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
    • "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.
    Journal of psychosomatic research 04/2015; 79(3). DOI:10.1016/j.jpsychores.2015.04.005 · 2.74 Impact Factor
    • "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., 2010, 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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    ABSTRACT: Impulsivity is a common feature shared by bipolar disorder (BD) and substance use disorder (SUD). SUD and recurrent mood episodes are considered to be risk factors for poor outcome in BD. However, the association between impulsivity, illness chronicity and SUD in BD remains unexplored. 103 BD patients with and without a lifetime history of SUD (36.82±11.34 years, 40 males) were recruited. Participants completed the SCID interview and were administered measures of impulsivity including the Barratt Impulsivity Scale (BIS) and selected tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Hierarchical regression analyses explored the relationship between illness chronicity, SUD, and impulsivity. Variance in the BIS, number of false alarms on the Rapid Visual Processing task and other impulsivity indicators of the Cambridge Gambling Task (CGT) was not explained by the chosen variables. Only an increased number of commission errors in the negative condition of the Affective Go/No Go task was significantly associated with illness chronicity. Furthermore there was a trend suggesting a relationship between a lifetime history of SUD and increased propensity to risk-taking during the CGT. Potential limitations include medication and patients׳ remission status from SUD. Contrary to our expectations impulsivity was generally not predicted by indicators of illness chronicity or SUD. While impulsivity could still be a marker of BD that is present before the onset of the disorder, the link between the number of mood episodes and specific indicators of impulsivity may be related to mechanisms of neuroprogression. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Affective Disorders 03/2015; 179:142-147. DOI:10.1016/j.jad.2015.03.010 · 3.38 Impact Factor
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    • "Therefore, studies have suggested higher health vulnerability within this clinical group. Bipolar disorder can be hypothesized as presenting cumulative stress to the extent that mood episodes, drug abuse, and other conditions progressively occur (Kapczinski et al., 2008). An important issue is that higher concentrations of corticotrophin (ACTH) dysfunction persist in patients when compared to controls even during remission of symptoms, indicating prolonged consequences of stress response (Vieta et al., 1997). "
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    ABSTRACT: Telomeres can be considered a marker of biological aging. Studies have suggested that telomere shortening may be associated with aging related diseases and also psychiatric disorders.Objectives Investigate whether bipolar disorder (BD) and its clinical specificities are associated with telomere shortening.Methods Eighty-five BD patients and 95 healthy controls were paired for age, sex and educational level. Volunteers were submitted to a psychiatric interview and clinical evaluation. Patients and controls were compared as a whole sample and within specific telomere range (short and long telomeres). Intrapatients group comparison involved type of BD and comorbidities. A Real Time Quantitative PCR was performed in order to verify leukocytes telomere length.ResultsBipolar disorder patients presented shorter telomeres when compared to controls (p<0.001). However, there was no significant difference in telomere length between different BD subtypes. When two groups of patients (long and short telomeres) were compared, only panic disorder showed an association with telomere categories (χ2=6.91; p=0.009; OR=4.27).LimitationsIt was not possible to collect information about time since diagnosis, which limited conclusions regarding BD chronicity and telomere length. Furthermore, medication interference upon telomere length was not controlled.Conclusions Results suggest that BD is associated with reduced telomere length. Also, panic comorbidity may represent an additive risk factor. Understanding aspects that contribute to determination of telomere size in bipolar patients allows us to understand what the impact on telomeres size is, which is a health vulnerability marker.
    Journal of Affective Disorders 10/2014; 172. DOI:10.1016/j.jad.2014.09.043 · 3.38 Impact Factor
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