A. Minelli, ItalyUniversity of Brescia Department of Molecular and Translational Medicine
Moderator Of 1 Session
The molecular factors involved in the pathophysiology of major depressive disorder (MDD) and related endophenotypes remain poorly understood. The complexity of the MDD phenotype may contribute to inconsistent results. Dr Mara Dierssen will do an overview concerning transcriptional factor mechanisms underpinning of neurodevelopmental disorders. One recent approach to examine the molecular basis of MDD is co-expression network analysis, which facilitates the examination of complex interactions between expression levels of individual genes and how they influence biological pathways that could be affected in MDD. Dr Bernhard Baune will present recent findings supporting dysregulated immune response and protein processing in the endoplasmic reticulum in MDD, thus providing novel insights into the pathophysiology of depression. Genome-wide transcriptome analysis of MDD patients clinically well characterize as well as of relevant risk phenotypes such as childhood traumatic experiences could represent an advance in this field. Dr Alessandra Minelli will present results from a transcriptomic study on the effect of childhood traumas. Moreover, she will show the role of environmental and genetic factors on the identified dysregulations. Based on the hypothesis that MDD could be characterized by accelerated aging, Dr Alessio Squassina investigated the role of telomere length and inflammation in this disorder. Findings showed that MDD patients have shorter telomeres compared to controls, and that treatment-resistant patients have higher levels of TNFα than non-TRD and controls, suggesting that TR might be associated with increased inflammation.
Presenter Of 2 Presentations
S0007 - The Effect of Childhood Trauma and Trauma-focused Psychotherapy on Blood Expression in Patients with Major Depressive Disorder
The only available genome-wide study (Minelli et al., 2018) indicated an association between the neglect CT and MED22, a transcriptional factor gene. To verify how the dysregulation of MED22 could be affected by environmental and genetic factors, we carried out an analysis on these components and a longitudinal study concerning the effect of trauma-focused psychotherapy in MDD patients that experienced CT.
On a large mRNA sequencing dataset including 368 MDD patients we computed the genetic (GReX) and the environmental (EReX) components affecting gene expression in relation to CT. Furthermore, we measured the expression of MED22 in 22 MDD patients treated with trauma-focused psychotherapy.
The dissection of MED22 expression profiles revealed an association of neglect with environmental and genetic components (p=6x10-3 p=2.6x10-4). Furthermore, in an independent cohort of 177 controls, we also observed a significant association between cis-eSNPs of MED22 and higher neuroticism scores (best p-value: 0.00848) that are usually associated with a decreased amount of resilience to stress events. Finally, the results of psychotherapy revealed a reduction of depressive symptomatology (p<0.001) and 73% of patients resulted responders at the follow-up visit. MED22 expression during psychotherapy showed a change trend (p=0.057) with an interaction effect with response (p=0.035). Responder and non-responder patients showed MED22 expression differences at different trauma-focused psychotherapy timepoints (p=0.15; p=0.012) and at the follow-up (p=0.021).
Our results provide insights suggesting that some biological and clinical consequences of CT depend on genetic background and environmental factors that could induce vulnerability or resilience to stressful life events.