The Role of Inflammation and Oxidative Stress on Depression and Affective Disorders

Depression and other affective disorders may be attributed to or worsened by chronic inflammation and oxidative stress in the brain according to several studies. Our bodies work in a system of checks and balances to maintain homeostasis. When the environment shifts from an antioxidant to a prooxidant one, this is what is referred to as oxidative stress. Oxidation occurs from byproducts of chemical reactions called free radicals or reactive oxygen species (ROS) for oxygen-mediated reactions. ROS  can alter cellular membranes affecting neurotransmitter signaling, lead to mitochondrial dysfunction and cause cellular death and recruit more inflammatory markers. Oxidative stress has also been hypothesized to cause telomere shortening, or shortening of DNA fragments, associated with aging and mood disorders such as schizophrenia, anxiety and affective disorder.¹

While taking in dietary or supplemental forms of antioxidants may favor an antioxidant environment and therefore improve symptoms of depression, it is imperative to first identify and remove prooxidant exposures to the best of one’s ability. Of course things like pollution might be difficult to avoid, but smoking, alcohol, pesticides, processed foods, sugar and charred meats and vegetables are all things that can be avoided, if not limited so as to not overburden an already burdened system. The best and easiest way to begin to increase antioxidants in the body is through diet. Foods rich in pigment and color contain flavonoids, such as proanthocyanidins and polyphenols that are mostly found in fruits and vegetables. Compounds found in green tea, turmeric root, ginkgo biloba and pine were further studied for their respective antioxidant and anti-inflammatory effect on the brain in regard to depression. 

Epigallocatechin gallate, or EGCG found in green tea, lowered inflammatory cytokines such as interleukin-6 and nitric oxide which was likely responsible for the marked antidepressant activity expressed by mice.² Curcumin, a compound found in turmeric, prevented lipid peroxidation (damage to cellular membranes), inhibited reduction of brain derived neurotrophic factor and serotonin metabolites thereby normalizing serotonin and dopamine levels in the brain.¹ A compound found in the ginkgo tree leaves called EGb761, improved sleep quality while reducing early awakenings often seen in depression.¹ Pycnogenol’s antioxidant effect, found in pine, was shown to reduce symptoms of attention deficit hyperactivity disorder.¹ Some minerals, amino acids and healthy fats also contain antioxidant and anti-inflammatory effects that may be useful in improving symptoms of depression.

N-acetylcysteine, or NAC, is a potent antioxidant that feeds into the glutathione pathway to detox the body from noxious toxins and free radicals. NAC was shown to reduce depression severity by improving the efficacy of antidepressant medications.¹ Magnesium deficiency can lead to mild inflammation, increase in ROS and nitric oxide and worsen symptoms of depression, especially in the elderly.¹ Selenium, an antioxidant mineral that promotes thyroid health can lower the probability of postpartum depression. However, too much selenium can have a counter effect.¹ A deficiency in the mineral, zinc can lead to cognitive decay as zinc promotes brain derived neurotrophic factor expression. It’s deficiency may also cause oxidative stress but a careful balance is also required as too much zinc may deplete copper levels.¹ 

Polyunsaturated fatty acids such as omega-3s exhibit anti-inflammatory effects which were found to be significantly depressed in depressed patients.¹ The standard American diet is rich in the inflammatory fatty acids such as trans-fats and omega-6 fatty acids which feed into the inflammatory arachidonic acid pathway. Improvements in cognition were seen just by eating fish once/week.¹ Not only are these healthy fats anti-inflammatory and antioxidant, one of the components of fish oil called docosahexaenoic acid, or DHA is responsible for the proper transfer of neurotransmitters such as dopamine, serotonin and norepinephrine.¹ 

By having a whole-foods based diet rich in antioxidants, the symptoms of depression and other affective disorders may be lessened if not prevented according to these studies. 


  1. PMID: 26078821
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