European Neuropsychopharmacology 13 (2003) 99–103 www.elsevier.com / locate / euroneuro Polyunsaturated fatty acid deficit in patients with bipolar mania a,b b c,d, c,d a * Chih-Chiang Chiu , Shih-Yi Huang , Kuan-Pin Su , Mong-Liang Lu , Ming-Chyi Huang , a c,d Chiao-Chicy Chen , Winston W. Shen a Laboratory of Biological Psychiatry, Taipei City Psychiatric Center, School of Medicine, and Taipei Medical University, Taipei, Taiwan b Graduate Institute of Nutrition and Health Sciences, School of Medicine, and Taipei Medical University, Taipei, Taiwan c Department of Psychiatry, Taipei Medical University Wan Fang Hospital, School of Medicine, and Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan d Department of Psychiatry, China Medical College and Hospital, Taichung, Taiwan Received 15 April 2002; accepted 26 September 2002 Abstract The aim of this study is to test the hypothesis that there is a depletion of polyunsaturated fatty acids of erythrocyte membranes in patients with bipolar disorder and to connect the previous therapeutic and psychoimmunological findings. Fatty acid compositions of erythrocyte membranes in 20 bipolar manic patients and 20 healthy controls were analyzed by thin-layer chromatography and gas chromatography. The major finding was significantly reduced arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) compositions in bipolar patients as compared to normal controls with P values of 0.000 and 0.002, respectively. There were no differences in total omega-3 and omega-6 polyunsaturated fatty acids. This abnormality may be related to the mechanisms of action of mood stabilizers and the previous findings on the abnormal psychoimmunology of patients with bipolar disorder. Larger sample sizes of medicated patients or drug-free manic, well-controlled designs on the diet and smoking, and fatty acid composition measurements during full remission after the index episode are warranted in future studies.  2002 Elsevier Science B.V./ECNP All rights reserved. Keywords: Omega-3 polyunsaturated fatty acids (PUFA’s); Pregnancy; Bipolar mania; Arachidonic acid (AA); Ecosapentaenoic acid (EPA); Docosahex- aenoic acid (DHA); Taiwan 1. Introduction (PUFA) in rat brain. Furthermore, a 4-month double-blind, placebo-controlled study, comparing omega-3 PUFAs vs. Several investigators (Stoll and Severus, 1996; Manji placebo, in addition to usual treatment, suggested that and Lenox, 1998) strongly suggested that the mechanism omega-3 PUFAs may exhibit mood-stabilizing properties of action of mood stabilizers is involved in postsynaptic in bipolar disorder (Stoll et al., 1999). Thus, PUFAs, as signal transduction processes. Two mood stabilizers well as lithium and antimanic anticonvulsants, seem to (lithium and valproate) appear to treat the same symptoms play an important role in the mechanism of mood stabiliza- of patients with bipolar disorder, through different effects tion by targeting parts of the ‘‘arachidonic acid cascade’’, on signal transduction in the brain. Recently, Chang et al. which may be functionally hyperactive in mania (Rapoport (2001) found that lithium and valproic acid have a and Bosetti, 2002). common action in reducing turnover of arachidonic acid It has been hypothesized that abnormalities in fatty acid (AA), the major omega-6 polyunsaturated fatty acids composition may play a role in psychiatric disorders (Horrobin and Bennett, 1999). Maes et al. (1996, 1999) reported that patients with major depression had a sig- *Corresponding author. Department of Psychiatry, China Medical nificantly elevated ratio of ecosapentaenoic acid (EPA; College Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan. Tel.: 20:5n-3) / docosahexaenoic acid (DHA; 22:6n-3), lower 1886-4-2206-2121x5076; fax: 1886-4-2236-1230. E-mail address: cobol@www.cmch.org.tw (K.-P. Su). level of EPA and total n-3 PUFAs, in both serum choles- 0924-977X / 02 / $ – see front matter  2002 Elsevier Science B.V./ECNP All rights reserved. doi:10.1016/S0924-977X(02)00130-X