Login | Register

Elucidating the Link Between the Environment, the Brain and Depression: Genetic and Epigenetic Mechanisms


Elucidating the Link Between the Environment, the Brain and Depression: Genetic and Epigenetic Mechanisms

Chiarella, Julian (2022) Elucidating the Link Between the Environment, the Brain and Depression: Genetic and Epigenetic Mechanisms. PhD thesis, Concordia University.

[thumbnail of Chiarella_PhD_S2023.pdf]
Text (application/pdf)
Chiarella_PhD_S2023.pdf - Accepted Version


The development and maintenance of depression is influenced by a combination of genetic and environmental factors, as well as their interactions. In recent decades, a number of candidate genes involved in stress-related systems have been implicated in major depressive disorder, shedding light on the genetic contributions to depression. Further, the study of epigenetic mechanisms has provided a potential mechanism by which the expression of genes implicated in depression are shaped by the environment, offering a bridge between environmental (e.g., early life adversity) and genetic factors. However, relative to adulthood, our knowledge of the genetic and epigenetic mechanisms of depression in childhood and adolescence remains limited. The current thesis aimed to address several gaps in our understanding of the genetic and epigenetic basis of depression in childhood and adolescence, while simultaneously exploring novel epigenetic methodology, which, in turn, could inform our understanding of depression across the entire lifespan. The projects that are described in this thesis used a variety of measures, including longitudinal ACE modelling of twin cohort data, (functional) magnetic resonance imaging, peripheral assessments of DNA methylation and in vivo assessment of epigenetic processes using positron emission tomography.
In study 1, we showed in a longitudinal cohort of 1344 twins that the association between externalizing symptoms at the preschool age and internalizing symptoms in early adolescence was essentially accounted for by genetic factors, suggesting a shared genetic vulnerability to externalizing and internalizing symptoms that is stable throughout childhood. In study two, we examined the association between DNA methylation at key genes within the serotonin and HPA axis systems (i.e., SLC6A4 and FKBP5 respectively) in 25 adolescents with major depressive disorder and 20 healthy controls. We found associations between DNA methylation, diagnostic status and frontolimbic structure/function that both converged with and diverged from findings in adults. In study three, we examined the link between childhood adversity, epigenetics and depression vulnerability while simultaneously addressing a common limitation in the epigenetic literature also present in study 2, the reliance on peripheral epigenetic measures. Using the novel [11C]Martinostat tracer in combination with positron emission tomography, we assessed levels of histone deacetylase (HDAC) in vivo. We found, in a sample of 14 healthy adult males, that HDAC density was associated with depressive symptoms and neuroticism in key frontolimbic regions. We found no association between early life adversity and HDAC density.
The results from the projects described in this dissertation may offer novel contributions to our understanding of the epigenetic and genetic basis of depression across childhood and adolescence, and validate the use of the novel [11C]Martinostat in the study of depressive symptoms and personality traits relevant to depression.

Divisions:Concordia University > Faculty of Arts and Science > Psychology
Item Type:Thesis (PhD)
Authors:Chiarella, Julian
Institution:Concordia University
Degree Name:Ph. D.
Date:14 July 2022
Thesis Supervisor(s):Booij, Linda
ID Code:991307
Deposited By: Julian Chiarella
Deposited On:21 Jun 2023 14:29
Last Modified:21 Jun 2023 14:29
All items in Spectrum are protected by copyright, with all rights reserved. The use of items is governed by Spectrum's terms of access.

Repository Staff Only: item control page

Downloads per month over past year

Research related to the current document (at the CORE website)
- Research related to the current document (at the CORE website)
Back to top Back to top