C4 and Schizophrenia

When I hear “C4” I immediately think of the television series “Lost” and explosive material. C4 is also the shortened name of Complement component 4- one of a group of proteins that work together to make the immune system.  The C4 gene that codes for this protein is on Chromosome 6, and everyone has different variations in this gene, referred to alleles. Researchers from the Broad Institute, Harvard Medical School and Boston Children’s Hospital, recently published a study with a hypothesis that a key cause of schizophrenia involves different alleles of this gene. The researchers noted that people who had schizophrenia were more likely to have a certain variation that promotes neural “pruning.”

Pruning is part of normal brain development during childhood, and especially during adolescence. Pruning is the process where synapses in the brain are eliminated. It is believed that the purpose of synaptic pruning is to remove unnecessary neuronal structures from the brain; as the human brain develops, the need to understand more complex structures becomes much more pertinent, and simpler associations formed at childhood are thought to be replaced by complex structures.

It may be that different alleles cause different amounts of pruning. Perhaps less pruning, which could lead to too much information being retained, could be a risk factor for mental health.  This could be one of the factors contributing to schizophrenia- there are likely many genetic and environmental factors. More knowledge of these mechanisms may be helpful in creating or refining treatment.

Here is the link to the study’s abstract:

http://www.nature.com/nature/journal/v530/n7589/full/nature16549.html#access

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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

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

freeimage-6744613-web genome

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

 

Do People With Mental Illness Age Faster Than People Who Are Unaffected?

Last week I attended a talk by Dr. Owen Wolkowitz, psychiatrist and professor at UCSF Langley Porter Institute.  His answer to this question is “yes.”  He refers to mental illness as “disorders of the whole body.”

There is data that people with mental illness die, on an average, 25 years earlier than people in the general population.  30-40% of people with mental illness die of suicide or accidents, but the remaining 60% die of natural causes earlier than the general population.

There are some obvious reasons as to why:

1)      Poor lifestyle – smoking , drinking, illicit drug use, bad nutrition

2)      Poor access to healthcare, poor medication compliance, homelessness

3)      Medication side effects such as obesity, increased lipids

Less obvious are some of the behind the scenes factors, such as inflammation due to stress.

It is also possible that mental illness actually changes our DNA, in particular our telomeres. Telomeres are the pieces of DNA at the ends of the chromosomes. Each time a cell divides, it duplicates its chromosomes, and a little bit of the end of the chromosome is lost. At some point, too much information is lost, and instead of dividing, the cell dies. This is the aging process in a nutshell. We can’t have cells that live forever (that’s what happens in cancer, the mechanism gets screwed up and the cell keeps dividing forever.)  Telomerase, the enzyme that adds the telomeres to the end of the chromosome, can be measured in the blood, and can be used as a marker for aging.

telemore-image2

Studies have been done on telomeres of people with mental illness. Studies of people with depression show telomere shortening. Adults with early life trauma have shorter telomeres, demonstrating perhaps a “scar in the brain.”  There’s evidence that people with schizophrenia who take anti-psychotic meds have longer telomeres than people with schizophrenia who aren’t taking any medication- demonstrating a potential benefit of medication. It’s possible that anti-psychotics can have an effect by reducing inflammation and oxidative stress.

The good news is that telomeres can lengthen. Factors known to extend telomere length to a healthy level include exercise, dietary restraint, multivitamins, folate, Omega 3’s, stress management, statins, estrogen and social support. So while good nutrition, good sleep, exercise and avoidance of illicit drugs are good plans for everyone, they are especially important for people with mental illness, or people at risk for mental illness.

Link to article on telemore shortening:

http://www.sciencedirect.com/science/article/pii/S0006322306001363

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:

http://www.nature.com/mp/journal/vaop/ncurrent/pdf/mp201391a.pdfmale anoerxia