How to prevent the malignant progression of bipolar disorder

Abstract

There is increasing recognition that, in a high percentage of cases, bipolar disorder is a progressive illness. Multiple types of sensitization (or increased reactivity to repetition of the same stimulus) drive illness progression. One of the clearest is that of episode sensitization, where increased numbers of prior episodes are associated with: faster recurrences; more dysfunction; disability; social, educational, and employment deficits; suicide; medical comorbidities; cognitive dysfunction; and an increased incidence of dementia in old age. Repetition of stressors and bouts of substance abuse can also result in sensitization. Each type of sensitization appears to have an epigenetic basis, such that preventing sensitization should minimize the accumulation of adverse epigenetic chemical marks on DNA, histones, and microRNA. New data emphasize the importance of early, consistent intervention after an initial manic episode. The cognitive dysfunction associated with a first episode improves only if there are no further episode recurrences during the next year. A randomized study has also shown that comprehensive multimodal prophylactic intervention for 2 years leads to improvements in illness course extending over a total of 6 years. Intensive treatment of the earliest stages of bipolar disorder can thus exert lasting positive effects on the course of illness.

25 Years of the International Bipolar Collaborative Network (BCN)

“…There are multiple safe agents that are already available that deserve testing for their ability to achieve indicated primary or secondary prevention. These could include omega-3-fatty acids, vitamin D3, L-methyl folate, N-acetylcysteine, acetyl-L-carnitine, minocycline and other anti-inflammatories, and phosphatidylcholine, among many others (Post 2020 ; Post et al 2020a , b ). While the ultimate trajectory of those a high risk is uncertain, many of the potential interventions themselves appear to have non-specific potential positive effects (such as omega-3-fatty acids potential effectiveness in depression, bipolar disorder, ADHD, and psychosis), so effectiveness could be assessed across a range of syndromes and not just for bipolar disorder (23).…”

The Challenges of Children with Bipolar Disorder

“…Other agents not listed in Table 1 also deserve consideration even though the data on effectiveness in children is not solid [41,46]. For example, there is a very high incidence of borderline or low levels of vitamin D3 in children with major psychiatric illness, so supplementation with this safe vitamin would appear worthy of consideration.…”

“…This and other suggestions for addressing some of the complexities of bipolar disorder are acknowledged to be inadequately supported in the literature sufficiently to merit routines use [46]. However, given the paucity of systematic studies in children and the wide range of impairing symptoms and syndromes seen in the illness [18,47], some consideration of using these agents on the basis of careful evaluation of their potential risk: benefit ratio may be a rational approach.…”

“…A variety of safe pharmacological interventions may have merit in primary and/or secondary prevention even if not fully validated by systematic studies [46]. Along with safety, the non-specificity of potential effectiveness across multiple symptoms and syndromes makes their early utilization in children worthy of consideration.…”

Assessment of the Impairment in Domain functionalities and Executive Functions in Euthymic Patients, with Bipolar Disorder I/II - Utilizing the FAST and FAB tests

“…This hypothesis is supported bythe involvement of the prefrontal cortex and prefrontal-subcortical pathways, which regulate both mood state and cognitive functioning, and might predispose to a greater magnitude of cognitive deficits and frequency of episodes To better relate the meanings of these clinical and cognitive changes which reflected in the FAB test, we needed to initially discuss and relate the neuroanatomical and pathophysiological changes with the results found. [8]; [9]. However, if there is an increase in the allostatic load, it produces a cumulative physiological dysregulation related to the dysfunction of the hypothalamic-pituitary-adrenal axis, altering immunity, thereby activating pro-inflammatory mechanisms with subsequent activation of oxidative stress states [130].…”