Allostatic load in bipolar disorder: Implications for pathophysiology and treatment

Bipolar Disorders Program and Laboratory of Molecular Psychiatry, Hospital de Clinicas de Porto Alegre, Ramiro Barcelos 2350, 90035-000, Porto Alegre, RS, Brazil.
Neuroscience & Biobehavioral Reviews (Impact Factor: 8.8). 02/2008; 32(4):675-92. DOI: 10.1016/j.neubiorev.2007.10.005
Source: PubMed


Current literature on the effects of chronic stress in general health converges to the concept of allostatic load (AL). AL is the bodily 'wear and tear' that emerges with sustained allostatic states. In the field of bipolar disorder (BD), AL offers an important clue as to why patients who undergo recurrent mood episodes are clinically perceived as less resilient. In addition, AL helps explaining the cumulative disruptive health effects of intermittent episodes and stressors. Stress- and episode-induced changes in brain regions involved in the emotional circuitry may lead to dysfunctional processing of information, which would render BD patients more vulnerable to subsequent environmental stressors, episodes, and drugs of abuse. Mood stabilizing agents exert opposite effects than chronic stress in neurons, increasing neuroprotective factors what may help to quench the cycle of affective episode recurrence and neural and bodily deterioration. Therefore, AL provides an explanatory link to apparently unrelated findings such as cognitive impairment and higher rates of physical comorbidity and mortality that are observed in the course of BD and further highlight the importance of effective long-term prophylaxis.

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Available from: Rodrigo Grassi-Oliveira, Nov 15, 2015
    • "Changes induced by allostatic load may affect functioning of specific brain regions involved in processing of emotions and cognition, leading to a progression of symptoms and increased vulnerability to stressors (Kapczinski et al., 2008). In patients with BD, recurrent mood episodes may be responsible for allostatic load, which in turn could determine accelerated cell senescence (Kapczinski et al., 2008). This allostatic-age model agrees with the hypothesis that BD is associated with accelerated aging, as supported by the findings of reduced life expectancy , premature mortality and high prevalence of comorbid age-related disorders in BD, such as cardiovascular conditions , metabolic imbalance and immunoscenescence (Rizzo et al., 2014). "
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    ABSTRACT: Telomeres consist of exanucleotide tandem repeats and proteins complexes at the end of chromosome ends. Telomeres shorten at each cell division, and as such telomere length is a marker of cellular age. Accelerated telomere shortening and cell senescence have been associated with a number of chronic medical conditions, including psychiatric disorders, where increased prevalence of age-related disorders and shorter telomere length has been reported. Shorter telomeres in psychiatric patients are thought to be the consequence of allostatic load, consisting in the overactivation of allostatic systems due to chronic exposure to severe medical conditions and failure to adapt to chronic stressful stimuli. Most of the studies on telomere length in psychiatry have focused on major depressive disorder, but recent findings have shown shorter leukocyte telomere length in bipolar disorder patients and suggested that lithium may counteract telomeres shortening. These findings provided new insights into the pathophysiology of bipolar disorder and the mechanism of action of lithium. In this review we will present findings from the literature on telomere length in bipolar disorder, with a specific focus on lithium. We will also discuss advances and limitations of published work as well as methodological issues and potential confounding factors that should be taken into account when designing research protocols to study telomere length.
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    • "The prevailing illness staging theory for BD encompasses the effects of both neuroprogression and allostatic load [4]. Allostatic load is the physiological change of a system in response to the cumulative exposure of a combination of stressful life events, genetic determinants, and environmental factors [4] [5]. Thus a later stage of BD represents years of neuroprogression and exposure to a cumulative effect of allostatic load, which may subserve the association of oxidative stress, mood severity and functioning [4]. "
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    ABSTRACT: In the field of bipolar disorder (BD) research there is an absence of validated biomarkers and limited understanding of the biology underlying excessive and premature cardiovascular disease (CVD). Oxidative stress is a potential biomarker in both BD and CVD. To examine psychiatric and cardiovascular characteristics associated with peripheral oxidative stress markers among adolescents with BD, who are at high risk for CVD. Participants were 30 adolescents, 13-19years old, with BD and without CVD. Ultrasonography was used to evaluate vascular function and structure. Traditional CVD risk factors were also measured. Psychiatric assessments were conducted via semi-structured interview. Serum levels of oxidative stress (lipid hydroperoxides (LPH) and protein carbonylation (PC)) were assayed. Compared to published data on adults with BD, adolescents had significantly lower levels of LPH and PC (t52(11.34), p<0.0001; t58(29.68), p<0.0001, respectively). Thicker mean and maximum carotid intima media thickness was associated with greater levels of LPH (r=.455, p=.015; r=.620, p<0.0001, respectively). LPH was associated with diastolic blood pressure (r=-.488, p=0.008) and pulse pressure (r=.543, p=0.003). Mood symptoms and medication were not significantly associated with oxidative stress. Adolescents with BD have lower levels of oxidative stress compared to adults with BD, supporting prevailing illness staging theories for BD. Oxidative stress is robustly associated with a proxy measure of atherosclerosis and may explain in part the increased risk of CVD in BD. Copyright © 2015 Elsevier Inc. All rights reserved.
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    • "The literature on the relationship between impulsivity, BD, and SUD is sparse, and it is unclear whether impulsivity is a marker of the bipolar disorder or rather the result of neural damage associated with repeated mood episodes and/or drug use. Theories of neuroprogression in mood disorders suggest that ongoing mood episodes lead to a state of chronic inflammation and eventually result in neurocognitive impairment (Berk et al., 2010Berk et al., , 2011 Kapczinski et al., 2008). Abusing drugs has negative effects on the brain reward mechanisms and on the dopaminergic and serotonergic neurotransmitter systems (Koob and Le Moal, 1997) and may induce hazardous reward seeking behaviors and poor decision making (Kirby et al., 2011 ). "

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