Psychiatric disorders are a significant source of disability worldwide. Increasing evidence indicates that disturbances of fatty acids and phospholipid metabolism can play a part in a wide range of psychiatric, neurological, and developmental disorders in adults. Essential fatty acids, ω-3 and ω-6 polyunsaturated fatty acids, play a central role in the normal development and functioning of the brain and central nervous system. The aim of this article is to discuss the overall insight into roles of essential fatty acids in the development of mental disorders (depression, schizophrenia, bipolar disorder) and, in light of the fact that disturbances of fatty acid metabolism can play a part in the above-mentioned disorders, to investigate the current knowledge of lipid abnormalities in posttraumatic stress disorder. The information in this review was obtained after extensive MEDLINE searching of each topic area through relevant published studies from the past 20 years. References from the obtained studies were also used. This review summarizes the knowledge in terms of essential fatty acids intake and metabolism, as well as evidence pointing to potential mechanisms of essential fatty acids in normal brain functioning and development of neuropsychiatric disorders. The literature shows that ω-3 fatty acids provide numerous health benefits and that changes in their concentration in organisms are connected to a variety of psychiatric symptoms and disorders, including stress, anxiety, cognitive impairment, mood disorders, and schizophrenia. Further studies are necessary to confirm ω-3 fatty acids’ supplementation as a potential rational treatment in psychiatric disorders.
OwenCReesAMParkerG. The role of fatty acids in the development and treatment of mood disorders. Curr Opin Psychiatry. 2008;21(1):19-24.
2.
FreemanMP. Omega-3 fatty acids in psychiatry: a review. Ann Clin Psychiatry. 2000;12:159-165.
3.
PauwelsEKJVolterraniD. Fatty acid facts, part I: essential fatty acids as treatment for depression, or food for mood?Drug News Perspect. 2008;21(8):446-451.
4.
HaagM. Essential fatty acids and the brain. Can J Psychiatry. 2003;48(3):195-203.
5.
LattkaEIlligTHeinrichJKoletzkoB. Do FADS genotypes enhance our knowledge about fatty acid related phenotypes?Clin Nutr. 2010;29:277-287.
6.
TrivediB. The good, the fad, and unhealthy. New Scientist. 2006;191(2570):42-49.
7.
MooreSAYoderESpectorAA. Role of the blood-brain barrier in the formation of long-chain omega-3 and omega-6 fatty acids from essential fatty acid precursors. J Neurochem. 1990;55(2):391-402.
8.
SchaefersHJHaselmannJGoppelt-StruebeM. Regulation of prostaglandin synthesis in Madin Darby canine kidney cells: role of prostaglandin G/H synthase and secreted phospholipase A2. Biochim Biophys Acta. 1996;1300(3):197-202.
9.
CalderPC. Immunomodulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids. Proc Nutr Soc. 1996;55(2):737-774.
10.
O’BrienJSSampsonEL. Lipid composition of normal human brain: gray matter, white matter, and myelin. J Lipid Res. 1965;6:537-544.
11.
O’BrienJSSampsonEL. Fatty acid and fatty aldehyde composition of the major brain lipids in normal human gray matter, white matter, and myelin. J Lipid Res. 1965;6:537-544.
12.
SalemNJrKimH-YYergeyJA. Docosahexaenoic acid: membrane function and metabolism. In: SimopoulosAPKiterRRMartinRE, eds. Health Effects of Polyunsaturated Fatty Acids in Seafoods. New York: Academic Press; 1986:263-317.
13.
IkemotoAKobayashiTWatanabeSOkuyamaH. Membrane fatty acid modifications of PC12 cells by arachidonate or docosahexaenoate affect neurite outgrowth but not norepinephrine release. Neurochem Res. 1997;22(6):671-678.
14.
BourreJM. Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during aging. J Nutr Health Aging. 2004;8:163-174.
15.
CookHW. In vitro formation of polyunsaturated fatty acids by desaturation in rat brain: some properties of the enzyme in developing brain and comparison with liver. J Neurochem. 1978;30:1327-1324.
16.
PurvisMClandininMTHackerRR. Chain elongation-desaturation of linoleic acid during the development of the pig: implications for the supply of polyenoic fatty acids to the developing brain. Comp Biochem Physiol. 1983;75B:199-204.
17.
DelašIPopovićMPetrovićTDelašFIvankovićD. Changes in the fatty acid composition of brain and liver phospholipids from rats fed fat-free diet. Food Technol Biotechnol. 2008;3:278-285.
18.
BourreJ-MDurandGPascalGYouyouA. Brain cell and tissue recovery in rats made deficient in n-3 fatty acids by alteration of dietary fat. J Nutr. 1989;119:15-22.
19.
SalemNMoriguchiTGreinerRS. Alterations in brain function after loss of docosahexaenoate due to dietary restriction of n-3 fatty acids. J Mol Neurosci. 2001;16:299-307.
20.
BourreJMFrancoisMYouyouA. The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats. J Nutr. 1989;119:1880-1892.
21.
BourreJMDumontOPascalGDurandG. Dietary alpha-linolenic acid at 1.3 g/kg maintains maximal docosahexaenoic acid concentration in brain, heart and liver of adult rats. J Nutr. 1993;123:1313-1319.
22.
SimopoulosAPLeafASalemNJr. Workshop statement on the essentiality of and recommended dietary intakes for omega-6 and omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids. 2000;63(3):119-121.
23.
CrawfordMASinclairAJ. Nutritional influences in the evolution of the mammalian brain. In: ElliottKKnightJ, eds. Lipids, Malnutrition and the Developing Brain. Amsterdam: Associated Scientific Publishers; 1972:267-287.
24.
SinclairAJ. Long chain polyunsaturated fatty acids in the mammalian brain. Proc Nutr Soc. 1975;34:287-291.
25.
BroadhurstCLCunnaneSCCrawfordMA. Rift Valley lake fish and shellfish provided brain-specific nutrition for early Homo. Br J Nutr. 1998;79(1):3-21.
26.
EatonSBEatonSBIIISinclairAJCordainLMannNJ. Dietary intake of long-chain polyunsaturated fatty acids during the Paleolithic. World Rev Nutr Diet. 1998;83:12-23.
27.
SimopoulosAP. Overview of evolutionary aspects of ω-3 fatty acids in the diet. World Rev Nutr Diet. 1998;83:1-11.
28.
UauyRMenaPRojasC. Essential fatty acids in early life: structural and functional role. Proc Nutr Soc. 2000;59:3-15.
29.
SalemNJr. Omega-3 fatty acids: molecular and biochemical aspects. In: SpillerGAScalaJ, eds. New Roles for Selective Nutrients. New York: Alan R. Liss; 1989:109-228.
30.
MitchellDCStraumeMLitmanBJ. Role of sn-2-polyunsaturated lipids and control of membrane receptor conformational equilibrium: effects of cholesterol and acyl chain unsaturation on the metarhodopsin I–metarhodopsin II equilibrium. J Biochem. 1992;31:662-670.
31.
MitchellDCLitmanB. Effect of cholesterol on membrane order and dynamics in highly polyunsaturated phospholipid bilayers. Biophys J. 1998;75:896-908.
32.
HusterDArnoldKGarwrishK. Influence of docosahexaenoic acid and cholesterol on lateral domain organization in phospholipid mixtures. J Biochem. 1998;37(49):17299-17308.
33.
LitmanBJMitchellDC. A role for phospholipid polyunsaturation in modulating membrane protein function. Lipids. 1996;31:S193-S197.
34.
HibbelnJRSalemNJr. Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. Am J Clin Nutr. 1995;62:1-9.
35.
StollALLockeCAMarangellLBSeverusWE. Omega-3 fatty acids and bipolar disorder: a review. Prostaglandins Leukot Essent Fatty Acids. 1999;60:329-337.
36.
MartinRE. Docosahexaenoic acid decreases phospholipase A2 activity in the neurites/nerve growth cones of PC12 cells. J Neurosci Res. 1998;56(6):805-813.
37.
WainwrightPEBulman-FlemingMBLevesqueSMutsaersLMcCutcheonD. A saturated-fat diet during development alters dendritic growth in mouse brain. Nutr Neurosci. 1998;1:49-58.
38.
IkemotoANittaAFurukawaSOhishiMNakamuraAFujiiY. Dietary n-3 deficiency decreases nerve growth factor content in rat hippocampus. Neurosci Lett. 2000;285:99-102.
39.
WalterRCBufflerRTBruggemannJHGuillaumeMMBerheSMNegassiB. Early human occupation of the Red Sea coast of Eritrea during the last interglacial. Nature. 2000;405(6782):65-69.
40.
SinclairAJO’DeaKDunstanGIrelandPDNiallM. Effects on plasma lipids and fatty acid composition of very low fat diets enriched with fish or kangaroo meat. Lipids. 1987;22(7):523-529.
41.
NaughtonJMO’DeaKSinclairAJ. Animal foods in traditional Australian Aboriginal diets: polyunsaturated and low in fat. Lipids. 1986;21(11):684-690.
42.
McIntyreRSO’DonovanC. The human cost of not achieving full remission in depression. Can J Psychiatry. 2004;49:10S-16S.
43.
PaykelESScottJTeasdaleJDJohnsonALGarlandAMooreR. Prevention of relapse in residual depression by cognitive therapy: a controlled trial. Arch Gen Psychiatry. 1999;56:829-835.
44.
RossBMWardPGlenI. Delayed vasodilatory response to methylnicotinate in patients with unipolar depressive disorder. J Affect Disord. 2004;82:285-290.
45.
RossBMSieswerdaLE. ω-3 Fatty acids in affective and psychotic disorders. In: TealeMC, ed. ω-3 Fatty Acid Research. New York: Nova Science Publishers; 2006:276-312.
46.
SontropJCampbellMK. ω-3 Polyunsaturated fatty acids and depression: a review of the evidence and a methodological critique. Prev Med. 2006;42:4-13.
47.
RossBM. ω-3 Fatty acid deficiency in major depressive disorder is caused by the interaction between diet and a genetically determined abnormality in phospholipid metabolism. Med Hypotheses. 2007;68:515-524.
48.
MaesMSmithRChristopheACosynsPDesnyderRMeltzerH. Fatty acid composition in major depression: decreased ω-3 fractions in cholesteryl esters and increased C20:4 ω-6/C20:5 ω-3 ratio in cholesteryl esters and phospholipids. J Affect Disord. 1996;38: 35-46.
49.
MaesMChristopheADelangheJAltamuraCNeelsHMeltzerHY. Lowered ω-3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Res. 1999;85:275-291.
50.
TiemeierHvan TuijlHRHofmanAKiliaanAJBretelerMM. Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam Study. Am J Clin Nutr. 2003;78:40-46.
51.
Frasure-SmithNLesperanceFJulienP. Major depression is associated with lower ω-3 fatty acid levels in patients with recent acute coronary syndromes. Biol Psychiatry. 2004;55:891-896.
52.
PeetMMurphyBShayJHorrobinD. Depletion of ω-3 PUFA levels in red blood cell membranes of depressive patients. Biol Psychiatry. 1998;43:315-319.
53.
EdwardsRPeetMShayJHorrobinD. ω-3 Polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients. J Affect Disord. 1998;48:149-155.
54.
de VrieseSRChristopheABMaesM. Lowered serum n-3 polyunsaturated fatty acid (PUFA) levels predict the occurrence of postpartum depression: further evidence that lowered n-PUFAs are related to major depression. Life Sci. 2003;7(73):3181-3187.
55.
JansLAWGiltayEJVan der DoesAJW. The efficacy of n-3 fatty acids DHA and EPA (fish oil) for perinatal depression. Br J Nutr. 2010;104:1577-1585.
56.
SubletteMEHibbelnJRGalfalvyHOquendoMAMannJJ. ω-3 Polyunsaturated essential fatty acid status as a predictor of future suicide risk. Am J Psychiatry. 2006;163:1100-1102.
57.
LoganA. Omega-3 fatty acids and major depression: a primer for the mental health professional. Lipids Health Dis. 2004;3:25.
58.
MoriguchiTGeinerRSSalemN. Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration. J Neurochem. 2000;75:2563-2573.
59.
MorrisMCEvansDATangneyCBieniasJWilsonRS. Fish consumption and cognitive decline with age in a large community study. Arch Neurol. 2005;62:1849-1853.
60.
TanskanenAHibbelnJRTuomilehtoJUutelaAHaukkalaAViinamakiH. Fish consumption and depressive symptoms in the general population in Finland. Psychiatr Serv. 2001;52:529-531.
61.
HibbelnJR. Fish oil consumption and major depression. Lancet. 1998;351:1213.
62.
TimonenMHorrobinDJokelainenJLaitinenJHervaARasanenP. Fish consumption and depression: the Northern Finland 1966 birth cohort study. J Affect Disord. 2004;82:447-452.
63.
HibbelnJR. 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.
64.
HakkarainenRPartonenTHaukkaJVirtamoJAlbanesDLonnqvistJ. Is low dietary intake of ω-3 fatty acids associated with depression?Am J Psychiatry. 2004;161:567-569.
65.
OttenWIaizzoPAEichingerHM. Effects of a high n-3 fatty acid diet on membrane lipid composition of heart and skeletal muscle in normal swine and in swine with the genetic mutation for malignant hyperthermia. J Lipid Res. 1997;38:2023-2034.
66.
KeelanMHuiDYWildGClandininMTThomsonAB. Variability of the intestinal uptake of lipids is genetically determined in mice. Lipids. 2000;35(8):833-837.
67.
DayRNielsenJAKortenA. Stressful life events preceding the acute onset of schizophrenia: a cross-national study from the World Health Organization. Cult Med Psychiatry. 1987;11(2):123-205.
68.
SimKChuaTHChanYHMahendranRChongSA. Psychiatric comorbidity in first episode schizophrenia: a 2 year, longitudinal outcome study. J Psychiatr Res. 2006;40(7):656-663.
69.
GoldnerEMHsuLWaraichPSomersJM. Prevalence and incidence studies of schizophrenic disorders: a systematic review of the literature. Can J Psychiatry. 2002;47(9):833-843.
70.
SimsA. Symptoms in the Mind: An Introduction to Descriptive Psychopathology. 3rd ed.Philadelphia: W. B. Saunders; 2003.
71.
MarčinkoDMarčinkoVKarlovićD. Serum lipid levels and suicidality among male patients with schizoaffective disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2007;32(1):193-196.
72.
FentonWSHibbelnJKnableM. Essential fatty acids, lipid membrane abnormalities, and the diagnosis and treatment of schizophrenia. Biol Psychiatry. 2000;47(1):8-21.
73.
KeshavanMSStanleyJAPettegrewJW. Magnetic resonance spectroscopy in schizophrenia: methodological issues and findings—part II. Biol Psychiatry. 2000;48:369-380.
74.
RossBMTurenneSMosczynskaA. Differential alteration of phospholipase A2 activities in brains of patients with schizophrenia. Brain Res. 1999;821:407-413.
75.
PeetMStokesC. Omega-3 fatty acids in the treatment of psychiatric disorders. Drugs. 2005;65(8):1051-1059.
76.
ChristensenOChristensenE. Fat consumption and schizophrenia. Acta Psychiatr Scan. 1988;78(5):587-591.
SumiyoshiTMatsuiMItohH. Essential polyunsaturated fatty acids and social cognition in schizophrenia. Psychiatry Res. 2008;157:87-93.
79.
AssiesJLieverseRVrekenPWandersRJDingemansPMLinszenDH. Significantly reduced docosahexaenoic and docosapentaenoic acid concentrations in erythrocyte membranes from schizophrenic patients compared with a carefully matched control group. Biol Psychiatry. 2001;49:510-522.
80.
ConnorWENeuringerMLinDS. Dietary effects on brain fatty acid composition: the reversibility of n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys. J Lipid Res. 1990;31:237-247.
81.
PeetMLaugharneJDHorrobinDFRangarajanN. Depleted red cell membrane essential fatty acids in drug treated schizophrenic patients. J Psychiatr Res. 1995;29:227-232.
82.
KhanMMEvansDRGunnaVSchefferREParikhVVMahadikSP. 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.
83.
ArvindakshanMGhateMRanjekarPKEvansDRMahadikSP. Supplementation with a combination of omega-3 fatty acids and antioxidants (vitamins E and C) improves the outcome of schizophrenia. Schizophr Res. 2003;62:195-204.
84.
PeetMShahSSelvamKRamchandCN. Polyunsaturated fatty acid levels in red cell membranes of unmedicated schizophrenic patients. World J Biol Psychiatry. 2004;5(2):92-99.
85.
ReddyRDKeshavanMSYaoJK. Reduced red blood cell membrane essential polyunsaturated fatty acids in first episode schizophrenia at neuroleptic-naive baseline. Schizophr Bull. 2004;30:901-911.
86.
RanjekarPKHingeAHegdeMV. Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatr Res. 2003;121(2):109-122.
87.
EvansDRParikhVVKhanMMCoussonsCBuckleyPFMahadikSP. Red blood cell membrane essential fatty acid metabolism in early psychotic patients following antipsychotic drug treatment. Prostaglandins Leukot Essent Fatty Acids. 2003;69(6):393-399.
88.
DorisABWahleKMacDonaldA. Red cell membrane fatty acids, cytosolic phospholipase-A2 and schizophrenia. Schizophr Res. 1998;31:185-196.
89.
MacleanRWardPEGlenIRobertsSJRossBM. On the relationship between methylnicotinate-induced skin flush and fatty acids levels in acute psychosis. Progr Neuropsychopharmacol Biol Psychiatry. 2003;27(6):927-933.
90.
GoodwinFKJamisonKR. Manic Depressive Illness. Oxford, England: Oxford University Press; 1990.
Basco RamirezM. The Bipolar Workbook: Tools for Controlling Your Mood Swings. New York: Guilford; 2006.
93.
GitlinMJSwendsenJHellerTLHammenC. Relapse and impairment in bipolar disorder. Am J Psychiatry. 1995;152:1635-1640.
94.
SchwarzEPrabakaranSWhitfieldP. High throughput lipidomic profiling of schizophrenia and bipolar disorder brain tissue reveals alterations of free fatty acids, phosphatidylcholines, and ceramides. J Proteome Res. 2008;7(10):4266-4277.
95.
HorrobinDFBennettCN. 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(4):217-234.
96.
StollALSeverusWEFreemanMP. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry. 1999;56(5):407-412.
97.
SperlingRIBenincasoAIKnoellCTLarkinJKAustenKFRobinsonDR. Dietary omega-3 polyunsaturated fatty acids inhibit phosphoinositide formation and chemotaxis in neutrophils. J Clin Invest. 1993;91:651-660.
98.
TappiaPSLadhaSClarkDCGrimbleRF. 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.
99.
ChiuCCHuangSYSuKP. Polyunsaturated fatty acid deficit in patients with bipolar mania. Eur Neuropsychopharmacol. 2003;13(2):99-103.
OsherYBersudskyYBelmakerRH. Omega-3 eicosapentaenoic acid in bipolar depression: report of a small open-label study. J Clin Psychiatry. 2005;66:726-729.
102.
TurnbullTCullen-DrillMSmaldoneA. Efficacy of omega-3 fatty acid supplementation on improvement of bipolar symptoms: a systematic review. Arch Psychiatr Nurs. 2008;22:305-311.
103.
MarangellLBSuppesTKetterTA. Omega-3 fatty acids in bipolar disorder: clinical and research considerations. Prostaglandins Leukot Essent Fatty Acids. 2006;75(4-5):315-321.
104.
SubletteMEBosettiFDeMarJC. Plasma free polyunsaturated fatty acid levels are associated with symptom severity in acute mania. Bipolar Disord. 2007;9(7):759-765.
105.
LiebJKarmaliRHorrobinD. Elevated levels of prostaglandin E2 and thromboxane B2 in depression. Prostaglandins Leukot Med. 1983;10:361-367.
106.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000.
107.
BauerMEWieckALopesRPTeixeiraALGrassi-OliveiraR. Interplay between neuroimmunoendocrine systems during post-traumatic stress disorder: a minireview. Neuroimmunomodulation. 2010;17(3):192-195.
108.
ZoričićZKarlovićDBuljanDMarušićS. Comorbid alcohol addiction increases aggression level in soldiers with combat-related posttraumatic stress disorder. Nord J Psychiatry. 2003;57: 199-202.
109.
Kozarić-KovačićDHercigonjaDKGrubišić-IlićM. Posttraumatic stress disorder and depression in soldiers with combat experiences. Croat Med J. 2001;42:165-170.
110.
KarlovićDBuljanDMartinacMMarčinkoD. Serum lipid concentrations in Croatian veterans with post-traumatic stress disorder, post-traumatic stress disorder comorbid with major depressive disorder, or major depressive disorder. J Korean Med Sci. 2004;19:431-436.
111.
SolomonSDGerrityETMuffAM. Efficacy of treatments for posttraumatic stress disorder: an empirical review. JAMA. 1992;268:633-638.
112.
DavidsonJRColketJT. The eight-item treatment-outcome post-traumatic stress disorder scale: a brief measure to assess treatment outcome in post-traumatic stress disorder. Int Clin Psychopharmacol. 1997;12:41-45.
113.
Džubur KulenovićAKučukalićAMalečD. Changes in plasma lipid concentrations and risk of coronary artery disease in army veterans suffering from chronic posttraumatic stress disorder. Croat Med J. 2008;49(4):506-514.
114.
KarlovićDMartinacMBuljanDZoričićZ. Relationship between serum lipid concentrations and posttraumatic stress disorder symptoms in soldiers with combat experiences. Acta Medica Okayama. 2004;58(1):23-27.
115.
SolterVThallerVKarlovićDCrnkovićD. Elevated serum lipids in veterans with combat-related chronic posttraumatic stress disorder. Croat Med J. 2002;43(6):685-689.
116.
KaganBLLeskinGHaasBWilkinsJFoyD. Elevated lipid levels in Vietnam veterans with chronic posttraumatic stress disorder. Biol Psychiatry. 1999;45:374-377.
117.
KaplanZMatarMKaminRCohenH. Possible deleterious effects of adjunctive omega-3 fatty acids in post-traumatic stress disorder patients. Neuropsychiatr Dis Treat. 2005;1(2):187-190.
