Fog Days of Summer

Here is some insight from a fellow native San Franciscan. A nice discussion of weather, mood and meds.

crosswalk confidential

Foggy night with fireworks at Aquatic Park Foggy night with fireworks at Aquatic Park Photo: Shawna Scott/Flickr

After a couple of weeks of abnormally warm weather in June, San Francisco has returned to its regularly scheduled summer weather programming. I have many childhood memories of bundling up in warm clothes to “watch the fireworks” from various local vantage points and mostly seeing colored flashes in the fog.

I can’t remember feeling oppressed by the grey days of endless fog growing up in San Francisco. Perhaps it was because I didn’t have anything to compare it to. It’s similar to living with anxiety and depression—you never question what your “normal” is until you’ve experienced something different. Though I don’t remember being gloom-sensitive as a kid, my mother would complain regularly about the lack of light in our basement apartment (undoubtedly struggling with her own depression). I was also lucky to have an annual break from the urban fog…

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Stem Cell Research Provides New Approach to Study Bipolar Disorder

 

Researchers have detected mitochondrial abnormalities, and differences in neuronal firing, in young neurons from patients with bipolar disorder by using induced pluripotent stem-cell (iPSC) technology. These stem cells are created from patient’s skin cells (fibroblasts) or from patient’s white blood cells (lymphocytes). It is possible to take skin cells or white blood cells and reverse engineer them back to the state where they have the ability to grow into different types of cells (basically back to the very early embryo state when the original template cells are just beginning to turn into different types of cells.)  Then these stem cells can be grown in the lab and encouraged to become neurons. By imaging these created neurons from people with and without bipolar disorder, researchers have seen a difference in neuron firing between people who respond to lithium treatment vs those who don’t respond to treatment. This hyperexcitability activity of young neurons in bipolar disorder was selectively reversed by lithium treatment only in neurons derived from patients who also responded to lithium treatment.

Mitochondria are structures found within all cell types, and they are the organelles that help provide energy for the cells, along with other important functions. Mitochondria contain their own DNA separate from the cell’s nuclear DNA. Mitochondria DNA is mainly inherited from the egg, therefore the maternal side of the family. In one study, in about 80% of the bipolar patients, hippocampal mitochondria were smaller than even the smallest of the control subjects’ mitochondria. The hippocampus is the elongated ridges on the floor of each lateral ventricle of the brain, thought to be the center of emotion, memory, and the autonomic nervous system. Differences in expression of the genes in the mitochondria were also found between subjects and controls. Is it possible then that a greater predisposition to bipolar disorder could be influenced by the maternal family side?

Brain research is complicated because tissue is difficult and dangerous to extract, and studying brain tissue after death doesn’t give us a good picture of cause and effect across the lifetime. In post-morteum brain tissue, abnormalities could be due to a number of different environmental exposures (such as drug treatment) or trauma such as concussions that are difficult to control in living subjects. A model that does not use living subjects is difficult to create.

However,  researchers have been able to use stem cell from patients to create tissue in the lab for study.  They can take stem cells and “engineer” them to create many different types of tissues; in this study they use patients’s stem cells to create neurons. The hyperexcitability of the neurons is one early indicator of bipolar disorder, and this model of iPSCs in this disease might be useful in developing new therapies and drugs aimed at its clinical treatment.

Here is a link to the study in Nature:

https://www.ncbi.nlm.nih.gov/pubmed/28242870

And a link to one of the earlier studies:

https://www.nature.com/nature/journal/v527/n7576/full/nature15526.html

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ACA pulls out of Tennessee after the state approves discrimination bill.

The American Counseling Association, of which I am a member, decided to move their national convention scheduled in Tennessee in 2017 to San Francisco. Tennessee legislature passed a bill in April that allowed counselors to refuse to see a client if counseling that client involves “goals, outcomes or behaviors that conflict with the sincerely held principles of the counselor or therapist.” This law is in direct opposition to the ACA code of ethics.  Thelma Duffy, ACA president who’s term just ended stated “We believed it was important that the ACA take a public and powerful stance in opposition to this bill, and relocating provided us with that opportunity. We also believe that is was important that we communicate with our members who voiced deep concern about continuing to hold conferences in Tennessee in light of the new law. And ultimately we made the move based on our long held belief of nondiscrimination and our commitment to advocacy for all people.”

Way to go ACA! I’ll feel a little more pride when I write that yearly dues check next time!

Leader of Landmark Gene Research on Schizophrenia to Speak at NAMI Convention

I’ll be there…will report back. Here’s the blurb from the NAMI website

By Marcy Baer | May. 20, 2016

Dr. Steven McCarroll, who led the research team responsible for a study that examines the gene that may be a risk factor for schizophrenia, will speak at this year’s NAMI National Convention, July 6–9 in Denver. Dr. McCarroll is an assistant professor in the Department of Genetics at Harvard Medical School and the Director of Genetics at the Broad Institute of MIT’s and Harvard’s Stanley Center for Psychiatric Research. The research findings revealed in Dr. McCarroll’s analysis were published in the Feb. 11 issue of the journal Nature. Titled “Schizophrenia: From genetics to physiology at last,” the article reviewed how the study identifies “a set of genetic variations that are strongly associated with the risk of developing schizophrenia” and “provides insights into the neurobiology of this destructive disease.” The basis of the research is a worldwide collection of DNA from more than 100,000 people to find genetic clues to mental illness. Called C4, the gene isolated by Dr. McCarroll and his team is known to work in the body’s immune system tagging viruses for destruction. Until now, the gene had no known role in the brain. A highly complex gene, C4 is difficult to identify because it takes various forms and structures in different people. Many researchers believe there is a strong relationship between the immune system and schizophrenia, so much of the work focused on finding that connection. Research and collaboration among neurobiologists, immunologists and other genetic experts confirmed that C4 damages the brain because it accelerates a process called synaptic pruning. According to Dr. Bruce Cuthbert, acting director of the National Institute of Mental Health, in many cases synaptic pruning can help the brain. “It’s like clearing away the underbrush so your brain can function more efficiently,” he explains. “But in people with this overactive version of the gene,” Dr. Cuthbert continues, “it may be like having an over-energetic gardener who prunes back so much that the bushes die off because they don’t have enough branches.” Dr. Cuthbert views this study as a “genetic breakthrough,” and “a crucial turning point in the fight against mental illness.” Dr. Eric Lander, a professor of biology at the Massachusetts Institute of Technology and founding director of the Broad Institute, believes this research may provide a new understanding of what causes schizophrenia in terms of brain biology. “For the first time,” Lander says, “we’re opening the ‘black box,’ looking inside, and seeing how the disease really arises. In my opinion, this study is the most important paper in schizophrenia since the disease itself was defined more than a century ago.” While such science may take years to translate into treatments, Dr. McCarroll is optimistic. “The finding connects all these dots, all these disconnected observations about schizophrenia, and makes them make sense,” he says. You can hear Dr. McCarroll’s presentation as part of the NAMI Convention’s Research Plenary on Saturday, July 9, from 8:45 to 10:30 a.m. For more information and to register for the NAMI National Convention, go to NAMI.org/convention.

 

 

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

Business Insider’s Discussion of Direct-to-Consumer Genetic Testing (with some quotes from yours truly)

I was interviewed for Business Insider Magazine regarding Kailos direct to consumer genetic tests. I think Lydia did a nice job discussing the benefits and limitations of at home genetic testing.genes

Here’s her article:

I shipped my spit to a genetics company to have it tested, 23andMe style — here’s what I found out

That information can be used for everything from finding out where your family came from to figuring out if you’re predisposed to certain diseases.

Companies like AncestryDNA and23andMe have been partnering with drug companies to try and figure out what role genetics plays in getting sick, and how it can help us get better faster.

But how much can the average consumer learn from his or her genes?

I decided to try out some tests from Kailos Genetics, a genetic-testing company based in Huntsville, Alabama, to find out. All of the tests Kailos offers are designed to help determine how you might respond to certain medications. These include antidepressants, contraceptives, breast-cancer medication, pain-management treatments, blood thinners, and stomach-acid reducers. You can also opt for an all-inclusive test that includes all of these genetic markers.

About me: I’m a 22-year-old woman who is, apart from some seasonal allergies, healthy. I ordered the contraceptives and antidepressant tests that Kailos offers, since those would be the types of medications I’d be most likely to use at this point in my life. I also have a family history of blood-clot problems, which in some cases can be worsened by oral contraceptives.

Here’s how it went down:

Sending my spit to Kailos

A week after ordering the two tests, I got a big purple envelope in the mail:

praxis envelope cropLydia Ramsey/Business Insider

The kit came with instructions, a letter explaining the test, two swabs, a collection bag, and an envelope:

kailos kitLydia Ramsey/Business Insider

I opened up the first swab and started collecting samples of my cheek tissue on the left side of my mouth. To get a good sample, I had to scrape the side of my cheek up and down with the swab for about 30 seconds.

IMG_4990Lydia Ramsey/Business Insider

After repeating the process with the other swab, I put both of them back in the collection bag, packed them all up in the return envelope, and shipped it off to Kailos for testing:

IMG_4992Lydia Ramsey/Business Insider

The results

Once Kailos’ diagnostic lab got my envelope, my sample went through an enrichment process to separate the genetic material — my DNA — from the rest of the stuff on the cotton swab so they can have a better look. Then, the lab technicians looked at my DNA and used a computer to home in on the genetic regions that are relevant to the specific test they were running.

Next, they turned the results over to Kailos’ in-house physicians to interpret the results. These doctors are what allow Kailos to sidestep the problem of needing a middleman — who’d most likely be my primary-care doctor — to discuss my results with me.

Instead of talking to a doctor, my results were posted online to my account on Kailos’ website, which I’d created to order the test.

Thumbs-up for medication No. 1

Screen Shot 2015 10 01 at 4.37.12 PMLydia Ramsey/Business Insider

For the first part of my results, which looked at whether I should avoid certain contraceptives, I saw two big “thumbs-up” symbols.

This meant that the test, which looked at two genes related to how my blood clots, found they were functioning normally — there was no reason they could see that I shouldn’t take the medication.

Those genes were my Factor 2 and Factor 5 genes. Research has found that people with a specific mutation, or tweak, on either of these genes can be at risk of dangerous blood clots, which can stop the blood from flowing from your heart to other parts of your body.

All of this is important for someone considering using contraceptives, since the kind that are taken orally (aka many traditional birth-control pills) can be linked with an increased risk of blood clots in some people; the hormone estrogen in the pills increases certain proteins in the blood that help it stick together and clot.

Thumbs-up for medication No. 1 … sort of

Screen Shot 2015 10 08 at 4.44.21 PMLydia Ramsey/Business Insider

The next part of my test results focused on whether I had genetic tweaks that could make it a bad idea for me to take antidepressants. The test looked at potential indications against taking three of the most popular types: tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs).

Genetics can give us clues about how good our body is at absorbing certain oral antidepressant medications. The CYP2D6 and CYP2C19 genes, for example, make proteins in the liver that break down a hefty proportion of prescription drugs, including antidepressants.

The good news? I should be good to go with all three types: I don’t have any mutations that would cause my body to absorb the drugs poorly.

But while my results suggested my body could handle any of these medications — should a psychiatrist or mental-health professional prescribe them to me, of course — experts say the results aren’t so clear.

Carmela Thompson, a genetic counselor with Genetic Discovery SF, told Business Insider that although she thinks genetic tests are great for figuring out if a person has a hereditary condition like Huntington’s disease, she wouldn’t recommend using them as the sole way to determine the best solution to treating psychiatric conditions.

At least not yet.

“As far as psychiatric conditions go, we’re not there yet and we may never be there,” said Thompson. That’s because the conditions often have multiple factors in addition to genes at play, like environmental factors, so what’s influenced by genetics isn’t quite as clear.

Why Kailos didn’t run into the same problem as 23andMe

Genetic testing companies, like 23andMe, have run into trouble with the FDA for not getting its approval before making their genetic-health tests, which are pretty similar to the ones Kailos offers, available.

But Kailos is already government regulated. As a Clinical Laboratory Improvement Amendments-regulated industry, Kailos’ lab facilities are regularly inspected by the Centers for Medicare and Medicaid Services, which is in charge of ensuring they’re up to par.

Also, having a physician analyze the tests on Kailos’ end is a key way to steer clear of the roadblocks other genetic-testing companies face. Instead of providing uninterpreted information directly to a consumer, that information is going through a trained professional who can make sure it’s interpreted accurately. Troy Moore, Kailos’ chief scientific officer, told Business Insider the reason they opted for more specific tests for certain medications came from their background as a clinical lab.

The verdict

While it was easy to submit my samples and see my results, I didn’t find the test incredibly helpful. I’m grateful to see my results were positive, but part of me was hoping to learn something more nuanced about how my genetics interacted with medicine, like if a certain type of contraceptive would have less negative side effects or would work better for me than another, or if I shouldn’t take contraceptives at all.

Along with the thumbs-up/thumbs-down rankings, Kailos also provides all the raw information for the genes each test looked at, which could help a doctor dive deeper into what the test means for me.

I could have asked a doctor to go over my results with me typically the tests Kailos provides are coordinated with a physician, but when I saw the thumbs-up signs, I didn’t think going over my results with a doctor was necessary.

Which brings up a potential concern when it comes to consumer tests overall: What if, after receiving his or her results, a patient who was on medication chose to use them to start making changes to when and how he or she takes it?

This was a concern Thompson brought up when I told her I hadn’t contacted my doctor about my results. Because parts of genetic tests can get really complex, it’s helpful to have people with at least a physician-level knowledge of genetics around to interpret what it all means, she said.

“It’s just a tool,” Thompson added.

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