Abstract
Background
Prior reports of decreased levels of essential fatty acids among schizophrenic patients
have generated several hypotheses proposing inherent abnormalities in phospholipid
and fatty acid metabolism and have provided the basis for treatment trials; however,
these essential fatty acid aberrations may be attributable to uncontrolled factors,
such as smoking, rather than abnormalities inherent to schizophrenia.
Methods
Erythrocyte fatty acid compositions were quantified in 72 medicated schizophrenic
or schizoaffective patients both at baseline and after 16 weeks of supplementation
with 3 g/day of either ethyl-eicosapentaenoic acid or placebo. Current smoking status,
gender, dietary survey, and Montgomery Asburg Depression Rating Scale, Repeatable
Battery for the Assessment of Neuropsychological Status, Abnormal Involuntary Movement
Scale, and Positive and Negative Syndrome Scale scores were assessed.
Results
Schizophrenic patients who smoked had lower baseline erythrocyte docosahexaenoic acid
percent (2.98 ± .7 vs. 3.59 ± 1.2, p < .005) and eicosapentaenoic acid (EPA) percent (.39 ± .13 vs. .47 ± .22, p < .05), compared with nonsmokers, with a significant gender interaction (p < .01) in multivariate analyses of variance. Baseline arachidonic acid did not differ.
Smokers reported lower dietary intake (percent total fat) of linolenic acid (F = 10.1, p < .003) compared with nonsmokers. Nonsmoking women reported greater dietary intake
of EPA compared with smoking men or nonsmokers of either gender.
Conclusions
Smoking status, gender, and dietary intake significantly predicted erythrocyte polyunsaturated
fatty acid status among schizophrenic patients. No evidence was found for subgroups
of schizophrenia or relationships to specific symptom severity on the basis of erythrocyte
fatty acids. Prior reports of abnormalities of essential fatty acid metabolism among
schizophrenic patients may have been an artifact of patients’ smoking behavior and
differences in dietary intake of ω-3 fatty acids.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Phospholipase A2 activity in serum of neuroleptic-naive psychiatric inpatients.Pharmacopsychiatry. 1993; 26: 94-98
- Significantly reduced docosahexaenoic and docosapentaenoic acid concentrations in erythrocyte membranes from schizophrenic patients compared with a carefully matched control group.Biol Psychiatry. 2001; 6: 510-522
- The role of phospholipase A activity in rat liver microsomal lipid peroxidation.J Biol Chem. 1987; 262: 1479-1484
- Phospholipase A2 activity in Epstein-Barr virus-transformed lymphoblast cells from schizophrenic patients.Biol Psychiatry. 1991; 29: 1058-1062
- Cigarette smoking and serum lipid and lipoprotein concentrations.BMJ. 1989; 298: 784-788
- Nutrient intake according to education, smoking, and alcohol in Italian women.Nutr Cancer. 1997; 28: 46-51
- 31phosphorus magnetic resonance spectroscopy of the frontal and parietal lobes in chronic schizophrenia.Biol Psychiatry. 1994; 36: 503-510
- Asymmetry of temporal lobe phosphorous metabolism in schizophrenia.Biol Psychiatry. 1995; 38: 279-286
- Substances affirmed as generally recognized as safe.Federal Register. 1997; 62: 30751-30757
- Differential prevalence of cigarette smoking in patients with schizophrenic vs. mood disorders.Schizophr Res. 1998; 1–2: 113-118
- Red cell membrane fatty acids, cytosolic phospholipase-A2 and schizophrenia.Schizophr Res. 1998; 31: 185-196
- A placebo-controlled trial of omega-3 fatty acid (ethyl-EPA) supplementation for residual symptoms and cognitive impairment in schizophrenia.Am J Psychiatry. 2001; 158: 2071-2074
- Essential fatty acids, lipid membrane abnormalities, and the diagnosis and treatment of schizophrenia.Biol Psychiatry. 2000; 47: 8-21
- Study of chronic schizophrenic patients using 31P magnetic resonance chemical shift imaging.Acta Psychiatr Scand. 1992; 86: 455-462
- Changes in levels of phosphorus metabolites in temporal lobes of drug-naive schizophrenic patients.Am J Psychiatry. 1999; 156: 1205-1208
- Haloperidol improves membrane phospholipid abnormalities in temporal lobes of schizophrenic patients.Neuropsychopharmacology. 1999; 21: 542-549
- Phosphorus magnetic resonance spectroscopy in schizophrenia.Prog Neuropsychopharmacol Biol Psychiatry. 1996; 20: 629-640
- Phospholipase A2 and the hypofrontality hypothesis of schizophrenia.Prostaglandins Leukot Essent Fatty Acids. 1996; 55: 109-113
- Increased serum phospholipase A2 activity in schizophrenia.Biol Psychiatry. 1990; 28: 495-501
- Increased plasma phospholipase-A2 activity in schizophrenic patients.Biol Psychiatry. 1987; 22: 421-426
- A red cell membrane abnormality in a subgroup of schizophrenic patients.Schizophr Res. 1994; 12: 53-61
- Effects of highly purified eicosapentaenoic acid and docosahexaenoic acid on hemodynamics in humans.Am J Clin Nutr. 1998; 68: 52-59
- Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids.Am J Clin Nutr. 1997; 66: 649-659
- Magnetic resonance imaging volumetric and phosphorus 31 magnetic resonance spectroscopy measurements in schizophrenia.J Psychiatry Neurosci. 1997; 22: 111-117
Hirai A, Terano T, Saito H, Tamura Y (1989): Omega-3 fatty acids: Epidemiological and clinical aspects. In: Spiller GA, Scala J, editors. New Protective Roles for Selected Nutrients. New York: Alan R. Liss Inc., pp 229–252
- The lipid hypothesis of schizophrenia.in: Skinner E.R. Brain Lipids and Disorders in Biological Psychiatry. Elsevier, New York2002: 39-49
- The membrane phospholipid hypothesis as a biochemical basis for the neurodevelopmental concept of schizophrenia.Schizophr Res. 1998; 30: 193-208
- Essential fatty acids in plasma phospholipids in schizophrenic patients.Biol Psychiatry. 1989; 25: 562-568
- Comparison of measures of fatty acid intake by subcutaneous fat aspirate, food frequency questionnaire, and diet records in a free-living population of US men.Am J Epidemiol. 1992; 135: 418-427
- No differences in phospholipase-A2 activity between acute psychiatric patients and controls.Schizophr Res. 1997; 26: 103-105
- Lateralized abnormality of high-energy phosphate and bilateral reduction of phosphomonoester measured by phosphorus-31 magnetic resonance spectroscopy of the frontal lobes in schizophrenia.Psychiatry Res. 1995; 61: 151-160
- The positive and negative syndrome scale (PANSS) for schizophrenia.Schizophr Bull. 1987; 13: 261-276
- Frontal lobe metabolism and cerebral morphology in schizophrenia.Schizophr Res. 1993; 10: 241-246
- Phospholipid abnormalities in postmortem schizophrenic brains detected by 31P nuclear magnetic resonance spectroscopy.Psychiatry Res. 2001; 106: 171-180
- Diet and lung cancer 20+ years later.Int J Cancer. 1997; 10: 22-29
- Translating research into practice.Schizophr Bull. 1998; 24: 1-10
- Smoking and schizophrenia.Schizophr Res. 1992; 8: 93-102
- Fatty acid composition of subcutaenous adipose tissue and diet in postmenopausal women.Am J Epidemiol. 1991; 54: 340-345
- Oxidative stress and role of antioxidant and ω-3 essential fatty acid supplementation in schizophrenia.Prog Neuropsychopharmacol Biol Psychiatry. 2001; 25: 463-493
- Nicotine-induced inhibition of neuronal phospholipase A2.J Pharmacol Exp Ther. 1997; 280: 1277-1283
- Schizophrenia symptoms and dietary intake of n-3 fatty acids.Schizophr Res. 1995; 18: 85-86
- A new depression scale designed to be sensitive to change.Br J Psychiatry. 1979; 134: 382-389
- Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans.Hypertension. 1999; 34: 253-260
- Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration.J Neurochem. 2000; 75: 2563-2573
- Preparation of fatty acid methyl esters and dimethylacetals with boron-fluoride methanol.J Lipid Res. 1959; 5: 600-608
- Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. Smoking as a cause of oxidative damage.N Eng J Med. 1995; 332: 1198-1203
National Institutes of Mental Health (1976): ECDEU Assessment Manual for Psychopharmacology. In: Guy W, editor. Washington, DC: U.S. Department of Health Education and Welfare
- CGI (Clinical Global Impression) Scale.Psychopharmacology Bulletin. 1985; 21: 839-840
- Phospholipase A(2)s and lipid peroxidation.Biochim Biophys Acta. 2000; 1488: 167-181
- Elevated PLA2 activity in schizophrenic patients and other psychiatric patients.Biol Psychiatry. 1993; 34: 641-649
- Initial investigation of the left temporoparietal region in schizophrenia by 31P magnetic resonance spectroscopy.Biol Psychiatry. 1991; 29: 1149-1152
- Increased platelet membrane lysophosphatidylcholine in schizophrenia.Biol Psychiatry. 1991; 30: 837-840
- Alcohol consumption in rhesus monkeys depletes tissues of polyunsaturated fatty acids and alters essential fatty acid metabolism.Alcohol Clin Exp Res. 1999; 23: 311-317
- Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia.Schizophr Res. 2001; 49: 243-251
- Phospholipid Spectrum Disorder in Psychiatry. Marius Press, Lancashire, UK1999
- Depleted red cell membrane essential fatty acids in drug-treated schizophrenic patients.J Psychiatr Res. 1995; 29: 227-232
- Arachidonic acid.Arch Gen Psychiatry. 1994; 51: 665-666
- Essential fatty acid deficiency in erythrocyte membranes from chronic schizophrenic patients and the clinical effects of dietary supplementation.Prostaglandins Leukot Essent Fatty Acids. 1996; 55: 71-75
- Association of the Ban I dimorphic site at the human cytosolic phospholipase A2 gene with schizophrenia.Psychiatr Genet. 1998; 8: 191-192
- 31P nuclear magnetic resonance spectroscopy.Schizophr Bull. 1993; 19: 35-53
- Alterations in brain high-energy phosphate and membrane phospholipid metabolism in first-episode, drug-naive schizophrenic patients. A pilot study of the dorsal prefrontal cortex by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy.Arch Gen Psychiatry. 1991; 48: 563-568
- Chemistry of lipid peroxidation.Methods Enzymol. 1984; 105: 273-282
- Cigarette smoke radicals and the role of free radicals in chemical carcinogenicity.Environ Health Perspect. 1997; 105: 875-882
- Sustained remission of positive and negative symptoms of schizophrenia following treatment with eicosapentaenoic acid.Arch Gen Psychiatry. 1998; 55: 188-189
- Eicosapentaenoic acid treatment in schizophrenia associated with symptom remission, normalisation of bloody fatty acids, reduced neuronal membrane phospholipid turnover and structural brain changes.Int J Clin Pract. 2000; 54: 57-63
- RBANS Manual-Repeatable Battery for the Assessment of Neuropsychological Status. Psychological Corp. (Harcourt), San Antonio, TX1998
- Delivery and turnover of plasma-derived essential PUFAs in mammalian brain.J Lipid Res. 2001; 42: 678-685
- Comparison between fat intake assessed by a 3-day food record and phospholipid fatty acid composition of red blood cells.Metabolism. 1995; 44: 1139-1145
- Increased phospholipid breakdown in schizophrenia. Evidence for the involvement of a calcium-independent phospholipase A2.Arch Gen Psychiatry. 1997; 54: 487-494
- Differential alteration of phospholipase A2 activities in brain of patients with schizophrenia.Brain Res. 1999; 821: 407-413
- Phospholipid and prostaglandin hypotheses of schizophrenia.in: Meltzer H. Psychopharmacology The Third Generation of Progress. Raven Press, New York1987: 759-764
- Formation and retention of cotinine during placental transfer of nicotine in human placental cotyledon.Pharmacology. 1998; 57: 104-116
- Influence of nicotine and cotinine on retinal phospholipase A2 and its significance to macular function.J Ocul Pharmacol Ther. 1998; 14: 447-458
- Frontal lobe membrane phospholipid metabolism and ventricle to brain ratio in schizophrenia.Eur Arch Psychiatry Clin Neurosci. 2000; 250: 169-174
- Relation of smoking and alcohol consumption to serum fatty acids.Am J Epidemiol. 1996; 144: 325-334
- A rating scale for extrapyramidal side effects.Acta Psychiatr Scand Suppl. 1970; 212: 11-19
- Membrane phospholipid metabolism and schizophrenia.Schizophr Res. 1994; 13: 209-215
- An in vivo study of the prefrontal cortex of schizophrenic patients at different stages of illness via phosphorus magnetic resonance spectroscopy.Arch Gen Psychiatry. 1995; 52: 399-406
- Genetic polymorphisms, lipoproteins and coronary artery disease risk.Curr Opin Lipidol. 2001; 12: 405-409
- Dietary change after smoking cessation.Br J Nutr. 1995; 74: 27-38
- A double blind trial of essential fatty acid supplementation in patients with tradive dyskinesia.Psychiatry Res. 1989; 27: 313-323
- A controlled trial of prostaglandin E1 precursor in chronic neuroleptic resistant schizophrenic patients.Psychopharmacology. 1986; 88: 362-367
- Schizophrenia, tardive dyskinesia and essential fatty acids.Schizophr Res. 1996; 20: 287-294
- Reduced phosphodiesters and high-energy phosphates in the frontal lobe of schizophrenic patients.Biol Psychiatry. 2000; 47: 954-961
- Increase of phosphodiesters during neuroleptic treatment of schizophrenic patients.Biol Psychiatry. 1999; 45: 1221-1225
- Metabolism and effects on platelet function of the purified eicosapentaenoic and docosahexaenoic acids in humans.J Clin Invest. 1985; 76: 2446-2450
- Reproducibility and validity of a semiquantitative food frequency questionnaire.Am J Epidemiol. 1985; 122: 51-65
- Membrane phospholipid abnormalities in postmortem brains from schizophrenic patients.Schizophr Res. 2000; 42: 7-17
- Red blood cell membrane dynamics in schizophrenia. III. Correlation of fatty acid abnormalities with clinical measures.Schizophr Res. 1994; 13: 227-232
- Red blood cell membrane dynamics in schizophrenia. II. Fatty acid composition.Schizophr Res. 1994; 13: 217-226
Article info
Publication history
Accepted:
July 10,
2002
Received in revised form:
July 2,
2002
Received:
December 31,
2001
Identification
Copyright
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
