Genetic Variance in Depressive Phenotypes Found to Vary by Sex

Patricia Pelufo Silveira, MD, PhD, associate professor at the Department of Psychiatry at McGill University in Montreal, Canada, discusses the results of her recent study that found that the genetic variance associated with depressive phenotypes are different between men and women.

"A sex-specific genome-wide association study of depression phenotypes in UK Biobank" was recently published in the journal Molecular Psychiatry. 

In Part 1 of this interview, Dr Silveira discusses the inspiration for the study, methods, and the most significant findings.

Part 2: Understanding Why Men and Women Differ in Medication and Treatment Response

Editor's Note: Answers have been lightly edited for clarity. 

Patricia Pelufo Silveira, MD, PhD, is an associate professor at the Department of Psychiatry at McGill University in Montreal, Canada. Dr Silveira obtained an MD (2001) and specialized in pediatrics (2002-2006). She received a MSc (2004) and a PhD (2007) in neurosciences from the Universidade Federal do Rio Grande do Sul (UFRGS), Brazil. She also completed a postdoctoral fellowship (2007–2009) in Dr Meaney´s Lab at the Douglas Institute. Before joining McGill and returning to the Douglas Institute in 2016, Dr Silveira was an assistant professor in the UFRGS Pediatrics Department (2009-2016) and led the externally funded lab, the DOHaD Porto Alegre group.

A pediatrician and neuroscientist with extensive research, teaching and clinical experiences, Dr Silveira has also shown significant leadership in preparing tomorrow’s research leaders, supervising over 30 PhD and MSc students and mentoring several post-doctoral fellows.

Dr Silveira’s research focuses on how perinatal and early-childhood environments can shape and modulate both health and disease across the lifespan, into old age. Her aim is to identify genetic/epigenetic markers that interact with environmental adversities in childhood, modifying endophenotypes (impulsivity, sensitivity to reward, food choices) that ultimately affect healthy growth and neurodevelopment, increasing an individual’s risk for developing chronic diseases and mental illnesses across their lifespan.

Read the Transcript:

Patricia Silveira, MD, PhD: My name is Patricia Pelufo Silveira. I'm an associate professor at the department of psychiatry at McGill University here in Montreal, Canada. And my lab is focused on gene-environment interactions and how early life adversity or stress influences the risk for disease in the long term. We work a lot with genetics data, functional genomics, but also with the environment and early life adverse.

Evi Arthur, DepressionCare 360: What led you and your colleagues to investigate depression phenotypes?

Dr Silveira: Depression is a highly prevalent condition in the population. It has a high morbidity and also associated mortality. Depression is also a condition that is difficult to prevent and to treat. Therefore, there is a lot to be researched and understood and learned about depression.

Arthur: Why did you feel it was important to specify by sex?

Dr Silveira: We were motivated by these large differences between men and women regarding the prevalence of depression, but also the clinical presentation of the depressive symptoms that can vary a lot between men and women. And there are even differences in terms of response to antidepressant treatment between men and women. So our idea was that if we had a better understanding of the biological mechanisms related to these differences that we see in the clinic, this could help us better manage the disease for both men and women. That was the intention with this study. It was really to go to specifically look for sex differences there.

Arthur: Could you briefly describe the study method?

Dr Silveira: We performed a genome-wide association study that is also called the GWAS. And in this study, the genetic background of individuals that have and don't have depressive symptoms, and that don't have a condition or trait. So we compare the genetic background between these two groups, and this way we can identify which variants are more prevalent in the group of affected individuals, and therefore we can characterize the genetic background associated with the risk for depressive phenotypes. The difference in this current study is that we did the analysis separately by sex. So separately men and women, while usually these analyses are done with the two sexes combined.

Arthur: What were your most significant findings from this study?

Dr Silveira: As we expected, the genetic variance associated with depressive phenotypes are different between men and women. There are also some commonalities. For example, the genetic background linked to depressive symptoms is correlated with the genetic background linked to other psychopathologies like schizophrenia, bipolar disorder, neuroticism, and insomnia in both male and female GWASs. However, the genetic background linked with depression was correlated with metabolic features like waist circumference and triglyceride levels only in females. This is in agreement with the clinical features of depression where we see more of these metabolic problems in patients with depression that are women, so women that have depressive symptoms.