The theory of bipolar disorder as an illness of accelerated aging: Implications for clinical care and research

Rizzo, Lucas B.; Costa, Leonardo Gazzi; Mansur, Rodrigo B.; Swardfager, Walter; Belangero, Síntia Iole; Grassi‐Oliveira, Rodrigo; McIntyre, Roger S.; Bauer, Moisés Evandro; Brietzke, Elisa

doi:10.1016/j.neubiorev.2014.02.004

Cited by 159 publications

(103 citation statements)

References 219 publications

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“…5 This finding is concordant with several aspects already known to be related to BD: increased prevalence of comorbid medical illness, structural brain alterations, cognitive and functioning impairments, oxidative stress and immunological imbalance, neurotrophic deficiencies that form the basis of neuroprogression, 44 and, ultimately, decreased telomere length. 5 A relation between AA and AL has been proposed, 5,9 whereby saturation of the body's ability to maintain homeostasis would lead to a series of maladaptive systemic alterations (AL) resulting in an increased occurrence of comorbidities, appearing as an AA process and, possibly, resulting in decreased life expectancy due to natural causes in patients with BD. 45 Limitations of this study include the small sample size, which precluded analysis of differences in effects of medication, smoking status, 46 and lifestyle factors 47 between specific subgroups of patients.…”

Section: Discussionsupporting

confidence: 81%

“…40 In addition, cell senescence is associated with increased cellular secretion of proinflammatory cytokines 41,42 contributing to the senescence-associated secretory phenotype (SASP), which may also link telomere shortening with age-associated medical conditions, most of which are highly prevalent in patients with BD. 5 Our results add to the evidence base because we classified BD participants into early and late stages of illness, with control groups matched for age and gender. This staging system allowed us to suggest that telomere shortening occurs early in the course of BD.…”

Section: Discussionmentioning

confidence: 61%

“…4 Patients with BD experience higher rates of illnesses associated with aging, such as type II diabetes, metabolic syndrome, cancer, immune dysregulation, dementia, osteoporosis, and cardiovascular and cerebrovascular illness. 5 Several explanations for these age-related comorbidities in BD have been proposed, such as increased oxidative stress, a chronic inflammatory process, and stress-related dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, culminating in the allostatic load (AL).…”

Section: Introductionmentioning

confidence: 99%

“…5 Telomeres are highly specialized DNA-protein structures located at the end of linear chromosomes in eukaryotic organisms. They preserve genetic information by mitigating non-homologous recombination, end-to-end fusion, and nucleolytic degradation.…”

Section: Introductionmentioning

confidence: 99%

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Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease

Barbé-Tuana

Parisi

Panizzutti

et al. 2016

Rev. Bras. Psiquiatr.

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Objective: Bipolar disorder (BD) has been associated with increased rates of age-related diseases, such as type II diabetes, metabolic syndrome, osteoporosis, and cardiovascular disorders. Several biological findings have been associated with age-related disorders, including increased oxidative stress, inflammation, and telomere shortening. The objective of this study was to compare telomere length among participants with BD at early and late stages and age-and gender-matched healthy controls. Methods: Twenty-six euthymic subjects with BD and 34 healthy controls were recruited. Genomic DNA was extracted from peripheral blood and mean telomere length was measured using real-time quantitative polymerase chain reaction. Results: Telomere length was significantly shorter in both the early and late subgroups of BD subjects when compared to the respective controls (p = 0.002 and p = 0.005, respectively). The sample size prevented additional subgroup analyses, including potential effects of medication, smoking status, and lifestyle. Conclusion: This study is concordant with previous evidence of telomere shortening in BD, in both early and late stages of the disorder, and supports the notion of accelerated aging in BD.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease

Barbé-Tuana

Parisi

Panizzutti

et al. 2016

Rev. Bras. Psiquiatr.

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“…However many subject-level variables, such as age, sex, genetic polymorphisms, "resiliency," education, history of early life adversities, parental responsiveness, socioeconomic status, health behaviors, diet, and latent or active viral infections (e.g., cytomegalovirus or herpes virus) may affect LTL, independent of the disease process being studied [38][39][40][41][42][43] .Other potentially important confounds in interpreting LTL in psychiatric illnesses are psychiatric and medical co-morbidities. Many psychiatric diagnoses has a high co-morbidity with secondary psychiatric illnesses such as substance abuse, various anxiety disorders, and PTSD.…”

Section: IVmentioning

confidence: 99%

Telomeres And Early Life Stress: A Review

Singh¹,

Y.R²,

Majumder³

et al. 2017

IOSR JDMS

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I. Stress, Coping And AgingIndividuals differ in their psychological and biological responses to stress. In particular, an individual"s appraisal or assessment of a specific psychological stressor determines their cognitive-emotional response, which in turn influences their biological response and hence the extent to which the stressor has the potential to "get under the skin" to influence physical health.1 According to the classic Lazarus and Folkman "Transactional Model of Stress and Coping", individuals who perceive that a stressor exceeds their resources to cope effectively will appraise the situation as threatening and exhibit a response characterized by threat-related cognitions and emotions such as worry and fear. In contrast, individuals who perceive that they have adequate resources to cope with a stressor will appraise it as challenging and exhibit a response characterized by challenge related cognitions and emotions such as perceived control and excitement.2 Subsequent research has shown that biological reactions to stressors appraised as threatening differ from those appraised as challenging, and that the former are associated with more harmful physiological reactions than are the latter .The biological response to stress involves the coordinated activity of several systems, including the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system, and the immune system. Acute activation of these systems serves to mobilize energy resources and prepare the individual for coping with stressors. With chronic stress exposure, however, attempts at adaptation can result in pathological perturbation of endocrine, immune, and metabolic systems. 3,4 There is possibility that certain psychiatric illnesses are associated with accelerated biological aging at cellular level. Whereas chronological age is measured in calendar units, biological age is defined physiologically and is more closely associated with disease processes. "Accelerated biological aging" occurs when biological age outpaces chronological age. II. TelomeresTelomeres (from the Greek telos [end] and meros [part]) are DNA-protein complexes at the ends of chromosomes, composed of tandem TTAGGG repeats ranging from a few to 15 kilobases in length mainly protecting chromosomes from damage. Telomeres shorten with repeated cell divisions in somatic cells due to incomplete replication of the telomere ends, replication and nuclease-associated telomeric DNA damage, and/or chronic exposure to oxidation, certain cytotoxins or inflammation and possibly chronic exposure to the stress hormones, cortisol and catecholamine.5 When telomeres reach a critically short length, cells undergo replicative senescence or can become genomically unstable.Leukocyte telomere length generally decreases progressively over the lifespan, with estimates of average attrition rate ranging between 14 to 103 base pairs (bp) per year (weighted mean of 21.9 bp per year) in cross-sectional studies, and between 32.2 to 45.5 bp per year (weighted mean of 40.7 bp per year) in lo...

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Bipolar Disorder from a Developmental Psychopathology Perspective: Focusing on Phenomenology, Etiology, and Neurobiology

Klimes‐Dougan

Kennedy

Cullen

2016

Developmental Psychopathology

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The purpose of this chapter is to consider how a developmental psychopathology perspective can advance our understanding of bipolar disorder. In this chapter we start by discussing the phenomenology of the disorder. As this is a field in which scientific controversies abound, this section begins by placing bipolar disorder in a historical context. We consider the origins of current clinical diagnostic approaches and evaluate newly emerging empirical approaches that utilize dimensions of symptoms, behaviors, and neurobiological indexes. We then review prominent etiological theories of the illness, including work on environmental stressors and hazards as well as behavioral and genetic approaches. We highlight some of the most promising theories that account for both environmental and biological mechanisms of bipolar disorder. Additionally, because bipolar disorder can be considered a neurodevelopmental disorder, biological mechanisms are also discussed in the context of brain imaging research. We conclude the chapter with suggestions for translational research by considering how these developmental and neurodevelopmental models can inform intervention science and help identify promising new directions for future research.

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The theory of bipolar disorder as an illness of accelerated aging: Implications for clinical care and research

Cited by 159 publications

References 219 publications

Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease

Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease

Telomeres And Early Life Stress: A Review

Bipolar Disorder from a Developmental Psychopathology Perspective: Focusing on Phenomenology, Etiology, and Neurobiology

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