Matthew Baum
Physician, Department of Psychiatry Brigham & Women’s Hospital
Seminars
Neuropsychiatric symptoms have long been approached from a behavioural lens, often leading to treatments that address symptoms without a clear mechanistic understanding of their root causes. However, recent advances in neuroimmunology are reframing mood disorders, especially late-onset and comorbid depression, as potentially biologically driven diseases with immune system involvement. This workshop will tackle the growing body of evidence suggesting that chronicinflammation, glial dysfunction, and even systemic immune activation play a key role in the onset and progression of depressive disorders. Through cross-disciplinary discussion, we’ll ask whether psychiatry is ready for a shift toward biologically targeted therapeutics and what that would require in terms of biomarkers, models, and trial strategy.
Key Topics to Be Explored:
- Examine the bidirectional relationship between immune activation and mood disorders – is neuroinflammation causative, or does it amplify pre-existing vulnerabilities?
- Discuss how shared inflammatory mechanisms in neurodegenerative diseases (e.g., Parkinson’s, Alzheimer’s) are helping redefine depression as a neurobiological condition rather than a purely psychological one
- Explore how lifestyle factors such as stress and substance use may initiate or exacerbate neuroinflammatory cascades contributing to depressive symptoms
- Evaluate emerging therapeutic approaches, including small and large molecules, aimed at modulating the immune system as a treatment for depression
- Highlight the critical need for robust biomarkers that can stratify patients based on inflammatory profiles and reduce placebo effects in depression trials
Psychosis and mood disorders have traditionally been treated as distinct psychiatric conditions, often approached through a behavioral lens. However, modern large-scale genetics studies suggest substantial overlap in both common and rare variant drivers of risk for schizophrenia, bipolar disorder and, to a lesser extent, major depressive disorder. Emerging evidence suggests that neuroimmune mechanisms may contribute to pathogenesis in one or more transdiagnostic subsets of patients. Beyond longstanding hypotheses involving systemic inflammation or peripheral cytokines, genetic and neurobiological studies implicate dysfunctional immune pathways and glial cells within the central nervous system as drivers of psychiatric symptoms. This workshop will explore recent and ongoing efforts to identify molecular biomarkers to stratify psychiatric patient populations, and insights from our evolving understanding of autoimmune contributions to psychiatric conditions. As boundaries blur between psychiatric diagnoses, between the clinical specialties of neurology and psychiatry, and mechanistic understanding accumulates, this session will use an interactive workshop format to explore what this convergence means for therapeutic development, biomarker discovery, and clinical trial design, and whether the field is ready to shift toward biologically targeted interventions.
Key Topics to Be Explored:
- What are some of the unique challenges to neuroimmune drug development for psychotic and mood disorders vs neurodegenerative disorders?
- What sort of data, tools or resources, if produced, would help “de-risk” investment in this area?
- For clinical progress, how important is it to have blood biomarkers (as opposed to CSF/imaging/ephys biomarkers)?
- If a person with a longstanding diagnosis of schizophrenia or bipolar disorder were to have complete symptom resolution after immunotherapy, does this mean they had been misdiagnosed? How relevant is the answer to this question to neuroimmune drug development efforts?
- What changes would need to happen in the way clinical psychiatry is practiced in the USA for neuroimmune drug development or deplopyment to be most successful in this space? How might these changes occur?
