How Inflammation Ignites New Approaches to Bipolar Disorder
Bipolar disorder (BD) has long been characterized by its dramatic mood swings between mania and depression. But beneath these visible symptoms, a quieter revolution is unfolding in research laboratories: the discovery that chronic inflammation may be driving the disorder's progression and shaping its devastating cognitive toll.
The link between inflammation and BD is rooted in overlapping biological pathways:
A landmark 2025 study identified 296 gene locations and 36 unique genes tied to BD, many overlapping with genes involved in immune regulation and inflammatory responses. These genes influence how the body detects threats and mounts immune defenses .
In BD patients, key inflammatory markers like interleukin-6 (IL-6) and C-reactive protein (CRP) are consistently elevated. IL-6, in particular, correlates with cognitive decline and hospitalizations. For every unit increase in IL-6, cognitive scores drop significantly, impacting memory and attention 9 .
A 2025 transcriptomics study revealed that the IL-17 signaling pathway—a key driver of autoimmune diseases—is hyperactive in BD. Genes like CXCL8 and IL17 are overexpressed, promoting chemokine production that triggers neuroinflammation. This pathway may explain why BD frequently coexists with conditions like lupus or psoriasis 6 .
| Biomarker | BD Patients | Healthy Controls | Function |
|---|---|---|---|
| IL-6 | 8.3 ± 28.4 pg/mL | <1.0 pg/mL | Promotes inflammation; linked to cognitive decline |
| hs-CRP | 0.2 ± 0.4 mg/L | <0.1 mg/L | Acute-phase protein; indicates systemic inflammation |
| IL-17 | Significantly ↑ | Baseline | Drives autoimmune responses; elevated in manic/depressive states 6 9 |
Unlike symptomatic treatments, disease-modifying therapies aim to alter BD's trajectory by targeting underlying mechanisms like inflammation. Lithium—the oldest BD drug—exemplifies this approach:
It reduces pro-inflammatory cytokines (e.g., IL-6) while boosting anti-inflammatory signals 8 .
It protects telomeres (caps on chromosomes) from stress-induced shortening, slowing cellular aging 3 .
Critically, starting lithium early in the illness course correlates with better outcomes, mirroring how disease-modifying drugs work in rheumatoid arthritis or multiple sclerosis 8 .
To test whether chronic inflammation directly increases BD risk, researchers analyzed data from 1.56 million adults in the UK's Our Future Health cohort—the world's largest health research biobank 1 4 .
Compared 37,808 adults with self-reported autoimmune diseases (e.g., rheumatoid arthritis, IBD) to 1.52 million without.
Screened for lifetime diagnoses of depression, BD, or anxiety via structured questionnaires.
Controlled for age, income, chronic pain, social isolation, and family history to isolate inflammation's role.
Calculated odds ratios (OR) for affective disorders in autoimmune groups vs. controls.
| Outcome | Autoimmune Group | General Population | Odds Ratio (OR) |
|---|---|---|---|
| Any Affective Disorder | 28.8% | 17.9% | 1.86 [1.82–1.90] |
| Current Depressive Symptoms | 31.7% | 23.4% | 1.53 [1.49–1.57] |
| Current Anxiety Symptoms | 28.1% | 21.6% | 1.48 [1.44–1.52] |
New treatments aim to quell inflammatory processes in BD:
TNF-α inhibitors (e.g., infliximab) used in autoimmune diseases are being trialed for treatment-resistant BD.
| Reagent/Method | Function | Example in BD Research |
|---|---|---|
| Transcriptomic Analysis | Profiles gene expression in immune cells | Identified IL-17 pathway dysregulation 6 |
| CRP/hs-CRP Assays | Measures systemic inflammation | Predicts cognitive decline in euthymia 9 |
| Cytokine ELISA Kits | Quantifies IL-6, IL-17, TNF-α in serum | Validated elevated IL-17 in BD patients 6 |
| Lithium Carbonate | Gold-standard mood stabilizer; modulates immunity | Reduces IL-6 and oxidative stress 3 8 |
Using genetic data to match patients with specific immunotherapies .
Tracking how cytokines alter brain structure over time.
Testing whether suppressing inflammation in high-risk youth delays BD onset.
The inflammation model of bipolar disorder represents more than a scientific breakthrough—it offers tangible hope. By reimagining BD as a disorder of immunity and resilience, we pave the way for therapies that don't just manage symptoms but halt the illness in its tracks. As one researcher notes, "Lithium isn't just a mood stabilizer; it's a disease-modifying shield" 8 . With large biobanks like BD² and Our Future Health generating unprecedented data, the goal of personalized, preventive care for BD is closer than ever.
"The greatest promise lies not in treating storms, but in calming the seas from which they arise."