Investigating demographic, psychosocial and epigenetic risk factors for depression in young adults

Abstract

There is a growing prevalence of mental health problems within the student population, with many students starting university life with pre-existing conditions such as depression. Depression has a complex aetiology with a range of symptoms that can negatively affect day to day life. Currently, there are no clinical tests or biological biomarkers to aid in the diagnosis and treatment of depression.

The aim of this thesis was to investigate the prevalence of mental health conditions, substance abuse and suicidality, risk factors for developing depression and help-seeking in the student population. In addition, this thesis aimed to identify potential epigenetic biomarkers suitable for aiding diagnosis and predicting treatment response for depression, to investigate if their expression was controlled by DNA methylation and to explore the possibility of using pyrosequencing as a possible epigenetic diagnostic method for DNA methylation biomarkers for depression.

This study revealed that many students were starting university with pre-existing mental health conditions, substance abuse and suicidality. Students who were female, over 21 and non-heterosexual were at a significantly higher risk for developing mental health conditions including depression. Alarmingly, low rates of help-seeking were reported and many students who reported mental health conditions were not receiving the appropriate support. Low rates of anti-depressant medication use were reported overall, however, students who were taking an anti-depressant medication reported higher rates of co-morbid mental health conditions than those who were not.

The impact of the COVID-19 pandemic on student mental health was assessed by comparing rates of depression and anxiety in year one (pre-pandemic) to years two and three (during the pandemic). Depressive symptoms generally increased while anxiety symptoms generally decreased. In addition, the number of students who experienced co-morbid depression, self-harm and suicide attempt increased from year one to year three.

Significantly higher rates of physical conditions, including respiratory, skin and muscular conditions were reported in students who have experienced depression, with inflammatory conditions such as asthma and eczema among the most reported specific conditions.

Whole methylome analysis using the EPIC array revealed FDR-significant differential methylation between individuals with depression and matched controls at several CpG sites across the genome. Gene ontology analysis revealed enrichment for immune response terms associated with depression and sensory perception terms associated with anti-depressant medication.

EPIC array results were successfully replicated using pyrosequencing, a quicker and more affordable technique which may be suitable for clinical use. RT-PCR confirmed that expression in some LCE genes associated with the
inflammatory skin conditions psoriasis, identified in the whole methylome analysis, were controlled by DNA methylation following treatment with the demethylating agent 5-Aza-2’-deoxycytidine (AZA).

In summary, this thesis provided evidence to support the growing prevalence rates of mental health problems and low rates of help-seeking behaviours in the student population. The novel epigenetic biomarkers identified provide further support for the link between inflammation and depression. These biomarkers may be useful for diagnosis of depression and anti-depressant treatment selection following validation in larger cohorts.

Date of Award	Jun 2023
Original language	English
Supervisor	Margaret Mc Lafferty (Supervisor), Colum Walsh (Supervisor) & Elaine Murray (Supervisor)