The Early Natural History of Bipolar Disorder: What We Have Learned from Longitudinal High-Risk Research

Abstract

Longitudinal high-risk research has provided convergent evidence that major mood and psychotic disorders often develop from nonspecific antecedents in predisposed people over time and development. For example, bipolar disorder (BD) appears to evolve from nonspecific childhood antecedents, including anxiety and sleep problems, followed by adjustment and minor mood disturbances through early adolescence, culminating in major mood episodes in later adolescence and early adulthood. Therefore, the current cross-sectional symptom-based diagnostic approach requires rethinking: it considers neither the familial risk nor the longitudinal clinical course, with the consequence that the early stages of illness are not recognized as belonging to the end-stage disorder. Emerging evidence of identifiable clinical stages in the development of BD has tremendous potential for early identification, development of stage-specific treatments, and advancing our understanding of the pathophysiology associated with illness onset and progression. The clinical staging model also has direct implications for the optimal organization of clinical services for high-risk youth. Specifically, specialty psychiatric programs are needed that break down traditional institutional barriers to provide surveillance and timely comprehensive psychiatric assessment during the entire risk period, from childhood through to early adulthood. In this regard, the development of specialty psychiatric programs aiming to identify youth in the early stages of evolving psychosis are substantially ahead of services for youth in the early stages of evolving major mood disorders.Can J Psychiatry. 2010;55(8):477-485. Highlights· Prospective longitudinal studies of the children of affected parents have provided an important opportunity to describe the early natural history of BD. · New evidence supports a clinical staging model that, if replicated, will improve early detection and provide a conceptual frame for early intervention and neurobiological research. · Implications of completed high-risk research point to the importance of a developmental approach to psychiatric diagnosis and highlight the need for specialty programs for youth at high risk of major mood disorders.

Childhood maltreatment and clinical outcomes of bipolar disorder

“…Considering such findings, it is plausible to suggest that childhood adversity may be related to increased vulnerability to BD symptoms during development. Keeping this in mind is crucial, as high-risk longitudinal studies have highlighted the heterogeneity of mood disorders during development and provide evidence of the evolution of psychopathology across the time (43,44). Because the studies included in this review evaluated childhood trauma retrospectively, conclusions about cause and effect are not possible and issues about memory bias should be considered.…”

“…Usually, clinical course, environmental factors, family history, and treatment response are not considered in the current diagnostic classification systems (44). Assuming that childhood abuse and neglect could accelerate the evolution of BD or may impact its pathophysiology, the incorporation of early life trauma in diagnostic and treatment decisions may assist in BD treatment planning and prognosis, emphasizing the imperative need of early intervention.…”

Toward a Comprehensive Clinical Staging Model for Bipolar Disorder: Integrating the Evidence

“…50,58,[72][73][74] Specifically, children of parents with BD with an excellent response to long-term lithium (lithium responders) had a completely normal or gifted early developmental course. In contrast, the children of parents who failed to respond to lithium prophylaxis (lithium nonresponders) manifest childhood problems with cognition, emotional regulation, socialization, and neurodevelopmental disorders.…”

Risk for emerging bipolar disorder, variants, and symptoms in children with attention deficit hyperactivity disorder, now grown up

“…For example an exclusionary clause might be created i.e., in the presence of childhood ADHD, more symptoms might be required, or "irritability" might be excluded as an A criterion. More longitudinal research is required, both of patients first identified by manic symptoms (e.g., LAMS), and of those first identified with ADHD, if we are to fully understand what symptoms should characterize "true" BD or its variants across development, in view of longitudinal studies of highrisk children from parents with BD [45] . These studies indicate that emerging BD is not characterized by early onset irritability or ADHD, but instead by unfolding anxiety symptoms and sleep disturbances, before the first manic or hypomanic episode.…”