B4101 - Sensitive periods for the effects of depression on suicide risk - 18/07/2022

B number: 
Principal applicant name: 
Alexandre A Lussier | Massachusetts General Hospital (United States)
Dr. Erin C. Dunn
Title of project: 
Sensitive periods for the effects of depression on suicide risk
Proposal summary: 

Depression is one of the most important risk factors for suicide. Almost 60% of people who die by suicide experienced depression at some point in their life. Yet, it remains unclear why only certain people with depression eventually become suicidal. Recent evidence suggests there are sensitive periods in development when life experiences, such as depression, can have stronger effects on mental illness. It is also well documented that suicidality results from both life experiences and genetic risk.
However, most studies of genetic risk for suicide, depression, and subsequent suicidal suicidality focus on people measured at a single timepoint. This limitation prevents us from 1) identifying people who are at the highest risk for future suicidal behaviours and 2) developing timely and effective interventions that prevent suicide in people with depression. As such, this project will use longitudinal data from two birth studies to determine when and how genetic risk and experiences of depression during childhood and adolescence influence suicide risk in early adulthood.
First, we will identify the specific ages and patterns of depression during childhood and adolescence that most predispose young adults to suicide. These results will help us build and implement interventions that are positioned at the best possible time to prevent suicide risk among youth affected by depression.
Second, we will determine whether children and adolescents with increased genetic risk for suicide or mental illness are more likely to become suicidal after experiencing depression at specific ages. These findings will improve our ability to identify youth who are at greater risk for suicide and provide insight into the genetic pathways leading to suicide.
Third, we will identify biological mechanisms that explain the link between depression and suicide. We will focus on epigenetic changes, as they are linked to human health and are thought to reflect both life experiences and genetics. Thus, they may represent a biological pathway through which suicide risk can become “molecularly programmed”. Identifying epigenetic changes that link depression to suicide risk will help guide the development of biomarkers that will allow us to identify at-risk youth quickly and effectively.
In sum, this project will highlight key periods and biological targets that can be used to predict and prevent suicidality among childhood and adolescents who experience depression. These will ultimately catalyse better interventions that prevent suicide in young adults.

Impact of research: 
Through this research, we will determine whether the timing of depression during development can predict future suicidality, as well as identify specific genetic and epigenetic mechanisms that might influence the relationship between depression and suicide risk. Specifically, this interdisciplinary study will identify (1) specific ages and patterns of depression during childhood and adolescence that increase future suicidality; and (2) genetic and epigenetic profiles that predict suicidality and link depression to suicide risk. Ultimately, these efforts will highlight developmental windows and biological mechanisms that can be targeted in interventions to reduce suicide risk among people who experience depression.
Date proposal received: 
Friday, 8 July, 2022
Date proposal approved: 
Monday, 18 July, 2022
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, Computer simulations/modelling/algorithms, GWAS, Statistical methods, Epigenetics, Genetics, Genomics