Student Seminar on Zoom - PhD Thesis Defense by Maya Amitai
Date:
Lecture / Seminar
Time: 10:00-11:00
Lecturer: Maya Amitai, MD, PhD
Organizer: Department of Brain Sciences
Details: Prof. Alon Chen Lab
Dept of Brain Sciences,WIS
Abstract: Depression and anxiety disorders are among the most common childhood psychiatric ... Read more Depression and anxiety disorders are among the most common childhood psychiatric disorders. Selective serotonin reuptake inhibitors (SSRIs) are generally considered first-line treatment for both depression and anxiety in this age group. However, 30%–40% of all patients who receive a sufficient dose and duration of treatment fail to respond. Moreover, SSRI use is frequently associated with adverse events (AEs), including activation symptoms, manic switch and increased suicidal behavior (SBs). These are particularly relevant in pediatric populations because of concerns about the suicide threat of SSRIs, resulting in a "black-box" warning. There are currently no biomarkers that can predict treatment response or AEs. Identification of such biomarkers could help to maximize the benefit-risk ratio for the use of SSRIs and speed the matching of treatment to patient. Given the fact that depression / anxiety risk is influenced by both genetic and environmental factors and that both state and trait factors will be important in treatment response prediction, a multidimensional biomarker panel covering several levels of biological information would likely be necessary.
The main objective of this research thesis is to identify biomarkers that will aid in the prediction of response and suicidal and other AEs of SSRI treatment in children and adolescents treated for depression and/or anxiety disorders. We examined the involvement of specific biomarkers (miRNA’s, DNA methylation, single nucleotide polymorphism [SNP's] and metabolites) in the response to SSRIs treatment in children and adolescents and in the differences observed between individuals exhibiting response or non-response/AEs to treatment with SSRIs.
Two hundred and sixty-six children and adolescents with depression and/or anxiety disorders were recruited and treated with fluoxetine. The overall response rate was 55%. Several targets from several biological domains (DNA methylation profile, miRNA’s and metabolites) were identifies as differentially expressed between responders and non-responders at baseline test. Pathway analysis of the predicted targets was carried out to assess their putative biological functions. Interestingly, when combining targets from the four biological domains, the targets were predicted to regulate specific biological pathways associated with immune system pathways and/or developmental pathways.
Dysregulation of complex gene networks in the developing brain is thought to underlie depression with childhood or adolescent onset. Thus, the identified molecules might play critical roles in transcriptional networks related to treatment response and AEs. These transcriptional networks are particularly relevant to the developing human brain and to neurodevelopmental disorders with childhood/adolescent onset, such as depression and anxiety disorders.
Zoom link: https://weizmann.zoom.us/j/91093085114?pwd=RVBKbEZXbjlsaVZrUVRuNThtVHB1UT09
Meeting ID: 910 9308 5114
Password : 419366Close abstract
