3 Prevention of Depression and Bipolar Disorder

The prevention of an individual’s first episode of depression is worthy of greater study among investigators concerned with mood disorders. Not only is the first episode devastating for individuals and those around them, but depression is among the top three major causes of societal and economic disease burden across the globe (Ferrari et al., 2013; Mathers & Loncar, 2006; World Health Organization, 2008). The sequelae following the first episode of major depressive disorder (MDD) are substantial. The probability of subsequent episodes is significantly increased, even to the point that most now consider MDD to be a chronic disease (e.g., Pettit, Hartley, Lewinsohn, Seeley, & Klein [2013] recently reported that approximately 73% of those teens who experienced a first episode before age 18 had a recurrence within the next 12 years). As noted in Chapter 1, the sequelae to MDD are numerous and include more life stress, poorer social relationships, increased substance abuse, increased use of medical services, interference with long-term cognitive functioning, significant comorbidity with major health problems, and younger ages of death (when deaths by suicide are taken into account). Most investigators of mood disorders believe that the first episode lays down neural pathways (especially among those with relevant genetic vulnerabilities) that are difficult to overcome and, without modification via medications or psychosocial interventions or their combination, are likely to be lasting pathways that impact individuals’ lives.

Even though prevention of MDD is an urgent and timely topic (England & Sim, 2009; see O’Connell, Boat, & Warner, 2009), empirical work regarding prevention is difficult and has been slow to progress. Considerably more work has been conducted on the prevention of second and subsequent episodes (Cox et al., 2012; Sheets et al., 2013), but the work designed to prevent the first episode of MDD remains meager. Prior to describing the empirical work on prevention of MDD, it is important to note the conceptual and historical context in which general prevention research has been defined.

During the 1990s three reports established an historical context and defined the mental health prevention classification system:

In 1998, the National Institute of Mental Health (NIMH) established an ad hoc committee to review the progress of mental health prevention research. The committee’s report, Priorities for Prevention Research at NIMH: A Report by the National Advisory Mental Health Council Workgroup on Mental Disorders Prevention Research, traced the history of prevention in mental health and proposed the following generational taxonomy.

The first generation of efforts to prevent mental disorder began in the 1930s when, as an outgrowth of the turn-of-the-century mental hygiene movement, the focus gradually expanded beyond ameliorating the plight of those in asylums to include the prevention of many forms of social and emotional maladjustment. The new goal was to ensure the well-being and “positive mental health” of the general population through primary-prevention interventions aimed at creating health-promoting environments for all. These efforts were based on humanitarian concern, but had minimal research underpinnings.

Beginning in the late 1960s, the second generation of interventions to prevent mental disorders reflected the impact of a growing health and mental health research knowledge base. Some scientists retained their broad-based emphasis on primary prevention, while others began to target specific “at-risk” groups for study and intervention. During the 1960s there had been a burgeoning of research on the causes, mechanisms, and effects of stress on bodily and mental functioning. “At-risk” persons were defined as those who would predictably experience periods of substantial life stress, such as domestic violence, divorce, bereavement, or unemployment as precursors of mental distress or disorder. During the same time period, prevention and changing behavior for health also became active areas of investigation; those studies placed a strong emphasis on preventing lung cancer and heart disease through programs to prevent or reduce smoking, obesity, high cholesterol intake, and sedentary lifestyles.

The NIMH committee observed that over the next decade mental health preventive interventions continued to proliferate. After reviewing progress in this field, however, the 1978 President’s Commission on Mental Health determined that previous investigations had been “unfocused and uncoordinated.” As a remedy the commission recommended the establishment of a Center for Prevention at NIMH to coordinate and enhance research in mental health primary prevention. The NIMH report determined that “during the last 20 years The NIMH Center for Prevention Research and its programmatic successors have stimulated considerable progress in building the scientific foundation of an interdisciplinary field of prevention research in areas of epidemiology, human development, and intervention research methodology” (NIMH, 1998). The committee concluded that sufficient progress had been made in establishing the scientific basis for mental health prevention to declare that we were then in a third generation of prevention activity. Thus, prevention research could build on accomplishments of prior preventive interventions and integrate these with advances in the biomedical, behavioral, and cognitive sciences.

Despite the described significance and need for prevention research and this sanguine view of the 1998 NIMH committee, the amount of work studying the prevention of an initial episode of depression has remained meager. In contrast, considerable progress has been made in the development of a nomenclature for prevention research. In order for the field to progress, it was necessary to develop a clear terminology for investigators to follow.

The Commission on Chronic Illness (1957) developed the original public health classification system of disease prevention. Three types of preventive interventions were identified: primary, secondary, and tertiary. During the last 40 years the definitions of these types of prevention have expanded to include an array of nuanced but related meanings.

In 1983 and in 1987, Robert Gordon proposed an alternative prevention classification system that was based on the empirical relationships found in practically oriented disease prevention and health-promotion programs. He labeled prevention programs as universal, selective, and indicated.

Although Gordon’s classification system was distinct from that of the Commission on Chronic Health, the use of these two classification systems slowly deteriorated into a confusing merging and mixing of definitions (e.g., “universal primary prevention”). This confusion was particularly problematic when this terminology was applied to the classification of the prevention of psychiatric disorders, because the classic public health prevention classification system and Gordon’s reclassification were both designed for use in the description of the prevention of other diseases, not of interventions to prevent psychiatric and psychological disorders. The 1994 Institute of Medicine (IOM) report, Reducing Risk for Mental Disorders: Frontiers for Prevention Intervention Research, presented a cogent discussion of the inherent pitfalls in applying general prevention classifications to problems in mental health.

One of the main problems has been the concept of “caseness” that is used in public health. It is often more difficult to document that a “case” of mental disorder exists than it is to document a physical health problem. Agreement regarding the occurrence of a case of psychiatric disorder varies with time, with the instruments and diagnostic systems employed, and with the theoretical perspective of the evaluators. Also, symptoms and dysfunctions may exist even though criteria for a DSM-IV or 5 diagnoses are not met. Finally, the outcomes in very young children (birth to age 5) are often not diagnosable as “psychiatric caseness” but rather as impairments in cognition and psychosocial development.

The IOM report (1994) chose to resolve the confusion in terminology by using the term prevention to refer only to interventions that occur before the initial onset of a disorder. In this system, prevention included all three elements of Gordon’s system (1983, 1987). Efforts to identify cases and provide care for known disorders were called treatment, and efforts to provide rehabilitation and reduce relapse and recurrence of a disorder were called maintenance/interventions. Further distinctions were made within the prevention category. We have employed these definitions throughout this chapter. The definitions are described in the following paragraphs.

Universal mental health prevention interventions are defined as efforts that are beneficial to a whole population or group. They are targeted to the general public or a whole population group that has not been designated or identified as being at risk for the disorder being prevented. The goal at this level of prevention is the reduction of the occurrence of new cases of the disorder.

Selective mental health prevention interventions are defined as those efforts that target individuals or a subgroup of the population whose risk for developing the mental health disorder is significantly higher than average. The risk may be immediate or lifelong. Biological, psychological, or social risk factors associated with or related to the specific mental health disorder are used to identify the individual or group level of risk. Those with the identified risk factors make up one group of those referred to as “at risk.”

Indicated prevention interventions are defined as those efforts that target high-risk individuals who are identified as having minimal but detectable signs or symptoms that predict the mental disorder or biological markers indicating predisposition to the disorder. For example, individuals who have some symptoms of MDD but do not yet meet criteria for the disorder would fall into this group; such individuals represent the second group of individuals referred to as “at risk.” Indicated prevention excludes individuals whose signs and symptoms meet diagnostic criteria for the disorder.

The IOM identified three aims or desired outcomes for mental health prevention: (1) reduction in the number of new cases of the disorder; (2) delay in the onset of illness; and (3) reduction in the length of time the early symptoms continue as well as halting the progression of severity so that individuals ultimately do not meet diagnostic criteria. The 1999 Mental Health: A Report of the Surgeon General agreed with the IOM and defined prevention as the “prevention of the initial onset of a mental disorder or emotional or behavioral problem, including prevention of comorbidity” (U.S. Department of Health and Human Services, 1999). Additionally, the report defined other terms that were often imprecisely used in discussions of prevention:

In addition to the IOM’s goals of reducing the number of new cases and delaying the onset of MDD and the insidious nature of the onset and course of MDD, there are other ancillary and associated goals of prevention programs. For example, prevention of initial MDD is likely to have an impact on school and work performance, social skills, and quality of life; to reduce the need of medical services; and to reduce MDD-related substance abuse disorders. In the long run, prevention programs may actually extend the lives of individuals who were at risk but did not develop the disorder, by reducing both the risk of suicide completion and the social, behavioral, and biological sequelae of an initial episode of the disorder.

Another goal of prevention programs is to teach resiliency to the program participants. Individuals at risk for MDD are likely to experience negative and traumatic events, as are other individuals in our society. Prevention programs have a goal of teaching at-risk individuals to become more resilient—to develop skills and abilities to recover from or adapt to adversity.

A further goal of prevention programs is to enhance and enrich the positive aspects of living. By changing cognitive processes, enhancing social skills, and increasing resiliency, individuals who otherwise might live a marginally happy life may have the opportunity to develop greater self-esteem and self-efficacy and live a more flourishing, successful, and adaptive life. This positive adaption in life may lead to the development of more adaptive neural pathways. Emotional intelligence (Goleman, 1995) may be enhanced by successful preventive programs.

The societal goals of depression prevention programs are also numerous. For example, even a modest reduction in new cases of MDD would reduce the economic burden of the disorder. The disorder itself would not have to be treated so frequently, nor would the associated (sometimes self-treatment) problems of alcohol, tobacco, and other forms of substance abuse. Each prevented case of MDD would increase the limited resources available to other health initiatives. Productivity would be increased in the workplace. Thus, the call for effective programs to prevent the first episode of MDD is a forceful and significant one—significant for individuals, families, and society as a whole (England & Sim, 2009).

To develop programs for individuals “at risk” for MDD, it is necessary to develop knowledge and understanding of factors and their interactions that render one likely to develop MDD. Chapter 1 provided evidence for many of the risk factors for MDD, so the details will not be reiterated here. These risk factors include dysfunctional parenting and family interactions; gender; personality, and temperament; cognitive vulnerabilities; internal and external stress, including negative life events; and poor interpersonal relationships.

In addition to the preceding risk factors, the following risk factors that have implications for prevention of MDD are important and worthy of further detailed review. These include subsyndromal depression, poverty, violence, and cultural factors.

Among adults, subsyndromal depression (two or more symptoms for 2 weeks or longer) appears to cause as much health impairment and economic burden as MDD, and these individuals are at increased risk for developing subsequent MDD (Fava, 1999; Johnson, Weissman, & Klerman, 1992; Judd, Akiskal, & Paulus, 1997). In longitudinal studies, subsyndromal depression among adolescents predicted poorer functioning when these individuals became adults (Devine, Kempton, & Forehand, 1994; Pettit, Hartley, Lewinsohn, Seeley, & Klein, 2013; Pettit, Lewinsohn, & Joiner, 2006). Subsyndromal depressive symptoms among adolescents predict MDD later on in adolescence and young adulthood (Pine, Cohen, Cohen, & Brook, 1999; Rao et al., 1995; Weissman, Warner, Wickramaratne, Moreau, & Olfson, 1997; see also Monroe & Harkness, 2011). Lewinsohn, Solomon, Seeley, and Zeiss (2000) found that increasing levels of depressive symptoms among a large sample of nondepressed adolescents (average age of 16.5) predicted increased levels of social dysfunction and incidence of MDD, as well as increased substance abuse at age 24. These data indicate that subsyndromal depression renders adolescents at risk for a first episode of MDD, and they are prime candidates for depression prevention programs.

Poverty has been linked with an early onset of depression. It is not clear whether this represents an independent risk factor or can be grouped among the more general examples of diversity that are associated with depression. Results from epidemiologic studies have linked lower socioeconomic status with depression and a multitude of other mental health problems (Robins, Locke, & Regier, 1991). This vulnerability is particularly strong for families living at poverty levels (Bruce, Takeuchi, & Leaf, 1991). This relationship may be explained in part by a phenomenon of selection, whereby those with mental health problems are more inclined to drift toward economic disadvantage and remain there (Dohrenwend et al., 1992). Longitudinal data have also demonstrated that socioeconomic disadvantage is largely a cause of higher vulnerability to psychiatric disorder, particularly for depression (Dohrenwend et al., 1992; Gilman, Kawachi, Fitzmaurice, & Buka, 2002; Johnson, Cohen, Dohrenwend, Link, & Brook, 1999; Kiely & Butterworth, 2013). In a study of over 4,000 Australian families, poverty caused a small but significant increase in risk when other sociologic variables were controlled (Spence, Najman, Bor, O’Callaghan, & Williams, 2002); this effect was more pronounced in girls than in boys.

If poverty is a generator for a variety of stressors, the possible mechanisms driving poverty-induced vulnerability appear boundless. A number of mediators between socioeconomic disadvantage and depression have been studied empirically. These include external mediators such as access to healthcare, quality of social networks and resources, quality of parenting and parent availability, and, of course, level of exposure to violence. Children of families who are of lower socioeconomic status are most likely to witness violence and to be the victims of abuse (Buka, Stichik, Birdthistle, & Earls, 2001; Sedlak & Broadhurst, 1996).

Internal individual mediators include self-esteem, health-risk behaviors, cognitive deficits, interpersonal skills, and academic achievement. Several comprehensive reviews on the consequences of poverty and mediating factors demonstrate the vast amount of knowledge we have accumulated on the relation between poverty and depression (Aber, Bennett, Conley, & Li, 1997; Leventhal & Brooks-Gunn, 2000; Turner& Lloyd, 1999). This literature highlights the importance of two larger factors: (a) the need for universal healthcare with parity for mental illness and physical illness and parity for services for adults and children and (b) the need to address large-scale public health risk factors that have a strong effect on the occurrence of adolescent depression (i.e., exposure to violence).

Exposure to violence during childhood is a potent risk factor for future psychological and psychiatric disorders (Kilpatrick et al., 2003; MacMillan et al., 2001) and also a risk factor for poor physical health (Felitti et al., 1998), in both the short and long term. The violence to which children are exposed has many forms. This includes being a victim of sexual or physical abuse as well as witnessing violence in the home (Devries et al., 2013; Heim et al., 2010; Kilpatrick et al., 2003). A large number of children also frequently witness violence in the community (Buka et al., 2001). Children who are exposed to violence are most often exposed to more than one type, and evidence suggests that the amount of violence-related adversities a child encounters has a substantial impact on the severity of the outcome (Felitti et al., 1998). The most disturbing illustration of this accumulation phenomenon is the gradation effect of violence-related adversities on risk for suicide attempt. Results from the Adverse Childhood Experiences Study demonstrated that for every additional adversity experienced as a child, the risk of suicide attempts increased from twofold to fivefold, such that children or adolescents who encounter seven or more adversities are 50 times as likely to attempt suicide as those without violence exposure (Dube et al., 2001). Although the mental health consequences of violence exposure are diverse, the most prevalent and commonly studied are posttraumatic stress disorder (PTSD) and major depression. This makes sense, particularly if violence exposure is viewed as a form of trauma.

Violence-related trauma experienced during childhood can have particularly devastating effects, because the trauma is inflicted during a critical period of development. Neurobiological and neuroendocrine studies of depressed women, which look at the volume of certain brain regions and at hormonal stress-response mechanisms, provide evidence that violence-related trauma experienced during childhood can have profound and lasting effects on brain structure and function (Heim et al., 2008; Klengel & Binder, 2013; Klengel et al., 2013). These alterations, in turn, increase vulnerability to stress-related disorders like depression.

Depression that is comorbid with PTSD or other disorders, as well as depression that has an established neurobiological etiology like that seen in childhood victims of trauma, are forms of the disorder that are particularly resistant to treatment and are associated with increased levels of impairment (Mervaala et al., 2000; Petersen et al., 2001). Thus, it is important that prevention strategies attend to violence exposure.

The role of ethnocultural factors has been understudied. Some ethnic groups appear to have higher rates of adolescent depression than others. For example, Mexican-Americans and African-American adolescents appear to have a higher risk for depression, whereas American adolescents of Chinese descent may be at lesser risk (Chentsova-Dutton & Tsai, 2009; Roberts, Roberts, & Chen, 1997). The rates of depression and the economic burden vary across countries around the world (Ferrari et al., 2013).

It appears that depression rates for some groups (e.g., African-American or Hispanic adolescents) may not show the gender disparity following puberty that is seen among those for Caucasian adolescents (Hayward, Gotlib, Schraedley, & Litt, 1999). Furthermore, some prevention or prevention of recurrence programs (reviewed later) have reported differential effectiveness for different ethnic groups within the United States (Cardemil et al., 2002).

In sum, there appear to be cultural and ethnic differences in both the prevalence of depression and in the symptomatology indicative of depression (Chentsova-Dutton & Tsai, 2009). Clearly this is a topic in great need of further study.

During the past two decades, a number of promising strategies for the prevention of childhood depression have emerged. The overarching principles of these programs are similar, and the specifics of preventive interventions for children and adolescents have taken into account the development level of the participants. The evaluated preventive strategies are based primarily on cognitive-behavioral and family-educational approaches that seek to reduce risk factors and enhance protective and resiliency factors relevant to depression in youth.

In general, progress in the field of prevention science has been made through the introduction of rigorous standards for the development and evaluation of manualized preventive strategies that are based on well-established theoretical frameworks and proceed through a series of orderly stages. This is best described in the 1994 IOM’s Report on the Prevention of Mental Disorder. The IOM suggested that prevention development and evaluation proceed through five stages. The first and second stages are identifying risk factors and describing the relative contributions of different factors to the disorder. The third stage is applying strategies developed in pilot studies and completing efficacy trials to evaluate the overall outcomes of these approaches. The fourth stage, carrying out effectiveness trials, involves the examination of such strategies in multiple sites in large-scale investigations under non-ideal, real-world conditions. The final stage consists of implementing such strategies in large-scale public health campaigns. Following this sequence and the articulation of a set of rigorous empirical standards by which to test preventive intervention approaches, a number of important strategies for prevention of depression have emerged. These have begun to be tested in randomized trial designs according to the recommended guidelines.

Consideration of the prevention of depression also must take place in the context of the remarkable progress in developmental neuroscience, the sequencing of a human genome, and psychiatric epidemiology. As these important scientific advances unfold, they will offer significant opportunities for future prevention programs. These findings will need to be integrated with adolescents’ developmental, social, cultural, and family contexts in the development of preventive interventions. Within the context of personalized medicine, the larger question becomes one of identifying which characteristics of “at risk” individuals indicate which treatment will work for which subgroups of “at risk” youth.

To date, two major conceptual frameworks have guided most of the development of the prevention studies. First, cognitive-behavioral programs have been used and show considerable promise (e.g., the Penn Group, Clarke and Garber and colleagues in the United States, Shochet and Spence in Australia, and Arnarson and Craighead in Iceland). The second conceptual framework is exemplified by Beardslee and colleagues, who have developed and evaluated a program designed to prevent depression in the family intervention context. All of these programs have in common a strong theoretical orientation—an orientation toward building strengths and resiliency; they have all been written into manuals for dissemination; and they have been or are being tested with randomized trials designs. It is important to note that these are programs for “at risk” individuals, and as noted earlier universal programs have limited supporting evidence. Further, the studies included in this review are for prevention programs; at the end of this review, data regarding those programs that combine prevention and prevention of relapse or recurrence programs will be noted. In the sections that follow, we first describe and evaluate studies designed to prevent initial episodes of depression; these include the Penn Prevention Program, the findings from groups working in Australia, the work in Iceland, and the work of Beardslee and associates. These descriptions of programs designed to prevent initial episodes of depression are followed by presentations of programs that were designed to prevent initial episodes of depression AND relapse and recurrence of depression; these latter studies include the work of Garber, Beardslee, Clarke, and their associates.

In the Penn Prevention Program (PPP), Seligman and colleagues (Gillham & Reivich, 1999; Gillham, Reivich, Jaycox, & Seligman, 1995; Jaycox, Reivich, Gillham, & Seligman, 1994) developed and evaluated a school-based “indicated” prevention program targeting 10- to 13-year-old children in school districts in the Philadelphia suburbs. The youth were defined as at risk for depression on the basis of elevated self-reported depressive symptomatology, self-reported parental conflict, or both. The PPP was based on a model of explanatory style introduced by Seligman and colleagues (Nolen-Hoeksema, Girgus, & Seligman, 1992) and on research identifying core cognitive deficits associated with youth depression, including negative self-evaluation, dysfunctional attitudes, poor interpersonal problem solving, and low expectations for self-performance (Garber, Weiss, & Shanley, 1993; Kaslow, Rehm, & Siegel, 1984; Quiggle, Garber, Panak, & Dodge, 1992). Participants recruited for the treatment group were assigned to one of three treatment programs: a cognitive training program, a social problem-solving program, or a combined program. Eighty-eight students, whose scores were matched to prevention participants, were recruited from nearby schools and made up the no-participation control group. Assessments included child self-report, teacher-report, and parent-report questionnaires.

Results indicated that relative to control participants, children who participated in any of the treatment groups reported significantly fewer depressive symptoms immediately following the program and at the 6-month and 2-year follow-ups, but not at the 12-month and 3-year follow-ups. Moreover, teacher reports at follow-up revealed better classroom behavior in treatment participants than in control participants. Finally, overall treatment effects were more significant for children who, at the screening phase of the study, reported more significant depressive symptomatology and more significant parental conflict at home. The major limitations of the study are the lack of randomization to intervention conditions, the use of only self-report measures, attrition of approximately 30% of participants during follow-up, and the failure to include diagnoses for clinical depression.

Over the past few years, this program has been slightly revised and is now referred to as the Penn Resiliency Program (PRP; Gillham, Reivich, & Jaycox, 2008); it added problem solving and coping skills to the more cognitive behavioral focus of PPP. The PPP/PRP program has been evaluated in multiple meta-analyses (e.g., Horowitz & Garber, 2006; Stice, Shaw, Bohon, Marti, & Rhode, 2009), and there has been at least one additional study since those meta-analyses (Gillham et al., 2012). As is typical of meta-analyses, the context, sample size, constituency of interventionists, and so forth have varied considerably. In sum, the PPP or PRP has been found to reduce depressive symptoms and depressive disorders relative to control groups, and these effects have been largely sustained at 12 months of follow-up. As has been found with other programs, when the PPP/PRP has been applied in a universal manner rather than in an indicated context, the program has only been effective with those “at risk” by way of baseline hopelessness or elevated depressive symptoms. Interestingly, the program has been effective with Latino adolescents but less so with African-American adolescents (Cardemil, 2002; Cardemil, Reivich, Beevers, Seligman, & James, 2007). This calls attention to the significance of possible ethnic and cultural differences that need to be noted in the development of prevention programs. Effects have varied considerably across studies, with universal programs and programs administered by less well-trained individuals having less immediate and lasting effects. Adding parental participation has had minimal additional effects to those achieved by the adolescent program, but it has been difficult to gain parental involvement and participation has been minimal. This may have precluded an enhanced effect from the inclusion of parents in the program (Gillham et al., 2012).

More recently, Seligman and his group at Penn have focused on “positive psychology” programs, which are likely to have an indirect effect of preventing episodes of MDD. These programs are included in Part VII of this book.

Several prevention programs (mostly universal) in Australia have been described and evaluated. Shochet and colleagues (2001) evaluated a “universal” prevention program applied in a school setting. This was a skills-based program of 11 sessions offered by a psychologist and based on a downward extension of principles of cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT). The student sessions could be supplemented with three parental sessions, but not many parents took advantage of this offer. There were 242 12- to 15-year-old subjects, who were assigned to assessment-only control, prevention without parental sessions, or prevention with parental sessions.

No differences were found between the two prevention groups, but students who completed either prevention program showed fewer depressive symptoms than controls on one measure of depression (but not another). The prevention program subjects also reported less hopelessness at the end of the project. All of these effects were maintained at a 10-month follow-up. The limitations of this program include the lack of random assignment of subjects (controls participated in one academic year, and intervention subjects in the next academic year), a small sample size, and the fact that assessments were conducted at different times of the year in different conditions. The findings, though limited, were encouraging for such a short program and short follow-up period.

A very sophisticated study evaluated the long-term impact of a universal, teacher-implemented, and school-based prevention program that was developed by Spence, Sheffield, and Donovan (2003). The program, Problem Solving for Life, is a combination of cognitive restructuring and problem-solving approaches, and it is designed to prevent a first episode of depression. Subjects were 1,500 eighth-graders (ages 12–14; mean = 12.9) attending 16 participating high schools in the Brisbane region of Queensland, Australia. The program of eight 1-hour classroom sessions was implemented by 28 teachers in eight randomly assigned schools (N = 751), while the control subjects (N = 749) attended the other eight schools. There were approximately equal numbers of girls and boys.

Appropriate data analyses indicated that the program significantly decreased depressive symptoms between the beginning and end of the program. This finding, however, was only true for those adolescents who had elevated (“high risk,” defined as 13 or higher on the Beck Depression Inventory) depression scores at the beginning of the study. Unfortunately, this difference was not maintained at a 12-month follow-up.

Sawyer and colleagues (2010) implemented the “beyondblue” extensive universal program designed to prevent symptoms of depression but also to address some environmental variables that may affect depression onset and extend beyond those typically addressed in depression prevention programs. Beginning in 2003, the group randomly assigned 25 schools to the prevention program and 25 schools to the assessment-only and treatment-as-usual control condition (except they were allowed to participate in the community forum aspects of the program). Participants were 5,633 students beginning eighth grade, and they participated in the program for 3 years and were then followed for 2 more years. This remains the largest, most comprehensive, and best designed universal program to date. Because of the magnitude of the study, all outcome measures were self-report and included measures of depression, anxiety, well-being, and parental support. In addition to classroom educational programs broadly based on CBT interventions, this study included attempts to improve the environment in the school (e.g., social relationships, safety) as well as outside-of-school programs (e.g., community forums) that provided information for students and families regarding possible clinical services for those who might need them. Adherence measures showed that the program was successfully implemented as described. The program materials can be downloaded at http://www.beyondblue.org.au/index.aspx?link_id=4.1305.

Unfortunately, the end-of-treatment data (3 years; Sawyer et al., 2010) and the follow-up data (5 years; Sawyer et al., 2010) showed no significant effects of the program on clinical symptoms (e.g., depression or anxiety) or well-being. Similar to those of most other universal programs, the outcomes were nonsignificant (Merry et al., 2011; Spence & Shortt, 2007; Stice et al., 2009). Even with a large sample size, the effect sizes of the program were small, even with a broadly based CBT program, and even with school environmental changes.

In an effort to understand the failure to find significant effects for the extensive universal “beyondblues” study, Spence and her colleagues (personal communication, Feb. 18, 2014) conducted an informative follow-up on secondary analyses of the previous outcome data. Namely, they evaluated the effects of family relationship support as a moderator of the outcomes of the program. Significant differences, including lower levels of depression and anxiety and higher levels of well-being, were found supporting the effectiveness of the program relative to the control group among those youth who had low levels of family support in eighth grade at the beginning of the program. No differences between prevention program and control groups were obtained for those who had higher levels of family support at the beginning of the program. Thus, level of family relationship support was a moderating variable affecting the outcome of this universal program.

The findings by Spence and colleagues (2014) highlight the importance of absent or limited effects of universal programs that fail to take into account moderator variables such as family support, level of depressive symptoms before the intervention (see Spence et al., 2003), or presence of a depressed parent (see below, Garber et al., 2009). Despite the conclusions by Merry and colleagues (2012) that a limited number of universal programs have some impact, these effects are minimal for prevention of depression for the reasons highlighted earlier: the effect sizes are very small even with large sample sizes, and the programs are largely applied to individuals who do not need them (e.g., no depressive symptoms, no prior depression, no depressed family member) and do not profit from them (no increase in resiliency or well-being, as these individuals are already high-functioning at baseline). It seems that the limitations and warnings noted by Spence and Shortt (2007) still accurately describe the universal prevention program outcomes.

Because of the stable population of Iceland and because most of the citizens live in one city, Reykjavik, Arnarson and Craighead spent several years translating and standardizing assessment instruments and developing a manualized, developmentally based, behavioral and cognitive program designed to prevent depression in Iceland. The primary aim of this study was to evaluate the effectiveness of a program designed to prevent an initial episode of major depression or dysthymia among adolescents “at risk” for depression. The initial participants in a screening process were 1,920 ninth-grade Icelandic adolescents who were 14 or 15 years old at the beginning of the study. Following the selection procedures and exclusion and inclusion criteria described in detail in Arnarson and Craighead (2009), study participants were 171 14-year-old “at risk” but never previously depressed Icelandic adolescents who were randomly assigned to a prevention program or a treatment-as-usual assessment-only control group. They were identified as “at risk” by reporting the presence of depressive symptoms or a negative attributional style. The program was based on a developmental psychosocial model of enhancement of resilience to factors associated with the occurrence of mood disorders. It is called the “Thoughts and Health” program and includes a student workbook as well as a group leader’s manual. It was administered in a school setting by trained school psychologists. The program comprised 14 sessions with groups of six to eight adolescents. Diagnostic clinical interview and self-report data were collected at baseline, posttest, 6-month follow-up, and 12-month follow-up sessions. There were no significant differences between the prevention and treatment-as-usual groups for dropout rates or for “dropouts” compared to the “completers” on any of the screening measures.

At posttest, diagnoses of new (initial) episodes of depression and/or dysthymia were reported in 2.5% of the control group but 0% of the prevention group. By the 6-month follow-up, the diagnosis for initial episodes of depression and/or dysthymia had occurred in 13.3% of the control group but only 1.6% in the prevention group; data for 12-month follow up were similar (21% for the control group and 4% for the prevention group). Twice as many girls as boys experienced an initial episode of depression/dysthymia (Arnarson & Craighead, 2009).

Survival curves for initial episode rates were separately estimated at 6- and 12-month follow-ups using the Cox proportional hazards model. Students not available for follow-up were treated as censored observations. At 6-month follow-up, the prevention program relative to treatment as usual significantly reduced the risk of development of a first episode of depression and/or dysthymia (χ² = 4.03, p = .0448; odds ratio [OR] = .122). Survival analysis for the 12-month follow-up data indicated continued group differences (χ² = 5.02, p = .025; OR = .182); at the end of 1-year follow-up a student who participated in the prevention program was only 18.2% as likely to have developed an initial episode of depression/dysthymia as a student who was in the control group. Stated differently, the prevention program relative to treatment as usual decreased the likelihood of having a first episode by 81.8%.

A logistic regression model was estimated for the control subjects in order to determine if the screening CDI, CASQ-NEG, and CASQ-POS predicted either the diagnosis of depression or dysthymia. Only the CDI significantly predicted the diagnosis of depression or dysthymia (estimate = .0997, standard error = .0467, Wald χ² = 4.55, p = .0330).

The program was originally drafted in English but was then adapted to the Icelandic culture and rewritten in Icelandic. As the program was pilot testing, the illustrations and examples were modified to reflect more accurately teen culture in Iceland. Subsequent to the completion of the study, the manuals have been translated into English, back-translated to Icelandic, and then retranslated into English, and they are available for research purposes. Most recently the manuals have been translated into Portuguese, and the program is being replicated by A.P. Matos and her colleagues in Coimbra, Portugal. Again, the examples, cartoons, classroom posters, and so forth have been adapted to Portuguese youth culture. Preliminary data, including baseline descriptive information, are available from A.P. Matos (see Matos et al., 2013).

Beardslee and associates, following the IOM stages, first studied risk and resilience, then developed pilot interventions and conducted a large efficacy trial, and then moved to effectiveness and programmatic interventions. Their prevention programs were designed to be public health interventions and useful to all families in which a parent is depressed. The programs (Family Talk and adaptations of this intervention) can be used by a range of health practitioners, including internists, pediatricians, school counselors, and nurses, as well as by mental health practitioners such as child psychiatrists, child psychologists, and family therapists. Moreover, this approach includes a strong emphasis on treatment, given that so much depression is undiagnosed and untreated, so in that sense they are not limited to prevention of depression.

Rates of depression are two to four times higher in children of depressed parents than for children of parents with no illness (Beardslee, Gladstone, & O’Connor, 2011; Beardslee, Versage, & Gladstone, 1998). To understand the transmission of depression, it is important to recognize that in many instances, depression in parents serves as an identifier of a constellation of risk factors that, taken together, result in poor outcomes. In Rutter’s classic epidemiological studies, six factors were identified, including maternal psychiatric disorder. When only one was present, there was no increased risk to the child, but when two or more were present, the risk increased dramatically. In a random health maintenance organization sample over a 4-year period, Beardslee and associates (1996) demonstrated that the same principles were evident in predicting who became depressed. They devised an adversity index consisting of parental major depression, parental nonaffective illness, and a prior history of disorder in the child. When no risk factors were present, less than 10% of the children became depressed. When all three were present, 50% of the children became depressed, with a gradation in between. A recent review of the effects of parental depression again highlighted the substantial risk and stressed the importance of both familial genetic factors and of current and past adversities in leading to depression. It further highlighted that epigenetic phenomena and developmental plasticity are important in weighing the balance of risk and protective factors. As is true throughout this chapter, they advocate addressing both specific risk factors for depression (e.g., having a parent who is depressed) and nonspecific risk factors (e.g., poverty and exposure to violence) (Beardslee et al., 2011).

In studying resilience, Beardslee and associates identified three characteristics that described resilient children of depressed parents (Beardslee & Podorefsky, 1988). The three characteristics, which were incorporated into the preventive intervention, were (a) support for activities and accomplishment of developmental tasks outside of the home; (b) a deep involvement in human relationships; and (c) the capacity for self-reflection and self-understanding, in particular, in relation to the parent’s disorder. Resilient youth repeatedly said that understanding that their parent was ill, that the disorder had a name, and that they were not to blame for it contributed substantially to their doing well. Correspondingly, parents who raised children resilient in the face of parental depression were deeply committed to parenting despite depression and to openness and communication. These principles became central parts of the preventive intervention strategy devised by this group.

Family Talk is a six-session intervention conducted by a clinician in collaboration with the parents. The clinician takes a history and provides psychoeducation to the parents. A child meeting with the clinician precedes the family meeting, and a follow-up meeting is conducted 6 months after the family discussion. This intervention is designed to prevent depression in offspring of depressed parents by improving family communication, relationships, and functioning; acknowledging the impact of parental depression; and encouraging parental and child resilience by building on family strengths. The program is specified within a manual. It has proved possible to train large numbers of people with fidelity, and Beardslee and associates made web-based training available through the FAMpod.org website.

Initial studies of Family Talk and adaptations of the program revealed that they were safe and feasible, and that families believed them to be helpful. A comparison active condition—two lectures about depression and resilience in families—has been compared to Family Talk. In an initial random-assignment study of the first 20 families enrolled, promising effects were observed 6 months after intervention, and a further follow-up study of parents’ reports showed sustained effects over 3 years. In addition, pilot studies revealed that greater benefits were associated with the clinician-facilitated intervention than with the lecture condition.

Beardslee, Gladstone, Wright, and Cooper (2003) presented findings from follow-up interviews conducted with their entire sample of families at the fourth data point, nearly 2.5 years after intervention. They followed 100 families of over 300 individuals. They chose the interval of 2.5 years postintervention because it was long enough to begin to see substantial, sustained changes in several main domains hypothesized to be affected by participation in the prevention programs. They focused on effecting change in a mediating variable that they described as parental child-related behavior and attitude change.

Results revealed several important findings about the primary prevention of depression and other forms of psychopathology in children at risk for dysfunction due to parental mood disorder. They found that these programs did have longstanding effects in how families problem solve about parental depression (i.e., behavior and attitude change). There was evidence that the clinician-facilitated program was more beneficial than the lecture program, and that the amount of change in parent’s child-related behaviors and attitudes increased over time. More importantly, the intervention was targeted to increase the children’s understanding of the disorder in their parents. Children’s understanding increased significantly in both groups, with greater change in the clinician-facilitated program. They found a significant relation between the amount of child-related behavior and attitude change manifested by parents and the amount of change in understanding manifested by children, even though change was rated entirely separately by assessors blind to the knowledge of the other subjects’ reports. Finally, they found that children who participated in the intervention programs reported decreased internalizing symptomatology over time.

After the success of the randomized trial, Beardslee and associates (2003) examined the mechanisms by which change took place. Briefly, they found that when families did make changes, they talked repeatedly about depression. Often, breaking the silence about depression led the families to talk and strategize successfully about many other things. This process was named the “emergence of the healer within.” Similarly, they found that what works for a child at 12 does not work for the same child at 16. In this sense, understandings of depression change both as the course of parental illness changes and as children grow and mature. Finally, many parents, despite the negativism and self-doubt of depression, end up functioning effectively as parents. In essence, they made peace with their disorder and moved on.

As part of a dissemination effort, Beardslee and associates then examined the effectiveness of the intervention in different populations and worked with colleagues to examine it in different systems. They first adapted the intervention for use with single-parent, multiple-risk, African-American families in Dorchester, MA. In a randomized trial, the intervention led to behavior and attitude changes, it was well tolerated, families were satisfied, and more change occurred in families receiving the clinician-based intervention. They then adapted the intervention for use with Latino families using a bicultural, bilingual team and demonstrated in an open trial that the same kinds of effects were obtained in these families. Beardslee and associates have argued that adapting an intervention to a different cultural group often transforms it for the better, as occurred in these two adaptations.

Family Talk has been used as part of countrywide programs for children of the mentally ill as systematic efforts to improve the health of families with mental illness (Solantaus & Toikka, 2006). Solantaus has led the effort in Finland, which is an entirely Finnish program. In developing the countrywide program, she used three strategies:

Family Talk has been used in countrywide programs in Holland, Sweden, and Norway, and an extensive adaptation in Costa Rica has led it to be part of the national health service there.

At the request of Federal Head Start, Beardslee developed a program based on these principles to be used in Head Start and Early Head Start, where the rates of depression in mothers can exceed 50%. This program is a teacher training and empowerment program designed to increase the staff’s ability to deal with parental adversity and to encourage resilience. Evaluations of the program have been favorable. These materials are available for free on the Head Start website (Beardslee et al., 2011).

Investigators have implemented several interventions designed to prevent the recurrence of MDD. These include maintenance treatment (Frank et al., 1990; Paykel et al., 1999), booster sessions (e.g., Jarrett et al., 2001), and specific programs for previously depressed individuals (Sheets et al., 2013) who are not currently depressed.

Several programs labeled “prevention programs” are largely prevention of recurrence programs because such a large percentage of the participants have experienced a previous depressive episode. Some of the findings, as noted below, have been impressive, but the designs of the studies preclude one from determining whether the program actually prevented an initial MDD or the recurrence of the disorder. Indeed, it may eventually be determined that the most effective programs are the same prevention programs for initial episodes and recurrences, but at the present time that conclusion is premature. Data indicate that causal factors may be different for initial episodes and recurrent episodes; for instance, both parental depression and minor depressive symptoms predicted the initial episode of MDD, but life events were also predictive of further occurrences over a 12-year longitudinal study (Pettit et al., 2013). Further, both epigenetic and neural pathways affected by an initial episode of MDD may render individuals subsequently more vulnerable to external stressors than are the pre-episode brains of “at risk” youth. It may also be that the first episode of MDD produces social, behavioral, and cognitive changes that result in individuals creating greater stress or being more reactive to stressors that occur in their lives following the first episode. Currently, we do not have adequate data to argue strongly that the interventions that prevent initial episodes also prevent recurrence; conversely, we do not know that they will fail to prevent second episodes.

Clarke and colleagues (1995) in Oregon were among the first to study prevention of MDD among adolescents, and they focused on the prevention of diagnosed clinical depression rather than the presence of depressive symptoms via self-report measures that have been used by many other prevention programs. In an excellent, well-designed study, 150 adolescent students from ninth and tenth grades were assigned randomly to either a “prevention” or “usual-care” group. The prevention program, entitled Adolescent Coping with Stress Course, was delivered in groups and was a prevention-focused adaptation of this group’s Adolescent Coping with Depression Course (Clarke, Lewinsohn, & Hops, 1990). The 5-week intervention was conducted within the adolescents’ school setting and comprised fifteen 45-minute group sessions (three after-school meetings per week). The usual-care youngsters were free to continue with preexisting treatment or seek new treatment. This program employed both behavioral and cognitive coping techniques designed to reduce vulnerability to future depressive episodes.

Participants were followed for 1 year, and the results were positive. Namely, significantly (p < .05) fewer prevention group subjects (14.5%; 8 of 55) were diagnosed with MDD or dysthymia than control group subjects (25.7%; 18 of 70). The major strengths of this study included random assignment of subjects, adequate sample sizes, diagnoses of clinical mood disorders, and encouraging outcomes. It is important to note, however, that approximately 36% of their participants had suffered a prior episode of MDD. Because 30% to 50% of adolescents who have had a prior episode can be expected to have a relapse or recurrence of the disorder during the time (18 months) of this study (Hart, Craighead, & Craighead, 2001; Lewinsohn, Rohde, Seeley, & Fischer, 1993; Rao et al., 1995), it very well may be that Clarke and colleagues actually had their biggest impact on preventing relapse or recurrence rather than on preventing a first episode of MDD. In addition, there was differential dropout between conditions (Clarke et al., 1995), but as the authors suggested, this probably operated against their favorable outcomes.

In an expansion of this program, Clarke and associates (2001) applied this approach to a health maintenance organization population of adolescents of parents with diagnosed depression and youngsters already manifesting symptoms. They screened all those at risk and divided them into three groups: low or no depressive symptomatology, medium symptomatology, and those already in episode. Those already meeting criteria for MDD were referred for treatment, and those with no depressive symptomatology were excluded. In this trial, those adolescents (ages 13–18) with moderate symptomatology were randomized into a usual-care condition (N = 49) or their cognitive-behavioral intervention group (N = 45). As in their previous study, prevention group subjects participated in 15 group sessions.

This intervention yielded substantial preventive effects, with significant treatment-by-time effects in the expected direction on the Center for Epidemiological Studies–Depression (CES-D) and the Global Assessment of Functioning scales; in other words, adolescents in the prevention condition did much better than those in the usual-care condition. Survival analysis indicated that over a 15-month follow-up period, there was a cumulative rate of major depression of only 9% in the experimental group in contrast to 28% in the usual-care condition (Clarke et al., 2001). Even though this is the most sophisticated prevention study to date, its specific implications for prevention are limited by the choice to include adolescents who had previously had an episode of depression; these subjects made up 67% of the adolescents in this study. Thus, as with the prior study, it is impossible to determine if the study prevented first episodes or relapse and recurrence of prior episodes of MDD.

Building upon the work of Clarke and his colleagues, Garber and colleagues (2009) reported the results of a multisite study that evaluated the Coping with Depression Course written into a prevention format (copies available at http://www.kpchr.org/research/public/acwd/acwd.html). Participants were identified by the presence of a parent with MDD currently or in the past (about 40% of participants), the adolescent having a history of prior MDD (about 80% of participants), and/or the presence of some current symptoms of MDD in the adolescent (sometimes referred to as minor depressive symptoms). Across four sites spread across the United States, 316 participants ages 13 to 17 were randomly assigned to participate in the treatment program or an assessment-only program (essentially a treatment-as-usual control group). The prevention group participated in eight weekly 90-minute group sessions that focused on cognitive restructuring and problem-solving skills. Data were reported for baseline, end of treatment, and 9-month follow-up; six continuation sessions focusing on behavioral activation, relaxation training, and assertiveness were conducted between the end of the 8-week intervention and the 9-month follow-up assessment (Beardslee et al., 2013; Garber et al., 2009).

The primary finding was that the program resulted in the prevention group experiencing significantly fewer depressive episodes (21.4%) than the control group (32.7%). There was, however, an interaction between treatment and “presence of active parental depression at enrollment” such that the prevention program resulted in significantly fewer depressive episodes among those adolescents who did not have a parent with active MDD at baseline, but the program was not significantly more beneficial than treatment as usual when parental MDD was present.

The strengths of the study include the sample size, the multiple sites and multiple investigators, the fact that intervention offered by a wide range of interventionists, the sophistication of the design and statistical analyses, and the sustainability of the findings. The delivery of the program was state-of-the-art, and the findings strongly support the effectiveness of the program to prevent initial and recurrent episodes of MDD. The interaction findings further highlight the previous work of Beardslee and his colleagues demonstrating the importance of parental depression in the development and prevention of MDD among adolescents. This study suggests that future prevention studies may need to address current depression in parents in order for offspring to benefit from preventive interventions. As noted in the work of Gillham and colleagues (2012), this is very difficult to do, but it remains extremely important. Indeed, it may be necessary to treat the parental depression or offer recurrence prevention programs separately for the parents of adolescents who are “at risk” for MDD.

Beardslee and colleagues (2013) reported a 33-month follow-up to the 2009 study by Garber and colleagues—that is, data for the 24 months following the 9-month follow-up previously reported. Impressively, the investigators were able to evaluate almost 85% of the adolescents at the 33-month follow-up. The primary outcome measure was the presence of MDD at any time during the follow-up period; the prevention group had a slower and lower rate (36.8%) of onset of MDD compared to the control condition (47.7%), corresponding to a number needed to treat of 10. As in the 9-month follow-up, there was a significant parental-depression-by-group interaction: among adolescents whose parents were not depressed at baseline, the prevention program participants’ rate of MDD was 32.1% versus 51.9% in the control group, corresponding to a number needed to treat of 6. On the other hand, among adolescents who had at least one parent who was depressed at baseline, the prevention program had virtually no impact (41.6% vs. 43.4%), with an estimated number needed to treat of 54. The findings were further complicated by a treatment-by-parental-depression-by-site interaction. The parental-depression-by-treatment-condition interaction varied such that the effects of parental depression on the treatment outcomes varied by site; however, the sample sizes within sites were small relative to the overall findings, precluding an interpretation of the cause of this finding (see Beardslee et al., 2013).

Brent and colleagues (2015) reported 6-year follow-up data for the preceding prevention cohort (Garber et al., 2009). They retained a remarkable 88% of the participants from the original prevention sample. The rate of depression remained significantly lower than the treatment-as-usual group, and as with the original finding, this was true for those participants who did not have a depressed parent in the house. As with the 3-year follow-up, the differential preventive effects of the prevention program were obtained by the end of the 9 months of intervention and did not increase further over the 6-year period; however, the positive 9-month effects were maintained at the 6-year follow-up. The new findings that emerged in the 6-year follow-up were that the successful participants (those in the program but without a depressed parent in the house) evinced greater developmental competence and functional adaptivity than did the other groups of participants.

In summary, the work of Clarke, Garber, Beardslee, and their associates indicates that the modified Coping with Depression Course can be used to prevent MDD among youth at risk for a first episode of depression or to prevent the recurrence of MDD among those who have previously had an episode. However, the program does not appear to have a positive preventive impact on adolescents who have a parent who currently has MDD. The program effects were maintained at 33 months, the longest follow-up to demonstrate a preventive program effectiveness. However, the moderating effects of parental depression and the three-way interactions with sites indicate that the program may only have its preventive effects for adolescents who have some symptoms of depression or who have been previously depressed but not for those with one or both parents with MDD.

Miklowitz and his colleagues have manualized his family-focused therapy (FFT; Miklowitz, 2008) for use as a prevention program for youth at risk for bipolar disorder (Miklowitz et al., 2013). The program was evaluated with 40 high-risk youth ages 9 to 17. “At risk” for bipolar disorders was defined as having a family member with a history of mania and a first-degree relative with bipolar I or bipolar II disorder. Participants were currently diagnosed with MDD, bipolar disorder not elsewhere classified, or cyclothymic disorder. Forty participants were randomly assigned to the FFT program or a two-session education control group; about 60% of the participants were receiving psychotropic medications. During this 1-year randomized clinical trial, FFT participants recovered more rapidly from their initial diagnosed symptoms, spent more weeks in remission of mood symptoms, and showed greater improvement in hypomania symptoms than did the participants in the education control group. As with clinical trials of FFT with bipolar patients, the treatment was most efficacious for youth from families with higher levels of Expressed Emotion. Despite the small sample sizes and other limitations of this study, it is encouraging in that a treatment with demonstrated efficacy with bipolar patients might be modified and employed in a preventive manner for youth at risk for bipolar disorders.

Based on the preceding summaries of outcomes, we should begin to disseminate CBT and family-based programs as a major public health initiative. Both the international consortium on the prevention of depression (Cuijpers, Beekman, & Reynolds, 2012) and others (Muñoz, Beardslee, & Leykin, 2012) have strongly suggested such an effort, with the outcome being population-level change in the incidence of major depression in the groups targeted. Based on the studies reviewed here, it seems likely that wider use of programs aimed at “indicated” or “at risk” populations will yield the greatest public health benefits.