Summary: A novel approach combines an online psychiatric assessment with a blood test to diagnose bipolar disorder, a condition often misdiagnosed as major depressive disorder.
This blood test, alongside the digital assessment, can accurately diagnose up to 30% of bipolar disorder cases. It provides not just a faster diagnostic tool but also an objective insight into the biological basis of this mental illness.
The blood test, coupled with an online assessment, can diagnose 30% of bipolar disorder cases, differentiating it from major depressive disorder.
The research incorporated more than 600 questions in its online mental health assessment and examined over 600 different metabolites in dried blood samples.
Nearly 40% of bipolar disorder cases are misdiagnosed as major depressive disorder, affecting up to 80 million people worldwide.
Source: University of Cambridge
Researchers have developed a new way of improving diagnosis of bipolar disorder that uses a simple blood test to identify biomarkers associated with the condition.
The researchers, from the University of Cambridge, used a combination of an online psychiatric assessment and a blood test to diagnose patients with bipolar disorder, many of whom had been misdiagnosed with major depressive disorder.
The researchers say the blood test on its own could diagnose up to 30% of patients with bipolar disorder, but that it is even more effective when combined with a digital mental health assessment.
Incorporating biomarker testing could help physicians differentiate between major depressive disorder and bipolar disorder, which have overlapping symptoms but require different pharmacological treatments.
Although the blood test is still a proof of concept, the researchers say it could be an effective complement to existing psychiatric diagnosis and could help researchers understand the biological origins of mental health conditions.
The results are reported in the journal JAMA Psychiatry.
Bipolar disorder affects approximately one percent of the population – as many as 80 million people worldwide – but for nearly 40% of patients, it is misdiagnosed as major depressive disorder.
“People with bipolar disorder will experience periods of low mood and periods of very high mood or mania,” said first author Dr Jakub Tomasik, from Cambridge’s Department of Chemical Engineering and Biotechnology.
“But patients will often only see a doctor when they’re experiencing low mood, which is why bipolar disorder frequently gets misdiagnosed as major depressive disorder.”
“When someone with bipolar disorder is experiencing a period of low mood, to a physician, it can look very similar to someone with major depressive disorder,” said Professor Sabine Bahn, who led the research.
“However, the two conditions need to be treated differently: if someone with bipolar disorder is prescribed antidepressants without the addition of a mood stabiliser, it can trigger a manic episode.”
The most effective way to get an accurate diagnosis of bipolar disorder is a full psychiatric assessment. However, patients often face long waits to get these assessments, and they take time to carry out.
“Psychiatric assessments are highly effective, but the ability to diagnose bipolar disorder with a simple blood test could ensure that patients get the right treatment the first time and alleviate some of the pressures on medical professionals,” said Tomasik.
The researchers used samples and data from the Delta study, conducted in the UK between 2018 and 2020, to identify bipolar disorder in patients who had received a diagnosis of major depressive disorder within the previous five years and had current depressive symptoms. Participants were recruited online through voluntary response sampling.
More than 3000 participants were recruited, and they each completed an online mental health assessment of more than 600 questions. The assessment covered a range of topics that may be relevant to mental health disorders, including past or current depressive episodes, generalised anxiety, symptoms of mania, family history or substance abuse.
Of the participants who completed the online assessment, around 1000 were selected to send in a dried blood sample from a simple finger prick, which the researchers analysed for more than 600 different metabolites using mass spectrometry.
After completing the Composite International Diagnostic Interview, a fully structured and validated diagnostic tool to establish mood disorder diagnoses, 241 participants were included in the study.
Analysis of the data showed a significant biomarker signal for bipolar disorder, even after accounting for confounding factors such as medication. The identified biomarkers were correlated primarily with lifetime manic symptoms and were validated in a separate group of patients who received a new clinical diagnosis of major depressive disorder or bipolar disorder during the study’s one-year follow-up period.
The researchers found that the combination of patient-reported information and the biomarker test significantly improved diagnostic outcomes for people with bipolar disorder, especially in those where the diagnosis was not obvious.
“The online assessment was more effective overall, but the biomarker test performs well and is much faster,” said Bahn. “A combination of both approaches would be ideal, as they’re complementary.”
“We found that some patients preferred the biomarker test, because it was an objective result that they could see,” said Tomasik. “Mental illness has a biological basis, and it’s important for patients to know it’s not in their mind. It’s an illness that affects the body like any other.”
“In addition to the diagnostic capabilities of biomarkers, they could also be used to identify potential drug targets for mood disorders, which could lead to better treatments,” said Bahn. “It’s an exciting time to be in this area of research.”
A patent has been filed on the research by Cambridge Enterprise, the University’s commercialisation arm. The research was supported by the Stanley Medical Research Institute and Psyomics, a University spin-out company co-founded by Sabine Bahn.
Sabine Bahn is Professor of Neurotechnology at the Department of Chemical Engineering and Biotechnology and is a Fellow of Lucy Cavendish College, Cambridge.
Metabolic Biomarker Signatures for Bipolar and Unipolar Depression
Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD) because of overlapping symptoms and the lack of objective diagnostic tools.
To identify a reproducible metabolomic biomarker signature in patient dried blood spots (DBSs) that differentiates BD from MDD during depressive episodes and assess its added value when combined with self-reported patient information.
Design, Setting, and Participants
This diagnostic analysis used samples and data from the Delta study, conducted in the UK between April 27, 2018, and February 6, 2020. The primary objective was to identify BD in patients with a recent (within the past 5 years) diagnosis of MDD and current depressive symptoms (Patient Health Questionnaire–9 score of 5 or more). Participants were recruited online through voluntary response sampling. The analysis was carried out between February 2022 and July 2023.
Main Outcomes and Measures
Patient data were collected using a purpose-built online questionnaire (n = 635 questions). DBS metabolites (n = 630) were analyzed using a targeted mass spectrometry–based platform. Mood disorder diagnoses were established using the Composite International Diagnostic Interview.
Of 241 patients in the discovery cohort, 170 (70.5%) were female; 67 (27.8%) were subsequently diagnosed with BD and 174 (72.2%) were confirmed as having MDD; and the mean (SD) age was 28.1 (7.1) years. Of 30 participants in the validation cohort, 16 (53%) were female; 9 (30%) were diagnosed with BD and 21 (70%) with MDD; and the mean (SD) age was 25.4 (6.3) years.
DBS metabolite levels were assessed in 241 patients with depressive symptoms with a recent diagnosis of MDD, of whom 67 were subsequently diagnosed with BD by the Composite International Diagnostic Interview and 174 were confirmed as having MDD. The identified 17-biomarker panel provided a mean (SD) cross-validated area under the receiver operating characteristic curve (AUROC) of 0.71 (SD, 0.12; P < .001), with ceramide d18:0/24:1 emerging as the strongest biomarker.
Combining biomarker data with patient-reported information significantly enhanced diagnostic performance of models based on extensive demographic data, PHQ-9 scores, and the outcomes from the Mood Disorder Questionnaire. The identified biomarkers were correlated primarily with lifetime manic symptoms and were validated in a separate group of patients who received a new clinical diagnosis of MDD (n = 21) or BD (n = 9) during the study’s 1-year follow-up period, with a mean (SD) AUROC of 0.73 (0.06; P < .001).
Conclusions and Relevance
This study provides a proof of concept for developing an accessible biomarker test to facilitate the differential diagnosis of BD and MDD and highlights the potential involvement of ceramides in the pathophysiological mechanisms of mood disorders.