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Objectives Early intervention and preventive strategies have become major targets of research and service development in psychiatry over the last few years. Compared to schizophrenia, bipolar disorder ( BD) has received limited attention in this regard. In this paper, we review the available literature in order to explore the public health significance of BD and the extent to which this may justify the development of early intervention strategies for this disorder. Methods The main computerized psychiatric literature databases were accessed. This included Medline and PsychInfo, using the following keywords: bipolar, early intervention, staging model, burden, caregiver, public health, and manic depression. Results BD is often recurrent and has an impact that goes well beyond symptomatic pathology. The burden it incurs is linked not only to its cardinal clinical features, but also to cognitive dysfunction, poor functional outcome, poor physical health, high rate of comorbidities, and suicide. At a societal level, BD induces enormous direct and indirect costs and has a major impact on caregivers. The available literature reveals a usually long delay between illness onset and the start of treatment, and the absence of specific guidelines for the treatment of the early phase of BD. Conclusions Considering the major impact of BD on patients and society, there is an urgent need for the development of early intervention strategies aimed at earlier detection and more specific treatment of the early phase of the disorder. [ABSTRACT FROM AUTHOR]

Objectives Clinical staging is widespread in medicine - it informs prognosis, clinical course, and treatment, and assists individualized care. Staging places an individual on a probabilistic continuum of increasing potential disease severity, ranging from clinically at-risk or latency stage through first threshold episode of illness or recurrence, and, finally, to late or end-stage disease. The aim of the present paper was to examine and update the evidence regarding staging in bipolar disorder, and how this might inform targeted and individualized intervention approaches. Methods We provide a narrative review of the relevant information. Results In bipolar disorder, the validity of staging is informed by a range of findings that accompany illness progression, including neuroimaging data suggesting incremental volume loss, cognitive changes, and a declining likelihood of response to pharmacological and psychosocial treatments. Staging informs the adoption of a number of approaches, including the active promotion of both indicated prevention for at-risk individuals and early intervention strategies for newly diagnosed individuals, and the tailored implementation of treatments according to the stage of illness. Conclusions The nature of bipolar disorder implies the presence of an active process of neuroprogression that is considered to be at least partly mediated by inflammation, oxidative stress, apoptosis, and changes in neurogenesis. It further supports the concept of neuroprotection, in that a diversity of agents have putative effects against these molecular targets. Clinically, staging suggests that the at-risk state or first episode is a period that requires particularly active and broad-based treatment, consistent with the hope that the temporal trajectory of the illness can be altered. Prompt treatment may be potentially neuroprotective and attenuate the neurostructural and neurocognitive changes that emerge with chronicity. Staging highlights the need for interventions at a service delivery level and implementing treatments at the earliest stage of illness possible. [ABSTRACT FROM AUTHOR]

Objective: Affective psychoses and bipolar disorders have been neglected in the development of early intervention strategies. This paper aims to gather current knowledge on the early phase of bipolar disorders in order to define new targets for early intervention. Methods: Literature review based on the main computerized databases (MEDLINE, PUBMED and PSYCHLIT) and hand search of relevant literature. Results: Based on current knowledge, it is likely that an approach aiming at the identification of impending first-episode mania is the most realistic and manageable strategy to promote earlier treatment. During the period preceding the onset of the first manic episode, patients go through a prodromal phase marked by the presence of mood fluctuation, sleep disturbance, and other symptoms such as irritability, anger, or functional impairment. Additionally, various risk factors and markers of vulnerability to bipolar disorders have been identified. Conclusions: In the few months preceding first-episode mania, patients go through a prodrome phase (proximal prodrome) that could become an important target for early intervention. However, considering the low specificity of the symptoms observed during this phase, criteria defining high-risk profiles to first-episode mania should also include certain risk factors or markers of vulnerability. While more research is needed in high-risk groups (e.g., bipolar offspring), retrospective studies conducted in first-episode mania cohorts could provide valuable information about this critical phase of the illness. [ABSTRACT FROM AUTHOR]

Objective Bipolar disorder is a multifaceted illness and there is often a substantial delay between the first onset of symptoms and diagnosis. Early detection has the potential to curtail illness progression and disorder-associated burden but it requires a clear understanding of the initial bipolar prodrome. This article summarizes the phenomenology of bipolar disorder with an emphasis on the initial prodrome, the evolution of the illness, and the implications for prevention and early intervention. Methods A literature review was undertaken using Medline, Web of Science, and a hand search of relevant literature using keywords (e.g., phenomenology, initial or early symptoms, risk factors, and predictors/prediction). Findings from the literature were reviewed and synthesized and have been put into a clinical context. Results Bipolar disorder is a recurrent, persistent, and disabling illness that typically develops in adolescence or early adulthood. The literature search yielded 28 articles, in which mood lability, nonspecific, non-mood symptoms, and cyclothymic temperament were the most cited prodromal features. Conclusions A small number of key prospective studies have provided evidence in support of an initial bipolar prodrome; however, methodological differences across studies have prohibited its clear delineation. It is, therefore, not currently possible to anticipate those who will develop bipolar disorder solely on the basis of early phenomenology. Accurate characterization of the bipolar disorder prodrome through high-quality, prospective research studies with adequate control groups will ultimately facilitate prompt and accurate diagnosis. [ABSTRACT FROM AUTHOR]

McMurrich S, Sylvia LG, Dupuy JM, Peckham AD, Peters AT, Deckersbach T, Perlis RH. Course, outcomes, and psychosocial interventions for first-episode mania. Bipolar Disord 2012: 14: 797-808. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: The course of bipolar disorder tends to worsen over time, highlighting the importance of early intervention. Despite the recognized need for adjunctive psychosocial treatments in first-episode mania, very few studies have evaluated psychological interventions for this period of significant risk. In this empirical review, we evaluate existing research on first-episode bipolar disorder, compare this body of research to parallel studies of first-episode schizophrenia, and identify strategies for future research. Methods: A comprehensive literature search of the MEDLINE and PsychINFO databases was conducted to identify studies of first-episode mania, as well as first-episode schizophrenia. Recovery and relapse rates were compared across studies. Results: In contrast to a number of studies of first-episode schizophrenia, the authors identified only seven independent programs assessing first-episode mania. Findings from these studies suggest that, while pharmacological treatment helps patients achieve recovery from acute episodes, it fails to bring patients to sustained remission. Early psychosocial intervention may be imperative in reducing residual symptoms, preventing recurrence of mood episodes, and improving psychosocial functioning. However, very few studies of psychosocial interventions for first-episode mania have been systematically studied. Conclusions: Studies of first-episode mania indicate a gap between syndromal/symptomatic and functional recovery. Novel psychosocial interventions for first-episode mania may help bridge this gap, but require controlled study. [ABSTRACT FROM AUTHOR]

Berk M, Brnabic A, Dodd S, Kelin K, Tohen M, Malhi GS, Berk L, Conus P, McGorry PD. Does stage of illness impact treatment response in bipolar disorder? Empirical treatment data and their implication for the staging model and early intervention. Bipolar Disord 2011: 13: 87-98. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S. The staging model suggests that early stages of bipolar disorder respond better to treatments and have a more favourable prognosis. This study aims to provide empirical support for the model, and the allied construct of early intervention. Pooled data from mania, depression, and maintenance studies of olanzapine were analyzed. Individuals were categorized as having had 0, 1-5, 6-10, or >10 prior episodes of illness, and data were analyzed across these groups. Response rates for the mania and maintenance studies ranged from 52-69% and 10-50%, respectively, for individuals with 1-5 previous episodes, and from 29-59% and 11-40% for individuals with >5 previous episodes. These rates were significantly higher for the 1-5 group on most measures of response with up to a twofold increase in the chance of responding for those with fewer previous episodes. For the depression studies, response rates were significantly higher for the 1-5 group for two measures only. In the maintenance studies, the chance of relapse to either mania or depression was reduced by 40-60% for those who had experienced 1-5 episodes or 6-10 episodes compared to the >10 episode group, respectively. This trend was statistically significant only for relapse into mania for the 1-5 episode group (p = 0.005). Those individuals at the earliest stages of illness consistently had a more favourable response to treatment. This is consistent with the staging model and underscores the need to support a policy of early intervention. [ABSTRACT FROM AUTHOR]

Miklowitz DJ, Chang KD, Taylor DO, George EL, Singh MK, Schneck CD, Dickinson LM, Howe ME, Garber J. Early psychosocial intervention for youth at risk for bipolar I or II disorder: a one-year treatment development trial. Bipolar Disord 2011: 13: 67-75. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S. Previous studies have identified behavioral phenotypes that predispose genetically vulnerable youth to a later onset of bipolar I or II disorder, but few studies have examined whether early psychosocial intervention can reduce risk of syndromal conversion. In a one-year open trial, we tested a version of family-focused treatment adapted for youth at high risk for bipolar disorder (FFT-HR). A referred sample of 13 children (mean 13.4 ± 2.69 years; 4 boys, 9 girls) who had a parent with bipolar I or II disorder participated at one of two outpatient specialty clinics. Youth met DSM-IV criteria for major depressive disorder (n = 8), cyclothymic disorder (n = 1), or bipolar disorder not otherwise specified (n = 4), with active mood symptoms in the past month. Participants were offered FFT-HR (12 sessions in four months) with their parents, plus psychotropic medications as needed. Independent evaluators assessed depressive symptoms, hypomanic symptoms, and global functioning at baseline and then every four months for one year, with retrospective severity and impairment ratings made for each week of the follow-up interval. Families were mostly adherent to the treatment protocol (85% retention), and therapists administered the FFT-HR manual with high levels of fidelity. Youth showed significant improvements in depression, hypomania, and psychosocial functioning scores on the Adolescent Longitudinal Interval Follow-up Evaluation. They also showed significant improvements in Young Mania Rating Scale and Children's Depression Rating Scale scores. FFT-HR is a promising intervention for youth at high risk for BD. Larger-scale randomized trials that follow youth into young adulthood will be necessary to determine whether early psychosocial intervention can reduce the probability of developing bipolar I or II disorder among genetically vulnerable youth. [ABSTRACT FROM AUTHOR]

Objective: Recent studies have shown that outcome in mania is worse than previously thought. Such studies have been conducted in selected samples with restrictive measures of outcome. We aimed to explore outcome and its predictors in a catchment area sample of first-episode psychotic mania of DSM-III-R bipolar I disorder. Methods: Prospective 6 and 12 months follow-up was conducted with 87 DSM-III-R first-episode psychotic mania patients admitted to Early Psychosis Prevention and Intervention Centre between 1989 and 1997. Syndromic and symptomatic outcome were determined with the Brief Psychiatric Rating Scale; functional outcome with the Quality of Life Scale and Premorbid Adjustment Scale subitems. Results: Symptomatic outcome was assessed in 67 patients at 6 months and 61 patients at 12 months, and functional outcome in 56 patients at 6 months and 49 patients at 12 months. Logistic regressions were conducted on 46 and 43 patients, respectively, to explore predictors of outcome. While 90% of patients achieved syndromic recovery at 6 and 12 months, 40% had not recovered symptomatically at 6 and 12 months, still presenting with anxiety or depression. A total of 66% of patients at 6 months and 61% of patients at 12 months failed to return to previous level of functioning. Age at intake, family history of affective disorder, illicit drug use and functional recovery at 6 months predicted functional outcome at 12 months. Conclusions: This study confirms poor symptomatic and functional outcome after first-episode psychotic mania. It suggests possible usefulness of early intervention strategies in bipolar disorders and need for developing specific interventions addressing anxiety, depression and substance abuse comorbidity. [ABSTRACT FROM AUTHOR]

The author discusses the study "Epigenetic basis of sensitization to stress, affective episodes, and stimulants: implications for illness progression and prevention," by Robert M. Post. Topics discussed include the association of epigenetics and affective disorders' neuroprogression, the impact of the early intervention in patients with bipolar disorder, and the challenges on bipolar disorder treatment.