Is Clinical Depression an Allergic Reaction?

Mast_cells

Interesting concept that researchers have been studying for some time: Is clinical depression an allergic reaction?

A study in 2008 showed that during manic episodes, pro-inflammatory cytokines, IL-2, IL-4 and IL-6, were increased in comparison with healthy subjects. Patients in depressive episode showed only increased IL-6 levels. There were no significant differences in cytokine levels between patients in remission and healthy subjects, except for IL-4.1

A double- blind study in 2006 in German of 40 patients with a diagnosis of clinical showed more improvement in the half who took anti-inflammatory drugs for a certain time, vs those that didn’t. All patients showed some improvement, perhaps from placebo effect, but those treated with anti-inflammatories did better.2

In 1999 a study of 6836 people in the U.S., subjects with a history of any allergy were more likely to report low-back pain, to be diagnosed with major depression, and much more likely to have both major depression and low-back pain.3

Perhaps depression is a response to the world around us, on a micro level- such as dust, or a macro level- such as stress from daily living. Inflammation, the common allergic reaction, is seen in patients with bipolar disorder and depression.

Even as far back as 1930, it was thought there was some hereditary element to allergies.

 

asthma allergy

Who know, in the future, people prone to a depressed allergic reaction may carry some kind of inhaler, like those for asthma. Or anti-inflammatory drugs may become the new “anti-depressant”.

1Elisa Brietzke, Laura Stertz, Brisa Simões Fernandes, Marcia Kauer-Sant’Anna, Marcello Mascarenhas, Andréia Escosteguy Vargas, José Artur Chies, Flávio Kapczinskicorrespondenceemail (2008). Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder. Journal of Affective Disorders, 116, 3, 214–217.

2N Müller, M J Schwarz, S Dehning, A Douhe, A Cerovecki, B Goldstein-Müller, I Spellmann, G Hetzel, K Maino, N Kleindienst, H-J Möller, V Arolt and M Riedel.(2006).  The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Molecular Psychiatry (2006) 11, 680–684

3Eric L. Hurwitz and Hal Morgenstern (1999).  Cross-Sectional Associations of Asthma, Hay Fever, and Other Allergies with Major Depression and Low-Back Pain among Adults Aged 20–39 Years in the United States. Am. J. Epidemiol. (1999) 150 (10): 1107-1116

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Resta’s Rules of Genetic Counseling

A reblog from Bob Resta- This is an excellent and funny summary of some of the challenges of genetics, genetic counseling and health care in general. My favorite one is #9.

The DNA Exchange

You will not find these pearls of wisdom in Psyche and Helix, Psychosocial Genetic Counseling, A Guide To Genetic Counseling, or the Journal of Genetic Counseling. I am certain that they will never be the source of correct responses on genetic counseling board certification exams. These insights are based on personal observations made during my 3+ decades of genetic counseling practice. There is almost no research to back them up but they are gospel truth nonetheless. Well, at least they seem true.

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1) All interactions with patients are primarily psychosocial encounters, no matter how much we or patients consciously or unconsciously try to focus on facts and figures.

2) All research studies are flawed in some way. Therefore, all facts, figures, and risk predictions that we so confidently quote are wrong, with the possible exception of Mendelian segregation ratios (but even there…). Quite often, several seemingly well designed studies…

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Show Me the Money: A Cynical Look at Gene Testing

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(note: while this post is somewhat cynical, usually I have a favorable opinion of humans in general)

Recently, an associate asked me about the new “suicide gene” discovered this summer. Johns Hopkins published a study that showed an increase in a variation of a protein produced by gene SKA2 in the brains of people who have committed suicide. They then screened a group of people and correlated the level of SKA2 in their blood and their risk for suicide. From this they then designed a model analysis that predicted which of the participants were experiencing suicidal thoughts or had attempted suicide with 80 percent certainty. Those with more severe risk of suicide were predicted with 90 percent accuracy.

Some of my associate’s colleagues had asked about testing for this gene. I told her my hunch would be “more research is needed” before a company could make a diagnostic test with this info.

There sure is an incentive for the drug companies to develop a test. There is an association between anti-depressant use and suicide. As 11% of the U.S. population over the age of 12 years is on anti-depressants, drug companies could make argue that a drug is safer in combination with a test to determine which of the 11% will attempt suicide. And it could save them money in future lawsuits.

There sure is an incentive for genetic testing labs to develop a test. There are approximately 313 million people in U.S. as of 2013. Children under the age of 12 are not tracked statistically, but about 24% are under age 18, so let’s say there are about 238 million over 18. Of that, 26 million are taking anti-depressants. A genetic screening test for 26 million would be a bonanza for the genetic testing companies, even if they are only testing a subset of that population, such as everyone taking Prozac.

However, approximately 750,000 people attempt suicide and approximately 30,000 people commit suicide in the U.S. each year. The main cause is thought to be untreated depression. So the challenge would be how to find the untreated people, and screen them. Hmmm. And if most of the people committing suicide are untreated, would it make more sense to spend money trying to get these people into treatment?
That could ultimately make money for the drug companies and genetic labs, because more people would be prescribed drugs and tested.

My feeling is; if some corporation can find out a way to make money, we’ll see some decrease in the suicide rate, harsh as that may sound.

As far as the genetics of mental health conditions, it’s been thought for a while that multiple genes contribute a small amount each to the overall condition. Most of the recent “suicide gene” studies look at only one gene- for example BDNF was described in Oct 2011, RGS2 was described in Oct 2011 and SKA2 was described in July 2014. A test will most likely need to include multiple genes, which can make interpretation difficult. Sundance Diagnostics claimed they would have a test for suicide risk for those taking Prozac and Zoloft available in early 2014. It’s almost 2015 and the test is not available yet.
Johns Hopkins is looking for partners to help “develop & commercialize the technology as a suicide risk diagnostic test.”
It will be interesting to see who makes it first to market.

link to Johns Hopkins SKA2 study:
http://ajp.psychiatryonline.org/article.aspx?articleID=1892819
Jerry Guintivano, Tori Brown, Alison Newcomer, Marcus Jones, Olivia Cox, Brion S. Maher, William W. Eaton, Jennifer L. Payne, Holly C. Wilcox, Zachary A. Kaminsky. Identification and Replication of a Combined Epigenetic and Genetic Biomarker Predicting Suicide and Suicidal Behaviors. American Journal of Psychiatry, 2014; DOI: 10.1176/appi.ajp.2014.14010008

If you want to partner with Johns Hopkins:
http://www.jhttonline.jhu.edu/TechnologyDetail.aspx?TechID=CE1227A3-B0EE-47FA-A06C-32F7B1CD5563&JHURef=C12394

“Schizophrenia” might include eight genetically distinct conditions

A study from the Washington University School of Medicine reports that Schizophrenia could be a catch phrase for eight genetically distinct conditions. This makes some logical sense as symptoms and drug response vary for people with schizophrenia. People rarely fit into discrete categories.

We know that these are not single gene conditions. This research looks at how multiple genes can work together. Someday it might help with a genetic risk profile.

Go to news.wustl.eustl.edu/news/pages/27358.aspx for more info. I’ll post a link to the abstract when I’m back home and at a better computer.

Robin Williams and the tipping point.

 

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According to CNN, Robin Williams took his life today. He was 63 years old.

Williams should be remembered for creative talent in comedy and acting, and as Larry King also mentioned, he should be remembered as a “genuine caring guy.”

 

Williams appeared to “have it all” in so many ways- marriage, family, money, a career in the competitive world of show business, unbridled talent.

 

He had a diagnosis of bipolar disorder and had dealt with addiction to alcohol and cocaine. He publicly addressed his disease and his decision to go to rehab. Even with all the resources possible at his disposal, he still got to a place that was so dark he could not find his way back.

 

My hope is that he will someday be remembered as the guy who tipped the scales on the stigma of mental illness. Maybe  Robin Williams’ death can become the tipping point for change.

The point where we accepted that mental illness is a disease that needs to be acknowledged without stigma.

 

The point where we realized that we need to help all people with their depression, mania or psychosis.

 

The point where we realized that money spent on mental health is a great investment in our community.

 

The point where we realized that it might make sense to offer voluntary screening programs to determine who is at risk for mental illness, and be able to offer intervention for those that need it and want it.

 

The point where we can say

 

“O Captain! my Captain! our fearful trip is done,

 

The ship has weather’d every rack, the prize we sought is won”

 

 

 

 

 

 

The Biggest Loser and the Anniversary of Karen Carpenter’s Death.

Karen_Carpenter

Feb. 4th, 2014 was the 31st anniversary of Karen Carpenter’s death. Karen was a drummer and singer, famous for her work with her brother in their duo, The Carpenters. Karen suffered from anorexia and died of heart complications related to the disease. She was only 32 years old.

Feb 4th, 2014 is also the day that the Biggest Loser competition crowned their current season’s winner, Rachel Frederickson. Rachel started the competition at 260 lbs, and lost 155 lbs, -almost 60% of her body weight.  At 105 lbs, Rachel is under the recommended BMI for her age and height.  A trip on the stairs while she walked to the scale was prehaps an indication of her fragile state.

Rachel was quoted on 2/5/14: “I’m at the maintenance point now so I need to find some balance and make sure I work out and I eat healthy and make good choices 90 percent of the time,” she told TODAY after the finale. “I’m not sure (I’ll maintain this weight), but I plan to try new exercises and just continue on this path and see where that takes me.”

While she may have just lost weight for the competition, everyone knows the real challenge begins after the show is over. For some, it’s keeping the weight off, for others, it might be coping with a new-found eating disorder.

Eating disorders have a genetic component, most likely involved with neurotransmitter pathways- pathways which help the brain sooth the body and reward survival behavior (sex, eating, exercise). People with disruptions in the neurotransmitter pathways often subconsciously look for external reward methods- drugs, alcohol, food, extreme exercise, or adrenaline producing behavior. People with eating disorders are often found to be competitive perfectionists. While Rachel may just have lost the extreme amount to win, who knows what hurdles she may now face without the reward of the competition.

While it is a coincidence that Rachel won with an anorexic body type on the 31st anniversary of Karen Carpenter’s death, let’s hope we’ve actually learned something from Karen’s life, and have an open conversation with Rachel about the potential trap. This is an extremely bad example for people who are trying to make a healthy change in their lives, and the Biggest Loser needs to step up and make some changes in the show’s rules to prevent this from happening again.

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23andMe Ordered by FDA to Stop Marketing Genetic Tests

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I’ve been on the fence about 23andMe’s personalized genetic tests.I like that it’s a cheap way to access your own DNA- which many of us may never have the opportunity to do. On the other hand, many of the gene allele interpretations are based on very small research studies that may not apply to the general population. The test has risk predictors for mental health conditions like schizophrenia, bipolar disorder, depression and alcholism. I have looked at the studies that 23andMe bases their intrepretations on, and I find them lacking. I would not recommend that anyone make decisions on treatment, medication, or personal life decisions such as having children, on such results.

23andMe is backed by Google, so obviously there is a lot of money behind the company. I think it is very important that the FDA takes this stand, and demonstrates to the American public that profit has to take a backseat to safety.

Alberto Gutierrez, director of the FDA’s Center for Devices and Radiological Health, said in a letter to the company made public on Monday that 23andMe had failed to address concerns raised on multiple occasions since the agency began working with it on compliance in July 2009. He commented that the the FDA does not have any assurance that the firm has analytically or clinically validated the tests for its intended uses.

23andMe responded  “We recognize that we have not met the FDA’s expectations regarding timeline and communication regarding our submission,” the company said in a statement. “Our relationship with the FDA is extremely important to us and we are committed to fully engaging with them to address their concerns.”

23andMe has plans to start markeing to the public via televison. As far as I can see from the report, they will not be able to do this immediately.

Here is a link to more information:

http://www.theguardian.com/science/2013/nov/25/genetics-23andme-fda-marketing-pgs-screening