Abstract

Stressful life events occurring in adulthood have been found able to affect mood and behavior, thus increasing the vulnerability for several stress-related psychiatric disorders. However, although there is plenty of clinical data supporting an association between stressful life events in adulthood and an enhanced vulnerability for psychopathology, the underlying molecular mechanisms are still poorly investigated. Thus, in this study we performed peripheral/whole-genome transcriptomic analyses in blood samples obtained from 53 adult subjects characterized for recent stressful life events occurred within the previous 6 months. Transcriptomic data were analyzed using Partek Genomics Suite; pathway and network analyses were performed using Ingenuity Pathway Analysis and GeneMANIA Software. We found 207 genes significantly differentially expressed in adult subjects who reported recent stressful life experiences (n=21) compared with those without such experiences (n=32). Moreover, the same subjects exposed to such stressful experiences showed a reduction in leukocyte telomere length. A correlation analyses between telomere length and transcriptomic data indicated an association between the exposures to recent stressful life events and the modulation of several pathways, mainly involved in immune-inflammatory-related processes and oxidative stress, such as natural killer cell signaling, interleukin-1 (IL-1) signaling, MIF regulation of innate immunity and IL-6 signaling. Our data suggest an association between exposures to recent stressful life events in adulthood and alterations in the immune, inflammatory and oxidative stress pathways, which could be also involved in the negative effect of stressful life events on leukocyte telomere length. The modulation of these mechanisms may underlie the clinical association between the exposure to recent Stressful life events in adulthood and an enhanced vulnerability to develop psychiatric diseases in adulthood.

Highlights

  • Among the top significant genes, we found several genes that have been found associated with mood disorders such as period circadian clock 1 (PER1),[50,51] interferon alpha 2 (IFNA2)[52] and period circadian clock 2 (PER2).[53]

  • Transcriptomic analyses in the blood of subjects characterized for recent SLEs exposure Our first aim was to identify differences in gene expression levels in association with recent SLEs exposure, we conducted a transcriptome analysis in the blood of subjects exposed (n = 21) and not exposed (n = 32) to recent SLEs and we found, comparing the two groups, significant differences in the expression of 207 genes

  • Correlation analyses between cortisol levels and transcriptomic profile identified 321 significantly correlated genes (Supplementary Table 4) and among the top significant ones we found several genes that have been found associated with inflammation and stress response such as CD69 molecule (CD69),[54] period circadian clock 1 (PER1)[55] and chemokine receptor type 4 (CXCR4).[56]

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Summary

INTRODUCTION

We recruited and assessed a total of 72 shortening can be influenced by alterations in the immune subjects. Blood samples were collected fasting in the morning by using PaxGene leukocyte telomere length is seen across many psychiatric Blood RNA Tubes (PreAnalytix, Hombrechtikonas, Switzerland) and BD disorders, with a larger effect size in post-traumatic stress disorder, anxiety disorders and depressive disorders as compared with psychotic and bipolar disorder that had smaller, but significant, effect size These data were partially in contrast with a recent systematic review and meta-analysis by Colpo et al.,[34] where they reported no significant difference of telomere length in bipolar. The two study groups were not significantly different for the presence of recent drug therapies These 2/21 were receiving drugs for thyroid disorders, 5/21 were receiving contrasting data suggest that the relationship between psychiatric cortisonic drugs, 2/21 were receiving psychotropic drugs, 1/21 was disorders and telomere length is not yet completely clear and receiving drugs for gastrointestinal disorders, 2/21 were receiving drugs needs further investigation. Correlation analyses between transcriptomics data and leukocyte telomere length, HAMD score, peripheral blood cortisol levels were run by using a Pearson correlation analyses; correlation analyses between telomere length or cortisol levels with smoking, gender, age were run by applying a Spearman correlation analyses

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RESULTS
DISCUSSION
56 Fc epsilon RI signaling
CONFLICT OF INTEREST
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