Elevated delta-6 desaturase (FADS2) expression in the postmortem prefrontal cortex of schizophrenic patients: Relationship with fatty acid composition

SCHIZOPHRENIA RESEARCH

卷:109

Article

Liu, Yanhong¹  Jandacek, Ronald²  Rider, Therese²  Tso, Patrick²  McNamara, Robert K.¹ 

[1] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA

[2] Univ Cincinnati, Dept Pathol, Cincinnati, OH 45237 USA

关键词: Schizophrenia;    Postmortem;    Prefrontal cortex;    Saturated fatty acids;    Monounsaturated fatty acids;    Polyunsaturated fatty acids;    Stearoyl-CoA desaturase (SCD);    Delta-5 desaturase (FADS1);    Delta-6 desaturase (FADS2);    Elongase (HELO1);    Peroxisome (PEX19);   

DOI  :  10.1016/j.schres.2008.12.027

来源: Elsevier

【 摘 要 】

Although emerging evidence Suggests that schizophrenia (SZ) is associated with peripheral and central polyunsaturated fatty acid (PUFA) deficits, there is currently nothing known about the expression of genes that mediate PUFA biosynthesis in SZ patients. Here we determined Delta 5 desaturase (FADS1), Delta 6 desaturase (FADS2), elongase (HELO1 [ELOVL5]), peroxisomal (PEX19), and Delta 9 desaturase (stearoyl-CoA desaturase, SCD) mRNA expression, and relevant fatty acid product: precursor ratios as estimates of enzyme activities, in the postmortem prefrontal cortex (PFC) of patients with SZ (it = 20) and non-psychiatric controls (n = 20). After correction for multiple comparisons, FADS2 mRNA expression was significantly greater in SZ patients relative to controls (+36%, p=0.002), and there was a positive trend found for FADS1 (+26%, p=0.15). No differences were found for HELO1 (+10%,p=0.44),PEX19(+12%,p=0.44),or SCD (-6%. p=0.85). Both male (+34%, p=0.02) and female (+42%, p=0.02) SZ patients exhibited greater FADS2 mRNA expression relative to same-gender controls. Drug-free SZ patients (+ 37%, p=0.02), and SZ patients treated with typical (+40%, p = 0.002) or atypical (+ 31 %, p = 0.04) antipsychotics, exhibited greater FADS2 mRNA expression relative to controls. Consistent with increased Delta 6 desaturase activity, SZ patients exhibited a greater 20:3/18:2 ratio (+20%, p = 0.03) and a positive trend was found for 20:4/18:2 (+ 13%, p = 0.07). These data demonstrate abnormal, potentially compensatory, elevations in Delta 6 desaturase (FADS2) expression in the PFC of SZ patients that are independent of gender and antipsychotic medications. Greater Delta 6 desaturase expression and activity Could have implications for central prostaglandin synthesis and proinflammatory signaling. (C) 2009 Elsevier B.V. All rights reserved.

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