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Title: Omega-3 PUFAs in children with ADHD
Author: Chang, Pei-Chen
ISNI:       0000 0004 7963 9500
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2019
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Attention deficit hyperactivity disorder, or ADHD, is a common childhood disorder with the prevalence rate of 5-10%. The prevalence rate in Taiwan is around 7-8%. There have been many theories proposed to explain ADHD, and one of them focuses on the deficiency of essential fatty acids (EFA), particularly omega-3 polyunsaturated fatty acids (n-3 PUFAs). Studies have shown that there is a positive correlation between EFA deficiency severity and ADHD symptoms and a negative association between blood PUFAs levels and ADHD symptoms, but not all studies have shown consistent findings. Moreover, although there have been some clinical trials showing that n-3 PUFAs, commonly a combination of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are effective in ADHD, the findings continue to remain controversial. Indeed, there is limited research on the effect of n-3 PUFAs on cognitive functions in children with ADHD. In addition, the mechanism underpinning the link between PUFAs, and ADHD is still unclear, although a role for cortisol and inflammation has been suggested. My PhD has addressed these research questions in a number of ways. First, I have performed systematic reviews and meta-analyses on the cortisol levels and PUFAs levels in ADHD, including both children and adolescents, and a systematic review and meta-analysis on the effects of n-3 PUFAs supplementation on ADHD symptoms and cognitive function in children with ADHD. Second, I have conducted a cross-sectional study comparing ADHD and typically-developing (TD) youth, and measured their salivary cortisol levels, 5 blood inflammatory biomarkers, neurotrophins and PUFAs levels. Next, I conducted a double-blind randomized controlled study (RCT) of n-3 PUFAs (EPA) in children with ADHD, and conducted cognitive function assessments, including Weschler Intelligence Scale for Children-Fourth Edition Digit Span Subtest (WISCDS) and Continuous Performance Test (CPT) measures, as the primary outcome; moreover, I have studied other ADHD severity measures and blood levels of inflammatory biomarkers and neurotrophins as secondary outcomes. In the systematic reviews and meta-analyses, children with ADHD had lower salivary cortisol levels (g = -.77, p = .04) and lower morning salivary cortisol levels (g = -1.21, p = .02), as well as lower levels of docosahexaenoic acid (DHA, g = -.76, p = .0002), EPA (g = -.43, p = .0002) and total n-3 PUFAs (g = -.58, p = .0001); moreover, n-3 PUFAs supplementation improved ADHD clinical symptoms scores (g = .38, p < .0001) and cognitive measures associated with attention (g = 1.09, p = .001). In the cross-sectional study, I have enrolled 98 with ADHD youth (mean age 9.32 + 3.05 years, 86% males) and 21 TD youth (mean age 9.19 + 2.96 years, 71% male). The ADHD youth have lower levels of bedtime salivary levels (p = .030), brain-derived neurotrophic factor (BDNF, p < .0001), tumor necrosis-factor alpha (TNF-α, p = .009), Linoleic acid (LA) (p = .003) and DHA (p = .018), and higher levels of high-sensitivity C- reactive protein (hs-CRP, p < .0001) and interleukin (IL-) 6 (p < .0001) than TD youth. 6 In the RCT of n-3 PUFAs (EPA 1.2g) supplementation, I have enrolled 105 children and adolescents with ADHD, and 98 had completed the 12-week RCT. The n-3 group with the lowest baseline EPA level has a greater improvement in the CPT measures, hit reaction time (HRT, p = .009), HRT standard deviation (HRTSD, p = .043) and HRT interstimulus interval changes (HRTISIC, p = .005); such findings are not present in the group with moderate and high baseline EPA levels. Moreover, n-3 group with the highest baseline hs-CRP has a greater improvement on WISCDS longest digit span backward score (p < .001), WISCDS digit span backward score (p = .001), WISCDS total score (p = .026) and prosocial behavior (p = .021). There were no significant changes in the parent-, teacher- and youth-reported ADHD symptoms, emotional symptoms, and blood levels of inflammatory and neurotrophin biomarkers between n-3 and placebo group. In conclusion, my findings provide evidence that ADHD youth have lower PUFAs, cortisol and BDNF levels, and a higher state of inflammation than TD youth. My findings further supported the efficacy of n-3 PUFAs, especially EPA, in improving inattention and vigilance associated cognitive measures in ADHD with a low EPA level at baseline; and improving working memory and prosocial behavior in ADHD with high baseline inflammation status. Further research is needed to explore the effects of EPA on the clinical symptoms of ADHD targeting a larger sample size of youth with different nutritional and inflammatory status.
Supervisor: Pariante, Carmine Maria ; Mondelli, Valeria ; Arseneault, Louise Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available