Anxiety disorders are highly prevalent among children and adolescents with estimates of 11.6% year prevalence in adolescents alone , and depression is highly prevalent among adolescents, with estimates of 3.8% year prevalence . Anxiety and mood disorders in childhood and adolescence not only have a high impact on present functioning [2, 3], but are also associated with long-term negative consequences [4, 5]. In the Netherlands alone, estimations are that as many as 37.400 adolescents (3.8%) suffer from depressive disorder , corresponding with a burden of disease of 7900 Disability Adjusted Life Years (DALYs), meaning that per year 7900 healthy years are lost due to depression alone in youngsters ‘Gezond Verstand’, . For anxiety disorders, estimates are 113.000 adolescents (11.6% year prevalence) and 15.000 DALYs.
From epidemiological research, we know that anxiety and mood disorders often run in families: the incidence of depression and anxiety is elevated by a factor 2–6 among offspring of patients with such a disorder (e.g. [7, 8]). There is considerable aetiological and phenomenological overlap between mood and anxiety disorders. Anxiety often precedes depression  with the age of onset of depression being typically 5 to 10 years later than that of anxiety disorders e.g. .
Given the high prevalence of anxiety and mood disorders, the high impact on individuals as well as the associated societal costs, there is a clear need for prevention of anxiety and mood disorders in youth. Since these disorders run in families, the family may be a good starting point for prevention.
During the last two decades, a variety of programs has been developed to prevent anxiety disorders or depression among children and adolescents [overview: [2, 11]. The results of universal prevention programs are disappointing for both anxiety and mood symptomatology [e.g. [2, 12]. For selective prevention (targeting high risk groups) and indicated prevention (targeting those with subclinical symptoms) results are more promising.
Despite of the relatively high risk in offspring, thus far the number of randomised controlled trials testing the efficacy of indicated prevention is very limited: Four randomised trials have aimed at offspring of depressed patients [13–16], with two studies reporting on cognitive behavioural group treatments for offspring, and two studies including more family-based treatments. Only one study reported on prevention in children of anxiety disordered parents .
In the first study, the effectiveness of the 15-session cognitive group training ‘Coping with stress’ was examined in adolescent offspring of a depressed parent . Adolescents (N = 94) were aged 13–17 years and had subclinical depressive symptoms or a history of depression themselves. The program encompassed cognitive restructuring techniques aimed at changing maladaptive thoughts in general and dysfunctional thoughts with regard to having a depressed parent. The intervention was not only effective in reducing depressive symptomatology, but also showed a significant reduction of new depressive episodes relative to care as usual. The program was also cost-effective .
Second, Garber and colleagues designed the largest multicenter trial in this field, including 316 youngsters aged 13–17 years. They were offspring of a parent with a current or prior depressive disorder, and had had a depression themselves or reported depressive symptoms. Adolescents were randomized to either care as usual or an 8-session CBT group training existing of cognitive restructuring and problem solving. Parents were invited to two parent information sessions. Adolescents were less likely to suffer from a depressive episode if they had received the training (21% versus 32% onset in 6 months), but only if the parent was remitted at the time of the intervention.
The third study investigated the effectiveness of a family program, including the 8–15 year-old offspring of at least one parent with an episode of depression in the past 18 months . At least one of the children in the family needed to be free of a depressive disorder. The 6–11 session family program was compared to two plenary group lectures for parents. Both interventions advocated open discussion about the parental illness and were directed at change in family dynamics. Both interventions proved equally effective in increasing family functioning and decreasing internalising behaviours up to 4.5 year follow-up (based on 105 families) . Families in the more intensive treatment reported more benefits in parent-child behaviours and regarding the child’s understanding of parental mental illness.
The fourth trial also investigated the effectiveness of a family intervention for families with at least one parent with a history of depression . The children did not need to report symptoms themselves to participate in the study. Participants included 111 families with 155 children aged 9–15 years, who were randomized to either written information only or to a 12-session cognitive behavioral family intervention in a group format . The family intervention focused on enhancing awareness of the role of depression in a family, on ameliorating parent–child interactions by teaching parenting skills (focusing on parental warmth and structure), and on learning general coping skills (for parents and children separately). Results indicate that children in the family program showed more benefits in terms of internalizing and externalizing symptoms in both parent and child reports. These gains were maintained at two year follow-up .
The only trial so far focusing on offspring of patients with anxiety disorders included 40 children aged 7–12 years, who were randomized to either an 8-session family-based CBT program focusing on coping and strengths or to a waitlist control condition. Children were not allowed to have a current anxiety disorder. Current or past symptomatology was not warranted for inclusion in the study. This trial was successful in preventing the onset of anxiety disorders in the offspring: offspring in the active condition did not develop anxiety disorders, whereas 30% of waitlist children met criteria for an anxiety disorder at 1 year follow-up.
In conclusion, results on interventions for offspring of depressed patients (4 studies) and anxious patients (1 study) were positive overall, including benefits on offspring symptomatology [20, 21], offspring onset of disorder [13, 14, 17, 20], parent‐child interaction , and offspring knowledge on the parent’s illness .
The current study builds upon these studies, while adding to them in a variety of ways: (1) we use additional risk factors to select ultra high risk individuals among offspring of patients with a mood or anxiety disorder; (2) we focus on both depression and anxiety; (3) we aim at symptom reduction as well as at increasing strengths and resilience; (4) we include mediators and moderators of change; (5) we include short and long-term cost-effectiveness analyses.
The aforementioned studies were either indicated prevention programs (youth with elevated symptoms) or selective prevention programs (youth with a high risk because of parental illness only). In our study, we aim at combining the two and thus selecting ultra high risk offspring. In line with earlier studies, we select youth with current symptomatology (of anxiety or mood). In addition, we wanted to make a selection of the symptom-free children. We know that some of the offspring may develop disorders over time, even though they currently do not report such symptoms. Recently, we have developed a prognostic index that predicts the development of anxiety or mood disorders in offspring (High Risk Index (HRI; de Vries, Landman-Peeters, Burger, Reichart, Nauta, den Boer, Nolen, Ormel, & Hartman: Predicting mood- and anxiety disorders in offspring of patients with a depressive disorder, unpublished manuscript)). This was done on the basis of a study examining offspring (n = 434) of patients with a unipolar mood disorder in a large prospective study, the ARIADNE-cohort (Adolescents at Risk of Anxiety and Depression, and Neurobiological and Epidemiological approach ). Three factors were associated with an increased risk of developing anxiety or mood disorders: female sex, having two affected parents, and suicide attempt(s) of one of the parents. In children with two or three risk factors (20% of the sample) the cumulative incidence of mood and anxiety disorders was 70% at the age of 20. In children with one or no risk factor, percentages dropped to 45% and 25% respectively. In the current study, inclusion is therefore based on the HRI as well as on symptomatology. Thereby, this study uniquely combines selected and indicated prevention .
For this group of high-risk offspring, we developed an individual cognitive behavioural therapy (CBT) based intervention targeting multiple risk and protective factors known to be associated with the onset of anxiety and depression (as recommended by Cuijpers ). Many prevention programs have focused on symptom reduction, whereas training of positive aspects and building resilience may be of utmost importance in prevention. Some at risk children may not show any symptomatology yet, and they may especially benefit from interventions focusing on strengths rather than vulnerabilities. Important protective factors in offspring include having knowledge on parental illness , having a supportive social network [22, 26] including a non-ill parent if available , as well as displaying active coping skills and flexibility in coping style across situations . Therefore, the offspring intervention includes psychoeducation for offspring, psychoeducation for parents, a focus on the social network, and problem solving skills training. With regard to the risk factors, we know that offspring may have a cognitive vulnerability in information processing: they report more negative and less positive self-statements . Interventions focusing on positive self-statements, positive emotions and positive events may enhance resiliency and may function as a buffer against developing negative mood or anxious feelings. A final risk factor are subclinical complaints. These symptoms are addressed by regular behavioural interventions, namely exposure exercises for anxiety and behavioural activation for depressive symptoms. Behavioural activation may be of particular importance, since engaging in activities and relationships outside of the home environment has been found to be an important protective factor in adolescent offspring .
So far, most prevention interventions were group-based. Individual programs allow for more tailoring to the specific needs, strengths and weaknesses of the child. This is crucial because of the heterogeneity of the target population (children with anxiety, or depressive symptoms, or no symptoms but an elevated score on the High Risk Index). In addition, living with a depressed suicidal parent differs in many ways from living with anxious dependent one, for example. An individual approach allows the therapist to tailor the intervention also to the specific background of the child.
To date, preventive interventions have been designed to prevent either mood disorders or anxiety disorders. Keeping in mind the significant overlap in symptoms between depression and anxiety disorders, prevention studies should focus on both. Indeed, epidemiological studies have found that elevated symptoms of anxiety and depression occur in offspring of both anxious  and depressed patients . Since the aetiology and pathogenesis of anxiety and depression also have considerable overlap, including offspring from patients with both mood and anxiety disorders provides the opportunity to study common mediating factors.
From a societal point of view, it is important to study the economic impact of psychiatric illnesses and possible effects of prevention programs, to assist future policy making and resource allocation. The economic evaluation in our study will focus on the differential effects on short and long term costs and health outcomes of the treatment conditions under study: CBT or minimal information. The study will be conducted from a societal perspective .
Treatment outcome studies typically include variables to study the treatment mechanisms (“how does the treatment work”) as well as the moderators of treatment outcome (“for what groups does the treatment work”). With regard to mediating factors in the current study, the intervention will aim at changing coping behaviour , increasing activities , and enhancing trust in the availability of attachment figures (in the social network). Even though we do not address cognitions directly through cognitive restructuring, we nonetheless want to investigate if the child’s attributional style changed through our behaviour intervention.
Moderating factors associated with (non)response are current parental psychopathology  and child’s symptomatology (internalising and externalising). We additionally measured some stable child characteristics that have been associated with the onset of anxiety or mood disorders, but have not been studied in relation to treatment outcome in offspring, namely reactive and regulative temperament , general executive functioning, and automatic self-associations . In addition, some of the presumed mediating factors may also function as moderators.
In summary, even though there is extensive evidence for the intergenerational transmission of anxiety and mood disorders, few preventive intervention studies in offspring have been carried out. Our study adds to the current state of the art in combining selective and indicative prevention, to focus on both anxiety and mood disorders in adult patients, to focus on both anxiety and depression symptoms in offspring, to work on both symptom reduction and resilience, to study cost-effectiveness, and to examine mediators and moderators of outcome.
Trial objective and purpose
The primary goal is to investigate whether a brief (10 + 2 sessions) cognitive behavioural treatment program on resilience and symptom reduction can prevent the incidence of depression or anxiety disorder in an ultra high risk sample of 8–18 year old offspring of patients with unipolar depression or anxiety disorder (sample defined by a High Risk Index or subclinical symptoms, or both). The second goal is to examine whether this intervention meets current standards for cost-effectiveness. A third goal is to explore the role of a number of factors that may potentially mediate or moderate the effect of the intervention. Mediating factors include coping, attributional style, daily activities, and optimism, while the selected moderating variables are child temperament characteristics and executive functioning, parental psychopathology (of both parents), child symptomatology, attachment, and (automatic) self-associations.