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Academic Research: We investigate how immune and metabolic mechanisms contribute to the development and progression of depression. Using large-scale cohort studies and biobanks, we pursue two interconnected goals:

1) Mapping depression's bio-clinical heterogeneity — by identifying bio-clinical profiles most strongly linked to immune and metabolic dysregulation, we aim to pinpoint patient subgroups most likely to benefit from treatments targeting these pathways.

2) Uncovering lifestyle and stress influences — by examining how a broad range of lifestyle and stress factors shape immune and metabolic biomarkers — measured through cutting-edge multi-omics technologies — we aim to identify promising targets for lifestyle-based interventions.

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Patient-Led Research: working in close collaboration with teams led by people with lived experience (PWLE), we will assess the current landscape of lifestyle-based interventions in severe mental illness (SMI) — examining the status of scientific evidence, barriers for implementation and best communication practices. These findings will then be disseminated through channels and media carefully tailored to reach all stakeholders, with a particular focus on patients and caregivers.​

What we are doing

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On the academic research side, we work with data from large-scale psychiatric cohorts such as the Netherlands Study of Depression and Anxiety (NESDA) — an ongoing naturalistic cohort of over 3,000 participants tracking the determinants and long-term course of depressive and anxiety disorders — and biobanks like the BIONIC project, which brings together genomic data on Major Depressive Disorder from more than 65,000 participants across 16 Dutch cohorts. Using cutting-edge analytical approaches, we integrate this data with large-scale open-access multi-omics datasets to investigate how immune and metabolic pathways, measured at a deep biological level, shape depression, its links to cardiometabolic disorders, and its heterogeneity. Our goal is to identify distinct clinical depression profiles driven by these biological alterations.

On the patient-led research side, we are preparing a series of publications for mental health digital outlets, reviewing the state of the art on lifestyle-based interventions in severe mental illness (SMI) and mapping the key barriers to their real-world implementation — barriers that can only be overcome through genuine collaboration between patients, clinicians, and researchers.

What we are planning to do

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We will leverage the rich longitudinal data from the NESDA cohort — featuring repeated assessments of major health determinants, psychiatric diagnoses, and biological parameters measured through cutting-edge multi-omics panels. We will systematically characterise how lifestyle factors and stress shape the immune and metabolic pathways relevant to depression, captured across omics layers that are particularly sensitive to environmental influences, such as epigenetics and metabolomics. The longitudinal design will allow us to track how changes in lifestyle and stress-related factors over time translate into shifts in epigenetic and metabolomic profiles — ultimately pinpointing the most promising biomarkers for future lifestyle-based interventions.

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We will also draw on data from previous clinical trials testing lifestyle interventions — including the large-scale European MOODFooD trial, which examined nutritional strategies for depression prevention in over 1,000 participants — to evaluate whether immune and metabolic pathways are effectively engaged by these interventions, and whether they represent viable targets for depression prevention and treatment.

Find out more

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In this expert review, we present the conceptual model of "immuno-metabolic depression" — a distinct bio-clinical profile characterised by immune and metabolic dysregulations and specific clinical manifestations. We propose this profile as a selection tool for clinical research testing interventions that target immune and metabolic pathways, whether through pharmacological approaches or lifestyle-based strategies.

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In this study combining data from multiple epidemiological psychiatric cohorts and international genomic consortia, we demonstrate that genetic risk for dysregulation in the immune and metabolic pathways governing energy homeostasis is linked to the emergence, during depressive episodes, of energy-conservation symptoms such as increased appetite and sleep.

In this study assembling large-scale genomic and transcriptomic datasets, we show that alterations in immune and metabolic pathways shared with atherosclerotic diseases — such as coronary artery disease and stroke — represent causal mechanisms in the development of depression.

Get involved

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