Microbiome and Major Depression (i.e. Bacteria and Mood)

probiotics

Embryos develop from a small ball of cells to a flat sheet of cells. This sheet rolls up into a tube. One end of the tube becomes the brain, the other end becomes the digestive tract.

There is communication along this brain-gut axis via nerves, hormones and the immune system (via the blood). And I’m probably not the only person who asked out loud for my stomach to stop growling, so there’s a cognitive connection too :).

There is some evidence that our intestinal micro biota, the bacteria that we harbor that aids in digestion, actually communicates with our brain via the immune system. Scientists are also investigating the hypothesis that modification of microbial ecology, for example by supplements containing microbial species (probiotics), may be used therapeutically to modify stress responses and symptoms of anxiety and depression.

A recent study from the Netherlands reported the first evidence that the intake of probiotics may help reduce negative thoughts associated with sad mood and suggest that probiotics supplementation warrants further research as a potential preventive strategy for depression.

The study was small, 40 people total for cases and controls, but it certainly works as a pilot study for more research.

The study was published with open access- you can read it here:

http://www.sciencedirect.com/science/article/pii/S0889159115000884

This also adds to the evidence that chocolate is good for us! Also, probiotics do not have to be taken as supplements. Besides chocolate, probiotics are found in fermented foods such as kim chi, and in yogurt.

http://www.webmd.com/digestive-disorders/features/what-are-probiotics

Advertisements

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

The Brain’s Most Miserable Molecule

Image

How, you might ask, do antidepressants work?

The easy answer is: We don’t know.  This makes drug treatment for depression and anxiety a guessing game where a multitude of drugs are prescribed in a course of trial and error.  One person may respond to one drug and not another; it’s difficult to predict individual response.  It’s no wonder that people get frustrated and often give up taking meds altogether. Or get kicked off reality TV shows like “Celebrity Rehab”.

Recently scientists discovered a 3D structure of a brain protein receptor, CRF1, a molecule on the outside of cells on the pituitary gland, that releases CRF, hormones involved in regulating our stress response that over time contribute to anxiety and depression.

This is great news, because knowing the structure can help researchers make drugs that mimic CRF1 and block it’s capability of creating the hormone that causing the stress response.

CRF1 is made by the gene CRHR1. I looked up the gene to see if there are any significant known mutations.  In mice models, disruption of the gene (knocking it out, or mutating it) reduced anxiety-related behavior under both basal conditions and following alcohol withdrawal.  According to the Online Mendelian Inheritance in Man “The results demonstrated a key role of the Crhr1 receptor in mediating the stress response and anxiety-related behavior. CRH had been previously identified as a potent mediator of endocrine, autonomic, behavioral, and immune responses to stress and had been implicated in the stress-like and other adverse consequences of drug abuse, such as withdrawal from alcohol.”

Could this mean the end of television shows like “Celebrity Rehab” and “Intervention”? Probably not. Stress response is a necessary tool for survival, honed over time by evolution. We can’t knock out the gene in people, but drugs may be able to mimic the knockout response.

At this time, a gene test wouldn’t reveal much information, but there could be different forms of the gene that produce more or less amount of the protein.

Link to article on CFR1:

http://www.popsci.com/science/article/2013-07/scientists-identify-molecule-responsible-stress-and-anxiety

High cost of drugs getting you down?

Image

Did you know that there’s now an injectable form of Abilify that lasts for about a month?  Did you know that if you don’t have insurance it costs $1000 per injection?

Wow.

I went to the meeting of the San Francisco chapter of NAMI (National Alliance on Mental Illness) last night for a discussion about medication.  Dr. Ralph Fenn was on hand to answer questions and provide information.  He gave us two great websites to check out

This site compares costs of drugs so you can find the lowest price:

http://www.prescriptiondiscount123.com/check-discount-drug-cost

This site has programs that can assist if you need medication but can’t afford it:

http://www.needymeds.org/indices/pap.htm

For patient assistance programs you generally need to make less than $28,000 a year, which I know is hard to live on in San Francisco, but It doesn’t require that you be on MediCal or MediCare. Check it out.

On a genetic side note: I asked Dr. Fenn if he thought genetic testing for drug response was appropriate.  He agreed and said if he were the patient he would even consider paying out of pocket for it.

Photo:

© Alexey Lisovoy | Dreamstime Stock Photos