Nutritional Neuroscience as Mainstream of Psychiatry: The Evidence- Based Treatment Guidelines for Using Omega-3 Fatty Acids as a New Treatment for Psychiatric Disorders in Children and Adolescents

Abstract

Omega-3 polyunsaturated fatty acids (or omega-3 PUFAs, n-3 PUFAs) are essential nutrients throughout the life span. Recent studies have shown the importance of n-3 PUFAs supplementation during prenatal and perinatal period as a potential protective factor of neurodevelopmental disorders. N-3 PUFAs have been reported to be lower in youth with attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD). N-3 PUFAs supplementation has shown potential effects in the improvement of clinical symptoms in youth with ADHD, ASD, and MDD, especially those with high inflammation or a low baseline n-3 index. Moreover, it has been suggested that n-3 PUFAs had positive effects on lethargy and hyperactivity symptoms in ASD. For clinical application, the following dosage and duration are recommended in youth according to available randomized controlled trials and systemic literature review: (1) ADHD: a combination of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) ≥ 750 mg/d, and a higher dose of EPA (1,200 mg/d) for those with inflammation or allergic diseases for duration of 16−24 weeks; (2) MDD: a combination of a EPA + DHA of 1,000−2,000 mg/d, with EPA:DHA ratio of 2 to 1, for 12−16 weeks; (3) ASD: a combination of EPA + DHA of 1,300−1,500 mg/d for 16−24 weeks as add-on therapy to target lethargy and hyperactivity symptoms. The current review also suggested that n-3 index and inflammation may be potential treatment response markers for youth, especially in ADHD and MDD, receiving n-3 PUFA.

Efficacy and Safety of Polyunsaturated Fatty Acids Supplementation in the Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in Children and Adolescents: A Systematic Review and Meta-Analysis of Clinical Trials

“…Our findings displaying an inadequate effect of PUFA in the treatment of ADHD is in line with many previous reviews on the subject [ 57 , 61 , 62 , 63 , 64 , 65 ], but not all [ 66 , 67 , 68 , 69 ].…”

“…When comparing our review to others reporting a beneficial effect, it becomes evident that there is a discrepancy in the methodology used to evaluate treatment effects, which may explain the discrepancy in results. In three of the reviews [ 66 , 67 , 69 ], no specific analysis to obtain pooled estimate of effects was performed, as results from the individual trials were only narratively described. This prevents a direct comparison between trials, including an assessment of the overall magnitude of effect.…”

Importance of EPA and DHA Blood Levels in Brain Structure and Function

“…Although a Cochrane meta-analysis of 2016 did not recommend EPA and DHA in the treatment of ADHD, other systematic reviews and meta-analyses reached more positive conclusions [ 81 , 82 , 83 ]. A very recent one concluded that, “a combination of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) ≥ 750 mg/d, and a higher dose of EPA (1200 mg/d) for those with inflammation or allergic diseases for duration of 16–24 weeks” would be beneficial in ADHD and that, “the current review also suggested that n-3 index and inflammation may be potential treatment response markers for youth, especially in ADHD and MDD, receiving n-3 PUFA.” [ 84 ].…”

“…These positive trials question the overall neutral result of an earlier meta-analysis of four trials in a total of 153 participants [ 90 ]. A recent review therefore recommended, “a combination of EPA + DHA of 1000–2000 mg/d, with EPA:DHA ratio of 2 to 1, for 12–16 weeks” for treatment of major depression in adolescents and suggested following treatment response with the Omega-3 Index [ 84 ].…”

Clinical and Neurobiological Aspects of TAO Kinase Family in Neurodevelopmental Disorders

“…Current clinical training intervention and medical treatments offered for NDDs are symptomatic and behavioral based therapy (Levy and Barak, 2021 ), which could be applied to any possible factors caused by NDDs. In addition, nutritional supplements (Chang and Su, 2020 ), non-invasive brain stimulation [including transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS)] (Khaleghi et al, 2020 ), and deep brain stimulation in certain cases (Beszłej et al, 2019 ; Lin et al, 2019 ) are being or will be applied in clinical treatments of NDDs.…”