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Depression – Canada Brain Power

Canada Brain Power

Tag: Depression

  • Discovery of differences in encoding threat discrimination in the brain of males and females

    Discovery of differences in encoding threat discrimination in the brain of males and females

    Brain Star Award Feature: Jessie Muir and Eshaan Sriram Iyer, McGill University, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    Learning to predict threat is essential, but equally important—yet often overlooked—is learning about the absence of threat. This study by Drs. Jessie Muir and Eshaan Sriram Iyer, working in the laboratory of Dr. Rosemary Bagot at McGill University, looks at mechanisms of threat encoding and discrimination in pathways relevant to depressive-like symptoms in mice. They identified sex differences in the circuits and mechanisms responsible for recognizing threats and suggest they may reflect differences in behavioral strategies that can be relevant for understanding sex differences in risk of psychiatric disorders.

    Depression is currently the leading cause of disability worldwide yet current antidepressant treatments remain ineffective in around 50% of the population. Women are twice as likely to develop depression compared to men. Given most pre-clinical studies have looked exclusively at males, there is a large gap in knowledge in the mechanisms underlying the disorder in females. Depression involves a disruption in many adaptive behavioral processes including discriminating aversive from neutral events.

    Read the full story here: https://can-acn.org/brain-star-award-winners-jessie-muir-and-eshaan-sriram-iyer/

    Featured scientific publication:

    Jessie Muir, Eshaan S. Iyer, Yiu-Chung Tse, Julian Sorensen, Serena Wu, Rand S. Eid, Vedrana Cvetkovska, Karen Wassef, Sarah Gostlin, Peter Vitaro, Nick J. Spencer & Rosemary C. Bagot Sex-biased neural encoding of threat discrimination in nucleus accumbens afferents drives suppression of reward behavior. Nature Neuroscience 27, 1966–1976 (2024). https://doi.org/10.1038/s41593-024-01748-7

    https://doi.org/10.1038/s41593-024-01748-7

  • Large-scale analysis reveals opposing brain signatures of sleep in task-based and resting-state conditions

    Large-scale analysis reveals opposing brain signatures of sleep in task-based and resting-state conditions

    Dr. Mohamed Abdelhack, Centre for Addiction and Mental Health, was awarded a Brain star award for this work

    Sleep and depression have a complex birectional relationship. For example, while most people suffering from depression also suffer from insomnia, others report hypersomnia. Contradictory results are also seen in scientific studies of this relationship. A new study by Mohamed Abdelhack and colleagues analyzed how brain signals change with differences in sleep habits, depression symptoms, and cognitive abilities in over 30,000 people. By performing such large scale and comprehensive analyses, they reveal opposing relationships between change in brain signals when a person is doing a task and when they are not (resting state). These results provide important insights into the relationship between depressive symptoms and sleep in the general population.

    By analysis data from over 30,000 participants from UK-Biobank and Human Connectome Project, the researchers found contradictions in brain-wide associations of sleep and depression depending on participant’s state. The researchers found brain regions were hyperconnected under resting conditions with insomnia and depression. These results indicate that, in insomnia and depression, resting-state dynamics are resembling those of rested-wakefulness. The brain is signalling a lack of need for sleep which could signal hyperarousal.

    When the researcher analysed data from people while they were performing a task, they instead observed a drop in connection between brain regions, which could be signifying a “local sleep” phase which decreases the cognitive performance as the brain is unable to recruit its resources to perform the task.

    This publication shows counterintuitive results where neural signatures of sleep and depression when the participant was doing a task contradicted those when the participant was not doing any task (resting state). It highlights the importance of probing the effect of mental health in different conditions. These results could also guide advances in clinical practice to investigate more details of sleep habits to optimize care plans while also tracking the cognitive load of patients to assess treatment efficacy.

    About Dr. Mohamed Abdelhack

    Mohamed is a Postdoctoral Fellow at the Whole Person and Population Modelling laboratory at the Krembil Centre for Neuroinformatics working on using statistical analysis of big data and machine/deep learning to model mental health and psychiatric disorders. He mainly uses fMRI imaging, statistical data analysis, and computational modelling.

    He previously worked as a Postdoctoral Researcher in Washington University in St. Louis where he was building machine learning models to predict post-surgical medical complications. He also worked as a researcher in Kyoto University Hospital studying neural activity markers of Schizophrenia using brain decoding and deep learning techniques. His doctoral work in Kyoto University focused on using deep learning models to understand robustness of human brain in recognizing degraded visual input.

    He also founded the Arabs in Neuroscience (AiN) not-for-profit, which is a grassroots organization that aims to enhance education and research among Arabic-speaking scientists and students all over the world. Through AiN, he runs an online introductory course in computational neuroscience. He is also a teaching assistant at the Computational Neuroscience Imbizo summer school and a member of The Africa I Know non-profit.

    Website: https://mabdelhack.github.io/

    Twitter handle: @mabdelhack

    Sources of funding

    This study was funded by grants for Daniel Felsky from The Koerner Family Foundation New Scientist Program, The Krembil Foundation, the Canadian Institutes of Health Research, the Canadian Foundation for Innovation, and the CAMH Discovery Fund. Author Mohamed Abdelhack was further supported by the CAMH womenmind postdoctoral fellowship.

    Source of text: Canadian Association for Neuroscience

    Scientific publication

    Abdelhack M, Zhukovsky P, Milic M, Harita S, Wainberg M, Tripathy SJ, Griffiths JD, Hill SL, Felsky D. Opposing brain signatures of sleep in task-based and resting-state conditions. Nat Commun. 2023 Dec 1;14(1):7927.

    https://rdcu.be/dEWTz

  • Identification of sex differences in stress response and major depressive disorder could pave the way to better diagnosis and treatment of depression.

    Identification of sex differences in stress response and major depressive disorder could pave the way to better diagnosis and treatment of depression.

    Major Depressive Disorder (MDD) is more frequent in women than men, and sex differences have been reported in symptoms and treatment response. The fact that individuals with cardiovascular disease or stroke are more prone to depression suggests vascular dysfunction may also be involved. New research by Laurence Dion-Albert, PhD student at Université Laval, shows for the first-time alterations in brain barrier integrity in female animals and women with depression that are different from those seen in males and men. They also identified potential biomarkers for depression that could help better diagnose and inform treatment strategies for depressive disorders.

    Laurence Dion-Albert won a CAN-CIHR-INMHA Brain Star award for these discoveries.

    Exposure to chronic stress induces changes in brain vascular integrity  and blood-brain barrier (BBB) leakiness through downregulation of a protein called Claudin-5 in the nucleus accumbens of male mice, a brain region critical for emotional responses. During her Masters degree, Laurence Dion-Albert investigated if sex-specific changes in BBB integrity could underlie sex differences in major depressive disorder. She found that female mice exposed to chronic stress presented major changes in expression of BBB-related genes and loss of Claudin-5 in a different brain region, the prefrontal cortex (PFC), a hub for anxiety and self-perception. Importantly, viral-mediated knockdown of Claudin-5 in the female PFC recapitulated social isolation as well as anxiety- and depressive-like behaviors without prior exposure to stress, highlighting a causal role for Claudin-5 in the establishment of detrimental stress coping behaviors. These findings were confirmed in post-mortem brain samples from depressed individuals of both sexes, adding critical translational value to the findings in animals. Finally, Laurence Dion-Albert explored several markers of vascular dysfunction in blood samples from stressed animals and individuals with MDD. She showed that sE-selectin, an indicator of vascular inflammation, is higher in stressed females and women with MDD, and could serve as a biomarker to assist in diagnosis.

    These results, which demonstrate sex-specific neurovascular alterations linked to depression for the first time, may explain sex-specific symptomatology and pave the way for the development of new, more effective treatments. 30-50% of individuals with MDD are unresponsive to traditional neuron-centered antidepressants, and a better understanding of the mechanisms involved in stress responses and mood disorders is essential to achieve breakthrough for them. Moreover, no reliable biomarker has been found for major depression, which is still diagnosed by questionnaires. Although it needs to be evaluated in larger cohorts, this study is the first to propose sE-selectin as a blood marker for MDD.

    Following these findings, Laurence Dion-Albert hopes to further decipher the mechanisms underlying the pathogenesis of MDD to produce tangible change for men and women with MDD across the world.

    About Laurence Dion-Albert

    Laurence Dion-Albert developed the experimental design with her supervisor, Dr. Caroline Menard, researcher at the CERVO Brain Research Centre, affiliated to Université Laval. She organized, optimized, and performed all the experiments included in the article. She also supervised colleagues who helped for surgeries and behavior analysis and helped write the manuscript and prepare figures. Beyond her direct contribution to the study, Laurence Dion-Albert has been actively involved in sharing these results with other scientists and the public through multiple presentations.

    Funding Source:

    Canadian Institutes of Health Research

    Scientific publication :

    Dion-Albert, L., Cadoret, A., Doney, E. Neutzling Kaufmann, F., Dudek, KA., Daigle, B., Parise, LF., Cathomas, F., Samba, N., Hudson, N., Lebel, M., Signature Consortium., Campbell, M., Turecki, G., Mechawar, N., Menard, C. Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue. Nat Commun 13, 164 (2022). https://doi.org/10.1038/s41467-021-27604-x

    https://www.nature.com/articles/s41467-021-27604-x

    More about this story

    This discovery was selected as one of the top 10 discoveries of 2022 by Quebec Science magazine:

    https://www.quebecscience.qc.ca/sciences/les-10-decouvertes-de-2022/depression-maladie-differente-sexe/

    https://lactualite.com/sante-et-science/depression-une-nouvelle-piste-pour-mieux-traiter-les-femmes/

    https://www.journaldemontreal.com/2022/01/10/decouverte-scientifique-a-luniversite-laval-la-depression-affecte-differemment-les-sexes

    https://ici.radio-canada.ca/nouvelle/1853141/depression-majeure-difference-hommes-femmes-decouverte-equipe-scientifiques-universite-laval-cerveau-biomarqueur

  • Video: Postpartum depression and tackling sex bias in research

    Video: Postpartum depression and tackling sex bias in research

    In this episode of Brain Bytes we meet with Aarthi Gobinath, PhD. She was curious about what depression looks like in the female brain and how postpartum depression manifests itself. She hopes her work can tackle the issue of researchers commonly using only male test subjects in their studies. Links: Voluntary running influences the efficacy of fluoxetine in a model of postpartum depression. https://www.ncbi.nlm.nih.gov/pubmed/2… Follow Brain Bytes on Twitter! @UBCBrainBytes https://twitter.com/UBCBrainBytes Aarthi Gobinath on Twitter: @aarthigobinath https://twitter.com/aarthigobinath Michael Ruffolo on Twitter: @mike_ruffolo https://twitter.com/mike_ruffolo Brain Bytes is a science communication initiative by graduate students within the Neuroscience Program at the University of British Columbia, in collaboration with the Graduate School of Journalism.