Living the Scientific Life (Scientist, Interrupted)

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ResearchBlogging.org

According to the United States Department of Health and Human Services, serious mental illnesses affect approximately 44 million Americans. Serious mental illnesses include mood disorders; depression and bipolar disorder. Unfortunately, correctly diagnosing mental illnesses, such as bipolar disorder, appears to be a sort of voodoo science that depends upon the skill of the mental health professional making the diagnosis and the patient’s willingness to accurately describe their symptoms. But a research paper was just published that describes a blood test that was designed to identify bipolar disorder and thus, this test could provide an objective method for diagnosis.

Bipolar I disorder, formerly known as “manic depression”, is a mood disorder characterized by sudden shifts in one’s emotional state from acute depression to mania and back again. It may also include episodes of psychosis. These mood changes can occur over a period of time ranging from minutes to hours or days and may persist from days to months for each episode, often independent of external circumstances. Many people with bipolar disorder will experience a “remission” of symptoms where they are socially and professionally functional for various periods of time, but some people are always in either a manic or depressed mood state, with few times when they are “in between” these two extremes.

“Patients aren’t sure how ill they really are, and neither is the clinician — sometimes dismissing their symptoms, sometimes overestimating them,” reports Dr. Alexander Niculescu, a psychiatrist at Indiana University School of Medicine in Indianapolis, who led the research team. “Having an objective test for disease state, disease severity, and especially to measure response to treatment, would be a big step forward.”

To do this work, the researchers identified a group of 29 individuals suffering from bipolar disorder and collected a blood sample from each of them. The mRNA (messenger RNA) present in the sample was isolated, copied into a more stable form, amplified and then screened to identify those mRNAs that showed extremely variable expression patterns that correlated with changes in each person’s mood shifts for all members of the study group.

Out of more than 40,000 genes that have been identified by the human genome project, the research team identified 21 novel high-threshold biomarker candidate genes, eight of which had been previously reported as showing some involvement in mood disorders by other research groups using multiple independent lines of study. These high-threshold candidate biomarkers demonstrate high degree of reliability because they were present in at least 75 percent of all study subjects at the time that they reported either a high or low mood state.

The team selected the ten best biomarkers (five for high mood and five for low mood) and used them as the basis for a screening test, which they named the BioM-10 Mood panel. The predictive value of the BioM-10 Mood panel was tested on the initial group of study subjects and found to have an 85 percent accuracy in predicting high mood and 77 percent accurate in predicting low mood. Then the BioM-10 Mood panel’s accuracy was tested against two other independent groups of people, 19 suffering from bipolar disorder and 30 suffering from a variety of psychotic disorders, such as schizophrenia. In this situation, the BioM-10 Mood panel’s diagnostic value was 71 percent accurate in identifying high mood and 68 percent accurate in identifying low mood.

According to Niculescu, even though this isn’t perfect, the BioM-10 Mood panel’s accuracy rate is within range of other medical tests, such as some cancer screening methods. But even though more work needs to be done, this test could be available on the market in as little as five years from now.

This screening test opens up other avenues of diagnosis and research as well.

“Panels of such biomarkers may serve as a basis for objective clinical laboratory tests, a long-standing Holy Grail for psychiatry,” write the research team in their paper. “Biomarker-based tests may help with early intervention and prevention efforts, as well as monitoring response to various treatments” and will play an important role in personalized medicine in psychiatry as well as in the development of new psychiatric medications.

Unfortunately, this test also presents the possibility for extreme abuse; employers, law enforcement, universities, insurance companies and landlords could use this test to discriminate against people with bipolar disorder. Even though there are many compelling arguments for developing and using tests such as this one, I know that I, as a person with bipolar I disorder, am deeply concerned about this because, based on previous examples of human behavior, I am absolutely certain that these tests will be used to discriminate against people like me.

Sources

Le-Niculescu, H., Kurian, S.M., Yehyawi, N., Dike, C., Patel, S.D., Edenberg, H.J., Tsuang, M.T., Salomon, D.R., Nurnberger, J.I., Niculescu, A.B. (2008). Identifying blood biomarkers for mood disorders using convergent functional genomics. Molecular Psychiatry DOI: 10.1038/mp.2008.11

MSNBC (quotes).

Comments

  1. #1 Bob O'H
    February 28, 2008

    This sounds promising, but I wonder – did they try this on normal people?

  2. #2 "GrrlScientist"
    February 28, 2008

    no they didn’t, according to what i read in their paper.

  3. #3 Scott Simmons
    February 28, 2008

    So in other words, this may just be a really, really expensive mood ring. :)

  4. #4 Mary
    February 28, 2008

    I’m going to make a fortune on BioM-10 Mood rings….

    No, just kidding. I hear ya. And agree 100% that this could be used to discriminate. With an affected sister, I could be carrying some alleles…

  5. #5 Mary
    February 28, 2008

    I’m going to make a fortune on BioM-10 Mood rings….

    No, just kidding. I hear ya. And agree 100% that this could be used to discriminate. With an affected sister, I could be carrying some alleles…

  6. #6 6EQUJ5
    February 28, 2008

    Put your money on insurance companies secretly having this added to the medical screening so they can avoid insuring any at-risk individual and can concentrate on insuring people worth insuring. (Black humor intended.)

    And, with data mining everywhere, the moment this shows up — all you sufferers, diagnosed or not — expect to get (1) a layoff notice, (2) an eviction notice, (3) a foreclosure notice.

    Smart business is all about ‘managing risk’ (read ‘cheating’).

  7. #7 Pierce
    February 28, 2008

    I’m not terribly stoked about a blood test. Sure, it’d be nice to have something to show, say, my wife, above and beyond the word of my doctor, but I’m also really leery of the potential for abuse. Besides, from my perspective, it’s not the diagnosis that’s problematic at this point (though that wasn’t true during the six years I was misdiagnosed as unipolar depressive and going thorough the entire useless pharmacopoeia for that), it’s finding a working treatment before the apocalypse when the VA limits me to one med update visit about every two months for a usually minor change to the drug regimen. Rinse. Repeat.

  8. #8 N.B.
    February 28, 2008

    99.9% good thing. I’m getting really sick of people talking about how this will inevitably be used to discriminate against people with bipolar disorder instead of providing objective diagnostic information, which is probably the most useful data we can get about any disease if we’re serious about identifying and treating it.

    Why are people afraid of this, but not afraid that we can measure blood pressure or blood sugar? It’s easy to imagine a workplace where people with diabetes could be discriminated against–after all, they might need extra lunch time if they have to inject insulin or check their blood sugar, and besides, their disease means that they might need more sick days for doctors appointments.

    There is no fundamental difference between “mental” illness and “physical” illness. Assuming that there are biological root causes for disease is the first step to treating it. And having established biomarkers for mental illness sure kills the “it’s all in your head” theory, doesn’t it?

  9. #9 Pierce
    February 28, 2008

    N.B.: There may be no fundamental difference between mental and physical illnesses from a medical standpoint, but there sure as hell is from a social one. It is with sad experience in the real world that I worry that someone, somewhere will find a way to misuse this information.
    And as far as diabetics go, the American Diabetes Association says “obtaining and keeping health insurance and life insurance can be very difficult or — sadly — impossible to do.” And I’m sure every manager in America is completely understanding of a diabetic person’s needs, too.

  10. #10 N.B.
    February 28, 2008

    Pierce: Here’s the way I see things.

    Incidentally, I don’t disagree with you about diabetics having trouble getting insurance or other such forms of discrimination. They happen. They will continue to happen if things stay they way they are. This is a consequence of private health insurance based on the capitalist system, but I digress.

    Diagnosing mental illness is iffy and subjective, even with DSM-IV guidelines. The point of the DSM is to make it less iffy and subjective, but it still requires a clinician to know exactly what he’s looking for.

    Measuring whether or not treatments for bipolar is effective essentially comes down to asking the patient “so, how have you been feeling lately?” and trying to use various scoring criteria to measure their quality of life on a standardized scale. The margin of error is much larger than it is for, say, diabetics; you can take their blood sugar or look at their hemoglobin A1c and know whether or not a treatment has been effective long-term.

    Saying “we shouldn’t be able to diagnose mental illness with a blood test because it will lead to discrimination” is jumping the gun. What if you’re mentally ill, but don’t display any signs of such because you’re adequately treated? Employers don’t (and can’t) require physical exams except when they can demonstrate that physical fitness is a requirement for the job (firefighters come to mind). Blood tests would be no different. And forget about landlords or universities getting their hands on your blood test results. How would they be able to demonstrate a legitimate need for access to your protected health information? HIPAA is clear that they don’t have a right to it.

  11. #11 R E G
    February 28, 2008

    I understand your desire to avoid the social stigma or insurance dilemmas of mental illnes.

    But please try to see past that. Would you avoid telling a new doctor that you have a history of cancer or heart disease? Would you cripple his/her ability to ensure your good health by leaving out such important information?

    There is very little encouraging news in mental health, but I do recall reading a study that found early treatment reduced the re-occurance of depressive episodes. Bipolar disorder is a lifelong,ever progressing illness that cannot be judged objectively by its victims.

    I’ve watched several family members loose all connection to the real world as they followed their ever increasing moods swings away from reality. On behalf of the caretakers of these people I implore you not to avoid any avenue of treatment. Bipolar patients do not suffer alone. Their families,(who may be borderline themselves) are also living in a world where random bipolar moods conrol their lives.

    I have often wondered if the root cause of depression and ” learned helplessness” is trying to make sense of a world where there is no logical cause and effect. The child of bipolar parents cannot see any relationship between his own behavior and its consequences. The consequences will, in the end, be determined by the mood phase the parent is in.

  12. #12 JPS
    February 29, 2008

    This study is in the good news/bad news category. It is much better that there is an objective physical test that can diagnose bipolar disorder, but considering the stigma (I am bipolar) it can be a curse for bipolar people in their lives.

  13. #13 Mary
    February 29, 2008

    @R E G: “Would you avoid telling a new doctor that you have a history of cancer or heart disease? Would you cripple his/her ability to ensure your good health by leaving out such important information?”

    I have withheld information from my doctors for fear of being unable to obtain insurance. I am a small business owner and it is very hard to get reasonable insurance.

    And I don’t think the point is that this immediately leads to discrimination–but that along with good benefits such as monitoring medications needed and other treatment issues that the data could easily be misused.

  14. #14 Timothy Chase
    March 1, 2008

    Regarding the social stigma of being bipolar…

    I am generally open about the fact that I am bipolar. Sure, it is a kind of mental illness, but bipolars tend to be achievers, oftentimes going into medicine or being the straight-A students. And I have personally known one who was a charming undersea photographer, another who is going into surgery, and another with business concerns on several continents. And then there are some software engineers who also take an interest in various aspects of the humanities.

    Likewise, it really is an illness — not “all in the head” as some might tend to think. The like-clockwork rapid cycling that I personally went through over a two-week period is a good way of getting across its biochemical nature. It is also possible to point out that it is genetically linked to other illnesses — such as autoimmune diseases. (I have psoriasis, something which shows up as a skin rash. Nothing major.) And it can be controlled with the right medication.

    *

    What does my being bipolar mean to me — ultimately? It doesn’t make me any less human than anyone else. It is just part of who I am — as one out of seven billion unique individuals whose genetic makeup has also had some effect upon their character. Bipolars will oftentimes pride themselves on achieving excellence, choosing to maintain the highest standards of rationality, or being artistic – before knowing that they are bipolar.

    In this way, it is somewhat paradoxical. We tend to think of mental illness as implying irrationality, and there are certainly times that the illness results in a bipolar individual behaving irrationally or having a warped view of the world — when in a nonmedicated state of mania or depression. But typically, when not in either state, a bipolar is likely to function above average, being especially good at puzzle-solving or making connections. They tend to cognitively operate at an above-average level. We to think of mental illness as being crippling — but they are more likely to be achievers. We tend to think of being logical as being at odds with being artistic — but they will often combine both elements.

    *

    The phenomena throws a different light on one of the deepest of questions: What does it mean to be human? I am comfortable with it, talking about it, living with it — and I expect those who I broach the subject with to be comfortable with it as well — then to set it aside and deal with me as an individual, the same individual they knew before I mentioned it, but as someone who honored them by sharing something personal — hopefully in an interesting way.

  15. #15 Timothy Chase
    March 1, 2008

    REG wrote:

    There is very little encouraging news in mental health, but I do recall reading a study that found early treatment reduced the re-occurance of depressive episodes. Bipolar disorder is a lifelong,ever progressing illness that cannot be judged objectively by its victims.

    It is progressive only if untreated. There is of course the issue that many bipolars will avoid taking their medication if it means giving up the mania which they believe makes them more productive or more creative (which it does — early on), but given the emphasis they will often place on being rational — and that without the medicine, there is the deterioration of the coherence of their thought over time, the marked absence of their ability to self-critically analyze their thought processes during states of mania, as well as the actual brain damage that results — it should be possible to convince them to get on and stay on the medicine. You really don’t need the mania to be be productive or creative, and what mania gives you in the longrun is a state of false ecstasy in which you are living in the illusion that you are more productive or creative — when in fact you are rapidly falling into the opposite.

    I personally regard the mania as worse than the depression. Besides, when in neither state, without the medicine, like most, I tend to suffer from a low-grade depression. I am happier when appropriately medicated, and I can learn from the moments of genuine creativity that I have experienced in the past how to achieve a similar level of creativity in the present — without the mania. And then it is something that I have earned and which is real.

  16. #16 Larry Smith
    March 1, 2008

    Did anyone here RTFA? This test won’t tell you if the patient is bipolar. It can discriminate high and low mood. The genes involved are also expressed in practically anything affecting mood ranging from alcoholism to epilepsy.

    It would be useful if it could discriminate bipolar from MDD for instance. Instead, you get a r=0.6 correlation with HamD. At best, this test can be used to diagnose an uncooperative patient as depressed or manic. But it won’t tell you why anymore than low serotonin can tell if you’re depressed, compulsive or in love.

  17. #17 Timothy Chase
    March 2, 2008

    Larry Smith wrote:

    Did anyone here RTFA?

    Don’t have a subscription and haven’t been able to find a copy as of yet.

    Larry Smith wrote:

    This test won’t tell you if the patient is bipolar. It can discriminate high and low mood. The genes involved are also expressed in practically anything affecting mood ranging from alcoholism to epilepsy.

    First couple comments they stated that this hadn’t been tried on “normal” people. Which suggests that you are right. So you think people may be getting a little ahead of themselves?

    Larry Smith wrote:

    It would be useful if it could discriminate bipolar from MDD for instance.

    You would think — as bipolars will often go into see the doctor about their depression, but won’t complain about their up mood — and the antidepressant for treating Major Depressive Disorder is likely to trigger a major manic episode — which will be the doctor’s first clue that this might actually be something other than MDD.

    I personally would like to know a little more about the actual genetic basis for the disease. For example, it is my understanding that the onset of the disease tends to be earlier in each successive generation — which suggests tandem repeats, perhaps a triple repeat disease.

    Beyond a certain number of repeat sequences (roughly ten), a tandem repeat tends to become unstable — and subject to hypermutation. The hypermutations are common enough that they can often be used to genetically distinguish between “identical” twins. (Schizophrenia, anyone? One twin comes down with the disease, the other does not.) Triple repeats in the coding sequences will result in mutations that still code for proteins without the frameshift which results in missense, and as such, are generally capable of performing the same function, but, for example, when these proteins are regulatory proteins, as in the case of a few genes in dogs, they result in differential expression of other proteins leading to most of the morpheological variation we see between different breeds. Then again, we could be speaking of repeats in promoters/enhancers, perhaps in an RNA-gene — which does not get translated to protein, but which nevertheless controls the expression of other genes. Copy number variation (where there exist multiple copies of the same gene) wouldn’t explain the “genetic anticipation” — why the onset is earlier in later generations.

    If we are talking about tandem repeats, going back far enough, we are probably talking about something generated by the poly tail of a SINE or LINE during retrotransposition, where SINEs are themselves generated by LINEs, and a LINE would be the relic of some ancient retroviral infection. Or if we are talking about an inverted repeat, I believe those are ultimately descended from some ancient plasmid — if I remember correctly. Not that any of this would be of much use to anyone, but I would still like to know. Simple curiosity.

    In any case, knowledge is power. A good diagnostic would bring us a great deal closer to a new treatment — for this and perhaps other diseases.

  18. #18 msn nickleri
    June 14, 2008

    You would think — as bipolars will often go into see the doctor about their depression, but won’t complain about their up mood — and the antidepressant for treating Major Depressive Disorder is likely to trigger a major manic episode — which will be

  19. #19 John
    June 20, 2008

    Not to change the subject from genetics, but in response to the comments toward the beginning of this blog, I agree that if this information gets in the wrong hands such as insurance companies, employers etc., it will be used to discriminate against such people. However, I feel that the potential benefit outweighs the risk. The possibility of early intervention to prevent or better treat this illness will lead to a more functional and satisfying life style to people afflicted with this illness. As it stands, it is very difficult to treat this illness in many people because it is hard to diagnose and its severity in each indivual is difficult to determine. Also, the existance of such a blood test further supports the biomedical model of this illness rather than the collective opinion of many, that it is a character flaw. Furthermore, insurance companies already know that individuals who are being treated for this illness have it. They help pay for their treatment. Also, laws are enacted to ensure patient confidentiality.
    The potential danger of a blood test for this illness lies in whether the insurance companies or employers obtain this information before a person is diagnosed or before they are hired. In conclusion, some of the concerns of having a blood test to determine bipoar disorder are already in existance. Tighter restrictions on such information and confidentiality must be a first priority if this blood test comes into fruition. In all, I believe the potential benefits of a blood test to determine bipolar disorder by far outweighs its risks.

  20. #20 seks shop
    June 27, 2008

    If we are talking about tandem repeats, going back far enough, we are probably talking about something generated by the poly tail of a SINE or LINE during retrotransposition, where SINEs are themselves generated by LINEs, and a LINE would be the relic of some ancient retroviral infection. Or if we are talking about an inverted repeat, I believe those are ultimately descended from some ancient plasmid — if I remember correctly.

  21. #21 rose
    July 25, 2008

    If the blood test could be used for diagnostic purposes, could it also be used for optimum dosage and/or correct meds ? If so, think of the time saved and the weeks of unneccessary psychotropic drugs that could be avoided. It could definitely improve the trial and error, hit or miss way of finally getting the right combination of meds that works for an individual!!

  22. #22 Dave Dragon
    September 3, 2008

    Another good article on the diagnosis of Bipolar Disorder.
    I agree the test is ripe for abuse by emplorers.
    Dave

  23. #23 mirc
    October 11, 2008

    You would think — as bipolars will often go into see the doctor about their depression, but won’t complain about their up mood — and the antidepressant for treating Major Depressive Disorder is likely to trigger a major manic episode — which will be

  24. #24 Ana
    October 14, 2008

    I am not bipolar, or may I am, I am not sure. My brother is bipolar and I am happy the diagnosis time may increase due to a blood test. We (my brother, my family and I) have lost many valuable years shifting from one doctor to the other, trying in vane many different medications, collecting wrong diagnostics… for better or for worse, a blood test may help many people in the future to have the right medication on time.

  25. #25 RxL
    November 19, 2008

    You would think — as bipolars will often go into see the doctor about their depression, but won’t complain about their up mood — and the antidepressant for treating Major Depressive Disorder is likely to trigger a major manic episode — which will be

    mirc kelebek

  26. #26 Laptop
    December 15, 2008

    So in other words, this may just be a really, really expensive mood ring. (:

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