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:
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:


Robin Williams and the tipping point.



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”







Is There A Link Between Football and Suicide?


Last night Frontline aired the documentary “League of Denial: The NFL’s Concussion Crisis”, a report about the connection between chronic traumatic encephalopathy (CTE) and football. CTE is is a form of encephalopathy, a progressive degenerative brain disease, which can only be definitively diagnosed after death in individuals with a history of multiple concussions and other forms of head injury.  This disease is known in boxers who receive multiple blows to the head during their careers. A debate ensues as to whether other athletes who receive multiple concussions and minor traumas over the course of their careers, such as football players and wrestlers, are also subject to brain damage as a result.

The documentary presents evidence that brain damage can result from multiple “sub-concussions” over time, and investigates as to whether the NFL knew about the evidence, ignored it, and failed to provide this information to professional football players.

In the documentary we are told about football players who committed suicide, such as Junior Seau, and players who suffered from depression and dementia, such as Mike Webster.  Pathologists have been able to dissect the brains of some of these players, and have found evidence of CTE.  Also presented are two young men, Owen Thomas, 21-year-old lineman at Penn, who committed suicide by hanging himself in 2010, and 18-year-old Eric Pelly, a high-school athlete who died after suffering a concussion in 2006.  Both young men were shown to have CTE on autopsy.

It is possible that depression and suicide in professional athletes can be due to steroid, alcohol and drug abuse, and the difficulty in adjusting to a new life and employment after a potentially short pro football career. This explanation is difficult to accept for these younger players. It could be possible that there is a link between the brain damage and the ensuing depression, addiction and suicide.

Of course not all football and ice hockey players, wrestlers and boxers wind up depressed or addicted, so CTE is not the only factor. My hunch is that some players are more likely genetically predisposed to encephalopathy, and the repeated minor trauma is the environmental factor which pushes them over the edge.  This could be an explanation for why some teens develop psychosis and others don’t when subject to traumatic brain injury. A meta-analysis from 2011 supported an increased risk of schizophrenia following traumatic brain injury, with a larger effect in those with a genetic predisposition to psychosis.

While more data is needed to show the links between contact sports and CTE, enough evidence is available to encourage more rules and better equipment to protect players from trauma. Children under the age of 16 should not be allowed to play tackle football, as their brains are smaller and still developing, with less protection from TBI. Perhaps pro football careers will have to have limits, such as Steve Young’s self-imposed retirement after he suffered his seventh concussion on a huge hit from Cardinals cornerback Aeneas Williams. As Steve Young says in the documentary “If my knees hurt, we can go deal with it. There is only one place in the body that we don’t understand… the brain is the last frontier.” You only get one brain.

Link to Frontline’s documentary “League of Denial: The NFL’s Concussion Crisis” :

Link to Traumatic Brian injury and schizophrenia

Genetic Clues to Anorexia Nervosa

Teen Anorexia Treatment

Anorexia nervosa is a complex disorder, a combination of genetic predisposition and environmental and behavioral factors. A recent study looked at 152 genes that are known to be involved in eating behavior, dopamine function, and brain communication to look for genetic variations that might be associated with Anorexia. Three groups of research subjects  were looked at for a total of 1205 case subjects and 1948 controls. Results from the study linked anorexia with two genes: ESR2 and EPHX2

ESR2 is an estrogen receptor. Estrogen receptors are found in both men and women, but play a higher role for women, particularly starting in adolescence. Anorexia is more common in women, and typically develops around the start of puberty, so the connection here at least follows logically. It may come to some as a surprise that men also can have anorexia, and men also need a small amount of estrogen for strong bones and brain function.

EPHX2 ‘s connection is not as obvious. The gene codes for the epoxide hydrolase protein which is involved in the breakdown of fats and toxins. EPHX2 is involved in cholesterol metabolism, and defects in the gene are associated with a disease called familial hypercholesterolemia. Anorexia nervosa patients often display hypercholesterolemia, which is counterintuitive, given the under-nutrition and low body weight of affected individuals. The study says, “It has been hypothesized that low levels of cholesterol may decrease the activity of serotonin receptors and transporters and that significantly lower cholesterol levels are associated with depressive symptoms, impulsive/self-harmful behavior (cutting and/or burning) and suicide thoughts/attempts in anorexia patients. Moreover, lower cholesterol levels have been associated with increased suicidality more broadly, including ideation and attempts, in depressed patients.”

Dr. Schork, one of the paper’s authors said, “The hypothesis would be that in some anorexics the normal metabolism of cholesterol is disrupted, which could influence their mood as well as their ability to survive despite severe caloric restriction.”

The study hopes that their results will provoke interest and more research into the connection between these genes and anorexia.  It’s exciting news for researchers studying eating disorders.

Here’s the link to the article: anoerxia

Can We Predict Who Will Attempt Suicide?



Scientists at the Indiana University School of Medicine are looking to answer this question by analyzing proteins in the blood of patients who have mood disorders such as bipolar disorder and schizophrenia/schizoaffective disorder.  They looked at the amount of these proteins in the blood when the person was in a suicidal state vs. a non-suicidal state. A significant difference in expression was found for proteins coded for by the genes SAT1, PTEN, MARCKS and MAP3K3.  SAT1 is involved in the Omega-3 signaling pathway. MARCKS is involved in sleep–wake cycles, as well as mood regulation. PTEN is involved in regulation of the cell cycle and MAP3K3 directly regulates the stress-activated protein kinase SAPK.

Their conclusion was that “suicidality may be underlined, at least in part, by biological mechanisms related to stress, inflammation and apoptosis.” Apoptosis is the natural programmed cycle of cell death. The researchers wrote “our results have implications for the understanding of suicide, as well as for the development of objective laboratory tests and tools to track suicidal risk and response to treatment.” At some point this information could be used to predict and differentiate future and past hospitalizations due to suicidality in patients with bipolar disorder and psychosis (schizophrenia/schizoaffective disorder).


The link to the complete article is here:

Schizophrenia? But she’s only six years old!


Yesterday while walking down Irving Street to the bank, I saw a guy on the corner yelling at passing cars. My first thought was “oops, forgot to take his meds this morning.” In San Francisco it’s  commonplace to see people hallucinating, and usually I feel some empathy and move on. But with this guy I started wondering about his childhood, and when was he diagnosed,  probably because I recently read Michael Schofield’s book January First: A Child’s Descent into Madness and Her Father’s Struggle to Save Her.  Michael Schofield’s daughter, January, received a diagnosis of schizophrenia at age 6. This came about after many years of coping with her violent behavior and genius IQ.  While it is difficult to like Schofield (whose depression manifests in anger, directed at everyone but himself), the book is an interesting study of a family history of mental illness. It is also a disturbing report of how difficult it is to get help for children with psychiatric disorders. Schizophrenia is rare in children, affecting only about 1 in 40,000, compared to 1 in 100 in adults. (The average age of onset is 18 in men and 25 in women).  With the illness manifesting so early in this family, I would expect a strong genetic component.

In the book Schofield reports the following:

His mother suffered from hallucinations and once tried to stab Michael with a kitchen knife because she thought Michael was her father trying to rape her. She never received a diagnosis, but it sound like some kind of psychosis.

His first cousin once removed had a diagnosis of schizophrenia and committed suicide.

Michael was on Ritalin from five years old to thirteen. He currently takes Lexapro for depression.  He attempts suicide during the time frame of the book.

Susan(January’s mother)’s paternal great uncle had a diagnosis of schizophrenia and was hospitalized in Napa State Hospital.

So, the risk to Michael and Susan having a child with any mental illness was definitely increased over the general population risk. The risk of ADHD is very high, owing to Michael’s diagnosis. The risk of having a second child with schizophrenia is about 10%, possible higher because the onset was so young, especially in a female child.   The Schofields do have another child, a boy, who is diagnosed with autism.  Some of January’s symptoms fall in the autism spectrum range, which beg the question of whether she also has an extreme case of autism or perhaps a dual diagnosis.

I found this statement written by a mother on a support group page:

“Having a mental illness is terrible, but if it has to happen to someone, it’s probably best that if happen before age 18 when parents can still make healthcare decisions for the child. Too often, when adults are diagnosed with mental illness, they are too ill to make rational decisions, and their loving parents are legally prohibited from making decisions for them, so they don’t get good treatment right away. Some never get treatment at all. Our sons are fortunate to not be in that situation. If a child gets effective treatment and becomes accustomed to adhering to it while he’s a minor, maybe he will stick with it during adulthood and live a healthier, happier, more independent life. IMHO, that’s the silver lining of childhood diagnosis.”

The guy I saw on the corner was gone by the time I was heading back from the bank. Hopefully he got what he needed.

Artist. Addict. Afflicted.

van gogh


Virginia Woolf. Carrie Fisher. Sinead O’Connor. Linda Hamilton. Richard Dreyfus. Spaulding Grey. Ernest Hemingway. Peter Gabriel. Abbie Hoffman. Kurt Cobain. Russell Brand. Ray Davies.  Brian Wilson. All have/had bipolar disorder.

On Monday night Mike and I rode down to the Mission to attend BAASICS.3: The Deep End- a series of lectures and performances that explored the brain in terms of creativity, mental illness and coping with brain damage.

Dr. Ketter, the chief of the Stanford Bipolar Disorder Clinic, gave a presentation of his research that looks at creativity and mood disorders. He gave a series of personality tests, and temperament tests to a group of people with bipolar disorder, a group of people with major depressive disorder, a group of people unaffected by mood disorders and a group of creative people (fine art, creative writing and design students).  He found that the group with bipolar disorder and the creative group scored similarly in many areas, whereas there was no correlation between the MDD group and the healthy controls with the other two groups.  This could explain why so many creative people have bipolar disorder, or why so many bipolar people are creative.  I asked Dr. Ketter about using the results to work backwards to find out who might be at risk for bipolar disorder, but he expressed that creativity can occur without bipolar disorder so it would not distinguish between someone being at risk for the disorder, or at risk for creativity (heck, in some cultures being creative is just as stigmatized as having mental illness.)

Well, of course I’m always looking for that early intervention angle!!

Aside: Did you know that people with Bipolar 1 have a 61% lifetime prevalence of substance use disorders-more than twice that of people with MDD and 15% higher than people with schizophrenia? And a high suicide rate- approximately 30 times the rate of the general population. That warrants some early intervention.

Dr. Viskontas of Memory and Aging Clinic presented some info on her patients with Alzheimer’s and dementia- and how sometimes creativity emerges with the onset of disease.  She presented some artwork of her patients.  At the end of her talk she pointed out that as a society we are mainly concerned about what we will lose with aging.  We should keep in mind that there may be something to gain.  I like her optimism.  And she sings opera too.



BAASICS will put the entire talk on their website at some point. (It’s not there as of 5/9/2013) I encourage you to check it out:

Link to Dr. Ketter’s study:

Dr. Viskontas website: