Progress in Neuro-Psychopharmacology and Biological Psychiatry
Oxidative stress in patients with primary insomnia
Highlights
► We have investigated the effects of primary insomnia on oxidative stress markers. ► Thirty patients with primary insomnia and 30 healthy volunteers were evaluated. ► GSH-Px, SOD, and MPO activities and levels of GSH and MDA were measured. ► The patients had significantly lower GSH-Px activity and higher MDA levels. ► These findings seem to have implications for future sleep research.
Introduction
Sleep is one of the most important factors contributing to health; however, insomnia is among the most prevalent health complaints in both the general population (LeBlanc et al., 2009, Morin et al., 2006) and some psychiatric samples (Gulec et al., 2011). Approximately one third of the general population suffers from at least one insomnia symptom (Bixler et al., 1979, Klink and Quan, 1987, Klink et al., 1992, Mallon et al., 2000, Quera-Salva et al., 1991, Welstein et al., 1983), and about 6% (Ohayon, 1997, Ohayon, 2001, Ohayon and Sagales, 2010, Ohayon and Smirne, 2002, Ohayon et al., 1997) meet the diagnostic criteria for insomnia of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 4th edition (APA, DSM-IV-TR, 2000). These studies on the epidemiology of insomnia were conducted in North America and various European countries. DSM-IV qualifies primary insomnia here as a complaint of difficulty initiating or maintaining sleep or of poor quality sleep, lasting for a period of at least a month. The diagnosis of primary insomnia requires exclusion of the direct physiological effects of a substance or general medical condition. Moreover, primary insomnia should not occur during the course of a mental disorder or other sleep disorder.
It is well known that oxidative stress is one of the factors that contribute to an increase in the speed of the cell cycle and consequent premature cell death, leading to many degenerative disorders, as well as psychiatric disorders (Herken et al., 2001, Savas et al., 2002, Tsaluchidu et al., 2008). Many physiological and pathological processes, such as aging, infections, environmental toxins, emotional or psychological stress, ionizing radiation, cigarette smoke, and alcohol increase the bodily concentration of oxidizing substances, known as free radicals (Ozkol et al., 2011b, Tsaluchidu et al., 2008). Free radicals that originate from molecular oxygen are generally named reactive oxygen species (ROS). These free radicals exert physiological and pathological effects by many different mechanisms, such as activation of phagocytes and the general immune system, lipid peroxidation, the electron transport system in mitochondria, ischemia, and trauma (Halliwell and Gutteridge, 2000). Oxidative stress occurs whenever there is an imbalance between oxidant production and antioxidant defenses, either because the production is increased or because the defenses are decreased, or both (Gopalakrishnan et al., 2004, Ozkol et al., 2011a). Primary antioxidant defense is provided by enzymes that can prevent uncontrolled formation of free radicals, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) (Halliwell and Gutteridge, 2000). Because of their short half-lives, free radicals can be evaluated indirectly by measuring some antioxidant enzyme activities, such as SOD, CAT, or GSH-Px, byproducts of lipid peroxidation, such as malondialdehyde (MDA), or some transition metal levels, such as copper, zinc, and iron (Leff, 1994).
Both sleep alterations and oxidative stress have been related to some kinds of psychopathologies. Sleep problems here are likely to play an important role in genesis and maintenance of the many psychiatric disorders, especially mood disorders (Gulec et al., 2011). Also, oxidative stress was considered to be associated with schizophrenia, mood disorders, obsessive–compulsive disorder, and panic disorder (Atmaca et al., 2008, Herken et al., 2006). These findings lead to speculation that the central nervous system is vulnerable to oxidative stress- and sleep disturbance-mediated injuries which might underlie the majority of mental disorders.
It has been proposed that cerebral free radicals accumulate during wakefulness and are removed during sleep (Reimund, 1994). Moreover, it has been claimed that removal of excess free radicals during sleep is accomplished by the decreased rate of formation of free radicals and increased efficiency of endogenous antioxidant mechanisms. However, the association between oxidative stress and sleep disorders still remains unclear. Studies of oxidative stress in clinical sleep research primarily have focused on obstructive sleep apnea syndrome (OSAS), a disorder marked by recurrent nocturnal obstruction of the upper airway, which leads to hypoxia and re-oxygenation (Ozturk et al., 2003, Schulz et al., 2000). It is well documented that oxidative stress in sleep apnea is produced by recurrent episodes of ischemia-reperfusion injury (Everson et al., 2005, Katsoulis et al., 2011, Lavie, 2003). To the best of our knowledge, there has not yet been a study evaluating the association between primary insomnia and oxidative stress. Therefore, for the first time in the literature, we aimed to investigate whether there is a correlation between primary insomnia and oxidative stress.
Section snippets
Patients and study design
The present study was conducted over a 12-month span, from March 2010 until March 2011, in the city of Van, Turkey. The participants of the study were (i) 30 primary insomnia patients and (ii) 30 healthy controls.
The primary insomnia diagnoses of the participants were made according to DSM-IV criteria via structured clinical interviews at the Psychiatric Outpatient Clinic of Yuzuncu Yil University Hospital. Primary insomniac participants were interviewed by an experienced psychiatrist, using
Results
The primary insomniac participants were 17 women and 13 men, with a mean age of 38.7 years (SD = 1.8; range 36–42). The healthy controls were 16 women and 14 men, with a mean age of 38.6 years (SD = 2.8; range 34–46). There were no significant differences between the groups in terms of gender, age, marital status, or mean educational level (p > 0.05). Descriptive statistics for controls and participants with primary insomnia are presented in Table 1.
Table 2 demonstrates MPO, GSH-Px, and SOD activities,
Discussion
In this study, for the first time in the literature, we investigated the effects of primary insomnia on certain oxidative stress biomarkers. Our results show that participants with primary insomnia had significantly lower GSH-Px (selenium-containing antioxidant enzyme) activity and higher MDA (an end-product of lipid peroxidation) levels, compared with the controls. In addition, it was found that poor sleep quality gave rise to higher levels of MDA concentrations as an oxidative stress factor,
Conclusion
In conclusion, these results may indicate the important role of sleep in renewing antioxidant defense systems; however, the sample size was not large enough to make definite conclusions. Further studies of larger groups are required to confirm or challenge our findings. In spite of these limitations, our findings provide suggestive evidence of the relationship between insomnia and oxidative stress, and they seem to have implications for future sleep research.
Acknowledgments
The authors disclosed no proprietary or commercial interest in any product mentioned or concept discussed in this article. And, we would like to thank Research Assist. Murat Boysan from Yuzuncu Yil University, Faculty of Arts and Science, Department of Psychology for the support in the statistical issues.
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