ReviewWhat you eat is what you are – A role for polyunsaturated fatty acids in neuroinflammation induced depression?
Section snippets
Inflammation and depression
Inflammatory disorders such as myocardial infarction are associated with unusually high levels of depressive disorder.1 Clinical studies show that 20% of individuals develop major depressive disorder within 18 months of myocardial infarction, while 65% experience depressive episodes.2 Pooled estimates reveal that at least one third of stroke survivors also experience clinical depression3, 4 compared to 13% of the control population.4 To date, the reasons why inflammatory conditions are
Polyunsaturated fatty acids (PUFAs)
PUFAs are dietary lipids found in cell membranes, most abundantly in the central nervous system.14 Structurally, PUFAs are those essential fatty acids containing two or more double bonds, or carbon atoms capable of bonding to two or more hydrogen atoms. The number of carbon atoms determines the length of the fatty acid chain. Short-chain essential fatty acids, containing 18 or less carbons, serve as a substrate for the more biologically active longer chain fatty acids, which contain 20 or more
PUFAs and apoptosis
PUFAs are widely acknowledged to influence cell death and are neuroprotective at optimal doses.11 In cultured cells AA and LA inhibit apoptosis at doses of 10 μg,11 while EPA inhibits cell death at doses of 10 μg–40 μg11, 29, 88 DHA reduces apoptosis at doses of 5, 10, 20, 25 and 50 μg after 24 h of incubation11, 88, 89, 90 and at doses of 25 μg and 0.5 lM after 48 h.56, 91 Human studies also confirm that 2 weeks of DHA (400, 800 mg) supplementation reduces apoptosis in monocytes of healthy
PUFAs and excitotoxicity
Inflammatory conditions are coupled with a high occurrence of excitotoxic cell death.102, 103 Excitotoxicity is a glutamate driven necrotic form of neuronal cell death104 associated with excessive intracellular calcium (Ca2+) influx105 and the induction of downstream apoptosis.106 In vitro cell culture studies reveal excitotoxicity associated intracellular Ca2+influx which results in the release of inflammatory ω-6 AA.107, 108 Arachidonic acid (AA) acts to potentiate Ca2+ sensitive N-methyl-d
Future directions and conclusions
Given the regulatory role of cytokines in mediating intrinsic apoptotic pathways and the association between apoptosis and depression,8, 9 it is not surprising that inflammatory conditions are associated with unusually high levels of clinical depression.4 Omega-3 PUFAs that have immune modulating properties are also capable of inhibiting cytokine activity suggesting that increasing the consumption of ω-3 comparative to ω-6 shifts the production of eicosanoids away from those with potent
Statement of authorship
The authors’ responsibilities were as follows—MCP, SGC, LMC, DPC: contributed to the conception and design of the manuscript, MCP, SGC: contributed to the literature search, and interpretation of data; MCP: wrote the manuscript; and SGC, LMC, DPC: critically appraised the manuscript.
Disclosure/Conflict of interest
The authors declare no conflict of interest.
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Traditional Brazilian diet and extra virgin olive oil reduce symptoms of anxiety and depression in individuals with severe obesity: Randomized clinical trial
2021, Clinical NutritionCitation Excerpt :Another difference is the study type, i.e. the PREDMED is a cohort study and the DieTBra Trial is a randomized clinical trial. Together with other studies that reported an association between a pro-inflammatory diet and risk of depression [44,45], the results herein strengthen the idea that diets with healthy profile, in addition to the health benefits already known, lead to positive effects on depression symptoms [46]. Although the physiological mechanisms involved are not completely clear, pro-inflammatory foods such as those rich in saturated fats may induce the release of pro-inflammatory cytokines impairing the activity of the dopaminergic system, while the intake of monounsaturated fats improve brain function [47].
DHA, EPA and their combination at various ratios differently modulated Aβ<inf>25-35</inf>-induced neurotoxicity in SH-SY5Y cells
2018, Prostaglandins Leukotrienes and Essential Fatty AcidsThe role of n-3 polyunsaturated fatty acids (n-3PUFAs) in affective disorders
2017, Journal of Affective DisordersCitation Excerpt :In this line, Paterniti et al. (2014) showed that supplementation with DHA reduced Bax expression in the brain tissues of mice. Moreover, previous studies suggested that pro-inflammatory cytokines appear to contribute to depression-associated cell death through intrinsic apoptotic pathways and that neurotoxic free radicals are a second apoptosis-mediating factor associated with depressive disorder (Paterniti et al., 2014; Pascoe et al., 2011; Mergenthaler et al., 2004). Finally, EPA supplementation has been associated with N-acetyl-aspartate (NAA) increase.
Polyunsaturated fatty acid composition and childhood adversity: Independent correlates of depressive symptom persistence
2017, Psychiatry ResearchCitation Excerpt :In addition, most PUFAs in the omega-3 series are anti-inflammatory, while those in the omega-6 series are pro-inflammatory (Calder, 2006). A balance in the PUFAs favoring the omega-6 component is therefore associated with increases in pro-inflammatory cytokines and, as an apparent consequence, with increased risks for depressive symptoms (Pascoe et al., 2011). PUFA measurements at one point reflect not only an individual's concurrent dietary habits, but also that person's activity of desaturases and elongases, enzymes responsible for the interconversion to effector omega-3 and omega-6 fatty acids (Lemaitre et al., 2011).
Longitudinal relationship of diet and oxidative stress with depressive symptoms in patients with metabolic syndrome after following a weight loss treatment: The RESMENA project
2014, Clinical NutritionCitation Excerpt :Several studies have evaluated the potential links between depression and metabolic syndrome (MetS), which have revealed that both diseases share several underlying metabolic pathways.2 In this sense, inflammatory processes play a significant role in both MetS and depression, and this has led to an increased interest in the study of pro-inflammatory cytokines.3 Also, a relationship between MetS and oxidative stress has been established,4 and some evidence suggests that oxidative stress is also linked to depression as higher concentrations of oxidative stress biomarkers have been found in depressed subjects.5,6
Dietary patterns are associated with the prevalence of elevated depressive symptoms and the risk of getting a hospital discharge diagnosis of depression in middle-aged or older Finnish men
2014, Journal of Affective DisordersCitation Excerpt :High consumption of vegetables and fruits (Jacka et al., 2010; Nanri et al., 2010) and fish (Astorg et al., 2008; Tanskanen et al., 2001; Timonen et al., 2004) has been associated with reduced likelihood of depressive disorders. A healthy, vegetable- and fish-oriented diet may beneficially modulate inflammatory and oxidative processes, brain plasticity, synthesis of monoaminergic neurotransmitters, brain cell membrane functions and the stress-response system (Jacka et al., 2011; Pascoe et al., 2011; Su, 2009). Depressed patients assigned to Mediterranean diet were found to have elevated plasma brain-derived neurotrophic factor (BDNF) concentrations compared to patients assigned to a control diet (Sanchez-Villegas et al., 2011), which suggests that diet potentially also influences factors related to neurogenesis.