Antioxidants as Antidepressants

Abstract

Depression is a medical condition with a complex biological pattern of aetiology, involving genetic and epigenetic factors, along with different environmental stressors. Recent evidence suggests that oxidative stress processes might play a relevant role in the pathogenic mechanism(s) underlying many major psychiatric disorders, including depression. Reactive oxygen and nitrogen species have been shown to modulate levels and activity of noradrenaline (norepinephrine), serotonin, dopamine and glutamate, the principal neurotransmitters involved in the neurobiology of depression. Major depression has been associated with lowered concentrations of several endogenous antioxidant compounds, such as vitamin E, zinc and coenzyme Q10, or enzymes, such as glutathione peroxidase, and with an impairment of the total antioxidant status. These observations introduce new potential targets for the development of therapeutic interventions based on antioxidant compounds. The present review focuses on the possible role of oxidative stress processes in the pathogenesis of depression. The therapeutic potential of antioxidant compounds as a co-adjuvant treatment to conventional antidepressants is discussed. For instance, N-acetyl-cysteine has been shown to have a significant benefit on depressive symptoms in a randomized placebo-controlled trial. Additionally, curcumin, the yellow pigment of curry, has been shown to strongly interfere with neuronal redox homeostasis in the CNS and to possess antidepressant activity in various animal models of depression, also thanks to its ability to inhibit monoamine oxidases. There is an urgent need to develop better tolerated and more effective treatments for depressive disorders and several antioxidant treatments appear promising and deserve further study.

Atypical antidepressants extend lifespan of Caenorhabditis elegans by activation of a non‐cell‐autonomous stress response

“…Consistent with our findings that Mianserin protects from oxidative stress in C. elegans , antidepressant treatment in rodents suppresses the accumulation of oxidative stress markers MDA and 4‐HNE generated by restraint stress in rodents (Abdel‐Wahab & Salama, 2011; Maes et al ., 2011; Spiers et al ., 2013). Similarly, patients suffering from major depression show increased oxidative damage and reduced antioxidant capacity in the blood (Scapagnini et al ., 2012). …”

“…In contrast to aging, where the role of oxidative stress has been de‐emphasized in recent years, oxidative stress has been gaining increased attention as a pathogenic mechanism underlying several major psychiatric disorders, including psychosis and depression (Scapagnini et al ., 2012; Pandya et al ., 2013). Behavioral paradigms in rodents that are depressogenic (e.g., restraint stress, forced swim test) increase lipid peroxidation in several tissues (Sahin et al ., 2004; Lucca et al ., 2009; Runkel et al ., 2013; Spiers et al ., 2013).…”

Obesity and psychiatric disorders: Commonalities in dysregulated biological pathways and their implications for treatment

“…Potentially, suffering from both conditions may increase neuroprogressive pathways and lead to worsening treatment outcomes, relapse or treatment resistance. Adjunct interventions that may be considered include the addition of anti-inflammatory drugs such as COX-2 inhibitors (Muller and Schwarz, 2008) and the TNF antagonist, infliximab (Raison et al, 2013), medications with neuroprotective properties (e.g., antidepressants, mood stabilisers) (Dodd et al, 2013, Malhi et al, 2012, herbs and nutrients with anti-inflammatory and antioxidant properties (e.g., curcumin, resveratrol, omega-3 fatty acids, green tea, n-acetyl cysteine, CoQ10, selenium, zinc, alpha lipoic acid and vitamins such as A, C and E) (Alappat and Awad, 2010, Floyd, 1999, Kim et al, 2008, Lopresti et al, 2012, Scapagnini et al, 2012 and lifestyle changes known to enhance neurogenesis (e.g., sleep hygiene interventions, meditation, yoga, relaxation therapies and exercise) (Doraiswamy and Xiong, 2007, Kiecolt-Glaser et al, 2010, Lopresti et al, 2013.…”

Curcumin for the treatment of major depression: A randomised, double-blind, placebo controlled study

“…Consequently, this has sparked interest in compounds that target these pathways. Examples include anti-inflammatory treatments influencing immuno-inflammation such as cyclooxygensase-2 (COX-2) inhibitors, aspirin, minocycline and polyunsaturated fatty acids (Berk et al, 2013a, Fond et al, 2014, Muller, 2013 and antioxidant therapies to increase antioxidant defences and lower free radical damage such as n-acetyl cysteine, Ebselen, vitamin E and coenzyme-Q 10 (Berk et al, 2013b, Scapagnini et al, 2012. Interestingly, despite pharmaceutical antidepressants originally being heralded as targeting monoaminergic actions, there is also evidence that they can modulate immuno-inflammation, reduce oxidative stress, enhance neurotrophic factors and influence HPA activity (Abdel-Wahab and Salama, 2011, Andrade and Rao, 2010, Hannestad et al, 2011, Kocki et al, 2012, Schule, 2007.…”