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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    • "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.
    The International Journal of Neuropsychopharmacology 05/2014; 17(09):1-11. DOI:10.1017/S1461145714000443 · 4.01 Impact Factor
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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.
    Current Neuropharmacology 03/2014; 12(2):108-19. DOI:10.2174/1570159X11666131120231448 · 3.05 Impact Factor
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    • "Increased Oxidative Stress (OxS) generates deleterious consequences on signal transduction, synaptic plasticity, and cellular resilience, especially by inducing lipid peroxidation in membranes , proteins and DNA (Grintzalis et al., 2013; Mahadik et al., 2001; Soeiro-de-Souza et al., 2013). DNA damage, which can be induced by oxidative stress, has been found to be associated with the severity of depressive symptoms in BD (Andreazza et al., 2007b). "
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    ABSTRACT: Several studies have described increased oxidative stress (OxS) parameters and imbalance of antioxidant enzymes in Bipolar Disorder (BD) but few is know about the impact of treatment at these targets. However, no study has evaluated OxS parameters in unmedicated early stage BD and their association with lithium treatment in bipolar depression. Patients with BD I or II (n = 29) in a depressive episode were treated for 6 weeks with lithium. Plasma samples were collected at baseline and endpoint, and were also compared to age-matched controls (n = 28). The thiobarbituric acid reactive substances (TBARS), and the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured. Subjects with BD depression at baseline presented a significant increase in CAT (p = 0.005) and GPx (p < 0.001) levels, with lower SOD/CAT ratio (p = 0.001) and no changes on SOD or TBARS compared to healthy controls. Regarding therapeutics, lithium only induced a decrease in TBARS (p = 0.023) and SOD (p = 0.029) levels, especially in BDII. Finally, TBARS levels were significantly lower at endpoint in lithium responders compared to non-responders (p = 0.018) with no difference in any biomarker regarding remission. The present findings suggest a reactive increase in antioxidant enzymes levels during depressive episodes in early stage BD with minimal prior treatment. Also, decreased lipid peroxidation (TBARS) levels were observed, associated with lithium's clinical efficacy. Overall, these results reinforce the role for altered oxidative stress in the pathophysiology of BD and the presence of antioxidant effects of lithium in the prevention of illness progression and clinical efficacy.
    Journal of Psychiatric Research 12/2013; 50(1). DOI:10.1016/j.jpsychires.2013.11.011 · 3.96 Impact Factor
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