Smoking, gender, and dietary influences on erythrocyte essential fatty acid composition among patients with schizophrenia or schizoaffective disorder

Joseph R. Hibbeln, Kevin K. Makino, Catherine E. Martin, Faith Dickerson, John Boronow, Wayne S. Fenton

Research output: Contribution to journalArticlepeer-review

106 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)431-441
Number of pages11
JournalBiological Psychiatry
Issue number5
StatePublished - Mar 1 2003
Externally publishedYes


  • Arachidonic acid
  • Docosahexaenoic acid
  • Eicosapentaenoic acid
  • Omega-3 fatty acids
  • Schizophrenia
  • Smoking

ASJC Scopus subject areas

  • Biological Psychiatry


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