One Bipolar Family: From Affliction toward Recovery

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A comprehensive evidence-based staging model of BD is important to promote early detection and intervention, as well as research aimed at identifying markers of illness predisposition and progression. The proponents of staging BD on the basis of neuroprogression and AL have focused on differentiating earlier- from later-stage illness in adult patients meeting full diagnostic criteria for the disorder.

These studies consider neither the evidence of early antecedent risk syndromes nor the developmental illness trajectory leading up to the full-blown diagnosis of BD, as reported in several large prospective studies of the offspring of parents with this condition. The proposed staging models should be examined with the caveat that these provide an aggregate view derived from research studies and will not apply to all high-risk offspring as environmental and epigenetic factors operate in the expression of the diathesis.

The problem with AL model proposed by Kapczinski et al.

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While Berk et al. Further, it does not incorporate family history as a way to identifying stage 0 high-risk individuals, although a positive family history is the most robust risk factor predicting for at least classical BD. Without the context of positive family history, the early stages are too nonspecific and would yield a very high rate of false positives.

Finally, the staging models will need to be refined and informed by future research advances to be of heuristic value. Staging of major psychiatric disorders is gaining momentum as the clinical significance of this framework is substantial.


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Several lines of research show that the course of principal mental disorders follows a predictable and evolving path, from milder to progressively more severe presentations; staging models foster better understanding of the trajectory of these illnesses. BD is a persistent, lifelong condition whose pathogenesis involves the interplay between dysfunctional genes and environmental factors; this interaction is expressed clinically as distinctly recognizable endophenotypes.

While the blueprint of any staging system does not of necessity imply that patients would pass through each phase sequentially, it does give an aggregate view of how the illness unfolds as it develops. The extrapolative nature of the staging schema helps in formulating individually tailored treatment plans and defining prognosis in patients with BD.

Appropriate and adequate treatment in the early phases should prevent advancement to the latter periods of the disease when lasting damage has in essence occurred. In susceptible individuals with an ultra high risk profile, interventions in the earliest stages give an opportunity to prevent the ailment from progressing and resulting in a whole host of undesirable sequelae. Each one of the existing staging models for BD has its merits and limitations, but unquestionably there is a great need for this proposal. It is expected that future research will lead to refinements in the staging protocols with better outcomes for the sufferers of BD, which indeed is an intractable condition with poor prospects for many patients.

National Center for Biotechnology Information , U. Journal List Clin Psychopharmacol Neurosci v. Clin Psychopharmacol Neurosci. Published online May Ather Muneer.

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Author information Article notes Copyright and License information Disclaimer. This article has been cited by other articles in PMC. Abstract Bipolar disorder is manifested as severe dysregulation of mood with recurrent manic and major depressive episodes.


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    Developmental Trajectory and Clinical Heterogeneity of Bipolar Disorder Classical, recurrent bipolar disorder BD is currently viewed as a spectrum illness which includes several phenotypes. Bipolar spectrum disorders Evidence supports that bipolar subtypes defined by either prophylactic response or nonresponse to lithium differ in clinical course, family history and neurobiological correlates.

    Prospective studies of offspring of parents with bipolar disorder A number of longitudinal, prospective studies of offspring of parents with confirmed diagnosis of BD have shown divergence in illness course based on subtypes of the illness. Staging Model Proposed by Duffy 35 Based on above observations, Duffy has come forward with a staging scheme that emphasizes the family history, early childhood precursors, and adolescent psychopathology.

    Neuroprogression as the Basis for Staging in Bipolar Disorder There is ample research evidence that BD is an evolving condition in which early stages have different clinical features compared to latter phases. Linking neurobiological and clinical findings to neuroprogression and staging. Allostatic Load as the Cause of Progression in Bipolar Disorder BD is a complex and multifactorial disease with genetic and environmental factors contributing to its clinical expression.

    Biomarkers of Bipolar Disorder Potential neuroimaging markers Many studies have reported the existence of changes in the brain structures of patients with BD. Oxidative stress Oxidative stress is the result of imbalance between oxidant and antioxidant enzymes, which usually results in cell damage. Inflammatory factors Inflammatory factors also known as cytokines are proteins or glycoproteins secreted by cells of the immune system in response to noxious stimuli. Staging model proposed by Kapczinski et al. Table 1 Evidence based staging models for bipolar disorder BD.

    Duffy et al. ND disorders, learning and motor disorders 1a Mild or nonspecific symptoms 1 Well defined euthymic periods. Therapeutic implications of staging In other fields of medicine staging is widely used to choose appropriate treatment and inform the prognosis.

    Gonzalez R.

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