Bipolar Disorder (BD) is a complex mood condition defined by distinct shifts between periods of mania or hypomania and depression. Currently, there is no single, definitive blood test used as a primary diagnostic tool for the disorder. BD’s symptoms often overlap with other conditions, leading researchers to actively search for biological indicators—or biomarkers—that could provide objective evidence of the condition’s presence. Finding a reliable test would transform the current diagnostic process, which relies entirely on subjective reporting and professional observation.
The Standard Clinical Diagnosis Process
Diagnosis of Bipolar Disorder is a procedural and behavioral assessment rooted in established clinical criteria. Clinicians conduct comprehensive psychiatric evaluations, gathering detailed information about a patient’s mood, energy levels, sleep patterns, and history of behavioral changes. This process often includes interviews with family members, who can provide crucial outside perspectives on the patient’s long-term patterns.
The formal diagnosis relies on the specific criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). BD-I requires at least one manic episode lasting a week or more, or any duration if hospitalization was necessary. BD-II requires at least one major depressive episode and one less severe hypomanic episode lasting a minimum of four consecutive days.
The current model is time-intensive and based entirely on observed symptoms and recollection of past events. Misdiagnosis is common due to the high frequency of depressive episodes shared with Major Depressive Disorder (MDD). The delay between symptom onset and correct diagnosis can often be five to ten years, highlighting the need for a more objective system.
Identifying Biological Indicators (Biomarkers)
Researchers are focused on finding biomarkers—measurable biological indicators of a state or condition—that can be detected in blood. This effort is driven by the understanding that BD is rooted in complex biological dysregulation. The search for a blood test centers on three major categories of measurable biological shifts visible in the bloodstream.
Genetic Markers
BD is a polygenic condition with a strong heritability component, meaning hundreds of gene variations contribute to the overall risk. Current research uses genome-wide association studies (GWAS) to identify specific gene variants, such as those in the CACNA1C and ANK3 genes, that are strongly associated with the disorder.
Inflammatory Markers
Evidence suggests a state of low-grade inflammation in individuals with BD. This involves measuring circulating pro-inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-6 (IL-6). Elevated levels of C-reactive protein (CRP), a common marker of inflammation, are also more pronounced during manic and depressive episodes.
Metabolic Shifts
This category explores changes in small molecules like lipids, amino acids, and hormones. Studies have shown alterations in oxidative stress markers, such as lipid peroxidation and nitric oxide, which indicate damage to cells. Researchers have also observed differences in amino acids like tryptophan and tyrosine, suggesting a shift in monoamine metabolism.
Current Commercial and Research Testing Efforts
While no test is yet a standard diagnostic tool, commercial and academic efforts are producing promising results, primarily to aid in diagnosis or treatment selection. One area of intense research involves the use of Polygenic Risk Scores (PRS), which aggregate the small risk contributions from thousands of genetic variants into a single score. These scores currently have modest predictive accuracy when used alone, often explaining only about four percent of the variation in BD risk.
The most impactful research efforts focus on differentiating BD from the far more common Major Depressive Disorder (MDD), a distinction that is often missed in clinical settings. A blood test developed by researchers at Indiana University, for instance, uses RNA biomarkers to distinguish between these two disorders and to inform tailored medication choices. Similarly, a recent Cambridge University study developed a test using a panel of 17 metabolites to identify individuals with BD who had been previously misdiagnosed with MDD.
In the commercial space, multi-gene pharmacogenomic (PGx) tests, like the GeneSight Psychotropic panel, are available, though their purpose is not diagnosis. These tests analyze genetic variations in liver enzymes, such as CYP2D6 and CYP2C19, to predict how a patient will metabolize certain psychiatric medications. By providing a color-coded report that categorizes medications based on potential gene-drug interactions, these PGx tests are designed to reduce the trial-and-error process of finding an effective drug, but they are not a substitute for clinical evaluation.
The Impact of Biological Testing on Care
The successful integration of a validated blood test into clinical practice would fundamentally shift the landscape of Bipolar Disorder care. A key benefit would be enabling “precision medicine,” allowing clinicians to tailor medication choices based on a patient’s specific biological profile and genetic makeup. Pharmacogenomic data could predict whether a patient is likely to respond well to treatments like lithium or experience severe side effects, allowing for more targeted prescriptions from the start.
Objective testing would also accelerate the path to a correct diagnosis, significantly reducing the five-to-ten-year delay currently experienced by many patients. This earlier detection, particularly in high-risk individuals with a family history, could allow for preemptive psychosocial and lifestyle interventions. Furthermore, a blood test could provide an objective measure for monitoring disease state, offering a way to track the severity of an episode or confirm treatment efficacy beyond subjective self-reports.