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Long chain omega-3 polyunsaturated fatty acids in the treatment of psychiatric illnesses in children and adolescents

Published online by Cambridge University Press:  24 June 2014

Edward H. Clayton ,
Tanya L. Hanstock ,
Manohar L. Garg  and
Philip L. Hazell
Edward H. Clayton*
Affiliation:
Nutraceuticals Research Group, University of Newcastle, Callaghan, NSW, Australia
Tanya L. Hanstock
Affiliation:
The Bipolar Program, Hunter New England Area Health Service, Newcastle, NSW, Australia Department of Psychology, University of Newcastle, Callaghan, NSW, Australia
Manohar L. Garg
Affiliation:
Nutraceuticals Research Group, University of Newcastle, Callaghan, NSW, Australia
Philip L. Hazell
Affiliation:
Central Clinical School, University of Sydney, NSW, Australia Discipline of Psychiatry, School of Medical Practice and Population Health, University of Newcastle, Callaghan, NSW, Australia
*
Dr Edward Clayton, Research Fellow, Nutraceuticals Research Group, Room 305B, Medical Sciences Building, University of Newcastle, Callaghan, NSW 2305, Australia. Tel: +61 249 215 343; Fax: +61 249 212 028; E-mail: edward.clayton@newcastle.edu.au
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Abstract

Objective:

Long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) are in increasing use in the general population to treat health problems. The objective of the current article is to review the evidence for the rationale and benefit of LCn-3PUFA in the treatment of common psychiatric disorders in children and adolescents.

Methods:

A search of Psychlit, PubMed and Cochrane Databases was conducted using the terms child, adolescent, bipolar, depression, psychosis, first-episode psychosis, schizophrenia, attention deficit hyperactivity disorder (ADHD), autism, psychiatric, omega-3, n-3, docosahexaenoic acid and eicosapentaenoic acid. Further studies were identified from the bibliographies of published reviews.

Results:

One small randomized controlled trial with LCn-3PUFA supplementation in depression in children found a small beneficial effect over placebo. Four placebo-controlled trials showed uncertain benefit of LCn-3PUFA for ADHD. Single placebo-controlled trials showed no benefit in autism or bipolar disorder. There is an absence of studies examining benefit for first-episode psychosis or schizophrenia in children and adolescents.

Conclusions:

While children and adolescents are receiving LCn-3PUFA for a range of psychiatric indications, there is only evidence of likely benefit for unipolar depression.

Keywords

ADHDadolescentsautismbipolarchildrendepressionDHAEPAomega-3psychiatryschizophrenia
Type
Review article
Information
Acta Neuropsychiatrica , Volume 19 , Issue 2 , April 2007 , pp. 92 - 103
Copyright
Copyright © 2007 Blackwell Munksgaard

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References

Simopoulos, AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr 1999;70:S560–S569. CrossRefGoogle ScholarPubMed
Pawlosky, RJ, Hibbeln, JR, Novotny, JA, Salem, N Jr. Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans. J Lipid Res 2001;42:1257–1265. CrossRefGoogle ScholarPubMed
Emken, EA, Adlof, RO, Gulley, RM. Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males. Biochim Biophys Acta 1994;1213:277–288. CrossRefGoogle ScholarPubMed
Garg, ML, Wood, LG, Singh, H, Moughan, PJ. Means of delivering recommended levels of long chain n-3 polyunsaturated fatty acids in human diets. J Food Sci 2006;71:R66–R71. CrossRefGoogle Scholar
Ollis, TE, Meyer, BJ, Howe, PR. Australian food sources and intakes of omega-6 and omega-3 polyunsaturated fatty acids. Ann Nutr Metab 1999;43:346–355. CrossRefGoogle ScholarPubMed
Howe, P, Meyer, B, Record, S, Baghurst, K. Dietary intake of long-chain omega-3 polyunsaturated fatty acids: contribution of meat sources. Nutrition 2006;22:47–53. CrossRefGoogle ScholarPubMed
Kemper, KJ. Dietary supplements for attention-deficit/hyperactivity disorder – a fishy business? J Pediatr 2001;139:173–174. CrossRefGoogle ScholarPubMed
Jorm, AF, Allen, NB, O’Donnell, CP, Parslow, RA, Purcell, R, Morgan, AJ. Effectiveness of complementary and self-help treatments for depression in children and adolescents. Med J Aust 2006;185:368–372. CrossRefGoogle ScholarPubMed
Das, UN. Perinatal supplementation of long-chain polyunsaturated fatty acids, immune response and adult diseases. Med Sci Monit 2004;10:HY19–HY25. Google ScholarPubMed
Romano, C, Cucchiara, S, Barabino, A, Annese, V, Sferlazzas, C. Usefulness of omega-3 fatty acid supplementation in addition to mesalazine in maintaining remission in pediatric Crohn’s disease: a double-blind, randomized, placebo-controlled study. World J Gastroenterol 2005;11:7118–7121. CrossRefGoogle ScholarPubMed
Belluzzi, A, Boschi, S, Brignola, C, Munarini, A, Cariani, G, Miglio, F. Polyunsaturated fatty acids and inflammatory bowel disease. Am J Clin Nutr 2000;71:S339–S342. CrossRefGoogle ScholarPubMed
Horrobin, DF. Essential fatty acid metabolism and its modification in atopic eczema. Am J Clin Nutr 2000;71:S367–S372. CrossRefGoogle ScholarPubMed
Schlanger, S, Shinitzky, M, Yam, D. Diet enriched with omega-3 fatty acids alleviates convulsion symptoms in epilepsy patients. Epilepsia 2002;43:103–104. CrossRefGoogle ScholarPubMed
Rudin, DO. The major psychoses and neuroses as omega-3 essential fatty acid deficiency syndrome: substrate pellagra. Biol Psychiatry 1981;16:837–850. Google ScholarPubMed
Leaf, A, Weber, PC. A new era for science in nutrition. Am J Clin Nutr 1987;45:1048–1053. CrossRefGoogle ScholarPubMed
Weissman, MM, Bland, RC, Canino, GJet al. Cross-national epidemiology of major depression and bipolar disorder. JAMA 1996;276:293–299. CrossRefGoogle ScholarPubMed
Hibbeln, JR. Fish consumption and major depression. Lancet 1998;351:1213. CrossRefGoogle ScholarPubMed
Edwards, R, Peet, M, Shay, J, Horrobin, D. Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients. J Affect Disord 1998;48:149–155. CrossRefGoogle ScholarPubMed
Hibbeln, JR. Seafood consumption, the DHA content of mothers’ milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. J Affect Disord 2002;69:15–29. CrossRefGoogle ScholarPubMed
Noaghiul, S, Hibbeln, JR. Cross-national comparisons of seafood consumption and rates of bipolar disorders. Am J Psychiatry 2003;160:2222–2227. CrossRefGoogle ScholarPubMed
Peet, M. International variations in the outcome of schizophrenia and the prevalence of depression in relation to national dietary practices: an ecological analysis. Br J Psychiatry 2004;184:404–408. CrossRefGoogle ScholarPubMed
Horrobin, DF, Manku, MS, Hillman, H, Iain, A, Glen, M. Fatty acid levels in the brains of schizophrenics and normal controls. Biol Psychiatry 1991;30:795–805. CrossRefGoogle ScholarPubMed
Sastry, PS. Lipids of nervous tissue: composition and metabolism. Prog Lipid Res 1985;24:69–176. CrossRefGoogle ScholarPubMed
McNamara, RK, Carlson, SE. Role of omega-3 fatty acids in brain development and function: potential implications for the pathogenesis and prevention of psychopathology. Prostaglandins Leukot Essent Fatty Acids 2006;75:329–349. CrossRefGoogle ScholarPubMed
Simopoulos, AP. Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr 1991;54:438–463. CrossRefGoogle ScholarPubMed
Farquharson, J, Cockburn, F, Patrick, WA, Jamieson, EC, Logan, RW. Infant cerebral cortex phospholipid fatty-acid composition and diet. Lancet 1992;340:810–813. CrossRefGoogle ScholarPubMed
Innis, SM. Perinatal biochemistry and physiology of long-chain polyunsaturated fatty acids. J Pediatr 2003;143:S1–S8. CrossRefGoogle ScholarPubMed
Willatts, P, Forsyth, JS. The role of long-chain polyunsaturated fatty acids in infant cognitive development. Prostaglandins Leukot Essent Fatty Acids 2000;63:95–100. CrossRefGoogle ScholarPubMed
Hirashima, F, Parow, AM, Stoll, ALet al. Omega-3 fatty acid treatment and t2 whole brain relaxation times in bipolar disorder. Am J Psychiatry 2004;161:1922–1924. CrossRefGoogle ScholarPubMed
Tappia, PS, Ladha, S, Clark, DC, Grimble, RF. The influence of membrane fluidity, TNF receptor binding, cAMP production and GTPase activity on macrophage cytokine production in rats fed a variety of fat diets. Mol Cell Biochem 1997;166:135–143. CrossRefGoogle ScholarPubMed
Mirnikjoo, B, Brown, SW, Seung Kim, HF, Marangell, LB, Sweatt, JD, Weeber, EJ. Protein kinase inhibition by w-3 fatty acids. J Biol Chem 2001;276:10888–10896. CrossRefGoogle Scholar
Seung Kim, HF, Weeber, EJ, Sweatt, JD, Stoll, AL, Marangell, LB. Inhibitory effects of omega-3 fatty acids on protein kinase C activity in vitro. Mol Psychiatry 2001;6:246–248. CrossRefGoogle ScholarPubMed
Chang, MC, Contreras, MA, Rosenberger, TA, Rintala, JJ, Bell, JM, Rapoport, SI. Chronic valproate treatment decreases the in vivo turnover of arachidonic acid in brain phospholipids: a possible common effect of mood stabilizers. J Neurochem 2001;77:796–803. CrossRefGoogle ScholarPubMed
Stoll, AL, Locke, CA, Marangell, LB, Severus, WE. Omega-3 fatty acids in bipolar disorder: a review. Prostaglandins Leukot Essent Fatty Acids 1999;60:329–337. CrossRefGoogle ScholarPubMed
Horrobin, DF, Bennett, CN. Depression and bipolar disorder: relationships to impaired fatty acid and phospholipid metabolism and to diabetes, cardiovascular disease, immunological abnormalities, cancer, ageing and osteoporosis. Possible candidate genes. Prostaglandins Leukot Essent Fatty Acids 1999;60:217–234. CrossRefGoogle ScholarPubMed
Peet, M, Stokes, C. Omega-3 fatty acids in the treatment of psychiatric disorders. Drugs 2005;65:1051–1059. CrossRefGoogle ScholarPubMed
Charlton, BG. The malaise theory of depression: major depressive disorder is sickness behavior and antidepressants are analgesic. Med Hypotheses 2000;54:126–130. CrossRefGoogle ScholarPubMed
Raison, CL, Capuron, L, Miller, AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 2006;27:24–31. CrossRefGoogle ScholarPubMed
Chang, MC, Grange, E, Rabin, O, Bell, JM, Allen, DD, Rapoport, SI. Lithium decreases turnover of arachidonate in several brain phospholipids. Neurosci Lett 1996;220:171–174. CrossRefGoogle ScholarPubMed
Chang, MC, Bell, JM, Purdon, AD, Chikhale, EG, Grange, E. Dynamics of docosahexaenoic acid metabolism in the central nervous system: lack of effect of chronic lithium treatment. Neurochem Res 1999;24:399–406. CrossRefGoogle ScholarPubMed
Rapoport, SI, Bosetti, F. Do lithium and anticonvulsants target the brain arachidonic acid cascade in bipolar disorder? Arch Gen Psychiatry 2002;59:592–596. CrossRefGoogle ScholarPubMed
De La Presa Owens, S, Innis, SM. Docosahexaenoic and arachidonic acid prevent a decrease in dopaminergic and serotoninergic neurotransmitters in frontal cortex caused by a linoleic and alpha-linolenic acid deficient diet in formula-fed piglets. J Nutr 1999;129:2088–2093. CrossRefGoogle ScholarPubMed
Zimmer, L, Delpal, S, Guilloteau, D, Aioun, J, Durand, G, Chalon, S. Chronic n-3 polyunsaturated fatty acid deficiency alters dopamine vesicle density in the rat frontal cortex. Neurosci Lett 2000;284:25–28. CrossRefGoogle ScholarPubMed
Kodas, E, Galineau, L, Bodard, Set al. Serotoninergic neurotransmission is affected by n-3 polyunsaturated fatty acids in the rat. J Neurochem 2004;89:695–702. CrossRefGoogle ScholarPubMed
Young, G, Conquer, J. Omega-3 fatty acids and neuropsychiatric disorders. Reprod Nutr Dev 2005;45:1–28. CrossRefGoogle ScholarPubMed
Freeman, MP. Omega-3 fatty acids in psychiatry: a review. Ann Clin Psychiatry 2000;12:159–165. CrossRefGoogle ScholarPubMed
Parker, G, Gibson, NA, Brotchie, H, Heruc, G, Rees, AM, Hadzi-Pavlovic, D. Omega-3 fatty acids and mood disorders. Am J Psychiatry 2006;163:969–978. CrossRefGoogle ScholarPubMed
McNamara, RK. The emerging role of omega-3 fatty acids in psychiatry. Prostaglandins Leukot Essent Fatty Acids 2006;75:223–225. CrossRefGoogle ScholarPubMed
Maes, M, Smith, R, Christophe, A, Cosyns, P, Desnyder, R, Meltzer, H. Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids. J Affect Disord 1996;38:35–46. CrossRefGoogle ScholarPubMed
Peet, M, Murphy, B, Shay, J, Horrobin, D. Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biol Psychiatry 1998;43:315–319. CrossRefGoogle ScholarPubMed
Sublette, ME, Hibbeln, JR, Galfalvy, H, Oquendo, MA, Mann, JJ. Omega-3 polyunsaturated essential fatty acid status as a predictor of future suicide risk. Am J Psychiatry 2006;163:1100–1102. CrossRefGoogle ScholarPubMed
Adams, PB, Lawson, S, Sanigorski, A, Sinclair, AJ. Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression. Lipids 1996;31:S157–S161. CrossRefGoogle ScholarPubMed
Maes, M, Christophe, A, Delanghe, J, Altamura, C, Neels, H, Meltzer, HY. Lowered omega-3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Res 1999;85:275–291. CrossRefGoogle ScholarPubMed
Su, KP, Huang, SY, Chiu, CC, Shen, WW. Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial. Eur Neuropsychopharmacol 2003;13:267–271. CrossRefGoogle ScholarPubMed
Marangell, LB, Martinez, JM, Zboyan, HA, Kertz, B, Kim, HF, Puryear, LJ. A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. Am J Psychiatry 2003;160:996–998. CrossRefGoogle ScholarPubMed
Silvers, KM, Woolley, CC, Hamilton, FC, Watts, PM, Watson, RA. Randomised double-blind placebo-controlled trial of fish oil in the treatment of depression. Prostaglandins Leukot Essent Fatty Acids 2005;72:211–218. CrossRefGoogle ScholarPubMed
Mamalakis, G, Kiriakakis, M, Tsibinos, G, Kafatos, A. Depression and adipose polyunsaturated fatty acids in an adolescent group. Prostaglandins Leukot Essent Fatty Acids 2004;71:289–294. CrossRefGoogle Scholar
Nemets, H, Nemets, B, Apter, A, Bracha, Z, Belmaker, RH. Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. Am J Psychiatry 2006;163:1098–1100. CrossRefGoogle ScholarPubMed
Hollis, S, Campbell, F. What is meant by intention to treat analysis? Survey of published randomised controlled trials. BMJ 1999;319:670–674. CrossRefGoogle ScholarPubMed
Moher, D, Schulz, KF, Altman, D. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. JAMA 2001;285:1987–1991. CrossRefGoogle Scholar
Lish, JD, Dime-Meenan, S, Whybrow, PC, Price, RA, Hirschfeld, RM. The National Depressive and Manic-depressive Association (DMDA) survey of bipolar members. J Affect Disord 1994;31:281–294. CrossRefGoogle ScholarPubMed
Vieta, E, Benabarre, A, Martinez-Aran, A. Brain imaging correlates of cognitive dysfunctions in bipolar disorder. Bipolar Disord 2004;6:19. Google Scholar
Goodwin, F, Jamison, KR. Manic-depressive illness. New York: Oxford University Press, 1990. Google Scholar
Goodwin, FK, Fireman, B, Simon, GE, Hunkeler, EM, Lee, J, Revicki, D. Suicide risk in bipolar disorder during treatment with lithium and divalproex. JAMA 2003;290:1467–1473. CrossRefGoogle ScholarPubMed
WHO, World Bank. The global burden of disease: summary. Cambridge, MA: The Harvard School of Public Health Harvard University Press, 1996. Google Scholar
Chiu, CC, Huang, SY, Su, KPet al. Polyunsaturated fatty acid deficit in patients with bipolar mania. Eur Neuropsychopharmacol 2003;13:99–103. CrossRefGoogle ScholarPubMed
Stoll, AL, Severus, WE, Freeman, MPet al. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind placebo-controlled trial. Arch Gen Psychiatry 1999;56:407–412. CrossRefGoogle ScholarPubMed
Keck, PE Jr, Mintz, J, McElroy, SLet al. Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder. Biol Psychiatry 2006;60:1020–1022. CrossRefGoogle ScholarPubMed
Post, RM, Leverich, GS, Altshuler, LLet al. An overview of recent findings of the Stanley Foundation Bipolar Network (Part I). Bipolar Disord 2003;5:310–319. CrossRefGoogle ScholarPubMed
Gracious, BL. An RCT of flax oil in children and adolescents with bipolar. National Institute of Mental Health (NIMH) Pediatric Bipolar Conference. Chicago, IL, April 2006. Google Scholar
Colquhoun, I, Bunday, S. A lack of essential fatty acids as a possible cause of hyperactivity in children. Med Hypotheses 1981;7:673–679. CrossRefGoogle ScholarPubMed
Mitchell, EA, Aman, MG, Turbott, SH, Manku, M. Clinical characteristics and serum essential fatty acid levels in hyperactive children. Clin Pediatr (Phila) 1987;26:406–411. CrossRefGoogle ScholarPubMed
Stevens, LJ, Zentall, SS, Deck, JLet al. Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder. Am J Clin Nutr 1995;62:761–768. CrossRefGoogle ScholarPubMed
Burgess, JR, Stevens, L, Zhang, W, Peck, L. Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder. Am J Clin Nutr 2000;71:S327–S330. CrossRefGoogle ScholarPubMed
Chen, JR, Hsu, SF, Hsu, CD, Hwang, LH, Yang, SC. Dietary patterns and blood fatty acid composition in children with attention-deficit hyperactivity disorder in Taiwan. J Nutr Biochem 2004;15:467–472. CrossRefGoogle ScholarPubMed
Voigt, RG, Llorente, AM, Jensen, CL, Fraley, JK, Berretta, MC, Heird, WC. A randomized, double-blind, placebo-controlled trial of docosahexaenoic acid supplementation in children with attention-deficit/hyperactivity disorder. J Pediatr 2001;139:189–196. CrossRefGoogle ScholarPubMed
Richardson, AJ, Puri, BK. A randomized double-blind, placebo-controlled study of the effects of supplementation with highly unsaturated fatty acids on ADHD-related symptoms in children with specific learning difficulties. Prog Neuropsychopharmacol Biol Psychiatry 2002;26:233–239. CrossRefGoogle ScholarPubMed
Littell, RC, Henry, PR, Ammerman, CB. Statistical analysis of repeated measures data using SAS procedures. J Anim Sci 1998;76:1216–1231. CrossRefGoogle Scholar
Stevens, L, Zhang, W, Peck, Let al. EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors. Lipids 2003;38:1007–1021. CrossRefGoogle ScholarPubMed
Hirayama, S, Hamazaki, T, Terasawa, K. Effect of docosahexaenoic acid-containing food administration on symptoms of attention-deficit/hyperactivity disorder – a placebo-controlled double-blind study. Eur J Clin Nutr 2004;58:467–473. CrossRefGoogle ScholarPubMed
Sinn, N, Bryan, J. Effect of supplementation with polyunsaturated fatty acids and micronutrients on attention and behavior problems associated with child ADHD. J Dev Behav Pediatr 2007 (in press).CrossRefGoogle ScholarPubMed
Richardson, AJ. Clinical trials of fatty acid supplementation in ADHD. In: Glen, AIM, Peet, M, Horrobin, DF, eds. Phospholipid spectrum disorders in psychiatry and neurology. Carnforth: Marius Press, 2003: 529–541. Google Scholar
Christensen, O, Christensen, E. Fat consumption and schizophrenia. Acta Psychiatr Scand 1988;78:587–591. CrossRefGoogle ScholarPubMed
Reddy, RD, Keshavan, MS, Yao, JK. Reduced red blood cell membrane essential polyunsaturated fatty acids in first episode schizophrenia at neuroleptic-naive baseline. Schizophr Bull 2004;30:901–911. CrossRefGoogle ScholarPubMed
Khan, MM, Evans, DR, Gunna, V, Scheffer, RE, Parikh, VV, Mahadik, SP. Reduced erythrocyte membrane essential fatty acids and increased lipid peroxides in schizophrenia at the never-medicated first-episode of psychosis and after years of treatment with antipsychotics. Schizophr Res 2002;58:1–10. CrossRefGoogle ScholarPubMed
Evans, DR, Parikh, VV, Khan, MM, Coussons, C, Buckley, PF, Mahadik, SP. Red blood cell membrane essential fatty acid metabolism in early psychotic patients following antipsychotic drug treatment. Prostaglandins Leukot Essent Fatty Acids 2003;69:393–399. CrossRefGoogle ScholarPubMed
Mahadik, SP, Mukherjee, S. Cultured skin fibroblasts as a cell model for investigating schizophrenia. J Psychiatr Res 1996;30:421–439. CrossRefGoogle ScholarPubMed
Hibbeln, JR, Makino, KK, Martin, CE, Dickerson, F, Boronow, J, Fenton, WS. Smoking, gender, and dietary influences on erythrocyte essential fatty acid composition among patients with schizophrenia or schizoaffective disorder. Biol Psychiatry 2003;53:431–441. CrossRefGoogle ScholarPubMed
Peet, M. The metabolic syndrome, omega-3 fatty acids and inflammatory processes in relation to schizophrenia. Prostaglandins Leukot Essent Fatty Acids 2006;75:323–327. CrossRefGoogle ScholarPubMed
Bell, JG, Sargent, JR, Tocher, DR, Dick, JR. Red blood cell fatty acid compositions in a patient with autistic spectrum disorder: a characteristic abnormality in neurodevelopmental disorders? Prostaglandins Leukot Essent Fatty Acids 2000;63:21–25. CrossRefGoogle Scholar
Vancassel, S, Durand, G, Barthelemy, Cet al. Plasma fatty acid levels in autistic children. Prostaglandins Leukot Essent Fatty Acids 2001;65:1–7. CrossRefGoogle ScholarPubMed
Amminger, GP, Berger, GE, Schafer, MR, Klier, C, Friedrich, MH, Feucht, M. Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study. Biol Psychiatry 2006;61:551–553. CrossRefGoogle ScholarPubMed
Goodnight, SH Jr, Harris, WS, Connor, WE. The effects of dietary omega 3 fatty acids on platelet composition and function in man: a prospective, controlled study. Blood 1981;58:880–885. CrossRefGoogle Scholar
Wensing, AG, Mensink, RP, Hornstra, G. Effects of dietary n-3 polyunsaturated fatty acids from plant and marine origin on platelet aggregation in healthy elderly subjects. Br J Nutr 1999;82:183–191. CrossRefGoogle ScholarPubMed
Woodman, RJ, Mori, TA, Burke, Vet al. Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypersensitive type 2 diabetic patients. Atherosclerosis 2002;166:85–93. CrossRefGoogle Scholar
Veldhuyzenvan Zanten, SJOV, Talley, NJ, Bytzer, P, Klein, KB, Whorwell, PJ, Zinsmeister, AR. Design of treatment trials for functional gastrointestinal disorders. Gut 1999;45:69–77. Google Scholar
Calabrese, JR, Rapport, DJ, Shelton, MD. Fish oils and bipolar disorder. A promising but untested treatment. Arch Gen Psychiatry 1999;56:413–414. CrossRefGoogle ScholarPubMed
Puri, BK, Richardson, AD. The effects of olive oil on omega-3 fatty acids and mood disorders. Arch Gen Psychiatry 2000;57:715. CrossRefGoogle ScholarPubMed
Brouwer, IA, Zock, PL, Wever, EFet al. Rationale and design of a randomised controlled clinical trial on supplemental intake of n-3 fatty acids and incidence of cardiac arrhythmia: SOFA. Eur J Clin Nutr 2003;57:1323–1330. CrossRefGoogle ScholarPubMed
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). E6 Good Clinical Practice: Consolidated Guidance. April 1996: Available at: www.tga.gov.au/docs/html/ich13595.htmGoogle Scholar
Peet, M, Horrobin, DF. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry 2002;59:913–919. CrossRefGoogle ScholarPubMed
Richardson, AJ, Montgomery, P. The Oxford-Durham study: a randomized, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder. Pediatrics 2005;115:1360–1366. CrossRefGoogle ScholarPubMed
Drevets, WC, Price, JL, Simpson, JR Jret al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature 1997;386:824–827. CrossRefGoogle ScholarPubMed
Biederman, J, James, RS. Advances in the neurobiology of pediatric bipolar disorder. Biol Psychiatry 2005;58:515–516. CrossRefGoogle ScholarPubMed
Kowatch, R, Davanzo, PA, Emslie, G. Pediatric mood disorders and neuroimaging. In: Ernst, M, Rumsey, JM, eds. Functional neuroimaging in child psychiatry. Cambridge: Cambridge University Press, 2000: 205–223. CrossRefGoogle Scholar
Wang, N, Anderson, RE. Synthesis of docosahexaenoic acid by retina and retinal pigment epithelium. Biochemistry 1993;32:13703–13709. CrossRefGoogle ScholarPubMed
Moore, SA, Yoder, E, Murphy, S, Dutton, GR, Spector, AA. Astrocytes, not neurons, produce docosahexaenoic acid (22:6 omega-3) and arachidonic acid (20:4 omega-6). J Neurochem 1991;56:518–524. CrossRefGoogle Scholar