The articles included in this supplement to the

Errata Due to significant editing errors, the article Prevention of Depression in Children and Adolescents, by Belinda E. Sims, PhD, Editha Nottelmann, PhD, Doreen Koretz, PhD, and Jane Pearson, PhD, which appeared in American Journal of Preventive Medicine, Vol. 31, No. 6 (Supplement 1): S99 103, 2006, has been republished. These errors have now been corrected. The publisher apologizes to the authors for any inconvenience that this has caused the readers of the supplement. Prevention of Depression in Children and Adolescents Belinda E. Sims, PhD, Editha Nottelmann, PhD, Doreen Koretz, PhD, Jane Pearson, PhD The articles included in this supplement to the American Journal of Preventive Medicine 1 7 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, 8 11 with few recent exceptions, 12 14 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. 15 ), and approximately half of first episodes of depression occurring in adolescence. 16 Prior to adolescence, girls and boys have similar rates of depression, but after adolescence, rates of depression onset is higher for girls. 17 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. 14,15 From Harvard University (Koretz), Cambridge, Massachusetts; and Division of Epidemiology, Services and Prevention Research, National Institute on Drug Abuse (Sims), Division of Pediatric Research and Treatment Development (Nottelmann), and Division of Services and Intervention Research (Pearson), National Institutes of Health, Bethesda, Maryland Address correspondence and reprint requests to: Belinda Sims, PhD, National Institute on Drug Abuse, 6001 Executive Boulevard, Room 5185, MSC 9589, Bethesda MD 20892-9589. E-mail: bsims@nida.nih.gov 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. 18 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 depres- Am J Prev Med 2007;32(5) 0749-3797/07/$ see front matter 2006 American Journal of Preventive Medicine Published by Elsevier Inc. doi:10.1016/j.amepre.2006.07.014 451

sion 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. 15 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. Overview of Supplement 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. Risk and Protective Factors for Depression in Children and Adolescents 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. Garber 1 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 Merikangas 2 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 highrisk youth. Finally, Flannery-Schroeder 3 focuses on anxiety as a risk factor for depression specifically, whether prevention and treatment of anxiety, which often precedes 452 American Journal of Preventive Medicine, Volume 32, Number 5 www.ajpm-online.net

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. 19 21 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. Burden of Depression in Children and Adolescents: Prevalence and Cost Implications 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 Clarke 4 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. Current Approaches for Preventing Depression 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. 22 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, 13 and, in at least one instance, the program resulted in significantly fewer depression episodes over time, relative to control. 23 Selective interventions targeting individuals with increased risk for depression infants/toddlers with depressed mothers, 24,25 youth with familial depression histories, 26,27 youth experiencing abuse and other traumatic events, 28 31 and adolescents at risk for school failure 32,33 were considered. Each of these programs demonstrated some evidence for reducing risk for depression. Universal interventions also were considered. 34,35 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, 36 for example, by disrupting risk trajectories as well as identifying individuals at high risk for depression. Judy Garber s article 1 reviews several of the prevention programs discussed at the workshop. In addition, Schmiege and colleagues 5 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 May 2007 Am J Prev Med 2007;32(5) 453

of these findings for understanding risk for depression in girls following the loss of a parent. Translational Research Opportunities 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. Rao 6 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 Cameron 7 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. Summary 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. Conclusion 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. 18,37 Challenges notwithstanding, this supplement outlines several opportunities for expanding research on child and adolescent depression prevention. The views expressed in this article do not necessarily represent the views of the National Institute of Mental Health, National Institute on Drug Abuse, National Institutes of Health, the Department of Health and Human Services, or the United States Government. No financial conflict of interest was reported by the authors of this paper. References 1. Garber J. Depression in children and adolescents: linking risk research and prevention. Am J Prev Med 2006;31(6S1):S104 25. 2. Avenevoli S, Merikangas KR. Implications of high-risk family studies for the prevention of depression. Am J Prev Med 2006;31(6S1):S126 35. 3. Flannery-Schroeder EC. Reducing anxiety to prevent depression. Am J Prev Med 2006;31(6S1):S136 42. 4. Lynch FL, Clarke GN. Estimating the economic burden of depression in children and adolescents. Am J Prev Med 2006;31(6S1):S143 51. 5. Schmiege SJ, Khoo ST, Sandler IN, Ayers TS, Wolchik SA. Symptoms of internalizing and externalizing problems: modeling recovery curves after the death of a parent. Am J Prev Med 2006;31(6S1):S152 60. 6. Rao U. Links between depression and substance abuse in adolescents: neurobiological mechanisms. Am J Prev Med 2006;31(6S1):S161 74. 454 American Journal of Preventive Medicine, Volume 32, Number 5 www.ajpm-online.net

7. O Connor TG, Cameron JL. Translating research findings on early experience to prevention: animal and human evidence on early attachment relationships. Am J Prev Med 2006;31(6S1):S175 81. 8. Barlow 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(2). 9. Durlak JA, Wells AM. Primary prevention mental health programs for children and adolescents: a meta-analytic review. Am J Community Psychol 1997;25:115 52. 10. Greenberg MT, Domitrovich C, Bumbarger B. The prevention of mental disorders in school-aged children: current state of the field. Prevention and Treatment 2001;4:1 63. 11. Webster-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 92. 12. Merry 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(2). 13. Horowitz JL, Garber J. The prevention of depressive symptoms in children and adolescents: a meta-analytic review. J Consult Clin Psychol 2006;74:401 15. 14. Commission on Adolescent Depression and Bipolar Disorder. Prevention of depression and bipolar disorder. In: Evans DL, Foa EB, Gur RE, et al., eds. Treating and preventing adolescent mental health disorders. What we know and what we don t know. New York: Oxford University Press; 2005. p. 55 67. 15. Costello 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 16. Kessler RC, Wai TC, Demler O, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:617 27. 17. National 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 18. National 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 19. Costello EJ, Mustillo S, Erkanli A, Keeler G, Angold A. Prevalence and development of psychiatric disorders in childhood and adolescence. Arch Gen Psychiatry 2003;60:837 44. 20. Birmaher BB, Ryan ND, Williamson DE, et al. Childhood and adolescent depression: a review of the past 10 years. Part I. Child Adolesc Psychiatry 1996;35:1427 39. 21. Weissman MM, Wickramaratne P, Nomura Y, Warner V, Pilowsky D, Verdeli H. Offspring of depressed parents: 20 years later. Am J Psychiatry 2006;163:1001 8. 22. Institute of Medicine. Reducing risks for mental disorders. Frontiers for preventive intervention research. Washington DC: National Academy Press, 1994. 23. Clarke GN, 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 34. 24. Cicchetti 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. 25. Cicchetti D, Toth SL, Rogosch FA. The efficacy of toddler parent psychotherapy to increase attachment security in offspring of depressed mothers. Attach Hum Dev 1999;1:34 66. 26. Beardslee WR, Gladstone TRG, Wright EJ, Cooper WA. A family-based approach to the prevention of depressive symptoms in children at risk: evidence of parental and child change. Pediatrics 2003;112:119 31. 27. Beardslee 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. 28. Leve LD, Chamberlain P, Reid JB. Intervention outcomes for girls referred from juvenile justice: effects on delinquency. J Consult Clin Psychol 2005;73:1181 5. 29. Chamberlain 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. 30. Sandler IN, Ayers TS, Wolchik SA, 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: 587 600. 31. Sandler 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. 32. Thompson EA, Eggert LL, Randell BP, Pike KC. Evaluation of indicated suicide risk prevention approaches for potential high school dropouts. Am J Public Health 2001;91:742 52. 33. Thompson EA. Preventing adolescent depression and suicide. Schoolbased prevention. Paper presented at Workshop on Prevention of Depression in Children and Adolescents. National Institute of Mental Health, National Institutes of Health, 2004. 34. Ialongo NS, Werthamer L, Kellam SG, Brown CH, 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;27:599 641. 35. Lambert 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. 36. Weich S. Prevention of the common mental disorders: a public health perspective. Psychol Med 1997;27:757 64. 37. Insel TR, Scolnick EM. Cure therapeutics and strategic prevention: raising the bar for mental health research. Molecular Psychiatry 2006;11:11 7. Erratum to the article by Huhman ME, Potter LD, Duke JC, Judkins DR, Heitzler CD, Wong FL. Evaluation of a National Physical Activity Intervention for Children: VERB Campaign, 2002 2004. Am J Prev Med 2007;32:38 43. In this article, reference 19 should have read: Welk GJ, Wickel E, Peterson M, Heitzler CD, Fulton JE, Potter LD. Reliability and validity of questions on the Youth Media Campaign Longitudinal Survey. Med Sci Sports Exerc 2007;39(4):612 21. The publisher regrets this error and any inconvenience it has caused the readers of AJPM. May 2007 Am J Prev Med 2007;32(5) 455