Functional outcome and disability in bipolar disorders: ongoing research and future directions

It has been over a century since Kraepelin first delineated manic depressive insanity (MDI) from schizophrenia (1). While acknowledging that significant diagnostic challenges are posed by many cases, Kraepelin left no doubt in a 1922 paper (2) about his view that these 2 disease entities should be distinguished. Among the many differential diagnosis guides he offered was the far greater likelihood of interepisode recovery with insight in MDI, relative to its extreme rarity in schizophrenia. This has in subsequent years been misread to suggest that Kraepelin viewed MDI, consisting of both bipolar disorder (BD) and what is now called unipolar major depressive disorder, as being free from interepisode disability. This view then entered into the psychiatric ‘conventional wisdom’ about BD, leading to the widespread assumption that this often debilitating disease has a uniformly favorable course and outcome (and hence that cases with poor outcome are misdiagnosed). The seminal Global Burden of Disease Study report (3) has done much to correct this false impression: BD has been reported to be the sixth leading cause of disability among all medical disorders in market economies worldwide. Bipolar disorder is ranked immediately behind schizophrenia, the fifth most disabling disease, although the 2 diseases have comparable prevalence. In his longitudinal sample of over 1,000 MDI cases, Kraepelin identified so-called ‘fundamental states’ in 38% of patients. These states were characterized by subthreshold symptoms with attendant cognitive deficits persisting between acute illness episodes. Recent empirical work further suggests that in many cases symptoms remain largely intractable (4) and most bipolar patients are symptomatic more than half of their lives, despite receiving pharmacological treatment. Furthermore, even with apparent remission of mood symptoms, most euthymic patients fail to achieve a complete functional recovery (5, 6). Hence, the naïve expectation of recent years that improved diagnostic and therapeutic methods would lead to full clinical and functional recovery is giving way to the more realistic awareness that a substantial gap remains between what can be achieved by clinical actions and what patients and their relatives can expect from health care providers. Keenly felt among these gaps is the disability that persists for so many patients even when symptomatic recovery is substantially achieved. Research into this area has been stymied by a paucity of adequate methods for measuring disability. Consequently, there have been few studies that aim to clarify its principal causes and alter its course. An initiative to promote research into this area was undertaken in 2004 by the International Society for Bipolar Disorders (ISBD). In support of the World Health Organization's (WHO) promotion of disability measurement projects, which aim to capture the consequences of diseases more thoroughly, the ISBD constituted a committee on functionality whose goal is to promote scientific activities that will enhance research and education focused on BD. More than 2 decades of such work in schizophrenia have culminated in a substantial series of recent program initiatives by the National Institute of Mental Health (NIMH) and the Food and Drug Administration (FDA) in the USA. These initiatives, known as MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) (http://www.matrics.ucla.edu) and TURNS (Treatment Units for Research on Neurocognition and Schizophrenia) (http://www.turns.ucla.edu) have promoted scientific dialogue, support to researchers, and recommendations for industry on targeting both cognitive deficits and disability. Similar recognition of the importance of disability as a critical treatment target for all psychiatric disorders has come from the European Medicines Evaluation Agency (EMEA). A greater appreciation of the type, extent, clinical correlates and predictors of disability in BD will be needed if a comparable initiative is to be embraced for BD. The editors of Bipolar Disorders, the official journal of the ISBD, have recognized this need and designated that a special issue should be devoted to the topic. Judith Jaeger, chair of the ISBD Committee on Functionality, initiated this process and invited Eduard Vieta to participate as a co-editor for his unique expertise and to assure global representation. Leading investigators in the field were then invited to submit relevant research reports to peer review for this special issue. The evidence that BD leads to substantial functional difficulties and disability in most patients, and the need for more knowledge in this area, is evident from the topics covered in this groundbreaking issue. Topics covered address the problem from the epidemiological, clinical, neurobiological, and even subjective personal perspectives. We learn that there may be multiple causes and correlates of disability and functional impairment in BD, including residual symptomatology (7–12), neurobiological and neuropsychological factors (12–15), and psychosocial variables (16–19). Potential solutions may emerge as we improve our understanding of these factors and our tools to measure disability, as discussed in this issue by several authors (20–22). The goal of these efforts is a rational basis for designing interventions, pharmacological and non-pharmacological, that may improve functional outcome in BD (23). Potential targets for pharmacological and psychosocial interventions might include residual symptoms, co-occurring conditions, cognitive dysfunction, and social factors including vocational access and support. It is hoped that this special issue of Bipolar Disorders will establish a foundation for further work in this area.