DEPRESSION IN TRANSLATION
Indigo Danielson 𝄅 Emery Vanderburgh 𝄅 Amanda Brown
The stigma surrounding mental illness persists because the person suffering is often blamed for experiencing symptoms outside of their control.
Our installation aims to visually represent the epigenetic and environmental factors that contribute to someone’s predisposition to depression and suicide such as early life adversity (ELA), and how these traumatic experiences epigenetically regulate how genes are transcribed and translated. Thereby, the work will illustrate the complex web of factors that lead to, and makeup, the nuanced etiology of depression and risk of suicide.
Each garment is created to impose deliberate restrictions on the person wearing them. All at once creating a sense of weight, tension, liberation and lightness. The dress that is revealed beneath the coat as well as the duality in the facial expression of the mask show the contrast between depression and resilience outcomes in people with the same risk genes but different experiences with early life adversity and epigenetic regulation.
A simple beaded headpiece was constructed to represent dopamine downregulation in depression, as the branches reflect the dopamine side groups, and the dangling pearl section a degradation of the benzene structure. Other elements, such as the addition of embroidery and video effects, portray factors like the neurotransmitters involved in depression, and the distortions to stress regulatory systems due to early life diversity.
The video animations were also created to enhance this feeling of cyclical duality through the use of layering, repetition and contrast. Thus, each element of the piece is considered in relation to how the depressive and resilient genes affect the person experiencing depression.
Based on research by Amanda Brown.
fullscreen is best
Outfit concept and jacket: Indigo Danielson
Model, dress reconstruction and mask: Amanda Brown
Directed by, special effects and sound design: Emery Vanderburgh
Indigo Danielson is currently pursuing an undergraduate degree in design for the theatre at Concordia University. Their work explores themes of identity and views the body as a vessel for communication. Their work is largely based on different forms of puppetry but their practice often includes drawing, printmaking, performance, costume design, wood carving and many other techniques. Indigo most notably headed Concordia’s installation presented at the Prague Quadrennial in 2019.
Amanda Brown is a Ph.D. candidate in the Department of Human Genetics at McGill University. She currently works in the McGill Group for Suicide Studies (MGSS), where she studies gene-environment interactions in depression and suicide. In particular, her work examines how early-life adversity (such as child abuse) is associated with sustained molecular changes that contribute to depression and suicide in adulthood. Outside of the lab, she fosters her personal passion for art through work with textiles and garment design, embroidery, sketched works, and painting.
Emery Vanderburgh is a multimedia artist currently pursuing a degree in Intermedia Arts at Concordia University. Her work presents colourful, surreal explorations of the self, disability, new materialism, and queerness. Her video and photography work uses performance, fashion, and dance to explore themes of the uncanny and otherness. Emery's art and disability advocacy have most notably been featured on CBC, CTV, and the Instagram homepage.
This piece is inspired by Amanda’s research on the epigenetic relationship between early-life adversity and depression/suicide undertaking. As well, it puts focus on the importance of the translation step of the central dogma in determining which differentially transcribed genes are actually synthesized into proteins, and therefore contribute to the depression and suicide phenotypes.
According to the World Health Organization (WHO), depression is currently the leading cause of global disability, with over 300 million people affected worldwide (1). Major Depressive Disorder (MDD) is characterized by depressed mood and anhedonia, as well as secondary symptoms of appetite or weight changes, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue, deficits in cognition and concentration, feelings of worthlessness, excessive guilt, and suicidality (2). The relationship between depression and suicidality is of particular interest to global health, considering that approximately 60% of suicides occur in individuals with a diagnosis of MDD (3).
One of the leading factors associated with both MDD and suicide is early-life adversity (ELA), which includes childhood sexual, physical, and emotional abuse, as well as neglect. ELA has also been studied in association with epigenetic alterations: heritable changes that do not affect the genome, yet still result in changes to gene expression- which can include DNA methylation, chromatin accessibility changes, and other alterations to gene expression. There is ample evidence that exposure to ELA can trigger sustained epigenetic alterations in certain genes related to stress and emotional regulation, that likely contribute to the MDD/suicide phenotype in adulthood(4).
Gene expression, which refers to the process by which DNA base-pair sequences are converted into functional gene products, begins with transcription. During transcription, particular sequences from the genome are copied into RNA (notably into mRNA for coding sequences that will produce protein products), the sum of which can be referred to as the transcriptome. When the transcriptome is altered via epigenetic regulation, we can describe the changes in genes present as “differentially expressed” (5).
Following transcription, coding mRNAs undergo the process of translation, whereby they are bound by ribosomes. In the ribosome, transfer RNAs or “tRNAs” with attached amino acids are recruited to the codons (or 3 nucleotide sequences) of the mRNA that match the codons at the bottom of the tRNA structure. Different codons correspond to different amino acids, and in this way, the translation machinery “reads” the mRNA to identify which amino acids to build the protein sequences with. The amino acids attached to the tRNAs link together to form amino acid chains as the tRNAs enter and then leave the ribosome after transferring their amino acid to the forming protein chain. This is how complex proteins that make up every tissue in the body are eventually formed(6).
This is all of the particular interest within the context of the ELA/MDD/suicide pathway as epigenetic changes- such as DNA methylation and differential gene expression- have already been demonstrated in the brain (particularly in the frontal cortex, Anterior Cingulate Cortex, and Amygdala, and Habenula) of individuals who experienced ELA and later were diagnosed with MDD and died by suicide, compared to non-ELA MDD/suicides and controls, but differential expression of tRNA genes and translational regulation have not (5). This represents an unexplored but crucial piece of the framework that I investigate in my research.
Specifically, I aim to use a methodology called 4-leaf clover qPCR (a specialized form of quantitative PCR) to validate tRNA differentially expressed genes (DEGs) in the anterior cingulate cortex (ACC) of individuals with MDD who died of suicide. In general, qPCR works by attaching fluorescent probes to specific DNA or RNA sequences (that have been converted to DNA via library construction), amplifying them via qPCR, and then quantifying the number of reads that correspond to each probe (7).
By doing so, I am hoping to identify any tRNA DEGs that reflect altered levels of translation in MDD/suicide, in ways that influence the MDD/suicide phenotype. One such hypothesis is that initiator methionine tRNAs- which always begin the translation process- will be dysregulated in MDD/suicides compared to controls in ways that indicate altered protein synthesis at the synapses in neurons (a phenomenon already observed in MDD in another piece of the translation machinery-MTORC1) (6).
In this way- it can be demonstrated that ELA, transcription, and translation all play crucial roles in the development of depression and in conferring risk for suicide.
World Health Organization. (2017). Depression and Other Common Mental Disorders Global Health Estimates. World Health Organization.
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.).
Cavanagh, J. T., Carson, A. J., Sharpe, M., & Lawrie, S. M. (2003). Psychological autopsy studies of suicide: A systematic review. Psychological Medicine, 33(3), 395-405.
Turecki, G. (2014). The molecular bases of the suicidal brain. Nature reviews neuroscience, 15(12), 802-816.
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., . . . Selbach, M. (n.d.). Global quantification of mammalian gene expression control. Nature, 473, 337-342.
Laguesse, S., & Ron, D. (2019). Protein Translation and Psychiatric Disorders. The Neuroscientist, 26(1), 21-42.
Honda, S., Shigematsu, M., Morichika, K., Telonis, A. G., & Kirino, Y. (2015). Four-leaf clover qRT-PCR: A convenient method for selective quantification of mature tRNA. RNA Biology, 12(5), 501-508.