Bipolar Disorder and the Immune System
Bipolar disorder is a chronic mental health condition that causes intense shifts in mood, energy levels, thinking patterns, and behavior. As science explores new treatments, the link between bipolar disorder and the immune system has gained significant attention in recent years. Growing research suggests that inflammatory processes and immune system irregularities may play a role in both the development and progression of bipolar disorder.
Understanding Bipolar Disorder
Bipolar disorder is a mental health condition that involves extreme mood swings between manic episodes of intense energy and depressive episodes of profound sadness. Unlike typical mood fluctuations that last only hours, bipolar episodes persist for days to weeks [1]. With onset typically before age 30, these episodes can disrupt relationships, work performance, and daily activities [2].
Formerly known as manic-depressive disorder, bipolar disorder appears to have significant genetic components. Up to 90% of those with the disorder have a relative with depression or bipolar disorder. Additionally, environmental factors like stress, sleep disruption, and substance use may trigger episodes in genetically predisposed individuals [1]. When it comes to bipolar disorder prevalence, approximately 4.4% of U.S. adults experience bipolar disorder at some point in their lives [2].
Types of bipolar disorder include [1]:
- Bipolar I Disorder: Bipolar I is characterized by depressive episodes that typically last at least two weeks and either manic episodes that last at least seven days or severe manic symptoms requiring immediate hospital care.
- Bipolar II Disorder: Defined by a pattern of depressive and hypomanic episodes, bipolar II doesn’t include full-blown manic episodes.
- Cyclothymic Disorder: Involving periods of hypomanic and depressive symptoms, cyclothymic disorder can last two years, but its symptoms don’t meet the criteria for hypomanic or depressive episodes.
Despite these troubling types and symptoms, treatment for bipolar disorder can help people manage their symptoms and lead fulfilling lives. Plus, ongoing research offers continued hope for novel therapies and improved care.
Fundamentals of Immune System Function
The immune system comprises a complex network of cells, tissues, and organs that work together to defend the body against harmful pathogens, cancer cells, and toxins. This sophisticated defense mechanism can be broadly divided into two main types of immunity [3]:
- Innate: The innate immune system provides immediate, nonspecific defense against pathogens, like viruses and bacteria. It includes physical barriers, like skin and mucous membranes, and cellular components, known as neutrophils, macrophages, dendritic cells, etc. These cells recognize pathogens and respond quickly by engulfing them and creating inflammation. Cytokines, special molecules that regulate immune responses, are released, causing the redness, heat, swelling, and pain associated with inflammation. Cytokines communicate with other body systems, including the brain.
- Adaptive: In contrast, the adaptive immune system creates responses to specific pathogens and remembers them for future protection. This system includes two main types of white blood cells: T lymphocytes (T cells) and B lymphocytes (B cells). T cells help manage the body’s defense by directing other immune cells and attacking infected cells. B cells work by making antibodies, which are proteins that stick to pathogens and help destroy them.
So, how might bipolar disorder and the immune system be linked? In effect, the brain and immune system talk to each other. As a result of this conversation, various types of immune dysfunction might impact mental health conditions like bipolar disorder.
Bipolar Disorder and the Immune System
Growing evidence suggests a significant link between bipolar disorder and immune system dysfunction. Specifically, recent research found people with bipolar disorder often have excess inflammation involving both the innate and adaptive immune systems [4].
What’s more, higher inflammation levels were found during all phases of the illness, including manic, depressive, and stable mood states. This suggests that inflammation might be a permanent feature of bipolar disorder and not just a problem that comes and goes with mood changes. The link between bipolar disorder and inflammation helps explain why people with this disorder often have other health problems like autoimmune disorders, heart disease, and metabolic problems [4].
Furthermore, bipolar disorder research shows that this inflammation affects the body and the brain, which has its own immune cells. Activation of these cells, a condition known as neuroinflammation, is commonly found in people with bipolar disorder. Neuroinflammation prompts the release of inflammatory chemicals that can damage nearby brain cells. Bottom line: Inflammation may contribute to brain changes that underlie bipolar disorder symptoms like mood swings, cognitive problems, and emotional regulation difficulties [4].
By exploring the role of the immune system in bipolar disorder, scientists are gaining further insights into what causes this mental health condition. While mood stabilizers and antipsychotic medications still form the basis of bipolar disorder treatment, therapies targeting the immune system may be on the horizon.
Inflammatory Comorbidities
People with bipolar disorder experience inflammatory medical conditions at significantly higher rates than the general population [5]. This connection further strengthens the link between bipolar disorder and immune system dysfunction.
For example, research shows people with bipolar disorder have elevated rates of autoimmune diseases. One meta-analysis found that the risk of developing comorbid autoimmune conditions is nearly doubled in people with bipolar compared to the general population. Common autoimmune conditions co-occurring with bipolar disorder include multiple sclerosis, rheumatoid arthritis, lupus, and inflammatory bowel diseases [5].
Metabolic disorders with inflammatory components (obesity, metabolic syndrome, and type 2 diabetes) are also more common in those with bipolar disorder. Similarly, cardiovascular disease, which has inflammatory components, is also more prevalent. While medication side effects and lifestyle factors may contribute to these associations, research suggests that shared inflammatory factors likely play a significant role [6].
T Cells and Bipolar Disorder
T cells are a type of white blood cell that protects the body from infections and diseases. Recent studies suggest that T cells may also be linked to bipolar disorder [7].
Various T cells exist, each with specific jobs. For example, helper T cells help activate other immune cells, while cytotoxic T cells kill infected or abnormal cells. Changes in T cell numbers and functions have been found in people with bipolar disorder. Specifically, research shows some types of T cells are lower in these people, which may indicate ongoing immune system activity [7].
T cells are also important for brain health. They help with brain development and function. A balance between certain T cells is important for maintaining healthy brain connections that affect thinking and emotions. Disruptions in this balance may lead to brain structure changes often seen in bipolar disorder [7].
Overall, these findings indicate that T cells may be an important link between immune system problems and brain changes in bipolar disorder. This offers potential new therapeutic targets for bipolar treatment.
Bipolar Disorder and Chronic Infections
Chronic infections are a compelling aspect of the immunology of bipolar disorder, or the study of how bipolar disorder and immune dysfunction overlap. Research shows that people with bipolar disorder are more likely to have been exposed to certain infections, such as Toxoplasma gondii, herpes simplex virus (types 1 and 2), cytomegalovirus, and Epstein-Barr virus, compared to the general population. These infections can remain dormant in the body for years, keeping the immune system active over time [5].
This ongoing immune response may contribute to the inflammation often seen in bipolar disorder. Some infections can also directly affect the brain, potentially disrupting mood-related brain functions. For example, human cytomegalovirus (HCMV) has been linked to bipolar disorder. While usually inactive, HCMV can cause changes in immune cells that mirror immune issues seen in bipolar disorder [5].
These findings suggest that treating chronic infections might help manage bipolar disorder in some patients, especially those with signs of immune system problems linked to infections.
Treatment for Bipolar Disorder
The standard treatment approach for bipolar disorder typically involves a combination of mood stabilizers, antipsychotics, antidepressants, and psychotherapy. Among pharmaceuticals, lithium remains the gold standard mood stabilizer, with robust evidence supporting its effectiveness in preventing both manic and depressive episodes [8].
However, given the role of science and the emerging evidence of immune dysfunction in bipolar disorder, novel immune-based treatment strategies are being explored. Among them, anti-inflammatory agents have shown promise as adjunctive therapies for bipolar disorder.
For instance, nonsteroidal anti-inflammatory drugs (NSAIDs) like celecoxib seem to reduce depressive symptoms for some people when added to conventional treatments. Along the same line, minocycline, an antibiotic with anti-inflammatory and neuroprotective properties, may also have benefits in bipolar depression [5].
Interestingly, some established treatments for bipolar disorder work in part by impacting the immune system. Lithium, for example, inhibits key inflammatory signaling pathways and reduces cytokines, which are proinflammatory. Similarly, valproate (used to treat bipolar disorder, epilepsy, and more) has anti-inflammatory properties that may contribute to its mood-stabilizing effects [6].
Ongoing bipolar disorder research is exploring other potential immune-targeted approaches. These novel strategies represent promising directions for enhancing treatment outcomes in this complex and challenging condition.
The Path Ahead
Marked by inflammation and cellular changes, the intricate connection between bipolar disorder and the immune system is reshaping the understanding of this condition. Research highlights how immune dysregulation, potentially influenced by genetics, infections, and comorbidities, contributes to the mood episodes and brain alterations seen in bipolar disorder.
This evolving knowledge isn’t just nice-to-know info. It’s paving the way for innovative treatments that target these immune pathways. For those living with bipolar disorder, this means that science is continuously seeking better, more personalized ways to manage symptoms and improve quality of life. The scientific horizon promises new ways to navigate this complex illness and foster well-being.
- American Psychiatric Association. (2024, April ). What are bipolar disorders? American Psychiatric Association. https://www.psychiatry.org/patients-families/bipolar-disorders/what-are-bipolar-disorders. Accessed 6 May 2025.
- National Institute of Mental Health. (n.d.). Bipolar disorder. National Institute of Mental Health. https://www.nimh.nih.gov/health/statistics/bipolar-disorder. Accessed 6 May 2025.
- Marshall, J. S., Warrington, R., Watson, W., & Kim, H. L. (2018). An introduction to immunology and immunopathology. Allergy, asthma, and clinical immunology: Official journal of the Canadian Society of Allergy and Clinical Immunology, 14(Suppl 2), 49. https://doi.org/10.1186/s13223-018-0278-1. Accessed 6 May 2025.
- Benedetti, F., Aggio, V., Pratesi, M. L., Greco, G., & Furlan, R. (2020). Neuroinflammation in Bipolar Depression. Frontiers in Psychiatry, 11, 71. https://doi.org/10.3389/fpsyt.2020.00071. Accessed 6 May 2025.
- Rosenblat, J. D., & McIntyre, R. S. (2017). Bipolar Disorder and Immune Dysfunction: Epidemiological Findings, Proposed Pathophysiology and Clinical Implications. Brain Sciences, 7(11), 144. https://doi.org/10.3390/brainsci7110144. Accessed 6 May 2025.
- Barbosa -Barbosa, I. G., Machado-Vieira, R., Soares, J. C., & Teixeira, A. L. (2014). The immunology of bipolar disorder. Neuroimmunomodulation, 21(2-3), 117–122. https://doi.org/10.1159/000356539. Accessed 6 May 2025.
- Chen, Z., Huang, Y., Wang, B., Peng, H., Wang, X., Wu, H., Chen, W., & Wang, M. (2023). T cells: an emerging cast of roles in bipolar disorder. Translational Psychiatry, 13(1), 153. https://doi.org/10.1038/s41398-023-02445-y. Accessed 6 May 2025.
- Mayo Clinic. (2024, August 14). Bipolar disorder: Diagnosis and treatment. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/bipolar-disorder/diagnosis-treatment/drc-20355961. Accessed 6 May 2025.
The Clinical Affairs Team at MentalHealth.com is a dedicated group of medical professionals with diverse and extensive clinical experience. They actively contribute to the development of content, products, and services, and meticulously review all medical material before publication to ensure accuracy and alignment with current research and conversations in mental health. For more information, please visit the Editorial Policy.
MentalHealth.com is a health technology company guiding people towards self-understanding and connection. The platform provides reliable resources, accessible services, and nurturing communities. Its purpose is to educate, support, and empower people in their pursuit of well-being.
Linda Armstrong is an award-winning writer and editor with over 20 years of experience across print and digital media.
Dr. Holly Schiff, PsyD, is a licensed clinical psychologist specializing in the treatment of children, young adults, and their families.
Medical Reviewer:
The Clinical Affairs Team at MentalHealth.com is a dedicated group of medical professionals with diverse and extensive clinical experience. They actively contribute to the development of content, products, and services, and meticulously review all medical material before publication to ensure accuracy and alignment with current research and conversations in mental health. For more information, please visit the Editorial Policy.
MentalHealth.com is a health technology company guiding people towards self-understanding and connection. The platform provides reliable resources, accessible services, and nurturing communities. Its purpose is to educate, support, and empower people in their pursuit of well-being.