DNA damage in bipolar disorder

Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul. Rua Ramiro Barcelos, 2600/Anexo. Zip code: 90035-003. Porto Alegre, Brazil.
Psychiatry Research (Impact Factor: 2.47). 10/2007; 153(1):27-32. DOI: 10.1016/j.psychres.2006.03.025
Source: PubMed


Bipolar disorder (BD) is a prevalent, chronic, severe, and highly disabling psychiatric disorder that is associated with increased morbidity and mortality due to general medical conditions. There is an emerging body of evidence correlating chronic medical conditions with DNA damage. The present study was designed to assess DNA damage in BD patients using the comet assay (CA). Thirty-two bipolar-I outpatients diagnosed using the Structured Clinical Interview for DSM-IV were matched with 32 healthy volunteers. Manic and depressive symptoms were assessed using the Young Mania Rating Scale and the Hamilton Depression Rating Scale, respectively. Peripheral blood samples were collected and a standard protocol for CA preparation and analysis was performed. The present study showed that BD outpatients present an increased frequency of DNA damage relative to controls. The frequency of DNA damage correlated with the severity of symptoms of depression and mania.

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    • "It has been demonstrated that patients with BD have significantly different levels of antioxidant enzymes, lipid peroxidation and nitric oxide (NO) levels [8], compared to patients without BD [3] [9] [10]. Aberrant oxidative stress levels may therefore contribute to the pathophysiology of BD [10]. "
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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.
    No preview · Article · Apr 2015 · Journal of psychosomatic research
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    • "Considering that PERK is essential to induce CHOP transcription (Harding et al., 2000; Okada et al., 2002) and that this pathway appears to be impaired in patients with BD, it is possible that the marked cell death observed in this group, if apoptotic, may have been induced by other mechanisms rather than solely by CHOP. Of note, high apoptosis in BD has already been demonstrated both in post-mortem tissues (Kim et al., 2010) and in peripheral blood samples (Andreazza et al., 2007), including peripheral blood mononuclear cells (Fries et al., 2014). "
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    ABSTRACT: Bipolar disorder (BD) is a severe chronic psychiatric disorder that has been associated with cellular dysfunctions related to mitochondria, neurotrophin levels, and oxidative stress. Evidence has shown that endoplasmic reticulum (ER) stress may be a common pathway of the cellular changes described in BD. In the present study we assessed unfolded protein response (UPR) and the effects of this cellular process on lymphocytes from patients with BD. We also evaluated whether the stage of chronicity of BD was associated with changes in UPR parameters. Cultured lymphocytes from 30 patients with BD and 32 age- and sex-matched controls were treated with tunicamycin, an ER stressor, for 12 or 24 h to measure levels of UPR-related proteins (GRP78, eIF2α-P, and CHOP) using flow cytometry, and for 48 h to analyse ER stress-induced cell death. In healthy controls but not in patients we found an increase in levels of GRP78, eIF2α-P, and CHOP after ER stress induction. In addition, tunicamycin-induced cell death was significantly higher in patients compared to controls. More importantly, early-stage patients did not differ from controls while the late-stage patients showed an impaired ER stress response. Thus, dysfunction in ER-related stress response may be associated with decreased cellular resilience in BD and illness progression.
    Full-text · Article · May 2014 · The International Journal of Neuropsychopharmacology
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    • "It is well known that oxidative stress is associated with DNA damage, endothelial dysfunction, and telomere shortening. Notably, patients with bipolar disorders have a marked increase of DNA damage in white blood cells and more importantly, this DNA damage is highly correlated with the severity of symptoms [109]. However, the degree of redox imbalance in these patients is not correlated to the degree or severity of the depressive symptoms. "
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    ABSTRACT: There is growing evidence that the imbalance between oxidative stress and the antioxidant defense system may be associated with the development neuropsychiatric disorders, such as depression and anxiety. Major depression and anxiety are presently correlated with a lowered total antioxidant state and by an activated oxidative stress (OS) pathway. The classical antidepressants may produce therapeutic effects other than regulation of monoamines by increasing the antioxidant levels and normalizing the damage caused by OS processes. This chapter provides an overview of recent work on oxidative stress markers in the animal models of depression and anxiety, as well as patients with the aforementioned mood disorders. It is well documented that antioxidants can remove the reactive oxygen species (ROS) and reactive nitrogen species (RNS) through scavenging radicals and suppressing the OS pathway, which further protect against neuronal damage caused oxidative or nitrosative stress sources in the brain, hopefully resulting in remission of depression or anxiety symptoms. The functional understanding of the relationship between oxidative stress and depression and anxiety may pave the way for discovery of novel targets for treatment of neuropsychiatric disorders.
    Full-text · Article · Mar 2014 · Current Neuropharmacology
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