A Blood Test For Depression and Bipolar Disorder

Summary: A new blood test can distinguish the severity of a person’s depression and their risk for developing severe depression at a later point. The test can also determine if a person is at risk for developing bipolar disorder. Researchers say the blood test can also assist in tailoring individual options for therapeutic interventions.

Source: Indiana University

Worldwide, 1 in 4 people will suffer from a depressive episode in their lifetime.

While current diagnosis and treatment approaches are largely trial and error, a breakthrough study by Indiana University School of Medicine researchers sheds new light on the biological basis of mood disorders, and offers a promising blood test aimed at a precision medicine approach to treatment.

Led by Alexander B. Niculescu, MD, PhD, Professor of Psychiatry at IU School of Medicine, the study was published today in the high impact journal Molecular Psychiatry . The work builds on previous research conducted by Niculescu and his colleagues into blood biomarkers that track suicidality as well as pain, post-traumatic stress disorder and Alzheimer’s disease.

“We have pioneered the area of precision medicine in psychiatry over the last two decades, particularly over the last 10 years. This study represents a current state-of-the-art outcome of our efforts,” said Niculescu. “This is part of our effort to bring psychiatry from the 19th century into the 21st century. To help it become like other contemporary fields such as oncology. Ultimately, the mission is to save and improve lives.”

The team’s work describes the development of a blood test, composed of RNA biomarkers, that can distinguish how severe a patient’s depression is, the risk of them developing severe depression in the future, and the risk of future bipolar disorder (manic-depressive illness). The test also informs tailored medication choices for patients.

This comprehensive study took place over four years, with over 300 participants recruited primarily from the patient population at the Richard L. Roudebush VA Medical Center in Indianapolis. The team used a careful four-step approach of discovery, prioritization, validation and testing.

First, the participants were followed over time, with researchers observing them in both high and low mood states–each time recording what changed in terms of the biological markers (biomarkers) in their blood between the two states.

Next, Niculescu’s team utilized large databases developed from all previous studies in the field, to cross-validate and prioritize their findings. From here, researchers validated the top 26 candidate biomarkers in independent cohorts of clinically severe people with depression or mania. Last, the biomarkers were tested in additional independent cohorts to determine how strong they were at predicting who is ill, and who will become ill in the future.

From this approach, researchers were then able to demonstrate how to match patients with medications–even finding a new potential medication to treat depression.

“Through this work, we wanted to develop blood tests for depression and for bipolar disorder, to distinguish between the two, and to match people to the right treatments,” said Niculescu.

This shows a hand holding up blood in test tubes
The test also informs tailored medication choices for patients. Image is in the public domain

“Blood biomarkers are emerging as important tools in disorders where subjective self-report by an individual, or a clinical impression of a health care professional, are not always reliable. These blood tests can open the door to precise, personalized matching with medications, and objective monitoring of response to treatment.”

In addition to the diagnostic and therapeutic advances discovered in their latest study, Niculescu’s team found that mood disorders are underlined by circadian clock genes–the genes that regulate seasonal, day-night and sleep-wake cycles.

“That explains why some patients get worse with seasonal changes, and the sleep alterations that occur in mood disorders,” said Niculescu.

According to Niculescu, the work done by his team has opened the door for their findings to be translated into clinical practice, as well as help with new drug development. Focusing on collaboration with pharmaceutical companies and other doctors in a push to start applying some of their tools and discoveries in real-world scenarios, Niculescu said he believes the work being done by his team is vital in improving the quality of life for countless patients.

“Blood biomarkers offer real-world clinical practice advantages. The brain cannot be easily biopsied in live individuals, so we’ve worked hard over the years to identify blood biomarkers for neuropsychiatric disorders,” said Niculescu. “Given the fact that 1 in 4 people will have a clinical mood disorder episode in their lifetime, the need for and importance of efforts such as ours cannot be overstated.”

Funding: This research was supported by the National Institutes of Health under Award Number 1DP20D007363 and R01mh117431 and a VA Merit Award 2I01CX000139.

About this depression and bipolar disorder research news

Source: Indiana University
Contact: Katie Duffey – Indiana University
Image: The image is in the public domain

Original Research: Open access.
Precision medicine for mood disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs” by H. Le-Niculescu, K. Roseberry, S. S. Gill, D. F. Levey, P. L. Phalen, J. Mullen, A. Williams, S. Bhairo, T. Voegtline, H. Davis, A. Shekhar, S. M. Kurian & A. B. Niculescu. Molecular Psychiatry


Abstract

Mood disorders (depression, bipolar disorders) are prevalent and disabling. They are also highly co-morbid with other psychiatric disorders. Currently there are no objective measures, such as blood tests, used in clinical practice, and available treatments do not work in everybody.

The development of blood tests, as well as matching of patients with existing and new treatments, in a precise, personalized and preventive fashion, would make a significant difference at an individual and societal level. Early pilot studies by us to discover blood biomarkers for mood state were promising, and validated by others.

Recent work by us has identified blood gene expression biomarkers that track suicidality, a tragic behavioral outcome of mood disorders, using powerful longitudinal within-subject designs, validated them in suicide completers, and tested them in independent cohorts for ability to assess state (suicidal ideation), and ability to predict trait (future hospitalizations for suicidality).

These studies showed good reproducibility with subsequent independent genetic studies. More recently, we have conducted such studies also for pain, for stress disorders, and for memory/Alzheimer’s Disease.

We endeavored to use a similar comprehensive approach to identify more definitive biomarkers for mood disorders, that are transdiagnostic, by studying mood in psychiatric disorders patients.

First, we used a longitudinal within-subject design and whole-genome gene expression approach to discover biomarkers which track mood state in subjects who had diametric changes in mood state from low to high, from visit to visit, as measured by a simple visual analog scale that we had previously developed (SMS-7).

Second, we prioritized these biomarkers using a convergent functional genomics (CFG) approach encompassing in a comprehensive fashion prior published evidence in the field.

Third, we validated the biomarkers in an independent cohort of subjects with clinically severe depression (as measured by Hamilton Depression Scale, (HAMD)) and with clinically severe mania (as measured by the Young Mania Rating Scale (YMRS)). Adding the scores from the first three steps into an overall convergent functional evidence (CFE) score, we ended up with 26 top candidate blood gene expression biomarkers that had a CFE score as good as or better than SLC6A4, an empirical finding which we used as a de facto positive control and cutoff.

Notably, there was among them an enrichment in genes involved in circadian mechanisms. We further analyzed the biological pathways and networks for the top candidate biomarkers, showing that circadian, neurotrophic, and cell differentiation functions are involved, along with serotonergic and glutamatergic signaling, supporting a view of mood as reflecting energy, activity and growth.

Fourth, we tested in independent cohorts of psychiatric patients the ability of each of these 26 top candidate biomarkers to assess state (mood (SMS-7), depression (HAMD), mania (YMRS)), and to predict clinical course (future hospitalizations for depression, future hospitalizations for mania). We conducted our analyses across all patients, as well as personalized by gender and diagnosis, showing increased accuracy with the personalized approach, particularly in women.

Again, using SLC6A4 as the cutoff, twelve top biomarkers had the strongest overall evidence for tracking and predicting depression after all four steps: NRG1, DOCK10, GLS, PRPS1, TMEM161B, GLO1, FANCF, HNRNPDL, CD47, OLFM1, SMAD7, and SLC6A4. Of them, six had the strongest overall evidence for tracking and predicting both depression and mania, hence bipolar mood disorders. There were also two biomarkers (RLP3 and SLC6A4) with the strongest overall evidence for mania. These panels of biomarkers have practical implications for distinguishing between depression and bipolar disorder.

Next, we evaluated the evidence for our top biomarkers being targets of existing psychiatric drugs, which permits matching patients to medications in a targeted fashion, and the measuring of response to treatment. We also used the biomarker signatures to bioinformatically identify new/repurposed candidate drugs. Top drugs of interest as potential new antidepressants were pindolol, ciprofibrate, pioglitazone and adiphenine, as well as the natural compounds asiaticoside and chlorogenic acid. The last 3 had also been identified by our previous suicidality studies.

Finally, we provide an example of how a report to doctors would look for a patient with depression, based on the panel of top biomarkers (12 for depression and bipolar, one for mania), with an objective depression score, risk for future depression, and risk for bipolar switching, as well as personalized lists of targeted prioritized existing psychiatric medications and new potential medications.

Overall, our studies provide objective assessments, targeted therapeutics, and monitoring of response to treatment, that enable precision medicine for mood disorders.

Precision medicine for mood disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs

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  1. I like that you mention that doctors could do a better job at choosing medications for people through these types of blood testing, and it also could help with monitoring treatment response. My niece was diagnosed with depression two weeks ago, and her parents are worried about how to ensure she gets the best treatment. Maybe it would help for them to consult a blood testing lab to discuss how this could help with her problem.

  2. I’m looking to find a way to combat ptsd and depression. I’ve tried many medications in my life and I feel like they did more harm than good. It would be wonderful to know what medication were going to work best with my body but I have yet to find anything. When will this be available for people anywhere?

  3. I’m somewhere on the bipolar spectrum. My first diagnosis was unipolar depression, but things have changed during the last 40 years. Effexor has been a miracle for me, however, sometimes it’s just not enough.I can’t help hoping that there’s something new and maybe better. Can you help?

  4. I live in New York and would like to be informed where I can go for this test. I suffer from Major Depressive Disorder.

  5. This is disgusting. I have this disorder, it’s not a joke and you cannot be legitimately diagnosed unless under 24 hour surveillance for 30 days. Do some research. This study is gross and the researchers should be ashamed (I have a MA in Public Policy; these people are ignorant and insulting).

  6. was Candidemia (candida albicans infection of the blood) eliminated as a confounding factor? Are you even aware that it is one; not only confounding, but also highly correlated with anxiety/depression/mood disorders? The CDC currently deems this yeast infection of the blood: “epidemic”.

  7. I would like to know if the blood test are available in the east coast, in NY state?
    And if is covered by the insurance

  8. I am a huge advocate for mental illness! I think any helpful advancement in the field is hugely appreciated by clients and professionals! Not to mention society who suffer as well. We need this and other help badly! Keep it up and do encompass everybody!

  9. This is normal itself within the medical community. Our blood labor work allows doctors to pinpoint what is actually within a normal range for various underlying conditions. What about someone who has to deal with angst prior to an appointment? Or An argument with a trying to be supportive family member or just heavy traffic. Normal nervousness or what about the coldness of the psychiatrist office as he or she tries to show you professional boundaries by coming off as the least likely person you’d like to meet at a kkk rally, prior to an appointment that is supposed to mean billions of dollars to an industry that thrives on everyday post-trigger trauma.

    People are going to have questions and it may be alarming some of my joking about this but blood testing is a good thing. Blood cannot lie or tweak itself to show something else. They give you medicines that place you in a coma post-zombie nation and then your family says I like you unawakened. You are easy to manage in your play like state where everything happens in slow motion and you get mad and angry with a 3-day or 3 week delay, ie, people hate me after funerals for a reason. In SOME case with depression, maybe having Real coping skills and new triggers and habits that snap people out and away from the trauma is necessary. For everything else, stay off of illicit illegal drugs that have a terrible effect on a mind that lacks common sense safe lifestyle practices and boundaries.

    Safe places to practice those triggers or habits that mean you as the client feel safe and the staffers feel safe too. This is supposed to be one on one or group therapy. But what if the leader of the therapy has bad blood literally and every member of the social group is affected long-term by his or her triggers. This blood test can make the difference between even the workers themselves who show a bad test and keep patients safer over the long run, too.

    Aside from safe places, people who seek psychological support may require a combination of practical life skills to show improvements. Co-hosting with working tours and silent types of work with other B2B quality care-takers should be a priority during the Biden administration because life happens outside of safe office spaces and the challenge is to not just be a stronger version of yourself, it is to re-program people with the new helpful and efficient triggers or habits that may overtime improve outlook. One of my friends mentioned a silent workshop he attended and how he was working in gardening and landscaping in exchange for free sleep quarters, food for a short time in his life. I had never seen a happier picture of him with such a great smile. And no, I am not talking about slave-labor, I am talking about practicality and spending a little time in nature, a little time laboring, a little time playing, a little time working and a little time smiling and crying with safe settings for emotion purging therapies along with sleep therapy. Stabilizing the patient is fine while in confinement is so different the level of drugs that are necessary for everyday work/play life balance.

    I think some people have mentioned that they are frustrated because they have been placed into a category where they are also permanently disable over the course of 20 to 30 years of their lives because they may be grieving, dealing with difficult transition or over or underwhelmed by short-term to long-term disturbances and after gaining life skills, they have determined that other optional supportive therapies may have improved their chances instead of a lifetime medicine that is safe for use over the life of the patience.

    Perhaps, there are spiritual, financial, emotional, medical, nutritional amalgam of supportive and networked systems which has to be interconnected into the patient care. I am not advocating for less care or more care and/or less adoptive negative chagrin based on external and internal interferences to mitigate a concrete definition of wellness and targets to achieve that with treatment just like with weight loss.

    Personally, I am advocating for supportive hand-holding until the patient can achieve a level of wellness that is more transparent. Preachers and priest always tell you that God loves you and you are never alone but being alone when you leave the church pew is different when the trigger for feeling alone because you are by definition living solo is denoted already. The triggers for self-harm or full-blown lack of self-care via lack of hygiene or dangerous niche vices geared towards people who are looking for escape or to experience the euphoria of an experience without having an experience since it is illegally or legally achieved thru medicinal therapists lacking proper testing and which will overtime demonstrate decline rather than patience who are properly screened by blood work to show the proper medications are in their systems and tracking of progress overtime to assist at least some patience in achieving wellness over a lifetime.

    The fact is that people are trying to help patients achieve that over time with blood testing perhaps, blood testing is a way to ensure patients come into an office and are tested before they see the doctor. Categorically, the doctor can address what that means with the patient and then add, remove or keep the recommended therapies in place until a level of wellness is achieved.

    No one is going to force you into the therapies that you do not want to take. If you are an adult, it is your money, your time, your life. These are decisions that you make for yourself. If it takes you 22 years to realize you need a break, or 29 years, at least you achieved a level of confidence or wellness and the health care workers kept you alive long enough to be able to get to that point in your life because what ever was going on you really cannot put a price on your life. You are worth so much more than 30 years of someone trying to get you to the point where you can stand up for yourself and on your own or just realize what the next level plan is to your present and future wellness. I mean that is quite an achievement for both sides and for one I am glad that you are still here but my perspective is there is no shame in the no pain/no gain therapies. Blood work in my opinion is a change in the right direction.

    1. I find in astonishing that this study, which hasn’t been replicated, is considered fact. A blood test can determine if someone will commit suicide or have a severe depression? So, this author believes his tests are psychic and can fortell the future. This study does not take into account environmental stressors, grief, accidents, disease dx, etc, which ALL affect people in different ways and DO cause depression and anxiety. That ANYONE can claim the ability to say when and if someone will get sick is a leap at best..even genetics can only say we have a predisposition for something not that disease process will ever present itself in said person.

      Something people are not taking into account is this test could be used by insurance companies to deny coverage. These companies already do not like covering mental health care. The stigma of mental health issues are already too much for many to handle. Now a scientist that studied 300 people, in a VA psych ward can claim that group represents all people.. one would think if someone is in a VA psych ward they probably suffer from PTSD and that is not representative of all people. That fact alone calls into question this study.

      Lastly, the main researcher owns the ONLY company that “tests” for these blood markers. So there is a financial motive for this author to have his research accepted as fact. A financial incentive creates inherent bias one which this site obviously doesn’t care about. Do better. I found out about his company on his LinkedIn page, then researched the company.

      Psychiatrists also claimed lobotomies would heal the mentally ill and asbestos was safe.
      Without replicated results by other researchers this study is not to be accepted as fact. All declarations in science have to be replicated and peer reviewed. So far, that hasn’t happened.

  10. I’m amazed by comments that depression is a “mind thing”. Depression is a brain thing. What is the mind anyway? It’s no recent discovery that Depression and bipolar have a biochemical basis. If these biomarkers in this test could better predict the appropriate medication rather than having to go thru months of trial and error, then I’m all for it.

  11. This is great as we need continued advancement in the field of mebtal health. Is the test available to public? If yes, how does one go abiut requesting it?

  12. I got an error message when trying to join the email list
    When is the potential availability for this test?
    My wife suffers from moderate depression and my 20 year old grandson is in serious need of something like this.
    Please add me to your list.

  13. No!
    Where is the trauma informed approach? Where is connection, being heard and supported?
    Human emotion can not, and should not, be within a medical model at all.
    With a diagnosis of bipolar and resulting 20 years of being heavily medicated. The obvious truth was that I was grieving, traumatised, under huge pressure and utterly alone. I was not “ill” i was having a natural emotional response.
    I have been entirely medication free for 6 years and my mental and physical health have never been better.
    The profit made from emotional distress disgusts and sadens me deeply!

  14. Im not an expert on this stuff and I didn’t read the entire article because I think it’s complete bullshit. Depression is a mind thing.

  15. I have been diagnosed with depression … bipolar. Manic depression…. it’s been 22 yrs…. been in carrier clinic and out pAtient. As well….. have been on more pills then I can tell and therapies……started on lithum and still am I’m 65 now…..ok. Just a short idea…. I would love to be tested. Guess it’s blood. Would love to find out where I stand and where I stood. Thank you.

  16. This is a very interesting thing for me as someone who has fought with major depression for the last almost 29 years now! I would have to say I worry about some of the medications listed as I know nothing about them or the side effects but think it would be nice to not have the trial and error with medications.

  17. I wanted to take some test for bipolar depression schizophrenia dementia alzcheimer insomnia paranoid paranormalism metabolism paralysis to sleep lm with a lot disturbance from evil one demonic evil spirits attachment evildoers and so on ………!!

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