DEPRESSION, AGGRESSION AND EFAS

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Several lines of research have established an association between major depressive disorders and omega-3 fatty acids in adults (Logan, 2003). Fish and seafood are the main dietary source of omega-3 PUFAs, and irregular fish intake cross culturally is linked with depression in epidemiological studies (Sontrop & Campbell, 2006). Research in this area has focused on links between specific nutrients and depression. The most studied nutrients, and for which the evidence is strongest, is omega-3 fatty acids and folic acid (Peet et al, 1998; Papakostas, Petersen, Mischoulon, Green, Nierenberg et al, 2004). High levels of fatty acids lead to an increase in the fluidity of membranes which in turn increases the transport of serotonin into the endothelial cells (Block & Edwards, 1987). People suffering from depression are reported to have reduced serotonin uptake (Block & Edwards, 1987) and therefore the role of fatty acids in depression has important implications.

The only placebo-controlled double-blind, pilot study to investigate EFAs and childhood depression was carried out by Nemets, Nemets, Apter, Bracha and Belmaker (2006). They recruited 28 children and randomised them into groups to receive one 1000 g of fish oil containing 190 mg EPA and 90 mg of DHA (active supplement) or placebo containing olive oil. Participants were recruited via the depression clinic or child psychiatry clinic in Israel.
Supplementation lasted 16 weeks and assessments of depression using the Childhood Depression Rating Scale (CDRS), Childhood Depression Inventory (CDI) and Clinical Global Impression (CGI) were taken at baseline, 2, 4, 8, 12 and 16 weeks. From the 28 children recruited, 20 completed at least 1 month’s ratings and were included in the data analysis (n=10 active and n=10 placebo). The results found highly significant effects of omega-3 fatty acids on self-rated symptoms of depression using the CDRS, CDI and CGI concluding that they may have therapeutic benefits in childhood depression. Further research is needed with larger sample sizes to replicate these findings

Affective impairment seen in attention deficit hyperactivity disorder (ADHD) may underlie co-morbid depression, anxiety and/or conduct disorder. Low levels of LC-PUFA, specifically omega-3 fatty acids in blood measures have been linked to a range of behavioural and mood disorders including ADHD. However, little is known about the relationship between omega-3 and brain function in humans. A recent study by Gow and colleagues found
that total red blood cell concentrations of omega-3 fatty acids are associated with emotion elicited neural activity in twenty adolescent boys with ADHD (Gow, Matsudaira, Taylor, Crawford, Ghebremeskel, Ibrahimovic, Vallée-Tourangeau, Williams & Sumich, 2009). They assessed the total lipid fractions in the red blood cells of the young boys (aged 12-16 years old) and their event-related potential (ERP) response to the presentation of facial expressions of happiness, sadness and fearfulness. The results supported the hypothesis of a positive association between EPA and a cognitive bias in orientation to overt expressions of happiness over both sad and fearful faces as indexed by midline frontal P300 amplitude. Additional exploratory analyses revealed a positive association between levels of DHA as well as the AA/DHA ratio and the right temporal N170 amplitude in response to covert expressions of fear. These findings indicate that EPA and DHA may be involved in distinct aspects of affect processing in ADHD and have implications for understanding currently inconsistent findings
in the literature on EFA supplementation in ADHD and depression (Gow et al., 2009).

Clinical Trials with EFAs in Adults

Although, the research in EFAs and depression in children is limited it is pertinent to mention the clinical investigations in this area with adults with depression due to the implications they hold for future research. The potential benefit of omega-3’s (specifically high EPA supplementation) has been explored as an adjunct to treatment with medication in adults. For example, Peet and Horrobin (2002) recruited patients with depression whose initial experience with antidepressant medication had been unsuccessful and gave them 1, 2, or 4g of ethyl-EPA. Those patients taking ethyl-EPA showed a significant improvement compared to those on placebo (see also Sontrop & Campbell, 2006 for a review; DeMar, Bell, Igarashi, Greenstein & Rapoport, 2006, for evidence supporting the link between EFA and depression in animals) A very strong negative correlation between fish consumption and global prevalence of major depression has been reported recently in The Lancet. Germany, Canada and New Zealand had the highest prevalence of depression and Japan the lowest (Hibbeln, 2007; NIAAA; Lancet, 1998). Iceland is also reported to have a very low incident of depression which could be due to the country’s overall very high consumption of fish (approximately 225 lbs per person per year) as per Japan (147lbs per person per year; Cott & Hibbeln, 2001). A recent placebo controlled double blind study by Jazayeri and colleagues recruited patients with depression (aged 20-59). The patients met the DSM-IV criteria for major depressive disorder without psychotic features and were randomised into 3 groups to receive 2 capsules of (i) (1000 mg) of EPA plus fluoxetine placebo, (ii) 1 fluoxetine capsule (20 mg fluoxetine) plus ethyl-EPA placebo, or (iii) 2 ethyl-EPA soft gels (1000 mg EPA) plus 1 fluoxetine capsule (20 mg fluoxetine) for 8 weeks. Psychiatric assessments were carried out at weeks 2, 4, 6, and 8. Compliance was set at 90% of consumption of the medication. Results showed that the fluoxetine and EPA combination was significantly better than fluoxetine or EPA alone. Fluoxetine and EPA appeared to be equally effective in controlling depressive
symptoms. Treatment was shown to have an effect at both weeks 4 and 6. Response rates ( > 50% decrease in baseline Hamilton Depression Rating Scale) were 50%, 56% and 81% in the fluoxetine, EPA and combination groups respectively. These findings suggest that EPA had equal therapeutic benefits to fluoxetine but was superior as an adjunctive treatment with fluoxetine. The authors suggested that the consumption of dietary supplements may be more acceptable to patients than antidepressants. Furthermore, because major depression is also a risk factor for cardiovascular disease, supplementation with EPA may be of mutual benefit, reducing inflammatory cytokines and controlling depressive symptoms. Larger trials are needed to replicate these findings (Jazayeri, Tehrani-Doost, Keshavarz, Hosseini, & Djazayery et al., 2008). Other studies have been conducted investigating the efficacy of omega-3 to aggression (which is comorbid with depression and anxiety) and psychopathic disorders. For example, Gesch, Hammond, Hampson, Eves, and Crowder (2002) examined the effect of supplementary essential fatty acids (in conjunction with a vitamin supplement) in a young adult UK prison (aged 18 – 21 years) population using a randomised, double blind design.

The aim of the study was specifically to investigate whether alterations in diet by way of supplementation could reduce anti-social behaviours among inmates. Two hundred and thirty one young offenders took active (1260 mg linoleic acid, 160 mg gamma linolenic acid, 80 mg eicosapentaenoic acid and 44 mg docosahexaenoic acid) or placebo supplementation for an average period of 142 days. The results revealed a marked reduction in anti social behaviour and violent offences for active versus placebo. It was concluded that the supplementation of
vitamins, minerals and essential fatty acids reduces anti-social behaviour in a prison population (Gesch et al., 2002).
The work of Gesch and colleagues (2002) investigating the link between diet and aggression is also supported by others. Itomura and colleagues, (2005) carried out a randomised, placebo-controlled, double blind trial in Japan. They reported a reduction in physical aggression following supplementation of fish oil (3600 mg of DHA, 840 mg of EPA in fortified foods) in school children aged 9 -12 years of age (Itomura, Hamazaki, Sawazaki,
Kobayashi, Terasawa, Watanabe & Hamazaki, 2005). In the USA, Schoenthaler (1983) carried out an experimental study substantially reducing the sugar content in the diets of 3000 imprisoned juveniles. Instead, the young offenders were given healthier snack options containing reduced sugar and refined foods. The results of the study over a 12 month period showed a 21% reduction in antisocial behaviour, 25% reduction in assaults, 75% reduction in physical restraints by staff and a 100% reduction in suicides (Schoenthaler, 1983). In a similar
study by the same author with 402 Californian prisoners those given 100% of the U.S. recommended daily allowance of vitamins committed fewer offences than those given 300% implying that the correct dose is crucial for optimum brain function (Schoenthaler, 1983).

Suicide Risk and Trends

Suicide trends among youths in the United States were reported to have increased by 18 percent during the year 2003 to 2004 (Bridge, Greenhouse, Weldon, Campo, Kelleher et al., 2008). Furthermore, questions have been raised concerning the safety and efficacy of both anti-depressant medication, and selective serotonin reuptake inhibitors (SSRIs), and the potential increased risk of suicidal thoughts and behaviour in young people (Moller, Baldwin, Goodwin, Kasper, Okasha et al., 2008). The link between mental health and nutrition in children is not well documented and investigations need to be undertaken to establish whether there is an association between nutrition and suicide risk in children. An elevated ratio of omega- 6/omega- 3 EFAs has however been found to predict the risk of suicide behaviour in depressed adult patients (Sublette, Hibbeln, Galfalvy, Oquendo & Mann, 2006). Sublette et al., (2006) measured the plasma levels of polyunsaturated fatty acid in the phospholipids in 33
medication-free depressed patients and monitored them for suicide attempts over a 2-year timeframe. On follow up, 7 patients in this group attempted suicide. A low DHA percentage, low omega-3 status and higher omega-6/omega-3 ratio of lipid profile predicted risk of suicidal behaviour. The authors concluded that low omega-3 fatty acids may adversely affect serotonergic and corticotrophic function, resulting in a greater susceptibility to suicide
(Sublette et al., 2006).

Mild Depression in Young People

Crowe, Murray, Skeaff, Green, and Gray, (2007) explored the relationship between the levels of omega-3 LC-PUFA in serum phospholipids and scores of self-reported mental and hysical well-being among adults and adolescents living in New Zealand. The study employed the short-form (SF-36) which is not a diagnostic tool for depression but rather assesses the mental and physical well being of a population. This study used data collected from the 1997 National Nutrition Survey which was a population-based survey that assessed the health status, health risk behaviours and health services in young adults aged 15 years and over. The 36 items were grouped into 8 scales that evaluate physical functioning (e.g., bodily pain and general health) and mental health (e.g., social functioning, limitations due to emotional health). The scales were standardised and aggregated by factor analysis to form a ental component and physical component score with a mean of 50 (SD = 10). The general health questionnaire also included 10 questions which constitute the Alcohol Use Disorders Identification Test. This test evaluates the consumption of alcohol and drinking behaviour over the past year. Values are ranked between, the lowest ‘abstainers’ and the highest ranking classification of ‘potential hazardous drinkers’. Multiple linear regression analyses were employed to examine the relation between key fatty acid indices and the mental and physical components.

The results showed significant inverse relationships for the proportion of women, those who had visited a mental health professional in the past 4 weeks across the quintiles of EPA.

Lower levels of DHA were related to the proportion of hazardous drinkers. There were no significant relationships across the quintiles of DHA for the physical or mental component scores. Over all, the results of this survey suggested that the amount of EPA and the ratio of EPA to AA in serum phospholipids were positively associated with self-reported physical well-being and there was a positive relationship between the ratio of EPA to AA and selfreported mental well-being. The authors concluded that higher levels of EPA may be a proxy for a diet with higher fish consumption which in turn was linked to increased rating of physical health. The results of this study are consistent with experimental evidence which shows that EPA is a better inhibitor than DHA of the synthesis of series-2 and series-4 leukotrienes from AA. The association has a solid biological plausibility and therefore deserves further investigation (Crowe et al., 2007). The American Psychiatric Association recently reviewed the evidence in this area and formulated several recommendations for the use of omega-3 fatty acids. Namely, 1) that all adults should eat 2 portions of fish per week; 2) patients with mood, psychotic disorders or impulse control should consume 1 to 9 grams of EPA and DHA per day; and 3) supplementation should be considered in patients with mood disorders (between 1 to 9 grams) with doses over 3 grams per day monitored by a physician (Freedman et al., 2006). Recommendations by the Food Standards Agency regarding fish consumption for children less than 16 years of age are currently set at 2 portions of fish per week, one of which should
be oily. However, children under 16 are advised not to eat shark, marlin and swordfish due to potential risk of mercury contamination.

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