morbidity. Many depressed youth experience impairment in one or more domains of functioning, have an increased likelihood of comorbid mental disorders and substance use disorders, and are at an increased risk for suicide.14Commission on Adolescent Depression and Bipolar DisorderPrevention of depression and bipolar disorder.in: Evans D.L. Foa E.B. Gur R.E. Treating and preventing adolescent mental health disorders What we know and what we don’t know. Oxford University Press, New York2005: 55-67Google Scholar, 15Costello EJ, Angold A, Egger H. Epidemiology of child and adolescent depression. Review paper for workshop on preventing depression in children and adolescents. Available at: www.nimh.nih.gov/scientificmeetings/pastevents.cfm.Google Scholar Depression in children and adolescents is a significant public health problem. In addition to effective interventions to treat depression, interventions to prevent depression in youth are indicated to reduce the overall burden. The NIMH underscored the need for preventive efforts in the 2003 publication of Breaking Ground, Breaking Through: The Strategic Plan for Mood Disorders Research.18National Institute of Mental Health. Breaking ground, breaking through: the strategic plan for mood disorders research. Bethesda MD: National Institute of Mental Health, National Institutes of Health, U.S. Department of Health and Human Services; 2003. NIH Publication No. 03-5121. Available at: www.nimh.nih.gov/strategic/stplan_mooddisorders.cfm.Google Scholar This strategic plan reviewed research advances in our understanding of the etiology, treatment, and prevention of major depression and bipolar disorder. It also identified research gaps and provided priorities for additional research on mood disorders. Referring to translational and transdisciplinary research opportunities resulting from advances in neurobiology and genetics, it laid out a research agenda encouraging the novel development or refinement of treatment and prevention interventions that can be translated further into real-world applications. Research opportunities and priorities relevant to prevention of mood disorders in children and adolescents include improving identification of subsyndromal (high risk for) mood disorders, examining “how cognitive, behavioral, and affective vulnerabilities influence the onset and prolongation of mood disorders,” and examining specific mediators and moderators of intervention outcomes in well-defined populations. With the Strategic Plan as a backdrop for the meeting, 29 NIH-funded researchers shared their expertise on issues specific to prevention of depression in children and adolescents, or work in related areas with implications for the prevention of depression in youth. The primary focus was on major depressive disorder, as most current approaches to prevention of depression in youth target major depressive disorder. The meeting began with summaries of best prevalence estimates and approaches to assessment of internalizing disorders, along with a summary of high-risk events and transitions associated with the onset of internalizing disorders. Next, current approaches to preventing depression in youth, using diverse prevention strategies targeting high-risk youth and general populations of youth, were discussed. In addition, lessons learned from large-scale prevention efforts were examined, foremost among them, prevention of cardiovascular disease—to consider what it would take to mount a public health campaign for universal prevention of depression in youth. Finally, opportunities for additional testing of existing prevention models were considered, with a specific focus on neurobiology and genetics, and comorbidity. Also considered were alternative approaches, such as interpersonal and culturally based models. The meeting concluded with a discussion of accomplishments, challenges and opportunities in the prevention of depression in children and adolescents. A summary of the meeting will be available on the NIMH website (www.nimh.nih.gov). A review of the available data on the epidemiology of depression in children and adolescents also will be available on the NIMH website.15Costello EJ, Angold A, Egger H. Epidemiology of child and adolescent depression. Review paper for workshop on preventing depression in children and adolescents. Available at: www.nimh.nih.gov/scientificmeetings/pastevents.cfm.Google Scholar It summarizes what is known about the prevalence of depression in children and adolescents; differences in prevalence by gender, race and ethnicity; functional impairment associated with depression; comorbid psychiatric and substance use/dependence problems; and risk factors and correlates of depression. In addition, the review provides implications for prevention, based on the available epidemiologic information. The articles that follow cover salient issues that must be addressed in efforts to prevent depression in youth: risk and protective factors, and models of depression prevention; the economic burden of depression in children and adolescents; the impact of depression prevention programs; and translational research opportunities. Although the articles do not cover exhaustively the current state of the science for youth depression prevention, they do address many of the challenges and opportunities for reducing the burden of depression in children and adolescents. Moreover, the authors have included specific implications for further work on the prevention of child and adolescent depression. At the meeting, risk and protective factors for depression were reviewed across infancy, childhood, adolescence, and through young adulthood, with attention to high-risk events and transitions; later risk for depression due to depressive and anxious symptoms in childhood; substance use (alcohol, tobacco, and other drugs); genetic influences (including gene–environment interactions and gene–environment correlations); and other moderating and mediating factors of risk or protection for depression. While, to a certain extent, each article addresses risk and protective factors for depression in youth, as they inform etiology and intervention research, three articles address them specifically. Garber1Garber J. Depression in children and adolescents: linking risk research and prevention.Am J Prev Med. 2006; 31: S104-S125Abstract Full Text Full Text PDF PubMed Scopus (229) Google Scholar reviews basic research that examines risk factors for depression in multiple domains: gender, genetic vulnerability, family history of depression, subsyndromal depression, anxiety, neurobiological dysregulation, temperament and personality, negative cognitions, experience of stress and response to stress, and interpersonal relationships. She crosswalks information on risk factors with current prevention approaches, and describes the target populations and outcomes. Garber concludes with suggestions for future prevention efforts that consider the multiple depression risk factors that youth often experience. Her synthesis of research on multiple biological and psychosocial risk factors for depression suggests novel prevention strategies and opportunities for further examination of mediators and moderators of existing prevention programs. The article by Avenevoli and Merikangas2Avenevoli S. Merikangas K.R. Implications of high-risk family studies for the prevention of depression.Am J Prev Med. 2006; 31: S126-S135Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar considers the utility of prospective high-risk family studies for informing the etiology of depression among children of parents with affective disorders, and for developing targets for prevention strategies. Longitudinal studies of families with depressed parents (or other adult relatives with depression) have shown that those children are more likely to develop depression in adolescence. Avenevoli and Merikangas also review possible genetic, family environment, and child-specific factors that account for transmission of depression risk from parents to offspring. In addition, they report secondary data analysis findings from the Yale High-Risk Study, a prospective longitudinal high-risk family study of comorbid anxiety and substance use, to examine potential pathways to offspring depression. The secondary analysis includes probands with substance dependence or anxiety disorder, their spouse, and their children aged 7 to 18 years. It examines whether parent diagnoses were related to diagnoses in the offspring. In addition, the authors examine possible mediators of parent diagnoses and depression in the offspring: diagnoses of the co-parent, family environmental factors, and comorbid disorders in the offspring. They conclude with suggestions for future research with high-risk families regarding targets and timing of prevention, structure and content of prevention programs, and direction of future studies with high-risk youth. Finally, Flannery-Schroeder3Flannery-Schroeder E.C. Reducing anxiety to prevent depression.Am J Prev Med. 2006; 31: S136-S142Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar focuses on anxiety as a risk factor for depression—specifically, whether prevention and treatment of anxiety, which often precedes and/or co-occurs with depression in youth, can be considered a form of depression prevention. Anxiety onset often occurs much earlier in development than depression, and numerous studies have demonstrated that children with anxiety are at increased risk for developing depression.19Costello E.J. Mustillo S. Erkanli A. Keeler G. Angold A. Prevalence and development of psychiatric disorders in childhood and adolescence.Arch Gen Psychiatry. 2003; 60: 837-844Crossref PubMed Scopus (2680) Google Scholar, 20Birmaher B.B. Ryan N.D. Williamson D.E. et al.Childhood and adolescent depression: a review of the past 10 years Part I.Child Adolesc Psychiatry. 1996; 35: 1427-1439Abstract Full Text PDF PubMed Scopus (1409) Google Scholar, 21Weissman M.M. Wickramaratne P. Nomura Y. Warner V. Pilowsky D. Verdeli H. Offspring of depressed parents: 20 years later.Am J Psychiatry. 2006; 163: 1001-1008Crossref PubMed Scopus (462) Google Scholar Flannery-Schroeder reviews possible explanations for the link between anxiety and depression, including whether anxiety is a causal risk factor for depression, and whether there are common and distinct biological and psychosocial risk factors for the disorders. She also reviews the research that suggests a reduction in anxiety might prevent depression. Her suggestions for future research, in particular, stress the need for longitudinal studies of anxiety treatment and prevention interventions, to examine their long-term impact on depression. Although no large-scale epidemiologic studies of mood disorders covering both childhood and adolescence exist (e.g., the National Comorbidity Study included adolescents aged 14 to 18 years), smaller epidemiologic and community samples consistently document the public health significance of the problem. Mental health burden inevitably produces economic burden. What is known about the economic burden associated with depression in youth, although sparse, was discussed at the workshop. Knowledge gaps and research opportunities were identified. Lynch and Clarke4Lynch F.L. Clarke G.N. Estimating the economic burden of depression in children and adolescents.Am J Prev Med. 2006; 31: S143-S151Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar provide a systematic review of published literature relevant for estimates of the cost of depression in youth as well as for estimates of cost benefits and cost effectiveness of prevention programs. Their review reveals the dearth of information on the economic burden of youth depression, and makes clear the challenge for assessment from currently available data. Limitations notwithstanding, available preliminary evidence suggests that depression costs are high for youth and extend beyond healthcare service costs to school services, and may include other social services costs, and family costs. Lynch and Clarke also comment on the potential cost effectiveness of prevention programs, and highlight methodologic and real-world challenges that need attention. Finally, they discuss opportunities for generating information on the economic burden of depression in childhood and adolescence as well as the cost effectiveness of prevention. They include maximizing findings across studies, through the use of common methods, and building on findings from economic research with adults. At the workshop, several researchers presented results of their interventions seeking to reduce risk for depression and internalizing disorders with indicated, selective, and universal interventions. Indicated interventions target individuals exhibiting symptoms of a particular disorder, but who did not meet diagnostic criteria of a particular disorder (subsyndromal), while selective interventions target individuals with increased risk for a disorder (e.g., result of environmental risk factors), and universal interventions target general populations regardless of their level of risk for a disorder.22Institute of MedicineReducing risks for mental disorders. National Academy Press, Washington DC1994Google Scholar Much of the evidence for reducing risk for depression was found with indicated prevention approaches targeting preadolescent and adolescent youth with symptoms of depression, but who did not meet diagnostic criteria for the disorder. Primarily, these prevention methods use cognitive–behavioral approaches or interpersonal psychotherapy strategies that have been found to be effective for treating depression in adults and youth. Intervention targets include reducing negative cognitions, increasing involvement in positive activities, strategies to promote optimism, and managing interpersonal and psychosocial stressors. Results have demonstrated intervention success at reducing symptoms, relative to control,13Horowitz J.L. Garber J. The prevention of depressive symptoms in children and adolescents: a meta-analytic review.J Consult Clin Psychol. 2006; 74: 401-415Crossref PubMed Scopus (547) Google Scholar and, in at least one instance, the program resulted in significantly fewer depression episodes over time, relative to control.23Clarke G.N. Hornbrook M. Lynch F. et al.A randomized trial of a group cognitive intervention for preventing depression in adolescent offspring of depressed parents.Arch Gen Psychiatry. 2001; 58: 1127-1134Crossref PubMed Scopus (452) Google Scholar Selective interventions targeting individuals with increased risk for depression—infants/toddlers with depressed mothers,24Cicchetti D, Toth S. Attachment theory informed interventions for families confronted with maternal depression. Paper presented at Workshop on Prevention of Depression in Children and Adolescents. National Institute of Mental Health, National Institutes of Health, 2004.Google Scholar, 25Cicchetti D. Toth S.L. Rogosch F.A. The efficacy of toddler–parent psychotherapy to increase attachment security in offspring of depressed mothers.Attach Hum Dev. 1999; 1: 34-66Crossref PubMed Scopus (171) Google Scholar youth with familial depression histories,26Beardslee W.R. Gladstone T.R.G. Wright E.J. Cooper W.A. A family-based approach to the prevention of depressive symptoms in children at risk: evidence of parental and child change.Pediatrics. 2003; 112: 119-131Crossref PubMed Scopus (381) Google Scholar, 27Beardslee WR. Prevention approaches for school-age and adolescent children. Paper presented at Workshop on Prevention of Depression in Children and Adolescents. National Institute of Mental Health, National Institutes of Health, 2004.Google Scholar youth experiencing abuse and other traumatic events,28Leve L.D. Chamberlain P. Reid J.B. Intervention outcomes for girls referred from juvenile justice: effects on delinquency.J Consult Clin Psychol. 2005; 73: 1181-1185Crossref PubMed Scopus (127) Google Scholar, 29Chamberlain P, Leve LD. Internalizing behaviors in girls with chronic delinquency: risk characteristics and intervention outcomes. Paper presented at Workshop on Prevention of Depression in Children and Adolescents. National Institute of Mental Health, National Institutes of Health, 2004.Google Scholar, 30Sandler I.N. Ayers T.S. Wolchik S.A. et al.The family bereavement program: efficacy evaluation of a theory-based prevention program for parentally bereaved children and adolescents.J Consult Clin Psychol. 2003; 71: 587-600Crossref PubMed Scopus (242) Google Scholar, 31Sandler IN, Wolchik SA, Khoo TK, Schmiege S, Tein JY, Ayers T. Promotion of resilience in disrupted families: bereavement and divorce. Paper presented at Workshop on Prevention of Depression in Children and Adolescents. National Institute of Mental Health, National Institutes of Health, 2004.Google Scholar and adolescents at risk for school failure32Thompson E.A. Eggert L.L. Randell B.P. Pike K.C. Evaluation of indicated suicide risk prevention approaches for potential high school dropouts.Am J Public Health. 2001; 91: 742-752Crossref PubMed Scopus (97) Google Scholar, 33Thompson EA. Preventing adolescent depression and suicide. School-based prevention. Paper presented at Workshop on Prevention of Depression in Children and Adolescents. National Institute of Mental Health, National Institutes of Health, 2004.Google Scholar—were considered. Each of these programs demonstrated some evidence for reducing risk for depression. Universal interventions also were considered.34Ialongo N.S. Werthamer L. Kellam S.G. Brown C.H. Wang S. Lin Y. Proximal impact of two first-grade preventive intervention on the early risk behaviors for later substance abuse, depression and antisocial behavior.Am J Community Psychol. 1999; 27: 599-641Crossref PubMed Scopus (315) Google Scholar, 35Lambert SF, Ialongo NS, Hubbard S. Impact of two universal preventive interventions on depressed mood in elementary school. Paper presented at Workshop on Prevention of Depression in Children and Adolescents. National Institute of Mental Health, National Institutes of Health, 2004.Google Scholar Discussion centered on the current lack of evidence for universal interventions relative to selective and indicated approaches, and the potential for universal prevention to provide opportunities for decreasing population levels of depression because of their broader reach across the risk spectrum,36Weich S. Prevention of the common mental disorders: a public health perspective.Psychol Med. 1997; 27: 757-764Crossref PubMed Scopus (48) Google Scholar for example, by disrupting risk trajectories as well as identifying individuals at high risk for depression. Judy Garber’s article1Garber J. Depression in children and adolescents: linking risk research and prevention.Am J Prev Med. 2006; 31: S104-S125Abstract Full Text Full Text PDF PubMed Scopus (229) Google Scholar reviews several of the prevention programs discussed at the workshop. In addition, Schmiege and colleagues5Schmiege S.J. Khoo S.T. Sandler I.N. Ayers T.S. Wolchik S.A. Symptoms of internalizing and externalizing problems: modeling recovery curves after the death of a parent.Am J Prev Med. 2006; 31: S152-S160Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar examine the effects of a selective prevention intervention for youth depression after the loss of a parent, modeling the rate of recovery from depressive symptoms over time for boys and girls in the intervention, relative to a control group. These youth are at risk for depression as well as externalizing disorders and other problem behaviors. The Family Bereavement Program targets specific risk and protective factors that affect multiple outcomes. Longitudinal growth curve analyses revealed different recovery patterns for girls and boys, suggesting a positive effect of the intervention for girls, but not boys. The discussion focuses on the utility of recovery curve methodology for studying intervention effects, and on the implications of these findings for understanding risk for depression in girls following the loss of a parent. At the workshop, basic researchers also laid out new opportunities offered by advances in neuroscience and genetics for informing our understanding of the etiology of depression, risk and protective factors, and processes of depression. In addition, the meeting focused on opportunities to develop novel interventions based on what is known about comorbidity and the availability of alternative models of depression, specifically interpersonal relations and culture. Two articles in this supplement focus on basic research that can inform the development of novel interventions for child and adolescent depression prevention. Rao6Rao U. Links between depression and substance abuse in adolescents: neurobiological mechanisms.Am J Prev Med. 2006; 31: S161-S174Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar considers the pathophysiological mechanisms underlying the development of comorbid depression and substance use in adolescence. Considering research with animals as well as humans, she examines the links between depression and substance use, from developmental, epidemiologic, clinical, and neurobiological perspectives, including theoretical models that support this relationship. Increased understanding of development of comorbid depression and substance use in adolescence, a time when the prevalence of both disorders increases, can lead to improved targeting of interventions, and maintenance of intervention effects. While the Rao article focuses primarily on adolescence, the paper by O’Connor and Cameron7O’Connor T.G. Cameron J.L. Translating research findings on early experience to prevention: animal and human evidence on early attachment relationships.Am J Prev Med. 2006; 31: S175-S181Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar focuses primarily on infancy and early childhood, to consider how basic research findings on early experiences can be translated into clinical practice, to reduce risk for depression and other developmental psychopathology in youth. The authors review animal and human models developed to explain the pathway from early adversity to later psychopathology and highlight the contributions and challenges of these models for preventive intervention. Several themes emerged from the articles in this supplement, as well as from the discussion at the workshop. First, the mental health burden of depression in children and adolescents is empirically supported. More research is needed to understand the economic burden resulting from youth depression, and the cost effectiveness of prevention. Second, psychosocial, biological, and environmental risk factors for depression have been identified across childhood and adolescence. A consistent theme in the articles on risk and protective factors was the need for additional research to improve identification of at-risk youth, based on current (e.g., symptoms and disorders) and past (e.g., family history, early onset internalizing disorders) levels of risk and protective factors and processes. Third, preventive interventions with demonstrated efficacy exist, primarily for high-risk populations. Evidence for the effectiveness of these preventive interventions in real-world settings is needed, including cost effectiveness as well as research on the dissemination of evidence-based interventions within community and practice settings. Fourth, basic research presents opportunities for furthering what is known about the etiology of depression and comorbid disorders as well as opportunities for developing novel interventions, and improving the targeting and timing of preventive interventions. As stated earlier, the articles in this supplement are not exhaustive of the current issues for depression prevention research. For instance, at the workshop, participants discussed whether the current evidence base warranted a large-scale prevention research effort. Targeted interventions have the strongest evidence base, but would require screening for symptoms of depression, or monitoring adverse life events that confer increased risk for depression. Regarding screening, issues related to whom to screen, when to screen, and how often to screen would need to be addressed for successful large-scale implementation of indicated strategies. Basic research on the pathophysiology of depression might one day lead to reliable biomarkers for depression that will aid in identifying individuals at high risk for depression.18National Institute of Mental Health. Breaking ground, breaking through: the strategic plan for mood disorders research. Bethesda MD: National Institute of Mental Health, National Institutes of Health, U.S. Department of Health and Human Services; 2003. NIH Publication No. 03-5121. Available at: www.nimh.nih.gov/strategic/stplan_mooddisorders.cfm.Google Scholar, 37Insel T.R. Scolnick E.M. Cure therapeutics and strategic prevention: raising the bar for mental health research.Molecular Psychiatry. 2006; 11: 11-17Crossref PubMed Scopus (186) Google Scholar Challenges notwithstanding, this supplement outlines several opportunities for expanding research on child and adolescent depression prevention.