Project description
Studying the link between anxiety and depression
More and more people around the world are struggling with depression and anxiety. These two mental health disorders often appear together, with anxiety usually coming first. Despite their widespread impact, scientists still do not fully understand what causes them or why they are linked. Without this knowledge, treatments remain limited, leaving millions without effective relief. In this context, the ERC-funded ZoomINs project aims to uncover the biological connection between anxiety and depression. Researchers will focus on special brain cells called GABAergic interneurons (INs) and how they interact with immune cells known as microglia. Using advanced techniques like gene sequencing and brain imaging, the project hopes to reveal new insights that could lead to better treatments.
Objective
Rates of depression and anxiety are constantly surging, resulting in a growing global mental health crisis. These two disorders have a remarkably high prevalence of comorbidity, with anxiety generally preceding depression. However, the biological basis of these disorders and their comorbidity is poorly understood, leaving millions of patients with inadequate treatments and thus an urgent need for improved medications. Accumulating evidence suggests that both disorders involve GABAergic deficits, but the nature of these deficits is undefined and may be the holy grail for cracking the mysteries of depression and anxiety comorbidity. Here, I will apply cutting-edge technologies to focus on hippocampal GABAergic interneurons (INs) and propose a data-driven hypothesis for the cellular and molecular basis of anxiety and depression comorbidity. I suggest that INs selectively recruit microglia to reshape inhibition in the depressed brain. This hypothesis may provide the missing link between major hallmarks of depression: GABAergic deficits, synaptic loss, and neuroinflammation. I seek to unravel the molecular adaptations of INs to stress that lead to microglia recruitment and connect them with anxiety preceding depression. Finally, I will elucidate a novel model for innate anxiolysis mediated by local dendritic translation in INs. I will combine, for the first time, the robustness of two analytical methods: translating ribosome sequencing and spatial transcriptomics to identify the involved genes, the INs subtypes expressing them, and their hippocampal location. These data will be complemented by calcium imaging, behavioral tests, imaging, connectomics, and electrophysiology. ZoomINs targets an urgent public health concern by providing a novel hypothesis for a long-standing question: what causes anxiety and depression comorbidity? The results of this ambitious project will set the ground for the development of INs-targeting medications, giving hope to millions worldwide.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Call for proposal
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(opens in new window) ERC-2023-STG
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91904 Jerusalem
Israel
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