Translational Neuroinflammation

May 9-16, 2026

Director: Lucile Capuron

INRAE-University of Bordeaux, France

Faculty:

Andrew H Miller, Emory University School of Medicine, Atlanta, USA

Valeria Mondelli, King’s College London, London, UK

Laurent Groc, CNRS-University of Bordeaux, France

Joseph Lewcock, Denali Therapeutics, San Francisco, USA

Pierre Gressens, Inserm-University Paris Cité, France

Neil Harrison, Cardiff University, UK

Lucile Capuron, INRAE-University of Bordeaux, France

Neuroinflammation has emerged as a critical contributor to the pathogenesis of a wide range of brain disorders, including neurodegenerative, neurodevelopmental, and psychiatric conditions. This interdisciplinary Advanced Course will explore the complex interplay between the immune system and the brain, with a strong emphasis on translational research bridging basic mechanisms and clinical applications.

The program will examine the cellular and molecular underpinnings of neuroinflammation, its impact on brain function and behaviour, and its relevance across the lifespan. A particular focus will be placed on neuropsychiatric disorders, with sessions exploring inflammation-driven neuropsychiatric symptoms (L Capuron), immune-metabolic mechanisms in schizophrenia and mood disorders (V Mondelli), and precision psychiatry approaches in major depression (AH Miller). Advances in neuroimaging will be addressed through lectures on the visualisation of neuroinflammation and its behavioural correlates (N Harrison), as well as molecular imaging techniques to unravel neuro-immune interactions (L Groc). The vulnerability of the newborn brain to inflammatory insults will be discussed, emphasizing early-life immune challenges and their long-term consequences (P Gressens). The Advanced Course will further provide insight into emerging immune-based therapeutic strategies for brain disorders, highlighting ongoing efforts in translational medicine (J Lewcock).

By bringing together internationally recognised experts in neuroscience, psychiatry, immunology, and imaging, the Advanced Course offers a unique platform for participants to gain a comprehensive and integrated perspective on neuroinflammation, foster interdisciplinary exchange, and stimulate new collaborations in this rapidly evolving field.

Andrew H Miller

Advancing an inflammatory subtype of depression: a precision psychiatry approach to diagnosis and treatment

Chronic inflammation plays a prominent role in multiple medical disorders including psychiatric diseases such as major depression. Exposure to inflammatory stimuli leads to changes in neurotransmitter systems and neurocircuits in the brain that are associated with depressive symptoms. In addition, anti-inflammatory agents can reduce depressive symptoms in medically ill and medically healthy depressed individuals. Moreover, increased biomarkers of inflammation are associated with an overrepresentation of neurovegetative symptoms including anhedonia, fatigue, and psychomotor slowing and can predict response to antidepressant treatments. Importantly, however, increased inflammatory biomarkers only occur in a subgroup of depressed individuals. Thus, there appears to be a subset of depressed patients with a unique symptom presentation and treatment response whose disease is primarily driven by inflammation. In this presentation, we will identify and characterize this inflammatory subtype of depression. Relevant mechanisms to be discussed will include the effects of inflammation on the neurotransmitters dopamine and glutamate as well as neurocircuits that mediate motivation and motor activity and threat sensitivity. In addition, the intersection of inflammation and metabolism in depression will be described. These mechanisms provide a wealth of targets for treatments that will be discussed along with how they can be employed to inform the design of clinical trials. In sum, by using this mechanism-based approach to parsing the heterogeneity of depression, we can refine our diagnostic nosology and model a strategy for precision medicine and the development of targeted therapeutics in psychiatry.

Joseph Lewcock

Immune therapeutic strategies for the treatment of chronic neurodegenerative disease

Neuroinflammation marked by glial activation is a key pathology observed in a range of chronic neurodegenerative diseases. In Alzheimer’s disease (AD), genome-wide association studies (GWASs) have identified variants in numerous genes expressed in microglia, underscoring their causal role in neurodegeneration. In this session, we discuss the recently characterised functions of these AD risk genes and how they can be targeted therapeutically to modify microglial cell states and slow the progression of AD. This includes candidate therapeutic approaches such as stimulating the microglial phagocytosis receptor TREM2, inhibiting the cell surface receptor PILRA, modulating the phospholipase PLCG2, and regulating ApoE function in glia. These alternative approaches to altering microglial function are under intensive investigation and offer new opportunities for innovative AD treatments, which may be used alone or in combination with conventional anti-amyloid treatments.

Valeria Mondelli

Immune-metabolic mechanisms in psychiatric disorders: Prevention and treatment strategies

The interaction between the immune and metabolic systems has gained increasing recognition in recent years. Previous research has highlighted the presence of both immune and metabolic abnormalities in individuals suffering from psychiatric disorders such as schizophrenia and depression. In this presentation, we will examine the latest studies on immune-metabolic mechanisms that may contribute to the development of psychiatric conditions and the effects of treatments targeting these mechanisms in people with psychosis or depression. Additionally, we will investigate these mechanisms in individuals with comorbid metabolic disorders such as obesity, alongside depression, to better understand the reasons behind the highly prevalent comorbidity of these disorders. We will then discuss the implications for preventive strategies, considering whether immune-metabolic abnormalities are already present before the onset of psychiatric illnesses and whether they could serve as potential targets for developing more effective prevention approaches in psychiatry.

Neil Harrison

Using advanced neuroimaging techniques to visualise neuroinflammation and broader actions of inflammation on the brain

Medical treatments that induce prolonged activation of the immune system frequently precipitate major depressive episodes. Conversely, treatments that block the action of inflammatory cytokines frequently have antidepressant properties. It is now clear that parallel neural, humoral and cellular interoceptive signalling pathways play a critical role in linking immune responses in the body and the brain. These signalling pathways can rapidly induce neuroinflammation, perturb neurotransmitter levels and disrupt brain function, leading to discrete changes in behaviour that contribute to common mental illnesses. In this session, we will discuss how diverse neuroimaging techniques can be used to capture interactions between the body and the brain’s immune systems, providing quantifiable indices of neuroinflammation that can be related to changes in behaviour. As our mechanistic understanding of these interoceptive pathways continues to emerge, it is revealing novel therapeutic targets, potentially heralding an exciting new era of immunotherapies in psychiatry.

Lucile Capuron

Inflammation-driven neuropsychiatric symptoms: evidence, mechanisms, and clinical implications

Heightened inflammatory signalling is a shared biological feature across several neuropsychiatric disorders, highlighting the importance of identifying the specific symptom dimensions that are mechanistically driven by inflammation. Findings from models of inflammation-induced depression have allowed the identification of distinct pathophysiological pathways affecting neurotransmitter metabolism, which are particularly relevant to the development of symptom clusters involving mood and cognitive symptoms or neurovegetative and motivational changes. These symptom dimensions also characterise disorders in which chronic, low-grade inflammation is frequently observed. Interestingly, converging evidence suggests that the expression of inflammation-related psychiatric symptoms is shaped by a set of vulnerability factors, including personality traits, stress exposure, metabolic context, and neuroendocrine regulation. This implies that inflammatory processes interact with individual predispositions to influence clinical presentation.
Together, these findings position inflammation as a key, overarching mechanism in psychiatric pathophysiology and support the development of therapeutic strategies that target inflammation, especially the pathways through which inflammatory processes selectively influence neurotransmitter metabolism and function. Such approaches hold significant promise for advancing prevention and treatment strategies within a personalised, precision-medicine framework in psychiatry.

Laurent Groc

Autoimmunity in neuropsychiatric disorders

Neurological and psychiatric symptoms, as well as cognitive deficits, represent a prominent phenotype associated with various forms of autoimmune encephalitis, regardless of the neurotransmitter receptor targeted by autoantibodies. The mechanistic underpinnings of these autoantibody-mediated conditions remain, however, still unclear, although they offer a unique opportunity to shed new light on major neurological and psychiatric disorders.
Using a combination of single molecule and super-resolution imaging, immunocytochemistry, and electrophysiology, we investigated the molecular and cellular impacts of patient-derived autoantibodies against the glutamatergic NMDA receptor and other targets in the hippocampus. We uncovered how autoantibodies trigger convergent network dysfunctions through a combination of shared and distinct mechanisms. Moreover, I will discuss a newly discovered unconventional way to tune NMDA receptor surface dynamics in these pathological models. This work paves the way for new therapeutic strategies in glutamatergic receptor-based neuropsychiatric conditions.

Pierre Gressens

Inflammation and the perinatal brain

Before birth and around birth, systemic inflammation can occur in the fetus/neonate for multiple reasons. The developing brain senses systemic inflammation, and this can lead to neuroinflammation that disrupts multiple neurodevelopmental steps. Epidemiological and clinical studies have shown strong associations between prenatal/perinatal inflammation and long-term negative neurological outcome, including cerebral palsy, cognitive impairment and other neurodevelopmental disorders such as autism, attention deficit, or developmental epilepsies. In addition, adult psychiatric disorders such as bipolar disorders and depression have been shown to be related to early-onset inflammation. In this context, prematurity and the so-called encephalopathy of prematurity (EoP) have emerged as a “prototypical” perinatal condition strongly associated with systemic inflammation/neuroinflammation and neurodevelopmental disorders (NDDs).
Different animal models of prenatal (maternal immune activation) or perinatal (modelling EoP) have been developed and characterised, including at the behavioural and connectivity levels, highlighting the key role of microglia and other glial cells in the pathophysiology of these modelled NDDs. In addition, more recent data support the key interactions between microglia-glia, border-associated macrophages (BAMs, primarily located in the choroid plexus, meningeal and perivascular spaces), and infiltrating immune cells (neutrophils, monocytes, and different subpopulations of T cells). State-of-the-art technologies have enabled us to demonstrate the wide variety of cell subtypes, highlighting the complex cellular and molecular networks that may underlie the pathophysiology of these NDDs.