Elevated Delta-6 desaturase (FADS2) gene expression in the prefrontal cortex of patients with bipolar disorder

Although evidence suggests that a dysregulation in polyunsaturated fatty acid (PUFA) homeostasis may contribute to the pathoetiology of bipolar disorder (BD), there is currently nothing known about the expression of genes that mediate long-chain PUFA biosynthesis in BD patients. In the present study we determined FADS1 (Δ5 desaturase), FADS2 (Δ6 desaturase), HELO1 [ELOVL5] (elongase), PEX19 (peroxisome), and SCD (stearoyl-CoA desaturase [Δ9 desaturase]) mRNA expression in the postmortem prefrontal cortex of non-psychiatric controls (n = 12) and BD patients (n = 12) by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Changes in the activities of corresponding enzyme products were estimated from fatty acid product: precursor ratios. After correcting for multiple comparisons, FADS2 mRNA expression was significantly greater in BD patients relative to controls (+27%, p = 0.004). Indices of Δ6 desaturase activity, including 20:4/18:2 (+18%, p = 0.15) and 20:3/18:2 (+12%, p = 0.25) ratios, were numerically, but not significantly, greater in BD patients relative to controls. There were no significant group differences in FADS1 (+17%, p = 0.32), HELO1 (+4%, p = 0.81), PEX19 (-2%, p = 0.91), and SCD (+4%, p = 0.85) mRNA expression, or indices of Δ5 desaturase (+5%, 0.59), elongase (+3%, p = 0.62), and stearoyl-CoA desaturase (-11%, p = 0.10) activities. These preliminary findings demonstrate that FADS2 mRNA expression is significantly and selectively elevated in the prefrontal cortex of BD patients, and may contribute to dysregulated central PUFA biosynthesis and pro-inflammatory signaling implicated in the pathophysiology of BD.