Article

Depression and possible cancer risk due to oxidative DNA damage

December 2005
Journal of Psychiatric Research 39(6):553-60

December 2005
39(6):553-60

DOI:10.1016/j.jpsychires.2005.01.009

Source
PubMed

Authors:

The potential link between depression and cancer is an important unsolved question. To clarify this, we compared a cancer-related oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OH-dG), in peripheral leukocytes between 30 patients with depression and 60 age- and gender-matched healthy controls, and examined the 8-OH-dG-related factors. The degree of depression was assessed by the scores of the Center for Epidemiologic Studies Depression scale (CES-D) and the Profile of Mood States (POMS). The patients showed significantly higher 8-OH-dG levels than the controls. There was a significant positive correlation between the CES-D scores and the 8-OH-dG levels in depressive, particularly female, patients. Multiple regression analysis indicated that whether the subjects were patients or controls was a significant predictor of the 8-OH-dG levels in male and total subjects, as was the CES-D score or the Depression-Rejection score of the POMS in female subjects. This study suggests that clinical depression is a risk factor for cancer initiation in view of oxidative DNA damage.

Severity of Anxiety– but not Depression– is Associated with Oxidative Stress in Major Depressive Disorder

Article

Full-text available

May 2017

Background Oxidative stress is implicated in both depression and anxiety, but it is currently unclear whether this relates to syndromal diagnoses or trans-diagnostic dimensional symptoms. We examined the relationship between oxidative stress and severity of depression and anxiety symptoms in individuals with Major Depressive Disorder (MDD). Methods Plasma oxidative stress markers F2-isoprostanes and oxidized glutathione (GSSG), and the antioxidant reduced glutathione (GSH), were assessed in 69 physically healthy, medication-free MDD subjects. Symptoms of anxiety and depression were assessed using the Hamilton Anxiety (HAM-A) and Hamilton Depression (HAM-D) Rating Scales. Total HAM-A and HAM-D scores, along with “core” anxiety and depression subscales, and individual HAM-D items “psychic anxiety” and “depressed mood,” were related to oxidative stress markers. Analyses controlled for age, sex, BMI, and smoking. Results Total HAM-A ratings were positively associated with F2-isoprostanes (β=.26, p=0.042) and GSSG (β=.25, p=0.049), but not GSH (β=.05, p=0.711). Core anxiety severity was positively associated with F2-isoprostanes (β=.34, p=0.012) and GSSG, although this did not reach significance (β=.24, p=0.074). None of the biological markers were significantly associated with total HAM-D or core depression ratings (all p>0.13). Subjects scoring high on “psychic anxiety” had elevated F2-isoprostanes (p=0.030) and GSSG (p=0.020). This was not seen with “depressed mood” scores (all p>0.12). Limitations We assessed peripheral oxidative markers, but their relationship to the brain is unclear. Conclusions Oxidative stress is more closely related to anxiety than depression symptoms in MDD. This highlights the importance of relating oxidative stress to specific symptoms and could provide new insights into the biological correlates of affective disorders.

Oxidative Stress and DNA Damage Association with Carcinogenesis: A Truth or a Myth?

Chapter

Full-text available

Oct 2015

Reactive oxygen and nitrogen species (ROS/RNS) possess the capacity to damage DNA (both nuclear and mitochondrial) and other cellular macromolecules, resulting in various outcomes for the cell such as loss of function and stability, mutation, senescence (mainly due to telomeric shortening) and/or cell death, unless removed rapidly by antioxidative mechanisms evolved by the cell. Over the last decade, great emphasis has been put on the potential role(s) and association of oxidative stress with ageing and certain diseases including cancer, and the idea of using several oxidatively generated DNA lesions as novel biomarkers of oxidative stress, chronic inflammation, and susceptibility to cancer gains more ground. The present chapter focuses on the description of genotoxic forms of oxygen, types of resulting oxidative DNA damage and their usage as potential biomarkers in several diseases including cancer.

Oxidative Stress and DNA Damage Association with Carcinogenesis: A Truth or a Myth?

Chapter

Full-text available

Nov 2015

Living organisms are constantly subjected to oxidative stress and free radicals. The production of a plethora of reactive oxygen and nitrogen species (ROS/RNS) may occur endogenously (intracellularly) or exogenously [ 1 – 3 ]. Exogenous and environmental triggers of oxidation relate to specifi c exposure of the organism to ionizing radiation (IR), like X-, γ- or cosmic rays and α-particles from radon decay, oxidizing chemicals and UVA solar light. Endogenous (intracellular) attack corresponds to natural origin such as through cellular signaling and metabolic processes or during infl ammation [ 3 – 8 ]. Examples such as hydroxyl radical ( • OH), superoxide anion radicals (O 2 •− ), hydrogen peroxide (H 2 O 2 ), singlet oxygen ( 1 O 2 ) and peroxynitrite are major toxic forms of oxygen [ 6 , 9 ]. These forms of oxygen are generated by mono- or divalent reduction of molecular oxygen through normal cellular processes (e.g. respiration) [ 10 – 12 ] and/or produced as metabolic by-products of biochemical pathways (e.g. lipoxygenase pathway) and mitochondrial respiration (e.g. oxidative phosphorylation) [ 13 , 14 ]. They may also be generated as a result of exposure to chemical agents (e.g. tamoxifen derivatives, paraquat) [ 15 , 16 ]. It is therefore widely accepted that oxygen, even though it is benefi cial for the aerobic organisms, can interact with DNA, proteins, lipids and other cellular components, through ROS generation, inducing disruption of normal synthesis and repair of DNA, inhibition/ inactivation of antioxidant key proteins and key enzymes, genomic instability, cellular toxicity and cell death [ 3 ]. There is substantial evidence that prolonged exposure of an organism to oxidative stress may be a causative effect of infl ammation, imbalance of homeostatic mechanisms and possible tumor formation [ 3 , 17 ]. In this chapter, we will go through the primary reactions of toxic forms of oxygen and their ability to damage cellular organic compounds such as DNA, proteins and membrane lipids causing in vivo toxicity, the different types of oxidative stressinduced DNA damage, the role of oxidative damage in carcinogenesis and the use of oxidative DNA lesions as possible cancer biomarkers.

Phobic Anxiety and Plasma Levels of Global Oxidative Stress in Women

Article

Full-text available

Jul 2015
EUR J PSYCHIAT

Background and objectives: Psychological distress has been hypothesized to be associated with adverse biologic states such as higher oxidative stress and inflammation. Yet, little is known about associations between a common form of distress - phobic anxiety - and global oxidative stress. Thus, we related phobic anxiety to plasma fluorescent oxidation products (FlOPs), a global oxidative stress marker. Methods: We conducted a cross-sectional analysis among 1,325 women (aged 43-70 years) from the Nurses' Health Study. Phobic anxiety was measured using the Crown-Crisp Index (CCI). Adjusted least-squares mean log-transformed FlOPs were calculated across phobic categories. Logistic regression models were used to calculate odds ratios (OR) comparing the highest CCI category (≥6 points) vs. lower scores, across FlOPs quartiles. Results: No association was found between phobic anxiety categories and mean FlOP levels in multivariable adjusted linear models. Similarly, in multivariable logistic regression models there were no associations between FlOPs quartiles and likelihood of being in the highest phobic category. Comparing women in the highest vs. lowest FlOPs quartiles: FlOP_360: OR=0.68 (95% CI: 0.40-1.15); FlOP_320: OR=0.99 (95% CI: 0.61-1.61); FlOP_400: OR=0.92 (95% CI: 0.52, 1.63). Conclusions: No cross-sectional association was found between phobic anxiety and a plasma measure of global oxidative stress in this sample of middle-aged and older women.

The Relationship between Oxidative Stress and Anxiety in a Healthy Older Population

Article

Jan 2021
EXP AGING RES

F2-Isoprostanes are putative markers of oxidative stress, one of the processes associated with biological senescence. Evidence exists for elevated F2-Isoprostanes in chronic conditions including psychiatric disorders. Few studies have examined the relationship between oxidative stress and mood in older healthy samples, to establish the influence on mental health. Given current aging demographics in many nations, management of brain and mental health is crucial for longevity, chronic disease management and quality of life.

Depressive symptoms, negative life events and incidence of lifetime treatment of cancer in the Hungarian population

Article

Full-text available

Mar 2010
J COGN BEHAV PSYCHOT

Cancer incidence and mortality rates in Hungary are the highest in the Central-Eastern European region. Our investigative study examined associations of cancer-prone behavioral risk factors, psychosocial variables and demographic characteristics with cancer treatment on a population level. Data were obtained from the Hungarostudy 2002, a cross-sectional, representative survey of the adult Hungarian population (n=12643). Controlling for all other study variables in a binary logistic regression model, results revealed that the odds of having been treated for cancer were almost twice as high among persons with depression and respondents who experienced negative life events than for those who were not depressed and reported no negative life events. These results send a warning signal to the Hungarian health care system regarding the widespread need for education, prevention, psycho-social screening programs and treatment of depression.

Major Depressive Disorder and Oxidative Stress: A Review of Peripheral and Genetic Biomarkers According to Clinical Characteristics and Disease Stages

Article

Full-text available

Apr 2023

Major depressive disorder (MDD) is currently the main cause of disability worldwide, but its pathophysiology remains largely unknown, especially given its high heterogeneity in terms of clinical phenotypes and biological characteristics. Accordingly, its management is still poor. Increasing evidence suggests that oxidative stress, measured on various matrices such as serum, plasma or erythrocytes, has a critical role in MDD. The aim of this narrative review is to identify serum, plasma and erythrocyte biomarkers of oxidative stress in MDD patients according to disease stage and clinical features. Sixty-three articles referenced on PubMed and Embase between 1 January 1991, and 31 December 2022, were included. Modifications to antioxidant enzymes (mainly glutathione peroxidase and superoxide dismutase) in MDD were highlighted. Non-enzymatic antioxidants (mainly uric acid) were decreased in depressed patients compared to healthy controls. These changes were associated with an increase in reactive oxygen species. Therefore, increased oxidative damage products (principally malondialdehyde, protein carbonyl content and 8-hydroxy-2′-deoxyguanosine) were present in MDD patients. Specific modifications could be identified according to disease stages and clinical features. Interestingly, antidepressant treatment corrected these changes. Accordingly, in patients in remission from depression, oxidative stress markers were globally normalized. This narrative review suggests the particular interest of oxidative stress biomarkers for MDD care that may contribute to the heterogeneity of the disease and provide the opportunity to find new therapeutic targets.

Nrf2: An all-rounder in depression

Article

Full-text available

Oct 2022

The balance between oxidation and antioxidant is crucial for maintaining homeostasis. Once disrupted, it can lead to various pathological outcomes and diseases, such as depression. Oxidative stress can result in or aggravate a battery of pathological processes including mitochondrial dysfunction, neuroinflammation, autophagical disorder and ferroptosis, which have been found to be involved in the development of depression. Inhibition of oxidative stress and related pathological processes can help improve depression. In this regard, the nuclear factor erythroid 2-related factor 2 (Nrf2) in the antioxidant defense system may play a pivotal role. Nrf2 activation can not only regulate the expression of a series of antioxidant genes that reduce oxidative stress and its damages, but also directly regulate the genes related to the above pathological processes to combat the corresponding alterations. Therefore, targeting Nrf2 has great potential for the treatment of depression. Activation of Nrf2 has antidepressant effect, but the specific mechanism remains to be elucidated. This article reviews the key role of Nrf2 in depression, focusing on the possible mechanisms of Nrf2 regulating oxidative stress and related pathological processes in depression treatment. Meanwhile, we summarized some natural and synthetic compounds targeting Nrf2 in depression therapy. All the above may provide new insights into targeting Nrf2 for the treatment of depression and provide a broad basis for clinical transformation.

Eugenol and its liposome-based nano carrier reduce anxiety by inhibiting glyoxylase-1 expression in mice

Article

Full-text available

Oct 2021
Braz J Biol

The most common form of psycho-social dysfunction is anxiety with depression being related closely without any age bar. They are present with combined state of sadness, confusion, stress, fear etc. Glyoxalase system contains enzyme named glyoxalase 1 (GLO1).It is a metabolic pathway which detoxifies alpha-oxo-aldehydes, particularly methylglyoxal (MG). Methylglyoxal is mainly made by the breakdown of the glycolytic intermediates, glyceraldehyde-3-phosphates and dihydroxyacetone phosphate. Glyoxylase-1 expression is also related with anxiety behavior. A casual role or GLO-1 in anxiety behavior by using viral vectors for over expression in the anterior cingulate cortex was found and it was found that local GLO-1 over expression increased anxiety behavior. The present study deals with the molecular mechanism of protective activity of eugenol against anxiolytic disorder. A pre-clinical animal study was performed on 42 BALB/c mice. Animals were given stress through conventional restrain model. The mRNA expression of GLO-1 was analyzed by real time RT-PCR. Moreover, the GLO-1 protein expression was also examined by immunohistochemistry in whole brain and mean density was calculated. The mRNA and protein expressions were found to be increased in animals given anxiety as compared to the normal control. Whereas, the expressions were decreased in the animals treated with eugenol and its liposome-based nanocarriers in a dose dependent manner. However, the results were better in animals treated with nanocarriers as compared to the compound alone. It is concluded that the eugenol and its liposome-based nanocarriers exert anxiolytic activity by down-regulating GLO-1 protein expression in mice.

Association of Lipid Peroxidation Product 4-Hydroxynonenal with Post-Traumatic Stress Disorder

Article

Full-text available

Sep 2021

Repeated activation of the hypothalamic-pituitary-adrenal axis system, sleep disturbances, and other symptoms related to posttraumatic stress disorder (PTSD) elevate reactive oxygen species, increase inflammation, and accelerate cellular aging, leading to neuroprogression and cognitive decline. However, there is no information about possible involvement of 4-hydroxynonenal (4-HNE), the product of lipid peroxidation associated with stress-associated diseases, in the complex etiology of PTSD. Therefore, the aim of this study was to compare the plasma levels of 4-HNE between war veterans with PTSD (n = 62) and age-, sex- and ethnicity- matched healthy control subjects (n = 58) in order to evaluate the potential of HNE-modified proteins as blood-based biomarker of PTSD. The genuine 4-HNE-Enzyme-Linked Immunosorbent Assay (HNE-ELISA), based on monoclonal antibody specific for HNE-histidine (HNE-His) adducts, was used to determine plasma HNE-protein conjugates. Our results revealed significantly elevated levels of 4-HNE in patients with PTSD. Moreover, the accumulation of plasma 4-HNE seems to increase with aging but in a negative correlation with BMI, showing specific pattern of change for individuals diagnosed with PTSD. These findings suggest that oxidative stress and altered lipid metabolism reflected by increase of 4-HNE might be associated with PTSD. If confirmed with further studies, elevated 4-HNE plasma levels might serve as a potential biomarker of PTSD.

The Role of Psychologic Stress in Cancer Initiation: Clinical Relevance and Potential Molecular Mechanisms

Article

Jul 2021

The hypothesis that the physiological response to psychological stress influences the initiation of cancer is highly controversial. The link between initiating stressors, the psychological stress response, and disease is plausible considering that the stress response is associated with defined physiological outcomes and molecular mechanisms. In light of this, we review the clinical relevance of psychological stress on the risk of cancer, and we propose potential molecular pathways that may link the stress response to early stages of malignant cell transformation.

Depression and stress levels increase risk of liver cancer through epigenetic downregulation of hypocretin

Article

Full-text available

Dec 2020

Recent studies suggest that Hypocretin (HCRT, Orexin) are involved in stress regulation of depression through the hypothalamic-pituitary-adrenal (HPA) axis. However, the molecular mechanism by which Hypocretin regulate neurobiological responses is unknown. Herein, the effects of chronic stress on the epigenetic modification of HCRT and its association with depression were explored with regard to a potential role in cancer progression. In the study, Sprague Dawley(SD) rats were used to establish an animal model of cancer with depression by administrating n-nitrosodiethylamine (DEN) and chronic unpredictable mild stress (CUMS). RNA-Sequencing was used to detect differentially expressed genes in the hippocampus of rats and quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the results of RNA-Sequencing. The status of HCRT promoter methylation was assessed by methylation specific polymerase chain reaction. Behavioral tests showed that rats exposed to CUMS had significant depressive-like behaviors. The number of liver tumors and tumor load in depressed rats exposed to CUMS was higher than in SD rats without CUMS. RNA-Sequencing revealed that HCRT was one of the most siginificantly downregulated gene in the hippocampus of SD rats with CUMS compared to non-stressed group, which was validated by qRT-PCR. HCRT mRNA expression was downregulated and the promoter for HCRT was hyper-methylated in those with depression. These results identified a critical role for chronic psychological stressors in tumorigenesis and cancer progression, via epigenetic HCRT downregulation. Such epigenetic downregulation may be the molecular basis for the association of cancer with depression.

THE PSYCHOEMOTIONAL/PSYCHOSOCIAL CONDITION OF SOCIETY IS ONE OF THE POSSIBLE REASONS FOR THE INCREASE IN CANCER INCIDENCE IN PRESENT-DAY RUSSIA

Article

Full-text available

Feb 2019
Vopr Onkol

A. Ilnitskiy

This brief analytical review adresses a possible impact of some special psychoemotional characteristics in the contemporary Russian society on cancer incidence. The possible effects of psychoemotional/psychosocial stress and chronic depression on carcinogenesis are considered. For this purpose, the findings of epidemiological, experimental, and anamnestic studies are discussed. The psychoemotional/psychosocial condition of society is one of the possible reasons for the increase in cancer incidence in present-day Russia.

Association between skin autofluorescence of advanced glycation end products and affective disorders in the Lifelines cohort study

Article

Full-text available

Jul 2020
J AFFECT DISORDERS

Background Oxidative stress may be a mechanistic link between affective disorders (depressive and anxiety disorders) and somatic disease. Advanced glycation end products are produced under the influence of oxidative stress and in the skin (measured by skin autofluorescence [SAF]) serve as marker for cumulative oxidative stress. Aim of study was to determine whether SAF is associated with presence of affective disorders. Methods Participants in the Lifelines cohort study who had completed the Mini-International Neuropsychiatric Interview for affective disorders and a SAF-measurement were included. Cross-sectional associations between SAF and presence of the following psychiatric disorders were investigated through logistic regression analyses adjusted for sociodemographic factors, cardiometabolic parameters, and somatic morbidities: major depressive disorder, dysthymia, generalised anxiety disorder, panic disorder or social phobia. Results Of 81,041 included participants (41.7% male, aged 18-91 years), 6676 (8.2%) were cases with an affective disorder. SAF was associated with presence of affective disorders (OR=1.09 [95%CI 1.07-1.12], P<.001 adjusted for sociodemographic factors). Association with major depressive disorder was strongest and significant after adjustment for all confounders (OR=1.31 [95%CI 1.25-1.36], P<.001 in the crude model; OR=1.12 [95%CI 1.07-1.17], P<.001 in the fully adjusted model). For other disorders, associations lost significance after adjustment for cardiometabolic parameters and somatic morbidities. Limitations Persons of non-Western descent and severely (mentally or physically) ill individuals were underrepresented. Conclusions SAF was associated with presence of affective disorders, suggesting a link between these disorders and cumulative oxidative stress. For major depressive disorder, this association was strongest and independent of sociodemographic, cardiometabolic factors, and somatic morbidities.

Therapeutic potential of glutathione-enhancers in stress-related psychopathologies

Article

May 2020
NEUROSCI BIOBEHAV R

The mammalian brain has high energy demands, which may become higher in response to environmental challenges such as psychogenic stress exposure. Therefore, efficient neutralization of reactive oxygen species that are produced as a by-product of ATP synthesis is crucial for preventing oxidative damage and ensuring normal energy supply and brain function. Glutathione (GSH) is arguably the most important endogenous antioxidant in the brain. In recent years, aberrant GSH levels have been implicated in different psychiatric disorders, including stress-related psychopathologies. In this review, we examine the available data supporting a role for GSH levels and antioxidant function in the brain in relation to anxiety and stress-related psychopathologies. Additionally, we identify several promising compounds that could raise GSH levels in the brain by either increasing the availability of its precursors or the expression of GSH-regulating enzymes through activation of Nuclear factor erythroid-2-related factor 2 (Nrf2). Given the high tolerability and safety profile of these compounds, they may represent attractive new opportunities to complement existing therapeutic manipulations against stress-related psychopathologies.

DNA damage and repair in neuropsychiatric disorders. What do we know and what are the future perspectives?

Article

Nov 2019
MUTAGENESIS

Over the past two decades, extensive research has been done to elucidate the molecular etiology and pathophysiology of neuropsychiatric disorders. In majority of them, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), bipolar disorder (BD), schizophrenia and major depressive disorder, increased oxidative and nitrosative stress was found. This stress is known to induce oxidative damage to biomolecules, including DNA. Accordingly, increased mitochondrial and nuclear DNA, as well as RNA damage, were observed in patients suffering from these diseases. However, recent findings indicate that the patients are characterised by impaired DNA repair pathways, which may suggest that these DNA lesions could be also a result of their insufficient repair. In the current systematic, critical review, we aim to sum up, using available literature, the knowledge about the involvement of nuclear and mitochondrial DNA damage and repair, as well as about damage to RNA in pathoetiology of neuropsychiatric disorders, i.e., AD, PD, ALS, BD, schizophrenia and major depressive disorder, as well as the usefulness of the discussed factors as being diagnostic markers and targets for new therapies. Moreover, we also underline the new directions to which future studies should head to elucidate these phenomena.

Association of Telomere Length, a Cellular Aging Marker, with Depression, PTSD and Hostility

Article

Dec 2018

The Association of Childhood Maltreatment With Lipid Peroxidation and DNA Damage in Postpartum Women

Article

Full-text available

Feb 2019

Childhood maltreatment (CM) is associated with an increased risk for the development of psychiatric and somatic disorders in later life. A potential link could be oxidative stress, which is defined as the imbalance between the amount of reactive oxygen species (ROS) and the neutralizing capacity of anti-oxidative defense systems. However, the findings linking CM with oxidative stress have been inconsistent so far. In this study, we aimed to further explore this association by investigating biological markers of DNA and lipid damage due to oxidation in a comprehensive approach over two study cohorts of postpartum women (study cohort I and study cohort II). The severity of CM experiences (maltreatment load) was assessed in both studies using the Childhood Trauma Questionnaire. In study cohort I (N = 30), we investigated whether CM was associated with higher levels of structural DNA damage in peripheral blood mononuclear cells (PBMC) by two methods that are highly sensitive for detecting nuclear DNA strand breaks (comet assay and γH2AX staining). In study cohort II (N = 117), we then assessed in a larger cohort, that was specifically controlled for potential confounders for oxidative stress measurements, two established serum and plasma biomarkers of oxidative stress, one representing oxidative DNA and RNA damage (8-hydroxy-2′-deoxyguanosine and 8-hydroxyguanosine; 8-OH(d)G) and the other representing lipid peroxidation (8-isoprostane). In study cohort I, the analyses revealed no significant main effects of maltreatment load on cellular measures of nuclear DNA damage. The analyses of peripheral oxidative stress biomarkers in study cohort II revealed a significant main effect of maltreatment load on free 8-isoprostane plasma levels, but not on total 8-isprostane plasma levels and 8-OH(d)G serum levels. Taken together, by combining different methods and two study cohorts, we found no indications for higher oxidative DNA damages with higher maltreatment load in postpartum women. Further research is needed to investigate whether this increase in free 8-isoprostane is a marker for oxidative stress or whether it is instead functionally involved in ROS-related signaling pathways that potentially regulate inflammatory processes following a history of CM.

Depression and anxiety symptoms are associated with prooxidant-antioxidant balance: A population-based study

Article

Jun 2018
J AFFECT DISORDERS

Background: Depression and anxiety are significantly associated with systemic inflammation. Moreover, oxidative stress resulting from a disturbance in the prooxidant-antioxidant balance is linked to inflammation-related conditions. Therefore, depression/anxiety symptoms may also be associated with oxidative stress. Objective: To examine the association between depression/anxiety symptoms and serum prooxidant-antioxidant balance (PAB) in adults who participated in a large population-based, cross-sectional study. Methods: Serum PAB values were measured in 7516 participants (62% females and 38% males) aged 35-65 years, enrolled in a population-based cohort study. beck depression and anxiety inventories were used to evaluate symptoms of depression and anxiety. Multinomial logistic regression was used to examine the effect of confounders on the status of serum PAB change. Results: Among men, serum PAB values were increased incrementally from 1.55 ± 0.47 to 1.59 ± 0.47, 1.69 ± 0.38, and 1.68 ± 0.38 in the no or minimal, mild, moderate and severe depression groups, respectively (Ptrend < 0.001). Serum PAB values also increased significantly across these four corresponding groups among women [1.70 ± 0.45, 1.73 ± 0.44, 1.75 ± 0.44, and 1.76 ± 0.40, (Ptrend = 0.005)]. About anxiety, serum PAB values increased significantly across the four groups in men (Ptrend = 0.02) but not in women (Ptrend = 0.2). The adjusted odds ratios for serum PAB values among men with severe depression and anxiety symptoms were 1.75 and 1.27, respectively. Moreover, the adjusted odds ratios for serum PAB values among women with severe depression and anxiety symptoms were 1.40 and 1.17, respectively. Conclusion: Symptoms of depression and anxiety appear to be associated with higher degrees of oxidative stress, expressed by higher serum PAB values.

Mental and physical stress of the Fukushima disaster evacuees as estimated by the measurement of urinary 8‑hydroxy‑2'‑deoxyguanosine

Article

Full-text available

May 2018

Following the accident at the Fukushima Daiichi Nuclear Power Plant in 2011, a number of evacuees were forced to live in temporary housing and suffered mental and physical stress. However, few reports have used objective or quantitative indicators to determine the evacuee's level of stress. The aim of the present study was to serially estimate the mental and physical stress of the evacuees from 2013 to 2015 by using the oxidative stress marker, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). A total of 773 evacuees from Namie town in Fukushima prefecture participated in the study. In the first year, 486 evacuees participated (age, 62.8±18.2 years; male/female, 217/269). Of these, 127 continually participated in the study for 3 years (age, 69.5±13.5 years; males/female 52/75) and 18.1% had no chronic disease after the first year. Urine samples were collected once per year. Urinary 8-OHdG was measured using immunochromatography and corrected by the concentration of urinary creatinine. For all the participants examined each year, mean values of urinary 8-OHdG significantly increased over time. For the 127 continual participants, mean values of urinary 8-OHdG were significantly higher in 2014 and 2015 than those in 2013. Age, gender and presence of chronic disease did not significantly influence the 8-OHdG values, suggesting that the stress level of the evacuees was not associated with these factors. The stress level of the individuals increased with the length of time spent living in the temporary housing. The evacuees in radiation disasters have different stressors from other natural disasters, which may accelerate mental and physical stress.

Chronic corticosterone-induced depression mediates premature aging in rats

Article

Jan 2018
J AFFECT DISORDERS

Background: Stress hormones such as corticosterone (CORT) play an essential role in the development of depression. Chronic CORT administration has been shown to induce dysfunction in the hypothalamic-pituitary-adrenal axis leading to depression, which was in turn associated with accelerated aging. However, the effect of CORT administration on aging remains unclear. Methods: Rats were acclimatized for 1 week and then injected daily with CORT (40mg/kg) or vehicle (n = 10 each) for 21 consecutive days. Age-related indexes were then compared between CORT-treated rats and control rats. Results: CORT induced affective behaviors indicative of depressive-like symptoms in rats, including reduced sucrose preference and increased immobility time in the forced swimming test. CORT-treated rats exhibited telomere shortening, possibly contributing to decreased telomerase activity and down-regulated expression of telomere-binding factor 2, correlated with enhanced oxidative damage. This was associated with inhibition of sirtuin 3 leading to reduced activities of superoxide dismutase 2 and glutathione reductase. CORT-treated rats showed degenerated mitochondrial functions represented by decreased adenosine triphosphate production, decreased nicotinamide adenine dinucleotide+ content, and decreased activity of nicotinamide phosphoribosyltransferase. Limitations: The group sample sizes were small, and only male rats and a single dose level of CORT were used. Conclusion: These findings demonstrate that CORT-induced depression may be involved in mediating the pathophysiology of premature aging in rats.

Perceived Stress, Depressive Symptoms, and Oxidative DNA Damage

Article

Jul 2017

Objective: Psychosocial stress may influence the risk of disease through its association with oxidative DNA damage. We examined whether perceived stress and depressive symptoms were associated with urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), with mutual interaction on 8-OHdG. Methods: This cross-sectional study included 6,517 individuals aged 45-74 years who participated, between 2010 and 2012, in a follow-up survey of an ongoing cohort study. Perceived stress during the past year was measured using a self-report questionnaire. Depressive symptoms were evaluated using the Zung Self-Rating Depression Scale. Urinary 8-OHdG concentrations were measured using a column switching high-pressure liquid chromatography system coupled to an electrochemical detector. Results: Higher perceived stress was significantly associated with higher 8-OHdG (2.1% increase per one category increase of stress; Ptrend = .025), even after controlling for sex, age, supplement use, psychosocial factors, psychotropic medication use, smoking, and body mass index. This association was modestly attenuated after further adjustment for physical activity, suggesting possible mediation or confounding by this factor. Depressive symptoms were not significantly associated with 8-OHdG. No significant interaction was detected between perceived stress and depressive symptoms on 8-OHdG. Conclusions: In a general Japanese population, we found a weak positive association between perceived stress and urinary excretion of 8-OHdG, whereas no association was observed between depressive symptoms and 8-OHdG. Further studies are needed to examine whether the association between perceived stress and 8-OHdG is modified by depressive symptoms.

Molecular Mechanisms Underlying the Anti-depressant Effects of Resveratrol: a Review

Article

Full-text available

Jun 2018
MOL NEUROBIOL

Major depression is a public health problem, affecting 121 million people worldwide. Patients suffering from depression present high rates of morbidity, causing profound economic and social impacts. Furthermore, patients with depression present cognitive impairments, which could influence on treatment adherence and long-term outcomes. The pathophysiology of major depression is not completely understood yet but involves reduced levels of monoamine neurotransmitters, bioenergetics, and redox disturbances, as well as inflammation and neuronal loss. Treatment with anti-depressants provides a complete remission of symptoms in approximately 50% of patients with major depression. However, these drugs may cause side effects, as sedation and weight gain. In this context, there is increasing interest in studies focusing on the anti-depressant effects of natural compounds found in the diet. Resveratrol is a polyphenolic phytoalexin (3,4',5-trihydroxystilbene; C14H12O3; MW 228.247 g/mol) and has been found in peanuts, berries, grapes, and wine and induces anti-oxidant, anti-inflammatory, and anti-apoptotic effects in several mammalian cell types. Resveratrol also elicits anti-depressant effects, as observed in experimental models using animals. Therefore, resveratrol may be viewed as a potential anti-depressant agent, as well as may serve as a model of molecule to be modified aiming to ameliorate depressive symptoms in humans. In the present review, we describe and discuss the anti-depressant effects of resveratrol focusing on the mechanism of action of this phytoalexin in different experimental models.

DNA redox modulations and global DNA methylation in bipolar disorder: effects of sex and illness state

Article

Mar 2017
EUR NEUROPSYCHOPHARM

Quality of life among post-menopausal women due to oxidative stress boosted by dysthymia and anxiety

Article

Full-text available

Jan 2017
BMC Wom Health

Background Menopause is the onset of aging in women. During this process, some women experience physical changes that may impact upon their psychological and social status, also affecting their quality of life. Furthermore, several psychological changes following menopause have been shown to act as pro-oxidant, but the association between the psychological status that modify the quality of life and oxidative stress in postmenopausal women is still unclear. The aim of this study was to determinate the relationship between oxidative stress with psychological disturbances, low self-esteem, depressive mood and anxiety, and quality of life in the postmenopausal women. Methods We carried out a cross-sectional study with101 premenopausal and 101 postmenopausal women from Mexico City. As markers of oxidative stress we measured plasma lipoperoxide levels, erythrocyte superoxide dismutase and glutathione peroxidase activities, and total antioxidant status. We calculate a stress score as global oxidative stress status, with cut-off values for each parameter; this score range from 0 to 6, representing the severity of markers modifications. All the women were rated using the Coopersmith Self-Esteem Inventory, the Zung Self-Rating Anxiety and the Zung Self-Rating Depression Scales, and the WHO Quality of Life-brief. Results The postmenopausal women with low quality of life in the WHO Quality of Life-brief and their subscales had higher stress score compared with premenopausal women with high quality of life (p < 0.05). We found a positive correlation among lipoperoxide levels and Zung Self-Rating Anxiety and Zung Self-Rating Depression score (r = 0.226 and r = 0.173, respectively, p < 0.05), and a negative correlation with WHO Quality of Life-brief scores (r = −0.266, p < 0.01) in postmenopausal women. Multiple linear regression analysis revealed that average lipoperoxide levels increase by 0.0007 μmol/L for every 1-point increase in the Coopersmith Self-Esteem Inventory and by 0.001 μmol/L for every 1-point decrease in the WHO Quality of Life-brief, after adjusted for pro-oxidant factors. Zung Self-Rating Anxiety and Zung Self-Rating Depression Scales scores also contribute to increase lipoperoxides levels, but not significant. Conclusion Our findings suggest that oxidative stress is increased in postmenopausal women with psychological disturbances and low quality of life.

Elevated Plasma Oxidative Stress Markers in Individuals with Intermittent Explosive Disorder and Correlation with Aggression in Humans

Article

Full-text available

Jan 2016

Background Animal and clinical studies suggest a link between inflammation and oxidative stress. Because oxidative stress is an inherent part of inflammation, and inflammation is associated with behavioral aggression in lower mammals and humans, we hypothesized that markers of oxidative stress would be related to aggression in human subjects. In this case-control study, markers of oxidative stress and aggression were assessed in human subjects with histories of recurrent, problematic, impulsive aggressive behavior and in nonaggressive comparator subjects. Methods Plasma levels of 8-hydroxy-2?-deoxyguanosine and 8-isoprostane were examined in the context of measures of aggression and impulsivity in physically healthy subjects with intermittent explosive disorder (n = 69), nonaggressive subjects with Axis I or II disorders (n = 61), and nonaggressive subjects with no history of Axis I or II disorders (n = 67). Results Levels of plasma 8-hydroxy-2?-deoxyguanosine and 8-isoprostane were significantly higher in subjects with intermittent explosive disorder compared with psychiatric or normal control subjects. In addition, both oxidative stress markers correlated with a composite measure of aggression; more specifically, 8-hydroxy-2?-deoxyguanosine correlated with measures reflecting a history of actual aggressive behavior in all subjects. Conclusions These data suggest a positive relationship between plasma markers of oxidative stress and aggression in human subjects. This finding adds to the complex picture of the central neuromodulatory role of aggression in human subjects.

Modelling-oxidative stress in human hippocampal progenitor cells: insights into putative underlying mechanisms of depression

Article

Full-text available

Jul 2016
FREE RADICAL BIO MED

Increased pregenual anterior cingulate glucose and lactate concentrations in major depressive disorder

Article

May 2016
MOL PSYCHIATR

There is ample evidence that glucose metabolism in the pregenual anterior cingulate cortex (PACC) is increased in major depressive disorder (MDD), whereas it is still unknown whether glucose levels per se are also elevated. Elevated cerebrospinal fluid (CSF) lactate concentrations in MDD patients might indicate that increased glycolytical metabolization of glucose to lactate in astrocytes either alone or in conjunction with mitochondrial dysfunction results in an accumulation of lactate and contributes to pathophysiological mechanisms of MDD. However, until now, no study investigated in vivo PACC glucose and lactate levels in MDD. Proton magnetic resonance spectroscopy was therefore used to test the hypothesis that patients with MDD have increased PACC glucose and lactate levels. In 40 healthy and depressed participants, spectra were acquired from the PACC using a maximum echo J-resolved spectroscopy protocol. Results show significant increases of glucose and lactate in patients, which are also associated with depression severity. These findings indicate impaired brain energy metabolism in MDD with increased fraction of energy utilization via glycolysis and reduced mitochondrial oxidative clearance of lactate. Targeting these metabolic disturbances might affect the balance of metabolic pathways regulating neuronal energetics and result in an attenuation of the elevated basal activity of brain regions within the neural circuitry of depression.Molecular Psychiatry advance online publication, 17 May 2016; doi:10.1038/mp.2016.73.

DNA Damage in Major Psychiatric Diseases

Article

Full-text available

Aug 2016
NEUROTOX RES

Human cells are exposed to exogenous insults and continuous production of different metabolites. These insults and unwanted metabolic products might interfere with the stability of genomic DNA. Recently, many studies have demonstrated that different psychiatric disorders show substantially high levels of oxidative DNA damage in the brain accompanied with morphological and functional alterations. It reveals that damaged genomic DNA may contribute to the pathophysiology of these mental illnesses. In this article, we review the roles of oxidative damage and reduced antioxidant ability in some vastly studied psychiatric disorders and emphasize the inclusion of treatment options involving DNA repair. In addition, while most currently used antidepressants are based on the manipulation of the neurotransmitter regulation in managing different mental abnormalities, they are able to prevent or reverse neurotoxin-induced DNA damage. Therefore, it may be plausible to target on genomic DNA alterations for psychiatric therapies, which is of pivotal importance for future antipsychiatric drug development.

Depressive symptoms are associated with oxidative stress in middle-aged women: A cross-sectional study

Article

Full-text available

Apr 2016

Masakazu Terauchi

Background Oxidative stress is known to be a factor in various diseases. In this study, we investigated whether physical and psychological symptoms of menopause, cardiovascular parameters, body composition, and lifestyle factors are associated with oxidative stress in middle-aged women. Methods This cross-sectional study used baseline data collected in a previous study that examined the effects of a dietary supplement on a variety of health parameters in 95 women aged 40 to 60 years. Participants had been assessed for age, menopausal status, body composition, cardiovascular parameters, physical and psychological symptoms of menopause, and lifestyle factors. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) level, an oxidative stress marker, had also been measured. Dichotomizing 8-OHdG levels as low (≤25 ng/mg creatinine) and high (>25 ng/mg creatinine), we sought to identify the health parameters that are associated with high 8-OHdG level. ResultsWomen with a high 8-OHdG level had lower body weight, lower body mass index, lower body fat mass, higher body temperature, scored higher for both anxiety and depression on the Hospital Anxiety and Depression Scale (HADS), and consumed more alcohol. Multiple logistic regression analysis revealed that the HADS-depression subscale (HADS-D) score was the sole independent contributor to high 8-OHdG level (adjusted odds ratio, 1.23 per point increase in HADS-D score; 95 % confidence interval, 1.06–1.45). Conclusion Depressive symptom score was shown to be independently associated with high 8-OHdG level in middle-aged women, suggesting a link between mood disorder and oxidative stress. Trial registrationUMIN-CTR UMIN000009353.

Daganatos distressz és életminőség - kutatási referenciák segítőknek

Book

Full-text available

Jan 2010

Dégi László Csaba

Dégi, L. Cs. (2010). Daganatos distressz és életminőség - kutatási referenciák segítőknek. Studium Kiadó — Országos Tankönyvkiadó / Editura Didactică şi Pedagogică, Marosvásárhely - Bukarest (94 old.)

Menopause and Oxidative Stress

Article

Full-text available

Sep 2015

In women, postmenopause may be considered the beginning of aging due to a series of changes that are caused by the decline of estrogen levels, some of which involve the skin. It is known that estrogens have an antioxidant activity and function as sex hormone; therefore, a decrease in estrogen levels during the postmenopausal period is one of the factors that control age-related oxidative stress. Oxidative stress refers to a serious imbalance between the oxidant species that are produced by metabolism and the effective action of the antioxidant system, and this imbalance can cause severe oxidative damage in cells. When the levels of these cytotoxic agents increase, serious damage occurs through the oxidative modification of macromolecules such as lipids, proteins, and DNA, and this process occurs more frequently with age. These disturbances may cause skin changes such as dryness, a reduction in epidermal and dermal thickness, a decrease in collagen content, a reduction in elasticity, fragility, and poor healing. Once women begin ovarian senescence, estrogen production becomes erratic, antioxidant protection is lost, and oxidative stress is assumed to increase. In this chapter, we review the general aspects of postmenopause that are linked to oxidative stress and its relationship with skin aging.

Immunological and Molecular Alterations in Posttraumatic Stress Disorder and the Reversibility through Psychotherapy

Thesis

Jan 2013

Julia Morath

Depression and negative life events as risk factors for cancer history

Conference Paper

Jun 2011
J PSYCHOSOM RES

The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders

Article

Full-text available

Dec 2015
BMC MED

Mitochondrial dysfunction and defects in oxidative metabolism are a characteristic feature of many chronic illnesses not currently classified as mitochondrial diseases. Examples of such illnesses include bipolar disorder, multiple sclerosis, Parkinson’s disease, schizophrenia, depression, autism, and chronic fatigue syndrome. While the majority of patients with multiple sclerosis appear to have widespread mitochondrial dysfunction and impaired ATP production, the findings in patients diagnosed with Parkinson’s disease, autism, depression, bipolar disorder schizophrenia and chronic fatigue syndrome are less consistent, likely reflecting the fact that these diagnoses do not represent a disease with a unitary pathogenesis and pathophysiology. However, investigations have revealed the presence of chronic oxidative stress to be an almost invariant finding in study cohorts of patients afforded each diagnosis. This state is characterized by elevated reactive oxygen and nitrogen species and/or reduced levels of glutathione, and goes hand in hand with chronic systemic inflammation with elevated levels of pro-inflammatory cytokines. This paper details mechanisms by which elevated levels of reactive oxygen and nitrogen species together with elevated pro-inflammatory cytokines could conspire to pave a major road to the development of mitochondrial dysfunction and impaired oxidative metabolism seen in many patients diagnosed with these disorders.

Implication of Monoamines, Cortisol, Brain Derived Neurotrophic Factor and Opioid Receptors Genes in the Depressive-like Effect of Isotretinoin in Adult Male Rats: Comparison with Clonidine

Article

Full-text available

Dec 2014

The present study describes the effect of isotretinoin (7.5 mg/kg body wt/ day, orally for 28 days) or clonidine (0.8 mg/kg body wt/day, i.p. for 7 days) on the concentrations of dopamine (DA), norepinephrine (NE), serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA) and brain derived neurotrophic factor (BDNF) and activity of monoamine oxidase (MAO) in the hippocampus and frontal cortex of adult male albino rats. The cortisol level was determined in serum. Gene expression of mu (MORs) and Kappa (KORs) opioid receptors genes and DNA damage were measured in the hippocampus-frontal cortex rat brains. The results show that administration of isotretinoin or clonidine caused an increase in DA, NE, 5-HIAA and BDNF concentrations, and a decrease in MAO enzyme activity in both the hippocampus and frontal cortex. In the hippocampus and frontal cortex, the 5-HT concentration increased significantly following clonidine treatment but not significantly changed after isotretinoin treatment. The level of serum cortisol increased following treatment with either isotretinoin or clonidine. Significant increases in MORs and KORs genes expression levels as well as in DNA damage of hippocampusfrontal cortex brain areas were also seen in isotretinoin or clonidine-treated rats compared with control rats. These results provide evidence that the depressive-like effects induced by isotretinoin or clonidine are exerted through alteration in monoamines, brain derived neurotrophic factor and cortisol levels as well as in opioid receptors gene expression.

Association of Oxidative Stress–Induced Nucleic Acid Damage With Psychiatric Disorders in Adults: A Systematic Review and Meta-analysis

Article

Aug 2022

Importance: Nucleic acid damage from oxidative stress (NA-OXS) may be a molecular mechanism driving the severely increased morbidity and mortality from somatic causes in adults with psychiatric disorders. Objective: To systematically retrieve and analyze data on NA-OXS across the psychiatric disorder diagnostic spectrum. Data sources: The PubMed, Embase, and PsycINFO databases were searched from inception to November 16, 2021. A hand search of reference lists of relevant articles was also performed. Study selection: Key study inclusion criteria in this meta-analysis were as follows: adult human study population, measurement of any marker of DNA or RNA damage from oxidative stress, and either a (1) cross-sectional design comparing patients with psychiatric disorders (any diagnosis) with a control group or (2) prospective intervention. Two authors screened the studies, and 2 senior authors read the relevant articles in full and assessed them for eligibility. Data extraction and synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Two authors performed data extraction independently, and a senior coauthor was consulted in cases of disagreement. Data were synthesized with random-effects and multilevel meta-analyses. Main outcomes and measures: The predefined hypothesis was that individuals with psychiatric disorders have increased NA-OXS levels. The main outcome was the standardized mean differences (SMDs) among patients and controls in nucleic acid oxidation markers compared across diagnostic groups. Analyses were divided into combinations of biological matrices and nucleic acids. Results: Eighty-two studies fulfilled the inclusion criteria, comprising 205 patient vs control group comparisons and a total of 10 151 patient and 10 532 control observations. Overall, the data showed that patients with psychiatric disorders had higher NA-OXS levels vs controls across matrices and molecules. Pooled effect sizes ranged from moderate for urinary DNA markers (SMD = 0.44 [95% CI, 0.20-0.68]; P < .001) to very large for blood cell DNA markers (SMD = 1.12 [95% CI, 0.69-1.55; P < .001). Higher NA-OXS levels were observed among patients with dementias followed by psychotic and bipolar disorders. Sensitivity analyses excluding low-quality studies did not materially alter the results. Intervention studies were few and too heterogenous for meaningful meta-analysis. Conclusions and relevance: The results of this meta-analysis suggest that there is an association with increased NA-OXS levels in individuals across the psychiatric disorder diagnostic spectrum. NA-OXS may play a role in the somatic morbidity and mortality observed among individuals with psychiatric disorders.

Psychological intervention to treat distress: An emerging frontier in cancer prevention and therapy

Article

Dec 2021
BBA-REV CANCER

Psychological distress, such as chronic depression and anxiety, is a topical problem. In the context of cancer patients, prevalence rates of psychological distress are four-times higher than in the general population and often confer worse outcomes. In addition to evidence from epidemiological studies confirming the links between psychological distress and cancer progression, a growing body of cellular and molecular studies have also revealed the complex signaling networks which are modulated by psychological distress-derived chronic stress during cancer progression. In this review, aiming to uncover the intertwined networks of chronic stress-driven oncogenesis and progression, we summarize physiological stress response pathways, like the HPA, SNS, and MGB axes, that modulate the release of stress hormones with potential carcinogenic properties. Furthermore, we discuss in detail the mechanisms behind these chronic stimulations contributing to the initiation and progression of cancer through direct regulation of cancer hallmarks-related signaling or indirect promotion of cancer risk factors (including obesity, disordered circadian rhythms, and premature senescence), suggesting a novel research direction into cancer prevention and therapy on the basis of psychological interventions.

Linking the Triad of Telomere Length, Inflammation, and Gut Dysbiosis in the Manifestation of Depression

Article

Sep 2021

Oxidative stress is associated with characteristic features of the dysfunctional chronic pain phenotype

Article

Aug 2021

The Dysfunctional Chronic Pain (Dysfunctional CP) phenotype is an empirically-identifiable CP subtype with unclear pathophysiological mechanisms that cuts across specific medical CP diagnoses. This study tested whether the multidimensional pain and psychosocial features that characterize the Dysfunctional CP phenotype are associated broadly with elevated oxidative stress (OS). Measures of pain intensity, bodily extent of pain, catastrophizing cognitions, depression, anxiety, sleep disturbance, pain interference, and function were completed by 84 chronic osteoarthritis patients prior to undergoing total knee arthroplasty. Blood samples were obtained at the initiation of surgery prior to incision or tourniquet placement. Plasma levels of F2-isoprostanes (IsoPs) and isofurans (IsoFs), the most highly specific measures of in vivo OS, were quantified using gas chromatography/negative ion chemical ionization mass spectrometry. Results indicated that controlling for differences in age, sex, and body mass index, higher overall OS (mean of IsoPs and IsoFs) was associated with significantly (p's < .05) greater pain intensity, more widespread pain, greater depressive symptoms and pain catastrophizing, higher pain interference, and lower function. OS measures were not significantly associated with sleep disturbance or anxiety levels (p's >.10). Results build on prior case-control findings suggesting that presence of a CP diagnosis is associated with elevated OS, highlighting that it may specifically be individuals displaying characteristics of the Dysfunctional CP phenotype who are characterized by elevated OS. Clinical implications of these findings remain to be determined.

Molecular correlates of mitochondrial dysfunctions in major depression: Evidence from clinical and rodent studies

Article

Sep 2020
MOL CELL NEUROSCI

Major depressive disorder (MDD) is one of the most prevalent stress-related mental disorders worldwide. Several biological mechanisms underlying the pathophysiology of MDD have been proposed, including endocrine disturbances, neurotransmitter deficits, impaired neuronal plasticity, and more recently, mitochondrial dysfunctions. In this review, we provide an overview of relevant molecular correlates of mitochondrial dysfunction in MDD, based on findings from clinical studies and stress-induced rodent models. We also compare differences and similarities between the phenotypes of MDD patients and animal models. Our analysis of the literature reveals that both MDD and stress are associated, in humans and animals, with changes in mitochondrial biogenesis, redox imbalance, increased oxidative damages of cellular macromolecules, and apoptosis. Yet, a considerable amount of conflicting data exist and therefore, the translation of findings from clinical and preclinical research to novel therapies for MDD remains complex. Further studies are needed to advance our understanding of the molecular networks and biological mechanisms involving mitochondria in the pathophysiology of MDD.

Oxidative stress and brain morphology in individuals with depression, anxiety and healthy controls

Article

Feb 2017
PROG NEURO-PSYCHOPH

Oxidative stress is a biological process, caused by an imbalance between reactive oxygen species (ROS) and antioxidants, in favour of the ROS. This imbalance leads to oxidative damage to lipids, proteins and DNA and ultimately cell death. Studies in rodents have shown that the brain, particularly the amygdala and hippocampus, is sensitive to oxidative stress, although studies on the association between oxidative stress and brain morphology in humans are lacking. Oxidative stress has also been associated with major depressive disorder (MDD) and may be related to volumetric abnormalities in the amygdala and hippocampus in MDD and anxiety disorders. In this study we aimed to examine the association between two robust measures of oxidative damage in plasma (8-OHdG and F2-isoprostanes) and volume of the hippocampus and amygdala in a large sample of individuals with and without MDD and/or anxiety (N = 297). In secondary analyses, we examine whether this association is similar in patients and controls. 8-OHdG and F2-isoprostanes plasma levels were determined using liquid chromatography tandem mass spectrometry and volume of the hippocampus and amygdala and hippocampal subfields was determined using Freesurfer. We found no association between plasma markers (or interaction with MDD and/or anxiety disorder diagnosis) and subcortical volume, suggesting that peripheral oxidative stress damage is not associated with subcortical brain volume.

Abstract # 1746 Inflammation and mitochondrial dysfunction in elderly women with major depressive disorder

Article

Oct 2016
BRAIN BEHAV IMMUN

Inflammatory processes are supposed to play an integral role in the pathophysiology of Major Depressive Disorder (MD). Chronically elevated levels of CRP, IL-6 and TNF-alpha may contribute to the high prevalence of secondary diseases observed with MD (e.g. autoimmune diseases, cardiovascular diseases, and cancer). Besides poor health outcomes, MD patients suffer from chronic fatigue, lack of energy and difficulties concentrating. These core symptoms of depression point towards disturbances in physiological energy homeostasis. The main energy suppliers of human cells, mitochondria, are in addition to the production of adenosine triphosphate (ATP), pivotally involved in the regulation of inflammatory processes. To this end, we analyzed in a study cohort of 44 elderly women (22 MD patients and 22 healthy age-matched controls) whether mitochondrial activity was altered in immune cells of MD patients and was associated with inflammation as assessed by serum CRP, IL-6 and TNF-alpha levels. Compared to healthy controls, MD patients presented in tendency higher levels of circulating CRP, IL-6, but not TNF-alpha. Mitochondrial activity, mitochondrial maximal capacity and oxygen consumption related to ATP production were substantially reduced in immune cells of MD patients. Maximal capacity was reduced and mitochondria were operating closer to their maximal capacity with higher levels of inflammation. Together these data support the hypothesis that immune dysregulation and mitochondrial dysfunction are possibly interconnected and inherent in the pathophysiology of MD.

The Behavioural Dimension of Cancer and Sickness

Chapter

Dec 2014

Animals behave in specific manners when they are sick, and some of those behaviours may be adaptive responses to disease, whereas others may be a more straightforward result of dysfunction. Conversely, behaviours such as stressful social interactions may affect the normal functioning of the organism contributing—alone or in conjunction with other factors—to disease development. We start this chapter by reviewing the biological aspects of the interface between behaviour and disease in animals, with special reference to cancer in humans, to then explore in more detail the relationship of human cancer with pain, fatigue, sleep disorders, nausea and the various senses.

Psychology and Cancer

Chapter

Dec 2014

In the previous chapter we have analysed the many links between behaviour, neurological, immune and endocrine activity and cancer with an emphasis on the physiological, cellular and molecular mechanisms that can explain such links. We now shift to the next level of analysis where the focus is on complex individual behaviours and how such behaviours interact with various aspects of our biology to potentially affect cancer development. Conversely, cancer may also cause psychological changes in the individual affected. We start with an analysis of psychological distress that may potentially conduce to depression, to then proceed to other emotional and also cognitive aspects of cancer, including cancer effects on memory. A very topical issue in behavioural oncology is the relationship between personality and cancer, a subject that will be reviewed in detail in this chapter. Cancer and psychology may be potentially associated at all levels of mental activity; here we also explore the relationship between cancer and dreams. The chapter continues with an analysis of the effects of cancer on sexual behaviour and the effects of gender and age on the psychology of cancer patients. Issues of behaviour and infectious causes of cancer will be analysed next, to end with a section on psychological morbidity in oncology, with special emphasis on mental effects of brain tumours.

Exploring the link between depression and accelerated cellular aging: telomeres hold the key

Article

Full-text available

Dec 2015

Ruby Yu, Jean Woo Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, SAR, China Abstract: Accumulating evidence suggests that telomeres may be a marker for biological aging and telomere length may be affected by multifactorial influences, including cumulative exposure to depression. Associations with telomere length have been reported for major depressive disorder, lifetime duration of depression, higher depression severity, and history of depression. The exact underling mechanisms for these associations have yet to be fully elucidated; however, oxidative stress, chronic inflammation, dysregulated hypothalamus-pituitary-adrenal axis, and altered cortisol levels may be important biochemical mediators. These mediators could also be influenced by psychological stress, unhealthy lifestyle behaviors, or other potential factors, such as childhood abuse, post-traumatic stress disorder, and anxiety that are commonly associated with depression. As such, stress reduction and lifestyle interventions that may affect the telomere maintenance system should be considered for individuals with depression.Keywords: depression, telomere length, biomarkers, cellular ageing

ASPECTE PSIHOSOCIALE ALE BOLILOR TUMORALE. EVALUARE ŞI INTERVENŢIE - EPUB

Data

Full-text available

Dec 2015

Dégi László Csaba

ASPECTE PSIHOSOCIALE ALE BOLILOR TUMORALE. EVALUARE ŞI INTERVENŢIE

Book

Full-text available

Oct 2015

Dégi László Csaba

http://www.editura.ubbcluj.ro/bd/ebooks/pdf/1853.pdf

Reasons and consequences of cancer diagnosis non-disclosure in Romania

Conference Paper

Jan 2010

Accelerated ageing and effects of psychotherapy on DNA strand break accumulation in individuals suffering from posttraumatic stress disorders

Article

Aug 2015
EXP GERONTOL

Depression and cancer mortality and morbidity: prospective evidence from the Alameda County Study

Article

Full-text available

May 2007

http://deepblue.lib.umich.edu/bitstream/2027.42/51465/1/Kaplan GA, Depression and Cancer Mortality, 1988.pdf

Psychological stress induced modulation of 1L-2 receptor gene expression and IL-2 production in peripheral blood leucocytes

Article

Full-text available

Sep 1990
ARCH GEN PSYCHIAT

We explored the expression of the interleukin 2 receptor (IL-2R) and the synthesis of IL-2R messenger RNA by peripheral blood leukocytes obtained from medical students experiencing examination stress in three independent studies. The peripheral blood leukocytes obtained at low-stress baseline periods had significantly higher percentages of IL-2R-positive cells when compared with cells obtained from the same individuals during examinations. In addition, IL2-R messenger RNA in peripheral blood leukocytes decreased significantly during examination periods in a subset of 13 subjects. In one study, we found an increase in the accumulation of interleukin 2 in cultures of cells showing down regulation of IL-2R expression and IL-2R messenger RNA levels. While there are ample data demonstrating stress-associated decrements in the immune response in humans and animals, these data provide the first evidence that this interaction may be observed at the level of gene expression. The data suggest one mechanism whereby the central nervous system modulates the immune response during psychological stress.

Depression and cancer mortality and morbidity: Prospective evidence from the Alameda County study

Article

Full-text available

Mar 1988

The association between the presence of depressive symptoms and cancer incidence and mortality and mortality from noncancer causes was studied in a population-based cohort of 6848 persons free of cancer who were followed from 1965 to 1982 as part of the Alameda County study. Age-adjusted and multivariate analyses involving over 111,000 person-years of follow-up demonstrated an association between high levels of depressive symptoms at baseline and deaths from noncancer causes but no association with either cancer incidence or cancer mortality. Our analyses suggest the possibility that the presence of previously diagnosed cases of cancer and the inclusion of items which tap somatic problems in depression scales may contribute to differences between these results and others in which depression has been linked to cancer mortality.

Effects of Stress on Methyltransferase Synthesis: An Important DNA Repair Enzyme

Article

Full-text available

Jan 1985

The enhancement of tumor development following acute stress has been demonstrated in some animal studies. This study was designed to explore mechanisms that would account in part for the relationship between stress and tumor development at the level of DNA repair, using a rat model. Forty-four rats were given the carcinogen dimethylnitrosamine in their drinking water, and half were randomly assigned to a rotational stress condition. The levels of methyltransferase, a DNA repair enzyme induced in response to carcinogen damage, were significantly lower in spleens from the stressed animals. These data suggest that stress may impair DNA repair.

Stress-Associated Modulation of Proto-Oncogene Expression in Human Peripheral Blood Leukocytes

Article

Full-text available

Jun 1993

Changes in the cellular immune response associated with psychological stress were studied by using an academic stress model with medical students. The authors examined the expression of 2 proto-oncogenes, c-myc and c-myb, in peripheral blood leukocytes (PBLs) obtained from medical students at the time of examinations and at a baseline period approximately 1 month prior to the examinations. The level of messenger ribonucleic acid (mRNA) expression of both protooncogenes was significantly lower in PBLs obtained during examinations than in those from the baseline period. In addition, a significant decrease in the level of mRNA to the glucocorticoid receptor and gamma interferon was also found in the same preparations. The decrease in mRNA content of c-myc, c-myb, the glucocorticoid receptor, and gamma interferon in PBLs obtained from subjects during examinations is consistent with data from previous studies using the same model that have demonstrated a down-regulation of T-lymphocyte activation and proliferation in response to mitogens.

Personality Factors and Breast Cancer Development: a Prospective Longitudinal Study

Article

Full-text available

Nov 1996

It has been estimated that approximately 25% of all breast cancers in women can be explained by currently recognized somatic (i.e., hereditary and physiologic) risk factors. It has also been hypothesized that psychological factors may play a role in the development of breast cancer. We investigated the extent to which personality factors, in addition to somatic risk factors, may be associated with the development of primary breast cancer. We employed a prospective, longitudinal study design. From 1989 through 1990, a personality questionnaire was sent to all female residents of the Dutch city of Nijmegen who were 43 years of age or older. This questionnaire was sent as part of an invitation to participate in a population-based breast cancer screening program. Women who developed breast cancer among those who returned completed questionnaires were compared with women without such a diagnosis in regard to somatic risk factors and personality traits, including anxiety, anger, depression, rationality, anti-emotionality (i.e., an absence of emotional behavior or a lack of trust in one's own feelings), understanding, optimism, social support, and the expression and control of emotions. Conditional logistic regression analysis was used to identify variables that could best explain group membership (i.e., belonging to the case [breast cancer] or the control [without disease] group). Personality questionnaires were sent to 28 940 women, and 9705 (34%) were returned in such a way that they could be used for statistical analyses. Among the 9705 women who returned useable questionnaires, 131 were diagnosed with breast cancer during the period from 1989 through 1994. Seven hundred seventy-one age-matched control subjects (up to six per case patient) were selected for the analyses. Three variables were found to be statistically significantly associated with an increased risk of breast cancer: 1) having a first-degree family member with breast cancer (versus not having an affected first-degree relative, odds ratio [OR] = 4.05; 95% confidence interval [CI] = 1.76-9.31); 2) nulliparity (i.e., having no children) (versus having had a child before the age of 30 years, OR = 2.67; 95% CI = 1.26-5.68); and 3) a relatively high score on the personality scale of anti-emotionality (versus a low score, OR = 1.19; 95% CI = 1.05-1.35). With the exception of a weak association between a high score on the anti-emotionality scale and the development of breast cancer, no support was found for the hypothesis that personality traits can differentiate between groups of women with and without breast cancer. We recommend that this study be continued and that other studies be encouraged to explore possible relationships between personality factors and the risk of breast cancer.

Vitamin C exhibits pro-oxidant

Article

Full-text available

May 1998

Vitamin C is marketed as a dietary supplement, partly because of its `antioxidant' properties. However, we report here that vitamin C administered as a dietary supplement to healthy humans exhibits a pro-oxidant, as well as an antioxidant, effect in vivo.

Mechanism-Based Cancer Prevention Approaches: Targets, Examples, and the Use of Transgenic Mice

Article

Full-text available

Mar 1999

Humans are exposed to a wide variety of carcinogenic insults, including endogenous and man-made chemicals, radiation, physical agents, and viruses. The ultimate goal of carcinogenesis research is to elucidate the processes involved in the induction of human cancer so that interventions may be developed to prevent the disease, either in the general population or in susceptible subpopulations. Progress to date in the carcinogenesis field, particularly regarding the mechanisms of chemically induced cancer, has revealed several points along the carcinogenesis pathway that may be amenable to mechanism-based prevention strategies. The purpose of this review is to examine the basic mechanisms and stages of chemical carcinogenesis, with an emphasis on ways in which preventive interventions can modify those processes. Possible ways of interfering with tumor initiation events include the following: i) modifying carcinogen activation by inhibiting enzymes responsible for that activation or by direct scavenging of DNA-reactive electrophiles and free radicals; ii) enhancing carcinogen detoxification processes by altering the activity of the detoxifying enzymes; and iii) modulating certain DNA repair processes. Possible ways of blocking the processes involved in the promotion and progression stages of carcinogenesis include the following: i) scavenging of reactive oxygen species; ii) altering the expression of genes involved in cell signaling, particularly those regulating cell proliferation, apoptosis, and differentiation; and iii) decreasing inflammation. In addition, the utility for mechanism-based cancer prevention research of new animal models that are based on the overexpression or inactivation of specific cancer-related genes is examined.

Early and chronic stress and their relation to breast cancer [In Process Citation]

Article

Full-text available

Jun 2000

The study examined the role of parental death and chronic depression with severe episodes in affecting risk of breast cancer. This avenue of research is in accord with oncology findings, which suggests that causative factors of breast cancer occur and develop over a period of 20 years or longer. Participants consisted of 1213 women in the Baltimore Epidemiologic Catchment Area study surveyed in 1980 and followed through 1994-1995. They were assessed for depressive and anxious disorders, paternal death in childhood and relatively recent adverse life events prior to cancer hospitalization. In the course of the study, 29 women were hospitalized for breast cancer and 10 died of breast cancer. The psychosocial variables that predicted increased risk of breast cancer were maternal death in childhood (OR = 2.56, P < 0.001) and chronic depression with severe episodes (OR = 14.0, P < 0.001). Neither relatively recent life events nor other depressive and anxiety disorders were associated with increased risk. Maternal death and chronic depression with severe episodes were reported to have occurred at least 20 years prior to breast cancer hospitalization. Maternal death and chronic and severe depression occurred at least 20 years prior to breast cancer hospitalization and could have been involved in the causation or facilitation of cancer development. The authors suggest that meta-analysis of other prospective studies are needed to create larger groups of individuals with these stresses to confidently establish these variables as risk factors.

Oxidative DNA damage: Mechanism, mutation, and disease

Article

Full-text available

Aug 2003
FASEB J

Oxidative DNA damage is an inevitable consequence of cellular metabolism, with a propensity for increased levels following toxic insult. Although more than 20 base lesions have been identified, only a fraction of these have received appreciable study, most notably 8-oxo-2'deoxyguanosine. This lesion has been the focus of intense research interest and been ascribed much importance, largely to the detriment of other lesions. The present work reviews the basis for the biological significance of oxidative DNA damage, drawing attention to the multiplicity of proteins with repair activities along with a number of poorly considered effects of damage. Given the plethora of (often contradictory) reports describing pathological conditions in which levels of oxidative DNA damage have been measured, this review critically addresses the extent to which the in vitro significance of such damage has relevance for the pathogenesis of disease. It is suggested that some shortcomings associated with biomarkers, along with gaps in our knowledge, may be responsible for the failure to produce consistent and definitive results when applied to understanding the role of DNA damage in disease, highlighting the need for further studies.

Psychological stress-induced modulation of interleukin-2 receptor gene expression and interleukin-2 production in peripheral blood leukocytes

Article

Jan 1990

The premorbid personality who developed cancer in a total population investigated in 1947 and 1957

Article

Jan 1966

O. Hagnell

Health and Ways of Living: The Alameda County Study

Article

Jul 1984

Repair of 8-oxoguanine in Saccharomyces cerevisiae: Interplay of DNA repair and replication mechanisms

Article

Jun 2002
FREE RADICAL BIO MED

8-Oxo-7,8-dihydroguanine (8-oxoG) is produced abundantly in DNA exposed to free radicals and reactive oxygen species. The biological relevance of 8-oxoG has been unveiled by the study of two mutator genes in Escherichia coli, fpg, and mutY. Both genes code for DNA N-glycosylases that cooperate to prevent the mutagenic effects of 8-oxoG in DNA. In Saccharomyces cerevisiae, the OGG1 gene encodes a DNA N-glycosylase/AP lyase, which is the functional homologue of the bacterial fpg gene product. The inactivation of OGG1 in yeast creates a mutator phenotype that is specific for the generation of GC to TA transversions. In yeast, nucleotide excision repair (NER) also contributes to the release of 8-oxoG in damaged DNA. Furthermore, mismatch repair (MMR) mediated by MSH2/MSH6/MLH1 plays a major role in the prevention of the mutagenic effect of 8-oxoG. Indeed, MMR acts as the functional homologue of the MutY protein of E. coli, excising the adenine incorporated opposite 8-oxoG. Finally, the efficient and accurate replication of 8-oxoG by the yeast DNA polymerase eta also prevents 8-oxoG-induced mutagenesis. The aim of this review is to summarize recent literature dealing with the replication and repair of 8-oxoG in Saccharomyces cerevisiae, which can be used as a paradigm for DNA repair in eukaryotes.

Psychological stress and phorbol ester inhibition of radiation-induced apoptosis in human peripheral

Article

The Hypothalamic-Pituitary-Adrenal Axis in Major Depressive Disorder

Article

Aug 2001

Background: One of the most enduring and replicated findings in biological psychiatry is activation of the hypothalamic-pituitary-adrenal (HPA) axis in a subset of patients with major depressive disorder. This review will discuss some of these findings and their pertinence to the assessment and treatment of depressed patients. Method: MEDLINE, PsychINFO, and Current Contents databases were searched for pertinent articles on the HPA axis in patients with depression. In addition, hand searches were conducted of references from these sources and abstracts from meetings and books on this topic. Articles that would provide an overview of major or interesting studies in the field were selected for inclusion. Results: The data support that HPA axis activation is common in depressed patients. Frequently reported findings include elevated cortisol and corticotropin-releasing hormone (CRH), nonsuppression on the dexamethasone suppression test, a blunted adrenocorticotropic hormone (ACTH) response to CRH, and hippocampal volume reduction. Evidence of HPA axis activation appears to have prognostic value and is associated with increased risk of depression relapse and even suicide. Conclusion: Future research in this area will focus on a better understanding of the etiology and long-term consequences of HPA axis activation in depressed patients. In addition, medications that act on the HPA axis are currently in development and may be part of the psychiatrist’s and primary care physician’s pharmacopoeia in the near future.

The CES-D Scale: A Self-Report Depression Scale for Research in the General Population

Article

Jun 1977
APPL PSYCH MEAS

Lenore Sawyer Radloff

The CES-D scale is a short self-report scale designed to measure depressive symptomatology in the general population. The items of the scale are symptoms associated with depression which have been used in previously validated longer scales. The new scale was tested in household interview surveys and in psychiatric settings. It was found to have very high internal consistency and adequate test- retest repeatability. Validity was established by pat terns of correlations with other self-report measures, by correlations with clinical ratings of depression, and by relationships with other variables which support its construct validity. Reliability, validity, and factor structure were similar across a wide variety of demographic characteristics in the general population samples tested. The scale should be a useful tool for epidemiologic studies of de pression.

The Profile of Mood States Manual

Article

Jan 1971

Mood States of Patients After the Diagnosis of Cancer

Article

Jul 1989

Data on the widely used Profile of Mood States (POMS) are presented for 923 recently diagnosed, previously untreated cancer patients. The patients' responses to the POMS were significantly different from those of other groups on which normative data are currently available. Therefore, the authors recommend that investigators who are conducting empirical studies of mood in patients with cancer use the tables in this article rather than previously published test norms on college students and psychotherapy patients.

Diagnostic and Statistical Manual of Mental Disorders: DSM-V

Book

Jan 1994

APA American Psychiatric Association

Minnesota multiphasic personality inventory‐rated depression and the incidence of breast cancer

Article

Feb 1988
CANCER-AM CANCER SOC

Using data from the Walnut Creek Contraceptive Drug Study (a prospective study begun in 1969 and continuing to the present), Minnesota Multiphasic Personality Inventory-(MMPI) measured scores for depression of 8932 women were studied in relation to the incidence of breast cancer. No statistically significant association between MMPI scores for depression and the subsequent development of breast cancer was found. There was neither an association of risk of breast cancer with repression/sensitization as measured on the MMPI nor with scores on the MMPI lie scale. This study is unique because it represents the largest reported prospective cohort in which the association between depression and breast cancer development has been examined.

IL-6 inhibits apoptosis and retains oxidative DNA lesions in human gastric cancer AGS cells through up-regulation of anti-apoptotic gene mcl-1

Article

Jan 2001

Apoptosis plays a critical role in maintaining genomic integrity by selectively removing the most heavily damaged cells from the population. Reactive oxygen species (ROS) and certain inflammatory cytokines are always elevated during the human carcinogenic process. However, the biological significance of the interplay between ROS and inflammatory cytokine remains elusive. This study demonstrates that interleukin-6 (IL-6) effectively protects gastric cancer cells from the apoptosis induced by hydrogen peroxide (H 2 O 2 ). The cell death signaling JNK pathway elicited by H 2 O 2 is also inhibited by IL-6. We further found that Mcl-1, but not other Bcl-2 family members, was up-regulated by IL-6, by a substantial level over 24 h. We further transfected a mcl-1 expression vector, pCMV- mcl-1 , into the AGS cells, and successfully obtained several mcl-1 -overexpressing clones. Flow cytometric analysis shows that these mcl-1 -overexpressing AGS cells are more resistant to the apoptosis induced by H 2 O 2 when compared with the neo control AGS cells. Consistently, the activation of the JNK pathway induced by H 2 O 2 is also blocked in mcl-1 -overexpressed cells. These results indicate that the anti-apoptotic effect of IL-6 is, at least in part, due to the up-regulation of mcl-1 . To our surprise, either IL-6 exposure or mcl-1 overexpression fails to reduce the level of intracellular peroxides in the AGS cells triggered by H 2 O 2 . This study also determined the level of 8-hydroxydeoxyguanosine (8-OH-dGua), an indicator for oxidative DNA lesions in IL-6-treated or mcl-1 -overexpressed AGS cells after treatment with H 2 O 2 . Notably, our results indicate that a majority of the 8-OH-dGua is efficiently removed in the AGS cells without IL-6 treatment, whereas only ~50% of the 8-OH-dGua was repaired in the IL-6-treated AGS cells after 24 h. Similarly, ~60–70% of the 8-OH-dGua also failed to repair and was retained in the genomic DNA of the mcl-1 transfectants. Results in this study provide a novel mechanism by which up-regulation of the Mcl-1 protein by IL-6 may enhance the susceptibility to H 2 O 2 -induced oxidative DNA lesions by overriding apoptosis.

Mind and Cancer

Article

Jul 2002

J. L. Hayward

We have reviewed the evidence for an association between major life events, depression and personality factors and the risk for cancer. We identified and included only those prospective or retrospective studies in which the psychological variable was collected independently of the outcome. The evidence failed to support the hypothesis that major life events are a risk factor for cancer. The evidence was inconsistent for both depression and personality factors. Chance, bias or confounding may explain this result, as many of the studies had methodological weaknesses. The generally weak associations found, the inconsistency of the results, the unresolved underlying biological mechanism and equivocal findings of dose–response relationships prevent a conclusion that psychological factors are established risk factors. However, certain intriguing findings warrant further studies, which must, however, be well conducted and large and include detailed information on confounders.

DNA base modifications in chromatin of human cancerous tissues

Article

Oct 1992

Free radical-induced damage to DNA in vivo is implicated to play a role in carcinogenesis. Evidence exists that DNA damage by endogenous free radicals occurs in vivo, and there is a steady-state level of free radical-modified bases in cellular DNA. We have investigated endogenous levels of typical free radical-induced DNA base modifications in chromatin of various human cancerous tissues and their cancer-free surrounding tissues. Five different types of surgically removed tissues were used, namely colon, stomach, ovary, brain and lung tissues. In chromatin samples isolated from these tissues, five pyrimidine-derived and six purine-derived modified DNA bases were identified and quantitated by gas chromatography/mass spectrometry with selected-ion monitoring. These were 5-hydroxy-5-methylhydantoin, 5-hydroxyhydantoin, 5-(hydroxymethyl)uracil, 5-hydroxycytosine, 5,6-dihydroxycytosine, 4,6-diamino-5-formamidopyrimidine, 8-hydroxyadenine, xanthine, 2-hydroxyadenine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, and 8-hydroxyguanine. These compounds are known to be formed typically by hydroxyl radical attack on DNA bases. In all cases, elevated amounts over control levels of modified DNA bases were found in cancerous tissues. The amounts of modified bases depended on the tissue type. Lung tissues removed from smokers had the highest increases of modified bases above the control levels, and the highest overall amounts. Colon cancer tissue samples had the lowest increases of modified bases over the control levels. The results clearly indicate higher steady-state levels of modified DNA bases in cancerous tissues than in their cancer-free surrounding tissues. Some of these lesions are known to be promutagenic, although others have not been investigated for their mutagenicity. Identified DNA lesions may play a causative role in carcinogenesis.

Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans

Article

Jan 1993

Oxidative DNA damage may be implicated in ageing, carcinogenesis and other degenerative diseases. Oxidative DNA damage can be assessed in humans in vivo from the urinary excretion of the DNA-repair product 8-hydroxydeoxyguanosine (8OHdG). We investigated factors influencing the excretion of 8OHdG in 24 h urine from 83 randomly selected healthy subjects (52 women) aged 40-64 years. For 2 weeks prior to urine collection the subjects kept a weighed diet record. 8OHdG was quantified by an automatic three-dimensional HPLC analysis with electrochemical detection. The 8OHdG excretion was 252 +/- 103 (mean +/- SD) pmol kg body weight/24 h with a range from 78 to 527. Multiple regression analysis identified three factors, smoking, body mass index (BMI) and gender, as significant predictors of the 8OHdG excretion. In 30 smokers the 8OHdG excretion was 320 +/- 99 pmol/kg/24 h opposed to 213 +/- 84 pmol/kg/24 h in 53 non-smokers. According to multiple regression analysis smokers excreted 50% (31-69%; 95% confidence interval) more 8OHdG than non-smokers. In 52 women the 8OHdG excretion was 240 +/- 106 pmol/kg/24 h opposed to 271 +/- 96 pmol/kg/24 h in 31 men. According to the multiple regression analysis men excreted 29% (10-48%) more 8OHdG than women. According to multiple regression analysis the 8OHdG excretion decreased with 4% (2-6%) per increment in BMI measured in kg/m2. The dietary distribution of energy demonstrated no important predictive value with respect to 8OHdG excretion. The intake of the antioxidant vitamins C and E and of vitamin A equivalents, including beta-carotene, was not associated with 8OHdG excretion. The results suggest that smoking increases oxidative DNA damage by approximately 50%. This effect implies potential serious health effects adding to the other well-known health hazards of smoking. The higher 8OHdG excretion in men and lean subjects may be related to a higher rate of metabolism with increased availability of reactive oxygen species. The apparent 7-fold individual variation in oxidative DNA damage carries implications regarding the rate of ageing and the risk of cancer and other degenerative diseases. The excretion of 8OHdG into urine offers a valuable tool for testing such hypotheses in humans.

Psychological stress and phorbol ester inhibition of radiation-induced apoptosis in human peripheral blood leukocytes

Article

Aug 1990
PSYCHIAT RES

Apoptosis is a process of genetically programmed alterations of cell structure that lead to failure of proliferation and differentiation, and eventual cell death. Apoptosis is induced by a variety of toxic insults including growth factor deprivation and ionizing radiation. This process may function to protect against the appearance of heritable phenotypic changes in cells and may be a critical factor in normal cellular immune function. Phorbol esters inhibit apoptosis, but little is known about factors that regulate this process physiologically. In this study, we demonstrate an association between an acute psychological stressor, taking examinations, and the induction of substantial and reversible changes in the response of peripheral blood leukocytes to gamma irradiation and to phorbol ester treatment. These data suggest that psychological stress may induce physiological changes that regulate the ability of immune cells to initiate apoptosis.

Distress and DNA repair in human lymphocytes

Article

Jan 1986

This research assessed differences in DNA repair in lymphocytes from high- and low-distressed individuals. A median split on Minnesota Multiphasic Personality Inventory (MMPI) Scale 2 divided 28 newly admitted nonpsychotic psychiatric inpatients into high- and low-distress subgroups. The high-distress subgroup had significantly poorer DNA repair in lymphocytes exposed to X-irradiation than low-distress subjects. We also found that lymphocytes obtained from this psychiatric sample had significantly poorer DNA repair than lymphocytes from nonpsychiatric control subjects when compared 5 hr after X-irradiation. A high level of distress therefore appears to be associated with significant dysfunctional differences at the molecular level which may have important implications for health. These data provide evidence for a direct pathway through which distress could influence the incidence of cancer.

Minnesota Multiphasic Personality Inventory-rated depression and the incidence of breast cancer

Article

Mar 1988

Personality and Risk of Cancer: 20Year Follow-up of the Western Electric Study

Article

Sep 1987

Psychologic depression as measured by the Minnesota Multiphasic Personality Inventory (MMPI) in a cohort of 2018 middle-aged men employed at the Western Electric Company in 1957-1958 was positively associated with 20-year incidence and mortality from cancer. The association with incidence was apparent only during the first 10 years of follow-up, but the association with mortality was observed for the full 20 years of follow-up. The association persisted after adjustment for age, number of cigarettes smoked, alcohol intake, occupational status, family history of cancer, body mass index, and serum cholesterol. The association did not appear to be stronger for one type of cancer than another, but the power of this study to detect differences among types of cancer was limited by small numbers. However, the association did appear to be stronger with risk of fatal cancer than with total incidence. No association was noted between other variables measured by the MMPI or Cattell 16 Personality Factor Inventory and subsequent incidence or mortality from cancer. Specifically, the data did not support the hypothesis that psychologic repression, as measured by Welsh R scale in the MMPI, would be associated with risk of cancer. These results are consistent with previously reported results that have suggested that psychologic depression might promote the development and spread of malignant neoplasms.

The Premorbid Personality of Persons who Develop Cancer in a Total Population Investigated in 1947 and 1957

Article

Feb 1966

Olle Hagnell

Hydroxylation of deoxyguanosine at the C-8 position by ascorbic acid and other reducing agents

Article

Mar 1984

The C-8 position of deoxyguanosine (dGuo) was hydroxylated by ascorbic acid in the presence of oxygen (O2) in 0.1 M phosphate buffer (pH 6.8) at 37°C. Addition of hydrogen peroxide (H2O2) remarkably enhanced this hydro-xylation. The Udenfriend system [ ascorbic acid, FeII, ethylenediaminetetra-acetic acid (EDTA) and 02] was also effective for hydroxylation of dGuo in high yield. Guanine residues in DNA were also hydroxylated by ascorbic acid. Other reducing agents, such as hydroxylamine, hydrazine, dihydroxymaleic acid, sodium bisulfite and acetol, were also effective for the hydroxylation reaction, as were metal-EDTA complexes (FeII-, SnII TiIII-, CuI-EDTA) An OH radical seemed to be involved in this hydroxylation reaction in most of the above hydroxylating systems, but another reaction mechanism may also be involved, particularly when dGuo is hydroxylated by ascorbic acid alone or ascorbic acid plus H2O2 The possible biological significance of the hydroxylation of guanine residues in DNA in relation to mutagenesis and carcinogenesis is discussed.

Depression in patients with cancer: Diagnosis, biology, and treatment

Article

Mar 1995
ARCH GEN PSYCHIAT

This article reviews the challenge of diagnosing depression in patients with cancer. Major depression and depressive symptoms, although commonly encountered in medical populations, are frequently underdiagnosed and undertreated. This is especially true for patients with cancer in whom the diagnosis of major depression is clouded by neurovegetative symptoms that may be secondary to either cancer or depression. Well-established biological markers for major depression are proposed as diagnostic adjuncts in patients with cancer. Studies using biological markers in depressed patients with and without cancer are reviewed, and the implications of diminished immune function in depressed patients with cancer are discussed. The limited database on treatment of depression in patients with cancer also is reviewed. Treatment of depression in these patients improves their dysphoria and other signs and symptoms of depression, improves quality of life, and may improve immune function and survival time. Guidelines for future research are proposed.

Overexpression of HSP25 Reduces the Level of TNFα-Induced Oxidative DNA Damage Biomarker, 8-Hydroxy-2′-Deoxyguanosine, in L929 Cells

Article

Jan 1998

Previously we and others have demonstrated that oxidative stress involving generation of reactive oxygen species (ROS) is responsible for the cytotoxic action of TNF alpha. Protective effect of small heat shock proteins (HSP) against diverse oxidative stress conditions has been suggested. Although overexpression of small HSP was shown to provide an enhanced survival of TNF alpha-sensitive cells when challenged with TNF alpha, neither the nature of TNF alpha-induced cytotoxicity nor the protective mechanism of small HSP has been completely understood. In this study, we have attempted to determine whether TNF alpha induces oxidative DNA damage in TNF alpha-sensitive L929 cells. We chose to measure the level of 8-hydroxy-2'-deoxyguanosine (8 ohdG), which has been increasingly recognized as one of the most sensitive markers of oxidative DNA damage. Our results clearly demonstrated that the level of 8 ohdG increased in L929 cells in a TNF alpha dose-dependent manner. Subsequently, we asked whether small HSP has a protective effect on TNF alpha-induced oxidative DNA damage. To accomplish this goal, we have stably transfected into L929 cells, which are devoid of endogenous small HSP, with the mouse small hsp cDNA (hsp25). We found that TNF alpha-induced 8 ohdG was decreased in cells overexpressing exogenous small HSP25. We also found that the cell-killing activity of TNF alpha was decreased in these cells as measured by clonogenic survival. Taken together, results from the current study show that a cytotoxic mechanism of TNF alpha involves oxidative damage of DNA, and that overexpression of the small HSP25 reduces this oxidative damage. We suggest that the reduction of oxidative DNA damage is an important protective mechanisms of small HSP against TNF alpha.

Analysis of a form of oxidative DNA damage, 8-hydroxy-2′-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis

Article

Jan 1998
MUTAT RES-FUND MOL M

Hiroshi Kasai

8-hydroxy-2'-deoxyguanosine (8-OH-dG) was first reported in 1984 as a major form of oxidative DNA damage product by heated sugar, Fenton-type reagents and X-irradiation in vitro. 8-OH-dG has been detected in cellular DNA using an HPLC-ECD method in many laboratories. Analyses of 8-OH-dG in animal organ DNA after the administration of oxygen radical-forming chemicals will be useful for assessments of their carcinogenic risk. Its analysis in human leucocyte DNA and in urine is a new approach to the assessment of an individual's cancer risk due to oxidative stress. The increase of the 8-OH-dG level in the cellular DNA, detected by HPLC-ECD method, was supported by its immunochemical detection and its enhanced repair activity. The validity of the general use of 8-OH-dG as a marker of cellular oxidative stress is discussed.

Lung Cancer Patients Have Increased 8-Hydroxydeoxyguanosine Levels in Peripheral Lung Tissue DNA

Article

Aug 1998
Jpn J Canc Res

The 8-hydroxydeoxyguanosine (8-OH-dG) levels in the peripheral parts of human lung tissues were compared between lung cancer patients (n=70) and non-cancer patient controls (n=15). An increased level of 8-OH-dG was observed in the lung cancer group, in both the adenocarcinoma and non-adenocarcinoma (mainly squamous cell carcinoma) groups, as compared to the non-cancer control group. This result suggests that reactive oxygen species are partly involved in the induction of lung carcinomas (both adenocarcinoma and non-adenocarcinoma).

Chronically Depressed Mood and Cancer Risk in Older Persons

Article

Jan 1999

Depression has been proposed as a predisposing factor for cancer, but prospective studies have been inconclusive. We examined whether a high level of depressive symptoms, present for a long time, is associated with increased risk of cancer in the elderly. Data were obtained and analyzed from persons who lived in three communities (Massachusetts, Iowa, and Connecticut) of the Established Populations for Epidemiologic Studies of the Elderly, a prospective cohort study with a mean follow-up of 3.8 years that included 4825 persons (1708 men and 3117 women) aged 71 years and older. Chronically depressed mood was defined as present when the number of depressive symptoms exceeded specific cut points on the Center for Epidemiologic Studies-Depression scale at baseline (1988) and 3 and 6 years before baseline. New cases of cancer were identified from Medicare hospitalization records and death certificates. Of the 4825 persons studied, 146 (3.0%) were chronically depressed. The incidence rate of cancer was 30.5 per 1000 person-years for the 146 persons with chronic depression and 21.9 per 1000 person-years for the 4679 nonchronically depressed persons. After adjustment for age, sex, race, disability, hospital admissions, alcohol intake, and smoking, the hazard ratio for cancer associated with chronically depressed mood was 1.88 (95% confidence interval = 1.13-3.14). The excess risk of cancer associated with chronic depression was consistent for most types of cancer and was not specific to cigarette smokers. When present for at least 6 years, depression was associated with a generally increased risk of cancer.

α-Tocopherol acetate significantly suppressed the increase in heart interstitial 8-hydroxydeoxyguanosine following myocardial ischemia and reperfusion in anesthetized rats

Article

Aug 1999
CLIN CHIM ACTA

The effect of alpha-tocopherol acetate, an aqueous form of alpha-tocopherol, on the increase in heart interstitial 8-hydroxydeoxyguanosine (8-OH-dG) levels following myocardial ischemia/reperfusion was investigated. A microdialysis probe was implanted in the left ventricular interstitial space of anesthetized rat hearts. Myocardial ischemia was induced by ligating the left anterior descending coronary artery. Levels of 8-OH-dG in microdialysates were analyzed via an on-line high-performance liquid chromatography system equipped with an electrochemical detector. The 8-OH-dG levels significantly increased (maximum 3.6-fold of increase relative to basal value) during the 60-min reperfusion stage following a 20 min ischemia. Administration of alpha-tocopherol acetate (20 mg/kg, intravenous, bolus) at 3 min prior to onset of reperfusion, significantly suppressed the reperfusion-induced increase in 8-OH-dG levels. These results suggested that one of the possible protective effect of alpha-tocopherol acetate was to reduce oxidative DNA damage during in myocardial ischemia and reperfusion.

Effect of increased vegetable and fruit consumption on markers of oxidative cellular damage

Article

Jan 2000

The goal of this study was to test the hypothesis that increased consumption of vegetables and fruit would reduce markers of oxidative cellular damage that can be assessed in blood or urine. Twenty-eight women participated in a 14 day dietary intervention. The primary end-points assessed were: 8-hydroxydeoxyguanosine (8-OHdG) in DNA isolated from peripheral lymphocytes, determined by HPLC with electrochemical detection; 8-OHdG excreted in urine, measured by ELISA; malondialdehyde (MDA) in urine, measured by fluorimetric detection following derivatization with thiobarituric acid and separation via HPLC; urinary 8-isoprostane F-2alpha (8-EPG) detected by ELISA. Pre- and post-intervention plasma levels of selected carotenoids were determined by HPLC. Subjects were free living and consumed a completely defined recipe-based diet that increased their average daily consumption of vegetables and fruit from 5.8 servings at baseline to 12.0 servings throughout the intervention. Overall, the level of 8-OHdG in DNA isolated from lymphocytes and in urine and the level of 8-EPG in urine were reduced by the intervention, whereas urine concentrations of MDA were minimally affected. The reduction in lymphocyte 8-OHdG was greater in magnitude (32 versus 5%) in individuals with lower average pre-intervention levels of plasma alpha-carotene (56 ng/ml) than in individuals with higher average pre-intervention plasma levels of alpha-carotene (148 ng/ml). The results of this study indicate that consumption of a diet that significantly increased vegetable and fruit intake from a diverse number of botanical families resulted in significant reductions in markers of oxidative cellular damage to DNA and lipids.

Cancer prevention: Epidemiology and perspectives

Article

Jan 2000
EUR J CANCER

F Levi

Following increases up until the late 1980s, some decline in cancer mortality has been observed in North America and in Western Europe. Approximately half the decline can be attributed to the levelling off in lung and other tobacco-related cancer epidemics and the rest to several factors, including reduced exposure to occupational carcinogens, prevention and early diagnosis, and improved treatment. Between 25 and 30% of all cancer deaths in Europe are due to tobacco smoking. In this review the effect of tobacco smoking on cancer incidence and mortality is examined, together with other important aetiological factors including alcohol, diet and environmental and occupational carcinogens. The effect of new treatments and the potential for prevention of cancer are also discussed.

Urinary 8-oxo-2′-deoxyguanosine — Source, significance and supplements

Article

Jun 2000

Oxidative damage to cellular biomolecules, in particular DNA, has been proposed to play an important role in a number of pathological conditions, including carcinogenesis. A much studied consequence of oxygen-centred radical damage to DNA is 8-oxo-2'-deoxyguanosine (8-oxodG). Using numerous techniques, this lesion has been quantified in various biological matrices, most notably DNA and urine. Until recently, it was understood that urinary 8-oxodG derives solely from DNA repair, although the processes which may yield the modified deoxynucleoside have never been thoroughly discussed. This review suggests that nucleotide excision repair and the action of a specific endonuclease may, in addition to the nucleotide pool, contribute significantly to levels of 8-oxodG in the urine. On this basis, urinary 8-oxodG represents an important biomarker of generalised, cellular oxidative stress. Current data from antioxidant supplementation trials are examined and the potential for such compounds to modulate DNA repair is considered. It is stressed that further work is required to link DNA, serum and urinary levels of 8-oxodG such that the kinetics of formation and clearance may be elucidated, facilitating greater understanding of the role played by oxidative stress in disease.

Gallo JJ, Armenian HK, Ford DE, Eaton WW, Khachaturian ASMajor depression and cancer: the 13-year follow-up of the Baltimore Epidemiologic Catchment Area sample (United States). Cancer Causes Control 11: 751-758

Article

Oct 2000

The relationship between depression and development of cancer is not well understood, with some studies finding a significant but small increase in risk for cancer among persons with depression. No studies have employed standardized interviews keyed to the diagnostic criteria for Major Depression. Our objective was to evaluate the relationship between Major Depression at baseline and new onset of cancer at follow-up. The study was based on a population-based 13-year follow-up survey of community-dwelling adults living in East Baltimore in 1981. After excluding 372 persons with a history of cancer or those whom reported their health as poor at the baseline interview, 3109 adults remained. Information on baseline depression status and cancer at follow-up was available for 2017 persons. A diagnosis of cancer was ascertained at follow-up through interview of survivors and from death certificates. There were 203 new cases of cancer among 2017 persons at risk. Neither Major Depression (relative risk (RR) = 1.0, 95% confidence interval (CI) 0.5-2.1) nor dysphoric episode (RR = 1.3, 95% CI 0.9-1.9) were significantly associated with increased risk of cancer at follow-up. However, among women with Major Depression, the risk of breast cancer was increased (adjusted RR = 3.8, 95% CI 1.0-14.2). We found no overall association of depression with cancer. However, among women, Major Depression (but not dysphoric episode alone) was associated with the onset of breast cancer.

Psychosocial Factors as a Potential Trigger of Oxidative DNA Damage in Human Leukocytes

Article

Apr 2001
Jpn J Canc Res

Although numerous studies have been carried out on the stress-cancer linkage, the results are still inconclusive. One of the useful, but rarely applied, methods to assess this linkage is to examine the relationship between psychosocial stress and cancer-predisposing genetic alterations simultaneously. We investigated whether various psychosocial factors can be associated with the levels of 8-hydroxydeoxyguanosine (8-OH-dG), a biomarker of cancer-related oxidative DNA damage, in peripheral blood leukocytes in 362 healthy workers (276 males and 86 females). After adjustments for age, body mass index, cigarette smoking, and alcohol use, female subjects showed positive relationships between the amount of 8-OH-dG and the Tension-Anxiety, Depression-Rejection, Anger-Hostility, Fatigue, and Confusion scores of the Profile of Mood States, respectively. The levels of 8-OH-dG also increased reliably in the female subjects who had poor stress-coping behaviors, particularly wishful thinking strategy, in the NIOSH general job stress instrument. There were positive relationships of the 8-OH-dG levels to average working hours, a self-blame coping strategy, and recent loss of a close family member in male subjects. These findings in a nonclinical sample of healthy adults not only provide evidence of a stress-cancer linkage, but also suggest possible sex differences in the mechanisms of stress-related cancer initiation.

Oxidative DNA damage in human peripheral leukocytes induced by massive aerobic exercise Free Radic

Article

Jan 2002
FREE RADICAL BIO MED

Reactive oxygen species produced during vigorous exercise may permeate into cell nuclei and induce oxidative DNA damage, but the supporting evidence is still lacking. By using a 42 km marathon race as a model of massive aerobic exercise, we demonstrated a significant degree of unrepaired DNA base oxidation in peripheral immunocompetent cells, despite a concurrent increase in the urinary excretion of 8-hydroxy-2'-deoxyguanosine. Single cell gel electrophoresis with the incorporation of lesion-specific endonucleases further revealed that oxidized pyrimidines (endonuclease III-sensitive sites) contributed to most of the postexercise nucleotide oxidation. The oxidative DNA damage correlated significantly with plasma levels of creatinine kinase and lipid peroxidation metabolites, and lasted for more than 1 week following the race. This phenomenon may be one of the mechanisms behind the immune dysfunctions after exhaustive exercise.

IL-6 inhibits apoptosis and retains oxidative DNA lesions in human gastric cancer AGS cells through up-regulation of anti-apoptotic gene mcl-1

Article

Jan 2002

Apoptosis plays a critical role in maintaining genomic integrity by selectively removing the most heavily damaged cells from the population. Reactive oxygen species (ROS) and certain inflammatory cytokines are always elevated during the human carcinogenic process. However, the biological significance of the interplay between ROS and inflammatory cytokine remains elusive. This study demonstrates that interleukin-6 (IL-6) effectively protects gastric cancer cells from the apoptosis induced by hydrogen peroxide (H(2)O(2)). The cell death signaling JNK pathway elicited by H(2)O(2) is also inhibited by IL-6. We further found that Mcl-1, but not other Bcl-2 family members, was up-regulated by IL-6, by a substantial level over 24 h. We further transfected a mcl-1 expression vector, pCMV-mcl-1, into the AGS cells, and successfully obtained several mcl-1-overexpressing clones. Flow cytometric analysis shows that these mcl-1-overexpressing AGS cells are more resistant to the apoptosis induced by H(2)O(2) when compared with the neo control AGS cells. Consistently, the activation of the JNK pathway induced by H(2)O(2) is also blocked in mcl-1-overexpressed cells. These results indicate that the anti-apoptotic effect of IL-6 is, at least in part, due to the up-regulation of mcl-1. To our surprise, either IL-6 exposure or mcl-1 overexpression fails to reduce the level of intracellular peroxides in the AGS cells triggered by H(2)O(2). This study also determined the level of 8-hydroxydeoxyguanosine (8-OH-dGua), an indicator for oxidative DNA lesions in IL-6-treated or mcl-1-overexpressed AGS cells after treatment with H(2)O(2). Notably, our results indicate that a majority of the 8-OH-dGua is efficiently removed in the AGS cells without IL-6 treatment, whereas only approximately 50% of the 8-OH-dGua was repaired in the IL-6-treated AGS cells after 24 h. Similarly, approximately 60-70% of the 8-OH-dGua also failed to repair and was retained in the genomic DNA of the mcl-1 transfectants. Results in this study provide a novel mechanism by which up-regulation of the Mcl-1 protein by IL-6 may enhance the susceptibility to H(2)O(2)-induced oxidative DNA lesions by overriding apoptosis.

Psychological Mediation of a Type of Oxidative DNA Damage, 8-Hydroxydeoxyguanosine, in Peripheral Blood Leukocytes of Non-Smoking and Non-Drinking Workers

Article

Mar 2002

The present study investigates whether the formation of 8-hydroxydeoxyguanosine (8-OH-dG), a known oxidative DNA damage relevant to carcinogenicity, can be associated with psychological factors, in order to clarify the possible stress-cancer linkage from a genetic viewpoint. We performed a cross-sectional study in which we examined the relationships of the levels of 8-OH-dG in peripheral blood leukocytes to various psychological factors, including the Profile of Mood States (POMS) and the Center for Epidemiologic Studies Depression Scale (CES-D) in 38 non-smoking and non-drinking workers (19 males and 19 females). The levels of 8-OH-dG in male subjects were negatively correlated with the Tension-Anxiety scores of the POMS. In contrast, the levels of 8-OH-dG in female subjects were positively correlated with the Depression-Rejection scores of the POMS and the CES-D scores, and negatively associated with the Vigor scores of the POMS, respectively. Male subjects who had self-blame coping strategy displayed significantly high levels of 8-OH-dG. Moreover, the worse the subjective closeness to parents in childhood, the higher the levels of 8-OH-dG became in male subjects. The levels of 8-OH-dG increased reliably in subjects who had experienced the loss of a close family member within 3 years, when compared with non-bereaved subjects. Psychological distress may be associated with cancer risk, although sex difference influences them. Inadequate coping styles, possibly resulting from a poor interpersonal relationship with parents since childhood, and experience of a relatively recent loss of a close family member also appear to influence the pathogenesis of cancer.

Mind and cancer. do psychological factors cause cancer?

Article

Aug 2002
EUR J CANCER

We have reviewed the evidence for an association between major life events, depression and personality factors and the risk for cancer. We identified and included only those prospective or retrospective studies in which the psychological variable was collected independently of the outcome. The evidence failed to support the hypothesis that major life events are a risk factor for cancer. The evidence was inconsistent for both depression and personality factors. Chance, bias or confounding may explain this result, as many of the studies had methodological weaknesses. The generally weak associations found, the inconsistency of the results, the unresolved underlying biological mechanism and equivocal findings of dose-response relationships prevent a conclusion that psychological factors are established risk factors. However, certain intriguing findings warrant further studies, which must, however, be well conducted and large and include detailed information on confounders.

ChemInform Abstract: Chemistry-Based Studies on Oxidative DNA Damage: Formation, Repair, and Mutagenesis

Article

Sep 2002
FREE RADICAL BIO MED

Hiroshi Kasai

Since the discovery of 8-OH-dG formation, various aspects of oxidative DNA damage have been studied. For example, 2-OH-dA and a glyoxal-dG adduct were discovered as new types of oxidative DNA damage; 2-OH-dATP was found to induce mutations and to be a good substrate of a nucleotide sanitization enzyme, the MTH1 protein; and efforts were continued to establish standard methodologies for 8-OH-dG analyses in urine and cellular DNA. By these studies, we found solid chemistry-based approaches were often useful to clarify the biological phenomena.

Effect of Vitamin E and eccentric exercise on selected biomarkers of oxidative stress in young and elderly men

Article

Jul 2003
FREE RADICAL BIO MED

Muscle damage resulting from eccentric exercise provides a useful model of oxyradical-induced injury and can be used to examine age-related responses to oxidative stress. Sixteen young (26.4 +/- 3.3 years) and 16 older (71.1 +/- 4.0 years) healthy men were randomly assigned to 1000 IU/d vitamin E or placebo for 12 weeks and ran downhill for 45 min at 75% VO(2)max, once before and following supplementation. Blood samples were obtained before (baseline) and immediately postexercise (0 h), and at 6, 24, and 72 h postexercise to determine antioxidant status, muscle damage, lipid peroxidation, and DNA damage. Following exercise, young and older men experienced similar increases in serum creatine kinase (CK), F(2alpha)-isoprostanes (iPF(2alpha); p <.001) and malondialdehyde (MDA; p <.01), although iPF(2alpha) peaked at 72 h postexercise and MDA peaked at 0 h. Oxygen Radical Absorbance Capacity (ORAC) decreased at 72 h (p <.01) and correlated with the rise in iPF(2alpha), MDA, and CK in the young men (p <.05). Leukocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG) was unaffected by exercise. Vitamin E decreased peak CK in young men, while in older men it decreased resting levels of iPF(2alpha) and suppressed the 24 h postexercise increases in iPF(2alpha) (p <.05). Thus, vitamin E supplementation induced modest changes eccentric exercise-induced oxidative stress, although differentially between the young and older subjects, while age had no direct influence on these responses among this group of physically fit subjects.

Urso ML, Clarkson PM. Oxidative stress, exercise, and antioxidant supplementation. Toxicology 189, 41-54

Article

Aug 2003
TOXICOLOGY

Cells continuously produce free radicals and reactive oxygen species (ROS) as part of metabolic processes. These free radicals are neutralized by an elaborate antioxidant defense system consisting of enzymes such as catalase, superoxide dismutase, glutathione peroxidase, and numerous non-enzymatic antioxidants, including vitamins A, E and C, glutathione, ubiquinone, and flavonoids. Exercise can produce an imbalance between ROS and antioxidants, which is referred to as oxidative stress. Dietary antioxidant supplements are marketed to and used by athletes as a means to counteract the oxidative stress of exercise. Whether strenuous exercise does, in fact, increase the need for additional antioxidants in the diet is not clear. This review examines the markers used to determine oxidative stress in blood and muscle samples (e.g. lipid peroxidation, expired pentane, malondialdehyde (MDA), F2-isoprostanes, congugated dienes, and 8-hydroxy-2'-deoxyguanosine (8-OhdG)), the changes in oxidative stress markers induced by exercise, and whether athletes require antioxidant supplements.

Depression in Cancer: New Developments Regarding Diagnosis and Treatment

Article

Sep 2003
BIOL PSYCHIAT

Considerable data demonstrate the high prevalence of symptoms of depression in patients with a wide variety of neoplastic disorders. Moreover, the dire consequences of these depressive symptoms in cancer patients have been well documented. Recent conceptual developments in the potential contributing mechanisms include increasing appreciation of the possibility that behavioral alterations in cancer patients may represent a "sickness syndrome" that results from activation of the inflammatory cytokine network. This sickness syndrome, which has been well documented in patients and laboratory animals exposed to inflammatory cytokines, includes symptoms that overlap with those seen in major depression. Conceptualizing these symptoms as components of cytokine-mediated sickness behavior has several important, and potentially novel, implications, including 1) an expansion of the neurobehavioral symptoms that are relevant to diagnosis and treatment; and 2) an increased appreciation of the potential diagnostic utility of peripheral markers of inflammation, as well as cytokine-related neurocircuitry alterations as defined by brain imaging. Treatment implications focus on the pathways by which inflammatory cytokines influence behavior, including therapeutic targets such as the inflammatory cytokines themselves, corticotropin-releasing hormone, and monoaminergic neurotransmitters and their precursors. Finally, recent data suggest that aggressive treatment strategies initiated before inflammation-inducing cancer treatments might prevent behavioral alterations, including depression, before they occur.

Depression and possible cancer risk due to oxidative DNA damage

Abstract

No full-text available

Recommended publications

Selective attention for negative information and depression in schizophrenia

Depressive Symptoms and Resilience among Pregnant Adolescents: A Case-Control Study

The trajectory of negative mood and depressive symptoms over two decades

Assessing subjective sleep reports in the first-degree relatives of antidepressant-treated depressed...