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Stress is a primary risk factor for psychiatric disorders such as Major Depressive Disorder (MDD) and Post Traumatic Stress Disorder (PTSD). The response to stress involves the regulation of transcriptional programs, which is supposed to play a role in coping with stress. To evaluate transcriptional processes implemented after exposure to unavoidable traumatic stress, we applied microarray expression analysis to the PFC of rats exposed to acute footshock (FS) stress that were sacrificed immediately after the 40 min session or 2 h or 24 h after. While no substantial changes were observed at the single gene level immediately after the stress session, gene set enrichment analysis showed alterations in neuronal pathways associated with glia development, glia–neuron networking, and synaptic function. Furthermore, we found alterations in the expression of gene sets regulated by specific transcription factors that could represent master regulators of the acute stress response. Of note, these pathways and transcriptional programs are activated during the early stress response (immediately after FS) and are already turned off after 2 h—while at 24 h, the transcriptional profile is largely unaffected. Overall, our analysis provided a transcriptional landscape of the early changes triggered by acute unavoidable FS stress in the PFC of rats, suggesting that the transcriptional wave is fast and mild, but probably enough to activate a cellular response to acute stress. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a common psychiatric disorder with a multifactorial aetiology determined by the interaction between genetic and environmental risk factors. Pieces of evidence indicate that inflammation and immune activation may contribute to the onset of MDD playing a role in the pathogenetic mechanism. To date, it is not known to which extent the association between MDD and inflammation is shaped by the genetic background or by the presence of environmental factors. To clarify this issue, we analyzed genotype and blood RNA profiles of 463 MDD cases and 459 controls (NIMH-Study 88/Site621) estimating the Genetic and Environmental Regulated eXpression component of gene expression (GReX and EReX respectively). Both components were tested for association with MDD. Many genes belonging to the α/β interferon signaling pathway showed an association between MDD and EReX, only two between MDD and GReX. Also other MDD differentially expressed genes were more influenced by the EReX than by GReX. These results suggest that impact of the genetic background on MDD blood gene expression alterations is much lower than the contribution of environmental factors and almost absent for the genes of the interferon pathway. [ABSTRACT FROM AUTHOR]

Alterations in peripheral vascular endothelial growth factor (VEGF) levels were observed in major depressive disorder and relative treatments and were shown to be influenced by genetic variants. The study objective was to explore, at a genome‐wide level, possible interplaying effects between the genetic background and major depressive disorder in regulating VEGF levels. Moreover, we aimed to investigate the association between these variants and response to electroconvulsive therapy. A genome‐wide association study was carried out both on controls and patients with major depressive disorder (n = 145; n = 121) in correlation with serum VEGF levels determined by ELISA. Five SNPs not included in SNP arrays were additionally genotyped. Seventy‐one patients with treatment‐resistant depression underwent electroconvulsive therapy and were evaluated as responders/nonresponders. An association between VEGF levels and a locus in 6p21.1, downstream the VEGF gene, was evidenced both in controls (best SNP: FDR‐corrected p = 2.4 × 10−5) and in patients with major depressive disorder (best SNP: FDR‐corrected p = 2.6 × 10–3). The alleles associated with lower VEGF concentrations in patients were also associated with nonresponse to electroconvulsive therapy (p =.01). These results confirm a role of SNPs in 6p21.1 locus as major influencers of circulating VEGF levels also in patients affected by major depressive disorder and indicate a possible implication in response to electroconvulsive therapy. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a major health problem with significant limitations in functioning and well-being. The World Health Organization (WHO) evaluates MDD as one of the most disabling disorders in the world and with very high social cost. Great attention has been given to the study of the molecular mechanism underpinning MDD at the genetic, epigenetic and proteomic level. However, the importance of RNA modifications has attracted little attention until now in this field. RNA molecules are extensively and dynamically altered by a variety of mechanisms. Similar to "epigenomic" changes, which modify DNA structure or histones, RNA alterations are now termed "epitranscriptomic" changes and have been predicted to have profound consequences for gene expression and cellular functionality. Two of these modifications, adenosine to inosine (A-to-I) RNA editing and m6A methylations, have fascinated researchers over the last years, showing a new level of complexity in gene expression. In this review, we will summary the studies that focus on the role of RNA editing and m6A methylation in MDD, trying to underline their potential breakthroughs and pitfalls. [ABSTRACT FROM AUTHOR]

Highlights from the article: B Background: b The Vascular Endothelial Growth Factor (VEGF) is an angiogenic cytokine playing neurotrophic roles in the CNS. Moreover, we aimed to investigate the association between these variants and response to electroconvulsive therapy (ECT), since we observed in a previous study an involvement of VEGF baseline levels in ECT outcome. The SNPs rs78355601/rs7767396 associated to lower VEGF levels in MDD patients were also significantly associated with no response to ECT (carriers of the minor allele vs. non carriers, p=0.04).

Highlights from the article: Sa49the effect of childhood trauma on blood expression of med22 in patients with major depressive disorder is mediated by cis-acting snps B Background: b There is evidence that childhood trauma (CT) increase the risk of developing severe mental illnesses, such as major depressive disorder (MDD), during adulthood. To clarify these issues, we carried out a reanalysis of genotype and blood expression data from a large mRNA sequencing dataset of MDD patients (368 patients) for whom information about CT was available.

Highlights from the article: B Background: b Major Depressive Disorder (MDD) is a complex disabling psychiatric condition among the top five leading causes of disability throughout the world. Analysis of EDeX and GReX gene expression levels in MDD and controls revealed some differentially regulated genes for both components, but none survived multiple test correction. Genes with low p-values in the analysis of GReX or EDeX were significantly over-represented among genes with an observed differential expression between MDD and controls.