LC-PUFA’s and mental health outcomes: the role of overall diet quality, genetic susceptibility and fatty fish intake

Fatty fish is a component of a healthy diet, and is included in dietary guidelines for both children/adolescents and adults. Dietary fatty fish provides long-chain poly-unsaturated fatty acids (LC-PUFA’s) that are important for brain development and brain functioning. LC-PUFA intake by means supplement use has been implicated in a wide range of beneficial mental health outcomes, including better cognitive performance in children after adequate maternal intake during pregnancy [1], reduction of inattention [2] and/or oppositional problems [3] in children and adolescents, reduction of depressive symptoms in adults [4], and better cognitive functioning in the elderly [5]. Unfortunately, there are a number of methodological problems with the available studies. Most importantly, clinical trials in small groups typically fail to replicate in larger samples. A Cochrane review on the role of LC-PUFA’s in depression found that the available evidence was of very low quality, and that there were strong indications for publication bias [6]. Observational studies of fatty fish intake rather than supplements are typically performed in larger samples, but those are mostly cross-sectional. Some find modest associations between LC-PUFA intake and mental health outcomes (e.g. [7][8]). However, most of these studies poorly address potential confounders, most importantly age, overall diet quality and socio-economic status.
The absence of strong associations between LC-PUFA intake and mental health outcomes at the group level may suggest individual differences: LC-PUFA intake might prove beneficial for some individuals, but not for others. In studies of diabetes [9], cardiovascular disease [10] and obesityrelated traits [11], LC-PUFA supplementation was shown to be beneficial in people carrying minor/variant alleles in the FADS1-2 and ELOVL2-5 gene clusters, but less so in people carrying the regular haplotypes. These effects are mediated by altered blood serum LC-PUFA levels, which are highly heritable [12]. FADS1-2 and ELOVL2-5 gene clusters code fatty acids desaturase  and elongase enzymes, that convert LA to DPA and EPA to DHA. Variants in these gene clusters have also been associated with depression [13], bipolar disorder [14], white matter development [15] and inflammatory diseases [16]. It is therefore interesting to investigate whether genetic risk score for serum LC-PUFA levels interact with LC-PUFA intake to determine mental health outcomes.