A familial risk enriched cohort as a platform for testing early interventions to prevent severe mental illness

Abstract

BackgroundSevere mental illness (SMI), including schizophrenia, bipolar disorder and severe depression, is responsible for a substantial proportion of disability in the population. This article describes the aims and design of a research study that takes a novel approach to targeted prevention of SMI. It is based on the rationale that early developmental antecedents to SMI are likely to be more malleable than fully developed mood or psychotic disorders and that low-risk interventions targeting antecedents may reduce the risk of SMI.Methods/DesignFamilies Overcoming Risks and Building Opportunities for Well-being (FORBOW) is an accelerated cohort study that includes a large proportion of offspring of parents with SMI and embeds intervention trials in a cohort multiple randomized controlled trial (cmRCT) design. Antecedents are conditions of the individual that are distressing but not severely impairing, predict SMI with moderate-to-large effect sizes and precede the onset of SMI by at least several years. FORBOW focuses on the following antecedents: affective lability, anxiety, psychotic-like experiences, basic symptoms, sleep problems, somatic symptoms, cannabis use and cognitive delay. Enrolment of offspring over a broad age range (0 to 21 years) will allow researchers to draw conclusions on a longer developmental period from a study of shorter duration. Annual assessments cover a full range of psychopathology, cognitive abilities, eligibility criteria for interventions and outcomes. Pre-emptive early interventions (PEI) will include skill training for parents of younger children and courses in emotional well-being skills based on cognitive behavioural therapy for older children and youth. A sample enriched for familial risk of SMI will enhance statistical power for testing the efficacy of PEI.DiscussionFORBOW offers a platform for efficient and unbiased testing of interventions selected according to best available evidence. Since few differences exist between familial and ’sporadic’ SMI, the same interventions are likely to be effective in the general population. Comparison of short-term efficacy of PEI on antecedents and the long term efficacy for preventing the onset of SMI will provide an experimental test of the etiological role of antecedents in the development of SMI.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-014-0344-2) contains supplementary material, which is available to authorized users.

Staging model raises fundamental questions about the nature of bipolar disorder

“…Several prospective studies are currently underway that in clude interventions; an example is the FORBOW project in Halifax, Nova Scotia, Canada. 21 However, early interventions will need to be adopted by a considerably larger number of programs to result in a detectable effect.…”

Cohort Multiple Randomised Controlled Trials (cmRCT) design: efficient but biased? A simulation study to evaluate the feasibility of the Cluster cmRCT design

“…Despite this, the published protocols of cmRCT either propose ITT for the primary analysis [9, 11, 12] or methods have not been stated yet [10, 13–16]. This follows the recommendation to use ITT for the analysis of pragmatic trials [5, 24, 38].…”

Concepts and misconceptions regarding clinical staging models

“…We have been involved in some of the longitudinal highrisk studies of young people at risk for bipolar disorder. [1][2][3] These studies, among others, described early stages of the illness and their comorbidities 4 as well as neuropsychological function ing 5 and structural brain findings. 6 Based on these studies as well as on observations of other authors, we be lieve that the point of heterogeneity of bipolar disorder and the need to sepa rate it from the concept of uniformly progressing illness are equally applica ble in the early stages as in the latter ones.…”