Food and Behaviour Research

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Association of Fatty Acid Desaturase Genes with Attention-Deficit/Hyperactivity Disorder

Brookes KJ, Chen W, Xu X, Taylor E, Asherson P. (2006) Biol Psychiatry. 60(10): 1053-61 

Web URL: View this and related abstracts via PubMed here

Abstract:

BACKGROUND: Fatty acids, in particular omega-3 fatty acids, have been found to affect behavior and cognition both directly and indirectly. Evidence to suggest a link with attention-deficit/hyperactivity disorder (ADHD) derives from three key areas: 1) animal dietary restriction studies observed increased locomotive hyperactivity and reduced cognitive ability in offspring; 2) animal dietary studies indicate alterations in the dopamine pathway; and 3) human studies report reduced plasma omega-3 fatty acids in ADHD subjects.

METHODS: We investigated three genes that encode essential enzymes (desaturases) for the metabolism of fatty acids by scanning for genetic association between 45 single nucleotide polymorphisms (SNPs) and ADHD.

RESULTS: Our findings suggest a significant association of ADHD with SNP rs498793 (case-control p = .004, odds ratio (OR) 1.6, 95% confidence interval (CI)1.15-2.23; transmission disequilibrium test (TDT) p = .014, OR 1.69) in the fatty acid desaturase 2 (FADS2) gene. As alcohol is known to decrease the activities of these desaturase enzymes, we also tested for interactions between ADHD subjects' genotypes and maternal use of alcohol during pregnancy. Two SNPs in the fatty acid desaturase 1 (FADS1) gene were nominally associated with ADHD only in the prenatal alcohol-exposed group of children; formal test for interaction was not significant.

CONCLUSIONS: These preliminary findings are suggestive of an association between FADS2 and ADHD.

FAB RESEARCH COMMENT:

Over 25 years ago, the UK Hyperactive Children’s Support Group first proposed that a lack of key omega-3 and omega-6 fatty acids could play a part in ADHD. (Colquhoun and Bunday, 1981).

They specifically suggested that ADHD children might have particular difficulty converting omega-3 and omega-6 essential fatty acids (EFA) into the highly unsaturated fatty acids (HUFA) that are most important to the brain. If so, they argued that adding the appropriate fatty acids to their diets might help these individuals.

As reviewed elsewhere (Richardson, 2006). blood biochemical studies since then have provided some support for this proposal; and so have some of the few treatment trials to date, although more evidence is still needed. But these studies couldn't show whether any apparent fatty acid deficiencies in ADHD were the result of dietary differences or constitutional (genetic)differences in metabolism.

A recent landmark study has already shown that individual variations in certain genes involved in fatty acid metabolism (FADS2 and FADS1)can significantly influence tissue concentrations of different omega-3 and omega-6 fatty acids. (See Schaeffer et al 2006.)

Two 'desaturase' enzymes (delta-6 and delta-5) are needed to convert the simplest omega-3 and omega-6 EFA (found in vegetables, nuts and seeds) to the more highly unsaturated fatty acids (HUFA) that the brain needs (otherwise found ready-made in meat, eggs and dairy products in the case of omega-6 HUFA, and fish and seafood in the case of the key omega-3 HUFA, EPA and DHA).

Delta-6 desaturase (coded by the FADS2 gene) is usually the rate-limiting enzyme in this pathway for HUFA synthesis within the body, although delta-5 (coded by FADS1)also plays a role.

The study reported here is the first to investigate these 'desaturase' genes in relation to ADHD, and a marker in the FADS2 region was found to relate to ADHD status.

These are very preliminary results, which still need to be confirmed and elaborated, but they could indicate what has long been suspected - namely, that people with ADHD (and possibly those affected by some of the many related conditions) may need more 'ready-made' HUFA than others in their diets.