Altered gene expression in the dorsolateral prefrontal cortex of individuals with schizophrenia

Abstract

The underlying pathology of schizophrenia (SZ) is likely as heterogeneous as its symptomatology. A variety of cortical and subcortical regions, including the prefrontal cortex, have been implicated in its pathology, and a number of genes have been identified as risk factors for disease development. We used in situ hybridization (ISH) to examine the expression of 58 genes in the dorsolateral prefrontal cortex (DLPFC, comprised of Brodmann areas 9 and 46) from 19 individuals with a premorbid diagnosis of SZ and 33 control individuals. Genes were selected based on: (1) previous identification as risk factors for SZ; (2) cell type markers or (3) laminar markers. Cell density and staining intensity were compared in the DLPFC, as well as separately in Brodmann areas 9 and 46. The expression patterns of a variety of genes, many of which are associated with the GABAergic system, were altered in SZ when compared with controls. Additional genes, including C8orf79 and NR4A2, showed alterations in cell density or staining intensity between the groups, highlighting the need for additional studies. Alterations were, with only a few exceptions, limited to Brodmann area 9, suggesting regional specificity of pathology in the DLPFC. Our results agree with previous studies on the GABAergic involvement in SZ, and suggest that areas 9 and 46 may be differentially affected in the disease. This study also highlights additional genes that may be altered in SZ, and indicates that these potentially interesting genes can be identified by ISH and high-throughput image analysis techniques.

GABAergic Control of Depression-Related Brain States

“…By contrast, PV transcript levels are normal in patients with MDD (Guilloux et al, 2012; Rajkowska et al, 2007; Sibille et al, 2011). However, reduced expression of SST is not exclusively found in MDD but has also been reported for schizophrenia (Guillozet-Bongaarts et al, 2014; Morris, Hashimoto, & Lewis, 2008). Collectively the data suggest that at the cellular and molecular level GABAergic deficits associated with schizophrenia and MDD include both disease-specific and common characteristics.…”

Perinatal Phosphatidylcholine Supplementation and Early Childhood Behavior Problems: Evidence for CHRNA7 Moderation

“…Chromosomal copy number variants in the CHRNA7 region, some isolating the gene itself, have been found in all three illnesses, along with positive association studies and genetic linkage (6–8). CHRNA7 is the most significantly decreased neocortical mRNA in schizophrenia, and it is decreased in ASD as well (9, 10). The aim of this study was to assess whether this genetic diathesis can be mitigated by an intervention during perinatal brain development.…”

Modulation of behavioral networks by selective interneuronal inactivation

“…26 The peptide was also increased following chronic stress 28 or amphetamine administration 29 in rodents, whereas clinical gene expression studies found it to be increased in one study of patients with mental illness 30 but reduced in another. 31 Peaks that were similarly upregulated in the hippocampus and cortex (m/z 1201.9, 1450.2, 1583.1 and 1907.3) were putatively identified as a phosphosphingolipid, a glycerophosphoglycerophosphoglycerol, an acidic glycosphingolipid and a neutral glycosphingolipid, respectively, using the Nature Lipidomics Gateway informatics platform (see Supplementary Methods for details). Further studies are needed to fully identify and evaluate these and other results in the data set.…”