Reduced expression of fatty acid biosynthesis genes in the prefrontal cortex of patients with major depressive disorder.
BACKGROUND
Major depressive disorder (MDD) is associated with central and peripheral deficits in long-chain polyunsaturated fatty acids (LC-PUFA), particularly those in the omega-3 fatty acid family. However, the etiology of these deficits remains poorly understood, and there is currently little known about the expression of genes that mediate fatty acid biosynthesis in MDD patients.


METHODS
The expression of FADS1 (Δ5 desaturase), FADS2 (Δ6 desaturase), HELO1 [ELOVL5] (elongase), PEX19 (peroxisome), and SCD (stearoyl-CoA desaturase [Δ9 desaturase]) was determined in the postmortem prefrontal cortex of MDD patients (n=10) and non-psychiatric controls (n=10) by real-time reverse transcriptase polymerase chain reaction (RT-PCR).


RESULTS
After correcting for multiple comparisons, FADS1 mRNA expression was significantly lower in MDD patients relative to controls (-27%, p=0.009), and there were trends for lower expression of FADS2 (-30%, p=0.07), HELO1 (-37%, p=0.02), and SCD (-43%, p=0.02). PEX19 mRNA expression did not differ between controls and MDD patients (-2%, p=0.92). There were no significant gender effects, and relative reductions in FADS1, HELO1, and SCD expression were greater in patients that did not commit suicide compared with patients that did commit suicide.


CONCLUSIONS
The sample size was small, and all MDD patients were receiving antidepressant medications.


CONCLUSIONS
Principal genes involved in LC-PUFA and monounsaturated fatty acid biosynthesis are down-regulated in the postmortem prefrontal cortex of MDD patients. Additional studies are needed to replicate and extend these findings in a larger sample that includes antidepressant-free MDD patients.
McNamara
Robert K
RK
Department of Psychiatry, Lipidomics Research Program, University of Cincinnati College of Medicine, Cincinnati, OH 45219, United States. robert.mcnamara@uc.edu
Liu
Yanhong
Y
D000123:Acetyltransferases / Q000378:metabolism; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D000090943:Delta-5 Fatty Acid Desaturase; D003865:Major Depressive Disorder / Q000378:metabolism*; D044943:Fatty Acid Desaturases / Q000378:metabolism; D000081031:Fatty Acid Elongases; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism
D000090943:Delta-5 Fatty Acid Desaturase; C000630954:ELOVL5 protein, human; D005231:Fatty Acids, Unsaturated; D008565:Membrane Proteins; C087343:PEX19 protein, human; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; C000716847:FADS1 protein, human; C533241:FADS2 protein, human; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases