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European Child & Adolescent Psychiatry

, Volume 28, Issue 4, pp 571–583 | Cite as

Behavioral and cognitive effects of docosahexaenoic acid in drug-naïve children with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled clinical trial

  • Alessandro CrippaEmail author
  • Alessandra Tesei
  • Federica Sangiorgio
  • Antonio Salandi
  • Sara Trabattoni
  • Silvia Grazioli
  • Carlo Agostoni
  • Massimo Molteni
  • Maria Nobile
Original Contribution

Abstract

This study aimed to investigate the efficacy of docosahexaenoic acid (DHA) dietary supplementation on behavior and cognition in school-aged, drug-naïve children with attention-deficit/hyperactivity disorder (ADHD). A total of 50 participants with ADHD aged 7 to 14 were enrolled in a 6-month randomized, placebo-controlled clinical trial and received either DHA or placebo. The primary outcome measure was the change in the ADHD rating scale IV Parent Version–Investigator (ADHD-RS-IV) after 4 and 6 months. Secondary outcome measures included Conners Parent Rating Scale-revised, other behavioral rating scales including quality of life and global functioning, and computerized cognitive tasks. Baseline assessment also addressed the blood fatty acids profile. No superiority of DHA supplement to placebo was observed on ADHD-RS-IV, the a priori primary outcome. DHA supplementation showed a significant, nonetheless quite small, effect on children’s psychosocial functioning, emotional problems, and focused attention. Neither major nor minor adverse events were reported throughout the trial. This study shows that 6-month DHA supplementation has no beneficial effect on the symptoms of ADHD in school-aged, drug-naïve children with an established diagnosis of ADHD. Nevertheless, the 6 months treatment with supplemental DHA appears to have small positive effects on other behavioral and cognitive difficulties, which, in light of the absence of side-effects, could be reasonably followed up in future intervention studies. (https://clinicaltrials.gov/ct2/show/NCT01796262: The Effects of DHA on Attention Deficit and Hyperactivity Disorder (DADA)).

Keywords

Attention-deficit/hyperactivity disorder (ADHD) Docosahexaenoic acid (DHA) Fatty acids Cognition Behavior 

Notes

Acknowledgements

The authors are grateful to all the children and their families for participating in the study. They also acknowledge the work of Morena Achilli and all nurses at Scientific Institute, IRCCS E. Medea, Child Psychopathology Unit, for their assistance with the collection of blood; Angelo Primavera, Ausilia Rausa, Stefania Conte, Veronica La Riccia, Silvia Busti Ceccarelli, and Silvia Colonna for their research assistance.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: this work was supported by unrestricted research grant from Dietetic Metabolic Food srl., which further provided the investigational product and respective placebo. Funders have not been involved in study design, data collection or analysis, or publication decisions.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Thomas R, Sanders S, Doust J, Beller E, Glasziou P (2015) Prevalence of attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Pediatrics 135(4):e994–e1001.  https://doi.org/10.1542/peds.2014-3482 CrossRefGoogle Scholar
  2. 2.
    Italian National Institute of Health (2014) http://www.iss.it/binary/adhd/cont/Newsletter_Registro_Italiano_dicembre_2014.pdf. Accessed 8 December 2017
  3. 3.
    Tesei A, Crippa A, Ceccarelli SB, Mauri M, Molteni M, Agostoni C, Nobile M (2017) The potential relevance of docosahexaenoic acid and eicosapentaenoic acid to the etiopathogenesis of childhood neuropsychiatric disorders. Eur Child Adolesc Psychiatry 26(9):1011–1030.  https://doi.org/10.1007/s00787-016-0932-4 CrossRefGoogle Scholar
  4. 4.
    Janssen CI, Kiliaan AJ (2014) Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: the influence of LCPUFA on neural development, aging, and neurodegeneration. Progr Lipid Res 53:1–17.  https://doi.org/10.1016/j.plipres.2013.10.002 CrossRefGoogle Scholar
  5. 5.
    Schuchardt JP, Hahn A (2011) Influence of long-chain polyunsaturated fatty acids (LC-PUFAs) on cognitive and visual development. In: Benton D (ed) Lifetime nutritional influences on cognition, behaviour and psychiatric illness. Woodhead Publishing, Oxford, pp 32–78.  https://doi.org/10.1533/9780857092922.1.32 CrossRefGoogle Scholar
  6. 6.
    Mozaffarian D, Wu JH (2012) (n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary? J Nutr 142(3):614S–625S.  https://doi.org/10.3945/jn.111.149633 CrossRefGoogle Scholar
  7. 7.
    Crippa A, Marzocchi GM, Piroddi C, Besana D, Giribone S, Vio C et al (2015) An integrated model of executive functioning is helpful for understanding ADHD and associated disorders. J Atten Disord 19(6):455–467.  https://doi.org/10.1177/1087054714542000 CrossRefGoogle Scholar
  8. 8.
    Bloch MH, Qawasmi A (2011) Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry 50(10):991–1000.  https://doi.org/10.1016/j.jaac.2011.06.008 CrossRefGoogle Scholar
  9. 9.
    Gillies D, Sinn JKH, Lad SS, Leach MJ, Ross MJ (2012) Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents (review). Cochrane Database Syst Rev 11(7):CD007986.  https://doi.org/10.1002/14651858.cd007986.pub2 Google Scholar
  10. 10.
    Sonuga-Barke EJS, Brandeis D, Cortese S, Daley D, Ferrin M, Holtmann M et al (2013) Nonpharmacological interventions for ADHD: systematic review and metaanalyses of randomized controlled trials of dietary and psychological treatments. Am J Psychiatry 170(3):275–289.  https://doi.org/10.1176/appi.ajp.2012.12070991 CrossRefGoogle Scholar
  11. 11.
    Hawkey E, Nigg JT (2014) Omega-3 fatty acid and ADHD: blood level analysis and meta-analytic extension of supplementation trials. Clin Psychol Rev 34(6):496–505.  https://doi.org/10.1016/j.cpr.2014.05.005 CrossRefGoogle Scholar
  12. 12.
    Cooper RE, Tye C, Kuntsi J, Vassos E, Asherson P (2015) Omega-3 polyunsaturated fatty acid supplementation and cognition: a systematic review and meta-analysis. J Psychopharmacol 29(7):753–763.  https://doi.org/10.1177/0269881115587958 CrossRefGoogle Scholar
  13. 13.
    Voigt RG, Llorente AM, Jensen CL, Fraley JK, Berretta MC, Heird WC (2001) A randomized, double-blind, placebo-controlled trial of docosahexaenoic acid supplementation in children with attention-deficit/hyperactivity disorder. J Pediatr 139(2):189–196CrossRefGoogle Scholar
  14. 14.
    Bourre JM, Bonneil M, Dumont O, Piciotti M, Nalbone G, Lafont H (1988) High dietary fish oil alters the brain polyunsaturated fatty acid composition. Biochim Biophys Acta 960(3):458–461CrossRefGoogle Scholar
  15. 15.
    American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, WashingtonGoogle Scholar
  16. 16.
    Goodman R, Ford T, Richards H, Gatward R, Meltzer H (2000) The development and well-being assessment: description and initial validation of an integrated assessment of child and adolescent psychopathology. J Child Psychol Psychiatry 41(5):645–655CrossRefGoogle Scholar
  17. 17.
    Wechsler D (2006) Wechsler Intelligence Scale for Children–III (WISC-III), Italian edn. Organizzazioni Speciali, FlorenceGoogle Scholar
  18. 18.
    Wechsler D (2012) Wechsler Intelligence Scale for Children–IV (WISC-IV). Organizzazioni Speciali, FlorenceGoogle Scholar
  19. 19.
    Petersen AC, Crockett L, Richards M, Boxer A (1988) A self-report measure of pubertal status: reliability, validity, and initial norms. J Youth Adolesc 17(2):117–133.  https://doi.org/10.1007/BF01537962 CrossRefGoogle Scholar
  20. 20.
    Hollingshead AB (1975) Four factor index of social status (Unpublished document). Yale University, New HavenGoogle Scholar
  21. 21.
    Arterburn LM, Hall EB, Oken H (2006) Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr 83(6 Suppl):1467S–1476SCrossRefGoogle Scholar
  22. 22.
    DuPaul GJ, Power TJ, Anastopoulos AD, Reid R (1998) ADHD Rating Scale IV: checklists, norms, and clinical interpretation. Guilford, New YorkGoogle Scholar
  23. 23.
    Conners CK (1997) Conners’ Rating Scales-Revised (Technical manual). Multi-Health Systems, TorontoGoogle Scholar
  24. 24.
    Goodman R (1997) The Strengths and Difficulties Questionnaire: a research note. J Child Psychol Psychiatry 38(5):581–586CrossRefGoogle Scholar
  25. 25.
    Landgraf JM, Abetz L, Ware JE (1996) The CHQ user’s manual. The Health Institute, New England Medical Center, BostonGoogle Scholar
  26. 26.
    Busner J, Targum SD (2007) The Clinical Global Impressions Scale: applying a research tool in clinical practice. Psychiatry (Edgmont) 4:28–37Google Scholar
  27. 27.
    Shaffer D, Gould MS, Brasic J, Ambrosini P, Fisher P, Bird H, Aluwahlia S (1983) A Children’s Global Assessment Scale (CGAS). Arch Gen Psychiatry 40(11):1228–1231CrossRefGoogle Scholar
  28. 28.
    de Sonneville LMJ (2000) ANT 2.1—Amsterdam neuropsychological tasks. Sonar, AmstelveenGoogle Scholar
  29. 29.
    Crippa A, Agostoni C, Mauri M, Molteni M, Nobile M (2016) Polyunsaturated fatty acids are associated with behavior but not with cognition in children with and without ADHD: an Italian study. J Atten Disord.  https://doi.org/10.1177/1087054716629215 Google Scholar
  30. 30.
    Sartori G, Job R, Tressoldi PE (1995) Batteria per la valutazione della dislessia e della disortografia evolutiva [Battery for the assessment of developmental dyslexia and spelling disorder]. Organizzazioni Speciali, FirenzeGoogle Scholar
  31. 31.
    Agostoni C, Galli C, Riva E, Risé P, Colombo C, Giovannini M, Marangoni F (2011) Whole blood fatty acid composition at birth: from the maternal compartment to the infant. Clin Nutr 30(4):503–505.  https://doi.org/10.1016/j.clnu.2011.01.016 CrossRefGoogle Scholar
  32. 32.
    Risé P, Eligini S, Ghezzi S, Colli S, Galli C (2007) Fatty acid composition of plasma, blood cells and whole blood: relevance for the assessment of the fatty acid status in humans. Prostaglandins Leukot Essent Fatty Acids 76(6):363–369CrossRefGoogle Scholar
  33. 33.
    Marangoni F, Colombo C, Galli C (2004) A method for the direct evaluation of the fatty acid status in a drop of blood from a fingertip in humans applicability to nutritional and epidemiological studies. Anal Biochem 326(2):267–272CrossRefGoogle Scholar
  34. 34.
    Simopoulos AP (2011) Evolutionary aspects of diet: the omega-6/omega-3 ratio and the brain. Mol Neurobiol 44(2):203–215.  https://doi.org/10.1007/s12035-010-8162-0 CrossRefGoogle Scholar
  35. 35.
    Montgomery P, Burton JR, Sewell RP, Spreckelsen TF, Richardson AJ (2013) Low blood long chain omega-3 fatty acids in UK children are associated with poor cognitive performance and behavior: a cross-sectional analysis from the DOLAB study. PLoS One 8(6):e66697.  https://doi.org/10.1371/journal.pone.0066697 CrossRefGoogle Scholar
  36. 36.
    Cohen J (1988) Statistical power analysis for the behavioral sciences. Routledge Academic, New YorkGoogle Scholar
  37. 37.
    Feingold A (2009) Effect sizes for growth-modeling analysis for controlled clinical. Psychol Methods 14:43–53.  https://doi.org/10.1037/a0014699 CrossRefGoogle Scholar
  38. 38.
    Faraone SV (2009) Using meta-analysis to compare the efficacy of medications for attention-deficit/hyperactivity disorder in youths. Pharm Ther 34(12):678Google Scholar
  39. 39.
    Cornu C, Mercier C, Ginhoux T, Masson S, Mouchet J, Nony P, Heuzey MF (2018) A double-blind placebo-controlled randomised trial of omega-3 supplementation in children with moderate ADHD symptoms. Eur Child Adolesc Psychiatry 27(3):377–384.  https://doi.org/10.1007/s00787-017-1058-z CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Alessandro Crippa
    • 1
    Email author
  • Alessandra Tesei
    • 1
  • Federica Sangiorgio
    • 1
  • Antonio Salandi
    • 1
  • Sara Trabattoni
    • 1
  • Silvia Grazioli
    • 1
    • 2
  • Carlo Agostoni
    • 3
  • Massimo Molteni
    • 1
  • Maria Nobile
    • 1
  1. 1.Scientific Institute, IRCCS E. Medea, Child Psychopathology UnitBosisio PariniItaly
  2. 2.Department of PsychologyUniversity of Milano-BicoccaMilanItaly
  3. 3.Pediatric Intermediate Care Unit, DISSCO Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca Granda—Ospedale Maggiore PoliclinicoUniversity of MilanMilanItaly

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