Altered expression of lipid metabolism and immune response genes in the frontal cortex of suicide completers.
BACKGROUND
Studies investigating the association between low cholesterol and suicidality have generated a range of ideas about how cholesterol might play a role in influencing suicide risk, extending studies to other aspects of lipid metabolism, as well as immune response, in relation to suicide.


METHODS
We performed large-scale microarray gene expression analysis using the Affymetrix HG-U133 chipset and focused our investigation on the expression profile of genes related to lipid metabolism and immune response in post-mortem brains from suicide completers and comparison subjects. We used tissue from three regions of the frontal cortex (Brodmann areas (BA) 8/9, 11, and 47) from 22 male suicide completers, 15 of whom were diagnosed with major depressive disorder, and 13 male comparison subjects.


RESULTS
Fatty acid desaturase (FADS1), leptin receptor (LEPR), phosphoinositide-3-kinase (class 2 alpha; PIK3C2A) and stearoyl-CoA desaturase (SCD) were consistently down-regulated in all three regions of the frontal cortex of depressed suicides compared to comparison subjects, and were among the genes for which significant correlations were observed between our microarray and real-time PCR data.


CONCLUSIONS
Given the absence of a non-suicidal depressed comparison group in this study, it cannot be ascertained whether the gene expression changes identified are associated with depression or suicide.


CONCLUSIONS
Our findings suggest a role for lipid metabolism and immune response genes in depressed suicide completers and lend further support to the relationship between lipid metabolism and suicidality.
Lalovic
Aleksandra
A
McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Verdun, Québec, Canada.
Klempan
Tim
T
Sequeira
Adolfo
A
Luheshi
Giamal
G
Turecki
Gustavo
G
D000293:Adolescent; D000328:Adult; D000090943:Delta-5 Fatty Acid Desaturase; D003865:Major Depressive Disorder / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005625:Frontal Lobe / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D040081:Protein Array Analysis; D054411:Receptors, Leptin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013405:Suicide / Q000523:psychology* / Q000706:statistics & numerical data*; D055815:Young Adult
D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases; D019869:Phosphatidylinositol 3-Kinases; D054411:Receptors, Leptin; D013230:Stearoyl-CoA Desaturase; C515448:LEPR protein, human; C523776:SCD1 protein, human; C000716847:FADS1 protein, human; C546621:PIK3C2A protein, human