Learning from Research, Slowly and Methodically.

Learning from Research, Slowly and Methodically.

I was given a challenge on Twitter, and some people dismissed me as a failure because I didn’t have the academic background to come back with a quick answer. (I also discovered that I knew the answer, but forgot the words because of post-surgical anomia. I digress.) I find that this is a problem with a lot of people with certain types of expertise. They forget what it was like back when they were first learning, and no longer have the patience to explain. I don’t think it helps that there is a shit-ton of people on the internet spouting nonsense and being taken seriously. Naturally, some of them will assume that I’m doing the same, but I really don’t want to be lumped in with them, so I’m going to show them the process I go through, and how seriously I take learning new things and separating fact from fiction.

As I said in my previous post, you guys are wicked smart, and I am very often in awe of how much you know. But one thing you’re not so good at is communicating to people outside your fields of expertise. This is why we have bad science journalism. Ask Ed Yong. However, if you want to stop all your discoveries from degenerating into misrepresentation or woo, then you need people who can translate Science into English.

I was given a long, information-dense study, Fidelity of the Methylation Pattern and Its Variation in the Genome by Malcolm M. Campbell, so it’s going to take several posts to dissect, research, learn the background information, and try to explain it in an accessible way. I fully expect to be wrong several times, and encourage people to correct me – in such a way that ordinary people can “get it.” So here goes:

Abstract

The methylated or unmethylated status of a CpG site is copied faithfully from parental DNA to daughter DNA, and functions as a cellular memory. However, no information is available for the fidelity of methylation pattern in unmethylated CpG islands (CGIs) or its variation in the genome. Here, we determined the methylation status of each CpG site on each DNA molecule obtained from clonal populations of normal human mammary epithelial cells.

Methylation turns genes or pieces of genes “on” or “off”. There’s a detailed explanation of various ways it does this in the components of the whole process from DNA to cell, but it’s kind of hard to understand if you haven’t done a lot of reading beforehand. I’ll give you the link anyway.

CpG sites – the quick and dirty Wikipedia definition is this: The CpG sites or CG sites are regions of DNA where a cytosine nucleotide occurs next to a guanine nucleotide in the linear sequence of bases along its length. If you don’t remember from your Biology classes, or your biology classes never taught you, your entire DNA strand consists of combinations of four nucleotides – Cytosine, Guanine, Taurine, and Adenosine. I’m not going to get into that right now, because it’s just going to confound this with too much information, but if you think about the movie “Gattaca,” you’ll notice those four letters. In a movie about genetic engineering. Because those are the four letters you see in an illustration of a piece of DNA. The researchers were looking at the parts where the cytosine and guanine were next to each other.

Specifically, they were looking at epithelial cells from normal breast tissue. The link may be a little difficult to understand, but I think if you read all the way through, you’ll at least understand some of the reasons these cells were chosen. They have a lot of unique characteristics, and they’re pretty tough.

So the idea here is that we already know that if the cytosine and guanine pair are methylated in the on position or the off position in the DNA, that they’re going to stay that way in the cells that are produced by those instructions from the DNA. What we don’t know is that if that pair is unmethylated, will the cells made from the DNA instructions also be unmethylated? IOW, if they’re not already told to be switched on or told to be switched off, will they still be in that “neutral” position? In order to test that, they took a bunch of those epithelial cells and tested each one to see if it was methylated or unmethylated so they could get them to reproduce and see what happened.

This illustration is not specific to this piece of research, but keep reading, and you’ll see how it relates.. I wanted to give you a visual aid in case you learn better that way.

Methylation pattern error rates (MPERs) were calculated based upon the deviation from the methylation patterns that should be obtained if the cells had 100% fidelity in replicating the methylation pattern. Unmethylated CGIs in the promoter regions of five genes showed MPERs of 0.018–0.032 errors/site/21.6 generations, and the fidelity of methylation pattern was calculated as 99.85%–99.92%/site/generation. In contrast, unmethylated CGIs outside the promoter regions showed MPERs more than twice as high (P < 0.01). Methylated regions, including a CGI in theMAGE-A3 promoter and DMR of the H19 gene, showed much lower MPERs than unmethylated CGIs. These showed that errors in methylation pattern were mainly due to de novo methylations in unmethylated regions. The differential MPERs even among unmethylated CGIs indicated that a promoter-specific protection mechanism(s) from de novo methylation was present.

This explains how they figured a reasonable range of variation. The “islands” of unmethylated cytosine/guanine pairs in five genes over 21.6 generations (this is statistics, not absolute numbers. You clone enough cells, you sure as heck can get six tenths of a generation.) stayed unmethylated most of the time. This came from promoter regions, which are the areas in DNA that call the shots. It’s more likely that instructions from promoter regions are going to be followed.

The unmethylated cells that didn’t come from promoter regions showed more deviations – the cells after several generations were twice as likely to be different from the originals than the ones that came from the promoter regions. The methylated cells, which, as I mentioned, already have the specific instructions to turn a gene on or off, were more likely to maintain their integrity even if they weren’t from promoter regions. The unmethylated cells didn’t’ have that instruction, and hadn’t been told to stay unmethylated (because they weren’t from promoter regions) and so they just did whatever seemed right at the time and, well, mistakes were made.

CpG methylation is known to serve as cellular memory, and is involved in various biological processes, such as tissue-specific gene expression, genomic imprinting, and X chromosome inactivation (Jones and Takai 2001; Bird 2002; Futscher et al. 2002;Strichman-Almashanu et al. 2002). These important functions of methylations are based upon the fact that the methylated or unmethylated status of a CpG site is faithfully inherited. The methylated status of a CpG site is inherited upon DNA replication by the function of maintenance methylase, represented by DNA methyltransferase 1, which is located at replication forks and methylates hemimethylated CpG sites into fully methylated CpG sites (Leonhardt et al. 1992; Araujo et al. 1998; Hsu et al. 1999). The unmethylated status of a CpG site is inherited by not being methylated upon DNA replication or any other occasions. Unmethylated CpG sites generally cluster to form a CpG island (CGI), and most CGIs are kept unmethylated (Gardiner-Garden and Frommer 1987; Bird 2002). Methylations of CGIs in promoter regions are known to cause transcriptional silencing of their downstream genes by changing chromatin structures and blocking transcription initiation (Bird 2002;Richards and Elgin 2002). There are limited numbers of CGIs that are normally methylated (normally methylated CpG islands; NM-CGIs) (De Smet et al. 1999; Futscher et al. 2002). CpG sites outside CGIs, especially those in repetitive sequences, are also normally methylated (Bird 2002).

CpG methylation is important. It is carried on pretty faithfully when cells reproduce. It’s also important that unmethylated CpG remains unmethylated, and that’s usually passed on to new cells as well. Most of the unmethylated sites form a cluster called a CpG Island, or CGI. If these unmethylated CGIs become methylated, then it changes what genetic instructions get turned on or off in future generations of cells, if they’re in promoter regions. But it’s not always bad for CGIs to be methylated, because sometimes that’s on purpose.

I’m going to hold off on the transcription and chromatin stuff for later, because I think it’ll stick better when the paper goes into more detail.

To keep the methylation pattern, maintenance of both methylated and unmethylated statuses of CpG sites during DNA replication is necessary. However, the fidelity of the methylation pattern has been analyzed only for the maintenance of the methylated status (Wigler et al. 1981; Otto and Walbot 1990; Pfeifer et al. 1990). The fidelity in maintaining the methylated status of an exogenously introduced DNA was shown to be 94% per generation per site by Southern blot analysis (Wigler et al. 1981). The fidelity in maintaining the methylated status of a CGI in the 5′ region of the PGK1 gene, which was derived from the inactive X chromosome, was estimated to be 98.8%–99.9% per site per generation by the ligation-mediated PCR method after chemical cleavage of DNA (Pfeifer et al. 1990).


We’ve already studied methylated CpG sites and found that it’s pretty consistent. Some studies attesting to that are cited. We know that keeping them unmethylated is also important, but that hasn’t been investigated to our satisfaction.

Normally unmethylated regions might show different fidelities from normally methylated regions. Even among the unmethylated CGIs, the fidelities of their methylation pattern have been suggested to be different according to their location against a gene promoter. Methylation of CGIs in promoter regions almost always leads to transcriptional silencing while that of CGIs outside promoter regions does not (Gonzalgo et al. 1998; Jones 1999). Considering the cellular expense in maintaining methylation pattern, a cell could sacrifice the fidelity of methylation pattern for CGIs outside promoter regions. In addition, by recent genomic scanning techniques for methylation changes (Ushijima et al. 1997; Toyota et al. 1999; Costello et al. 2000; Jones and Baylin 2002), aberrant methylations of CGIs in cancers are observed in a nonrandom manner (Toyota et al. 1999; Costello et al. 2000; Kaneda et al. 2002a; Kaneda et al. 2002b). It is indicated that CGIs outside promoter regions were more frequently methylated than those in promoter regions (Nguyen et al. 2001; Takai et al. 2001; Kaneda et al. 2002a; Asada et al. 2003).

Unmethylated CGIs are more likely to change than methylated ones. Unmethylated CGIs from promoter regions of the DNA pretty consistently shut down the things they’re supposed to shut down, exactly as planned. Unmethylated CGIs from outside promoter regions of the DNA are not so good at that – they’re more likely to become methylated when they’re supposed to stay unmethylated. Some of this methylation of unmethylated CGIs has been seen in cancer. So that’s one example of why we don’t want this to happen.

Here, we analyzed the methylation status of each CpG site on each DNA molecule by the bisulfite sequencing technique (Clark et al. 1994) in six clonal populations of normal human mammary epithelial cells (HMECs), for CGIs in the promoter regions, CGIs outside the promoter regions, and CpG sites outside CGIs. By analyzing the deviation from the most common two patterns, MPERs, which reflected the fidelity in replicating both methylated and unmethylated statuses, were measured.

Like a five-paragraph essay here. Restating what they’re going to do and how they’re going to do it. Remember the illustration? Bisulfite sequencing technique. (Really detailed explanation, Wikipedia explanation).

And now my brain is very, very tired. I am going to watch “Besharam” because I’m also trying to learn Hindi, and I might as well be looking at Ranbir Kapoor while I’m doing it. Heh. I will continue this in a later post. Feedback is welcome and encouraged.

Science People!

Science People!

I’ve been getting a lot of attention on Twitter for the last couple of posts, and that’s given me a lot of articles to read, blogs to keep up with, and Twitter users to follow. Some people got a little testy, and I don’t blame them, because they know more than I do. I get it.

Let me tell you something right now. I am not a professional scientist. I got my Bachelor’s degree in Spanish Language and Literature back in the early 80s, and distanced myself from science since I had to take my only B-track class in all of High School in Biology. I didn’t get it, I didn’t see the point, I put no effort in, and I sucked at it.

That’s ADHD.

But then I started reading books about the brain, and that struck a chord with me because my brain is not the nice neurotypical model. I started reading blogs and websites about the brain, and medicine, and genetics. I learned how to read published research (and occasionally got friends who would sneak me links to full text articles) and would search in the middle of searches when I found terms I didn’t understand or biological processes or mechanisms that were new to me but essential to understanding what I was reading.

This obsessive pursuit of information is also ADHD, BTW.

This means that there are gaps in my knowledge. I am not ashamed to admit that you know more than I do. Please don’t get angry with me when I’m wrong – explain to me why I’m wrong and then tell me how to understand it the right way. I don’t want to be right to win arguments or lord it over people, I want to be right because I have the correct information. You can help me with that.

Thing is, one thing I know I’m really good at is teaching other people things. I take my mistakes, the process by which I figured something out, and the way it works at the most basic level, and try to use that to explain what I know in a way so that other people can “get it.” There are several college students out there pursuing degrees in science because I got them all excited about it. They’re getting the chance I missed out on.

So, you want more minions? (MUHAHAHAHA!!) Give me comments. Help me understand. Because if you help me understand, I can help other people understand. I’m an intelligent woman, I’ll get it pretty quickly, and when I don’t, I’m not in the least ashamed to admit that I was wrong. We can have a mutually supportive and respectful interchange, and I’ll do my part to explain things in an accessible way, using the tools you give me.

Really. Comment. email. Bring it on. I love you guys!

Epigenetics Made Easy, Part 2

Epigenetics Made Easy, Part 2

Let’s reiterate from the previous post, just in case you need a recap:

All cells are made from other cells; we start with a few that are the same, and as the number of cells increases, they begin to differentiate and become cells for specific body parts.

DNA is the blueprint for the final product (a sexually mature adult human being, for illustration purposes.) RNA is a segment of DNA that begins the process of cell differentiation, but the mechanism that actually creates the proteins that build cells is the epigenetic process, which depends upon histones interpreting the genetic instructions.

Once we are full grown, our bodies are almost always replacing cells rather than making new ones, and the new cells may not be exact duplicates of the cells that created them.

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histone modification

Yes, there is such a thing as histone modification. Yes, gene expression (in the form of cells that follow specific genetic instructions) can be changed during the epigenetic process. Yes, it’s possible for some of these changes to become heritable (passed on from parent to offspring.) But let me explain what’s reasonable and rational about these possibilities.

Histone Modification

You’ve heard of this, but usually in the form of “you can change your DNA by doing this thing or eating that thing” which is, essentially, not true. Histone modification takes place on a cellular level, and changes in different ways depending on what the chemicals that can modify histones are doing. I’ll save the technical terms and illustrations for another time. Baby steps.

What happens is that while a cell is preparing to replicate itself, a chemical can make the histones do something differently from the way they were instructed, and that makes the resulting copied cell different from the cell that created it. Right now, we have some very specific examples of changes that depend on specific chemical exposures (some from external environment, some from internal environment.) DNA is huge. We have a hundred trillion or so cells in our bodies. The genome is almost infinitely diverse. There are very few examples right now of direct cause and effect, and each one we discover in the future will be just as limited.

The number of possibilities alone makes it pure speculation to assume that a food given to a pregnant mouse that changes her babies’ fur color and body shape is going to do the same thing for a fully-grown adult, or even something similar!

Now the add another layer of complexity, these are the things that can happen when you modify the histones in a cell:

*a beneficial gene is suppressed
*a detrimental gene is suppressed
*a beneficial gene is activated
*a detrimental gene is activated

So if someone claims that a food or something “methylates” your genes (besides being wrong) it could easily be a bad thing!

Changing Gene Expression

I mentioned the prenatal modification above, and that’s because it’s an important thing to study. Why? Because in order for histone modification to have any observable and verifiable effect, it needs to happen early. Think about it. If you modify the histones of a four or eight celled creature, then a lot more cells are going to be made not according to plans. In an adult, modifying a single cell, or even a few cells, out of all the cells in our bodies, is going to have minimal impact. In order to change gene expression in an adult, exposure needs to be intense enough or prolonged enough to influence a large number of cells.

I like to use the example of skin, partly because it’s a cell type that’s replaced frequently, and partly because we can see a lot of the possible changes to it. It’s a good way to illustrate that an environmental factor can produce a change that does not alter gene expression, and how the level of exposure can make a difference in whether an epigenetic change is even possible.

If you go out into the sun, your skin changes color. It could get burned, it could get tanned. But when those darker skin cells make their replacements and die, the replacements are your original skin color. You have exposed yourself to an environmental factor that has an obvious effect on your body, but it doesn’t change your gene expression. Why? Because the exposure was not prolonged enough that the visible change was messing around with histones while the replacement cell was being created.

On the other hand, if you’re out in the sun all the time so that your skin is constantly in a damaged state, then those cells are more likely to be in that damaged state when they’re replicating themselves. This could still even be temporary, but it could change gene expression so that the replacement cells are cancerous, for example. (Cancer is epigenetic – but it could be caused by environment *or* part of the plan all along.) So you need to expose the same group of cells to the same environmental factor for long enough that most of the cells begin reproducing with the alteration in gene expression. . .and that is not guaranteed to be a good thing, so don’t buy into the hype.

Heritability of Epigenetic Changes

Yep, this has been studied, too, and it does sometimes happen. The most repeatable changes happen when the fathers’ bodies have changed. I credit that to the fact that sperm are constantly being made, and things like stress hormones or chemical exposures, or starvation, can change what genes go into what chromosomes in the sperm cells at that time. Give the dads some time to recover, you get a completely different result.

Keep in mind that the normal set of instructions is the default. If you look at plants or other animals who’ve been genetically altered, a lot of times you’ll find that their offspring regress to the original, dominant form. In both human and animal studies, most of the epigenetic changes that were brought about by environmental exposure get passed down to the next generation, maybe the generation after that, and in a few cases, the third generation. Then things go back to normal.

I probably missed a few things, but I hope this is clear. Ask me stuff, tell me stuff. Thanks!

Epigenetics Made Easy.

Epigenetics Made Easy.

Tightly wrapped histones

No, not really. That’s a misleading title, but my hope here is that I can explain this in terms that are simple enough for people who aren’t scientists to understand. I’m hoping that because I’m not a professional scientist but am really, really into this stuff, the language and illustrations I use serve as a bridge for the gap in understanding.

So let’s start with the cell, and let’s use humans as an example. Even though epigenetics happens in every living thing, even plants, I want you to be able to identify personally with this so the information takes hold a little better. What do we know about genetics and conception and fetal development? Well, we start off with an assortment of genes and 46 chromosomes. We got all of them from our parents and grandparents and so on down the line, but it’s a mix between Mom’s side and Dad’s side, because her eggs start off with a random selection of 23 chromosomes (see my previous post about what random means) and his sperm also start off with a random selection of matching chromosomes.

Sperm meets egg, and there you go, 46 chromosomes in a single cell, and a complete, unique strand of DNA that has all the information needed to build a human body.

If you’ve watched videos of human development, you’ve seen how that one cell splits into two, two into four, four into eight, and then things really start to happen. In the beginning, each of those cells is exactly the same. Each time they split, they’re making another cell that’s just like they are. Remember this, because I’m going to mention it again later. . . Here’s how it looks, in case you haven’t actually seen it, in a video on in-vitro fertilization:

After this point, the cells begin to differentiate. Instead of simply reproducing copies of themselves, they start to become more specialized. They still contain all the DNA, but some of the instructions will be used, and some will be silenced. This starts with the transcription from DNA to RNA. What we used to believe (or at least what I was taught in school days in ancient times) was that the RNA was the sole messenger, containing only the information needed to make cells. That’s only kind of sort of true, and doesn’t explain a lot of confusing things that happen to human bodies. You see, it is part of the picture in cell differentiation, which is, to put it in simple terms, the process that makes one cell be a bone cell and another be a heart cell and another be a brain cell and so on. The RNA puts this in process by taking the pieces of the DNA that are needed to make a specific call and creating the proteins that manufacture that cell. With these instructions, cells continue to divide, but they’re not just making carbon copies of themselves.

We see this in fetal development because parts of the body from the brain, the eyes, the internal organs, to the fingers and toes, go from being kind of blobby and alien-looking, to functional and human-like. The manufacturing of differentiated cells continues throughout fetal development, and the differentiation is pretty much complete by the time a baby is born.

But there’s a piece missing – we know that RNA has instructions for making the proteins that manufacture differentiated cells, but it doesn’t make those proteins all by itself. This is where epigenetics comes in. The actual work of taking the orders from the RNA and making the proteins is done by histones. The DNA has the construction diagrams, the RNA is barking orders, the histones are doing the work.

This is still happening inside a cell. The cells are still dividing. It’s just that this epigenetic process is making two different cells out of one cell instead of two identical cells. The new cells aren’t coming out of nowhere, they’re coming from existing cells that are multiplying.

As we get older, we tend to go back to more of a model of cell replication. A cell duplicates itself, then dies after the new cell has been made. The epigenetic process takes place then, as well. Sometimes the cells won’t necessarily die, because we’re growing and need more cells. That’s done epigenetically, too, because the blueprint from the DNA says what the final adult product is supposed to be like, not just the infant version. As we get really older, the cells are trying to replace themselves, but they don’t do quite as good a job, and that’s an epigenetic process as well, because the instructions are getting messed up *after* the RNA. The histones just aren’t doing such a great job after a while.

The point here is that epigenetics is part of the process of cell development that is already written out in the DNA. The way it works without interference is genetic and heritable, and every single one of the many trillions of cells in your body was created the same way. The DNA has the plans, the RNA is the subcontractor, the histones are giving the orders to the proteins based on the instructions from the higher-ups.

Keep this in mind when you hear things about the amazing effects of environment on epigenetics. Yes, this is the part where things can get screwed up, because, yes, histones can be modified. But I’m going to save that for later, because this is a lot to absorb. I hope this makes sense, and if anyone has questions or corrections, please comment – I want to hear from you.

Epigenetics – I do not think that word means what you think it does.

Epigenetics – I do not think that word means what you think it does.

And I kind of have a bone to pick with Scientists who are actually contributing to the problem. Epigenetics is an essential biological process that takes place at the molecular level. Each one of the hundred trillion or so cells in the human body was created via the epigenetic process. Nothing has to magically happen. All you need is cells, food for the cells (usually glucose, yum!) and DNA.

Unfortunately, the amazing and fascinating research into epigenetics has led to a description of epigenetics as “genes plus environment.” If you are a scientist, or even understand science, you recognize that this does not mean that some sort of environmental factor from outside the body is necessary for the epigenetic process to take place. But if you’re a layperson, that’s exactly what you might think when you hear that. In fact, for quite some time I’ve been debating with a couple of people who believe in this magical concept of epigenetics, and you scientists (whom I otherwise love dearly) are just not helping!

The agouti mouse study that showed a change in coat color (linked along with other references in this previous post) was really exciting, and the public glommed onto it because there was the evidence, right in front of their eyes. In no time at all, alt-med proponents and the general public were certain that this was the answer to everything that was wrong with us. It was a great boon for supplement manufacturers, diet book writers, food conspiracy theorists, and anyone who was looking for something to blame for what was wrong with them (or society, but usually themselves.) I mean, clearly if what a mother mouse ate changed the color of her babies’ fur, then what horrible things are all these toxins doing to our genes?!?!

The thought seems to be that epigenetics is a highly unstable process that actually depends upon the correct “environment” in order to occur, and that even an unpleasant event in childhood can somehow upset it and result in a dramatic condition that can be passed down to one’s offspring. Once a person has gotten this idea into his head, it is darn nigh impossible to get it out. Homeopathic amounts of a “toxin” can have traumatic results, even worse than actual poisoning from that substance, because epigenetics. Psychiatric and neurological conditions are inflicted upon perfectly healthy infants by insufficient parental attachment or attunement. Everything is caused by environmental disruption of the epigenetic process, and everything in the environment messes up epigenetics.

Look, the reality is that what epigenetics does is take the information that’s been put into the RNA from the DNA, turn on the genes that are needed and turns off the ones that aren’t, then sends proteins off with the instructions to make new cells. At conception, when there are only a few cells, there’s not a lot of differentiation, but as fetal development continues, these instructions become more specific. “Make fingers.” “Make retinas.” “Make heart valves.” Stuff like that. During growth, the instructions are more like “make more of these cells.” During adolescence, it’s “make these a little different.” As we age, it’s “make another one just like this,” and “eh, what was that, sonny?”

The environment comes in because it is the epigenetic process during which an environmental factor can possibly alter the process, turning a genetic instruction on that should have been off or vice versa. It’s quite likely that this is what triggers many cancers that are strongly associated with exposure to a particular substance. But the possibility that exposure can impact gene expression is not the same as the inevitability of exposure altering gene expression. And this, people, is a big problem. Scientists, please think about this when you talk about epigenetics. Non-scientists, I’m going to put an explanation of how this works in the simplest terms I can come up with in another post.

Your Inner Fish

Your Inner Fish

I loved this book, and now PBS is making a miniseries with Neil Shubin. I can’t wait.

A long time ago, right after I read it, I put up a series of posts on a forum detailing the wonderful things I had learned from it. After a while, the threads were hijacked by people who just didn’t get it – or didn’t want to get it – and they disappeared into obscurity. But I stand by what I wrote, and now that this book is back in public view, I want to share these thoughts again. This is a long read, over 4,000 words, and it’s taken from a forum thread, so there are parts that don’t flow entirely well, but I don’t want to edit or rewrite it because it captures the wonder and excitement I felt when I first read the book and I don’t want to change that.

So settle down with a nice cup of tea if you’re ready to go below the fold.

Read the rest of this entry

My Brain Diary, Part 13

My Brain Diary, Part 13

I went through a long day of neuropsych testing, and it was quite interesting. Obviously, I can’t reveal everything about the experience, because you don’t want people who might go through the testing themselves to know too much. What I can say is that even during the testing, I could tell which areas were giving me particular difficulty – and after the testing, I started seeing some patterns in specific difficulties in performance among different tests.

Some things were obvious. Verbal memory was horrendous. I already knew that I’m having more trouble than ever remembering things that have been said to me, but one test involved repeating a very short story back to the examiner after she read it. On the first go-through, I repeated only the general ideas, and had trouble remembering enough to answer questions about the stories. On the second go-round, I remembered even less, and had trouble answering questions even with prompts. Other parts that required memory were not quite so abysmal, but it was clear that I was having some trouble.

When I went in for the evaluation, the neuropsychologist pointed out that other parts of the tests showed something much more telling – my pattern of answering, and the difference between tests with and without feedback, indicated that I had a big problem with impulsivity that was impairing my performance. Some of the tests were observed and some were just me and a machine of some kind, and the performance differences and the way I responded while observed showed some significant anxiety.

I don’t know if that’s an inherent anxiety, or just the anxiety that’s been overwhelming me for the last several months, but I have to tell you that I thought that I was cool, calm, and collected the whole time.

Some parts of the test were taken from IQ assessments. I performed quite impressively on those – but I’m not surprised because I already know my IQ and I know I’m intelligent. I swear I’m not bragging – it’s just a thing about me that is. But what this meant to the doctor is that my results on the other test segments compared to the intelligence parts demonstrated that I do have impairments that are functionally significant.

We’ve had a couple of counseling sessions, and will continue once a week for a while. Once I have the right medication and get my depression under control, I’ll probably undergo some speech therapy and occupational therapy. Since there doesn’t appear to be any lesions on my brain, there’s a possibility that my brain is plastic enough to re-learn some things.

Patience is not my strong suit. Obviously. But this is sort of like parts of my brain fell asleep from the pressure of the tumor, and the pins and needles stage is going to last for a while. I need to shake it out a bit. And put up with it until things start working again. Also not one of my personal strengths. Since I have no choice, though, I suppose that eventually I’ll learn.

10 Things I Have Learned About Abortion from Pro-lifers.

10 Things I Have Learned About Abortion from Pro-lifers.

1. Women choose to have sex. Men are apparently not involved in this decision-making process.

2. Women who do not use birth control are irresponsible and should never have sex.

3. Women who use birth control are also irresponsible, because they know that birth control is not 100% foolproof and should never have sex.

4. Being pro-life has absolutely nothing to do with religion. It’s just a coincidence that my God is opposed to abortion, and if yours isn’t, then you’re worshiping the wrong God.

5. No matter how many examples you find of God-sanctioned infanticide in the Bible, it in no way indicates that God is OK with baby-killing. Baby-killing on his orders is OK because reasons. If he says it’s OK, it’s OK, but he definitely didn’t say abortion was OK except in the parts where he did.

6. All the aborted babies could have gone on to do great things. None of the aborted babies would have been “welfare queens” or criminals or deranged genocidal dictators.

7. People are lined up to adopt babies. If you give your baby up for adoption, it will find a loving family. It definitely, positively, won’t join the half million kids already available for adoption or be one of the 23,000 who age out of the system without being adopted every year. Oh, and it will be happy with its family, who will never turn out to be abusive in any way.

8. It is never OK to abort a baby that resulted from consensual sex. Conception circumstances are paramount, which is why it’s OK to abort rape babies. Consensual sex babies are alive at the moment of conception because of consent. Rape babies are alive at the moment of conception, too, but it’s OK to abort them because they aren’t the consequences of the choice of an irresponsible woman. Don’t ask me to explain this, I’ve tried and tried and still don’t get it.

9. If abortions are illegal, nobody will need them. Only 1% of all abortions are for high-risk situations like the life of the mother or significant defects in the fetus, and letting women die and having babies who are severely handicapped (even if they’re guaranteed to die after birth) is a risk that people who aren’t dealing with these situations are willing to accept.

10. Even if you are too poor to support a child, too young to be a parent, too ill mentally or physically to be a parent, addicted to drugs and unemployed and homeless, married to an abusive spouse or a pedophile, the baby is a gift from God and all your problems will go away as long as you don’t get an abortion.

My Brain Diary – Part 12

My Brain Diary – Part 12

I’m trying to think of ways to keep my expectations reasonable and realistic. This is really difficult, because I really thought that the problems I had from the tumor would clear up so much more completely after it was gone. What this means is that when I notice an improvement but still have problems, I get frustrated and depressed thinking of the remaining shortcoming and forget about being happy for what I’ve recovered.

Well I was going through photos and happened to find one from a year before my surgery when I had a grand idea that I was going to use Photoshop to try out potential hairstyles. It was pretty bizarre, because I don’t have too many photos of myself, and the changes I saw in the mirror were gradual enough not to notice. I was shocked at the asymmetry, and no matter how hard I tried to make the muscles in the right side of my face mimic the ones on the left, I couldn’t – and I had no idea why this was happening. I don’t know how long I hadn’t noticed it, either. But anyway, the heck with vanity, here’s a side by side comparison of the photo from November 2011 on the left, and 2/26/2014 on the right.

droopface

My surgery was October 12, 2012. 16 months later, you can see that I’m still somewhat lopsided. If a simple muscle function doesn’t return completely, then it’s reasonable to assume that the cognitive deficits are going to fall short of what they used to be as well. I can look at my face and think, “Oh, well, I guess it’s stuck like that.” I think I need to try to change my attitude towards the other things to something more along those lines. I got used to the different face. Even though it doesn’t impact me as much as the different speech and the different memory and the different visual perception, I still need to get used to those being different too. I need to accept them even though I remember what it was like when they were better.

I hate talking on the phone. On the phone, I can’t make gestures to try to get across the word that I’ve lost, and I can’t look it up in Google without breaking up the conversation. I just sound stupid. This is frustrating because I’m just as intelligent as I was before, but you wouldn’t know it if you were talking to me on the phone. In person it’s only slightly better because, you know, I’m forgetting words and playing Charades to try to get you to understand what I mean. This is why those of you who don’t email or Skype me haven’t heard from me in a while. It’s frustrating and embarrassing, and that’s harder to get over than a lopsided face.

The memory and visual perception are easier to deal with, and are also something that the neuropsych will be able to help me with over time. Still frustrating, but easier to use the face analogy to tolerate.

Just complaining. Only a few more weeks before the testing and evaluation. I can show people my droopy face as proof that I’m not stupid, just slightly brain damaged. But not on the phone.

ADHD and Pharmaceutical Fearmongering.

ADHD and Pharmaceutical Fearmongering.

It’s never difficult to find articles about how ADHD is some trumped-up condition made up to excuse poor behavior and/or line the pockets of the medical industry. Whether the writer assumes one or both of these, it’s necessarily bound together with denial, ignorance, and hyperbolic claims. Sometimes all you can do is get angry, but other times the writer gives you a chance to deconstruct his points. The Price of ADHD Business is that second kind.

He opens with this blockbuster:

Over 12 million children and young adults consume ADHD stimulant and psychiatric medications in the United States. Pharmaceutical corporations generated near 9 billion dollars in 2012 for ADHD stimulant drug sales, representing 5x the 1.7 billion in sales ten years ago.

Shocking, isn’t it? Except that in the US, the Pharmaceutical Industry makes about $345 billion a year. That means that psychiatric medications make up a whopping 2.6% of the bottom line. Hardly one of their biggest players, compared to drugs for cholesterol, pain management, and cancer treatment, which are much better performers when it comes to percentage of business. Also, notice the subtle slide from “ADHD stimulant and psychiatric medications” to “ADHD stimulant drug sales,” because this will be important.

More alarming, this rate of consumption represents 3x the world’s children combined, according to data collected by Scientific American. The business model of behaviorally assessing and prematurely medicating young school age children with powerful stimulant and psychoactive drug therapy for over 40 years is now under fire. The Government Accountability Office (GAO) Child Foster Care Drug Audit Report uncovered dangerous and unethical prescribing practices. Widespread abuses of overmedicating young foster care children with ADHD stimulant as well as psychiatric medications prior to ruling out nutritional, physiological, and environmental risk factors were uncovered by the largest child foster care prescription drug audit in American history.

Of course, being a first-world country, it’s more likely that we have 3x the children being treated for, say, cancer or juvenile diabetes, or any number of other childhood diseases, so there’s something of a leap from claiming that 3x the children being treated means that something is being treated too much – or “prematurely.” I notice also that the source of the alarmist rhetoric comes from a study of children in foster care. Well, this is a problem with foster care, not with all children. Foster care children are more likely to have disabilities, both physical and mental, meaning they’re more likely to actually need treatment. They’re also covered by state medical programs that make it pretty easy to get treatment that a self-payer parent might not be able to obtain. There’s more, but if a mere scratch on the surface can reveal that we’re comparing apples to oranges, there’s not much need to go even deeper.

In today’s America parents, educators, and prominent healthcare professionals challenge the 40-year ADHD business model, as the ADHD diagnosis rate surpasses epidemic status in 2014. The symptoms of ADHD are real and in many cases can be debilitating to children as well as adults. Especially in the young child population, the ADHD business model of assessment and treatment requires immediate reform. Children have a right to receive comprehensive bio-assessments as well as behavioral assessments to determine cause of their symptoms prior to powerful stimulant and psychoactive drug therapy.

Yes, we have a serious epidemic of about 5-8% of the population. That’s massive. Not. Notice how he snuck in the disclaimer (like, some of my best friends have ADHD!!!) but still calls the diagnosis and treatment of ADHD a “Business Model.” I sense a broken irony meter. Also, have you ever taken any of these medications? The stimulants are among the least powerful ones out there, with the most immediate effect (no two-month waiting period) and little to no withdrawal problems. Lumping them in with all psychoactive medications is disingenuous, especially for someone banking on his rep as a Pharmacist.

The Diagnostic and Statistical Manual for Mental disorders (DSM) lists ADHD as a mental disorder. The DSM diagnosing criteria, created by psychiatrists, involves a subjective behavioral assessment process which forces children primarily into premature drug therapy. Although seven out of ten children may exhibit an initial positive behavioral response to stimulant drug therapy for focus and attention, the long term side effects are now known.

Yes, they are, and they’re not terribly scary. Children who start using methylphenidate or dextroamphetamine medications may grow up to be as much as one centimeter shorter than their peers. Of course, they’ll also grow up happier and more successful and less likely to abuse drugs than their non-medicated ADHD peers, but that runs counter to the narrative here.

The Johns Hopkins Child Center Study results of 2013 prove that stimulant drug therapy should not be the primary intervention in young children. This study followed four year old preschool children who were diagnosed by their physicians for ADHD and medicated with stimulant drug therapy for a six year period. When the ADHD assessments were reviewed at age ten, over ninety percent of the children were worse off in their condition. Long term side effects of ADHD stimulants may include anxiety, minor depression, as well as aggressive behavior. Additionally, the Hopkins study determined that ADHD causes an economic burden to the US exceeding 45 billion dollars, annually.

To the first sentence I say, “Well, duh.” The primary intervention should be behavioral, with medications added to supplement as needed. This is not news, and it does not run counter to what any Medical Association is recommending, even the American Psychiatric Association, which says “Behavioral therapy and medication can improve the symptoms ofADHD. Studies have found that a combination of behavioral therapy and medication works best for most patients.” Add to this yet another lie, because what the Johns Hopkins study revealed was (prepare to be shocked) that ADHD doesn’t go away, and medications don’t cure it, just relieve the symptoms while they are in effect. And the economic burden he’s talking about? That relates to the consequences of untreated ADHD – people in jail, people who are substance abusers, people who are unable to work, people who have other health issues that are related to ADHD.

Many parents are not aware that a diagnosis of ADHD for their child is a diagnosis for mental disease in accordance to the DSM. Once a young child is placed on ADHD stimulants including Adderall or Ritalin prior to ruling out causative risk factors, there is an increased health risk. Additional medications for the treatment of long term side effects may be required due to the development of other behavioral symptoms.

Actually, parents know this, because lots of the evaluations are related to getting assessments for school. And it’s not the stimulants that increase the risk of further diagnoses and additional medications as much as the fact that ADHD is usually not alone, and the co-morbid conditions are discovered because the children are being observed and treated by doctors. The medications don’t produce these problems.

For example, the GAO drug audit uncovered a 2,200 percent increase in drug expenditures for atypical antipsychotic medication reimbursement to the state of Michigan during an eight year period from 2000 to 2008. Children in foster care, as the report states, were abusively prescribed powerful antipsychotic medications including Abilify, Zyprexa, Seroquel, Geodon and Risperdal. The Michigan Medicaid system was billed an increase of 40 million dollars during an eight year period just for this one class of medications in foster care children. US Senator Thomas Carper, requestor of the GAO drug audit and chairman of the Homeland Security & Government Affairs Committee, stated “I was almost despondent to believe that the kids under the age of one, babies under age one, were receiving this kind of medication”.

Remember what I said about the creep from the “all psychiatric medications” to “ADHD stimulant medications”? Here we go with another false equivalency. Antipsychotic medications are the last resort, used for treating not just ADHD, but ADHD with serious comorbids that would make the children a danger to themselves or others. Also, remember that this is the foster children, not all children with ADHD as a whole. AND keep in mind that several of these antipsychotics are essential for the treatment of schizophrenia and seizure disorders, which are probably too legitimate to mention in the context of this article. So the figures on antipsychotics for foster children in one state is cherry-picked data that in no way reflects that there is an epidemic of children with ADHD receiving inappropriate medications.

Should ADHD be labeled a mental disease especially in young children who have not been given the right to find the cause of their symptoms prior to stimulant drug therapy? Or, should ADHD be classified as a symptom of condition with underlying causative nutritional, physiological, and environmental risk factors?

Um, yeah, it should. Get inside our heads, mister – it’s definitely a mental disease. It’s certainly not something we can choose or turn off at will. And the cause of their symptoms is mental – the other “causative” factors have been thoroughly debunked as “causes” in study after study. So this is a giant flaming strawman.

The German magazine, Der Spiegel, quoted a prominent American ADHD psychiatrist in their February 2, 2012 issue. Dr. Leon Eisenberg, who coined the term ADHD over forty years ago, stated “ADHD is a prime example of a fictitious disease.” At age 87, this was Dr. Eisenberg’s last interview prior to his death. During the last forty years, he was involved in pharmaceutical trials, research, teaching, as well as the development of social policy pertaining to child psychiatry. He was a recipient of the Ruane Prize for Child and Adolescent Psychiatry Research. Currently, over fifty percent of psychiatrists on the DSM panel responsible for ADHD diagnosing and treatment protocols have direct business ties to drug manufacturing corporations.

All that education, and Mr. Granett doesn’t know how to check snopes. How sad. As to that second claim, well, a link would be nice, but I’m not surprised it’s absent, since the actual ties would be openly disclosed and not as incriminating as the author would like them to be.

Dr. Thomas Insel, Director of National Institute of Mental Health, stated on April 29, 2013 “patients with behavioral conditions deserve better… the current assessment process lacks validity.” He supports research that better treats and may even prevent the development of behavioral symptoms in children.”

Again with a diversionary link. Psych Central has some validity, but “The Verge”? Really? Why not link to the NIH’s Research Domain Criteria which explains that what this means is that the NIH wants to have research focused on multidimensional approaches to research, and research that is targeted towards evaluation of symptoms and behaviors rather than whole conditions, because we now know that there’s a lot of crossover and and a narrower approach will produce more successful and useful research. Oh, but that would not support the POV of the author. That’s OK, now you can see what Insel was really talking about. You’re welcome.

ADHD symptoms can be reversed through a process of differential diagnosing. The elimination of nutritional, physiological and environmental risk factors prior to premature drug therapy is the new ADHD Business Model for helping children and adults reclaim their behavioral and mental health. The Action Plan for Childhood Behavioral Conditions discussed in the book Over Medicating Our Youth as well as the upcoming 2nd edition T he American Epidemic: Solutions for Over Medicating Our Youth provides critical bio-assessment information to find the cause of ADHD symptoms. This action plan provides an informational template to unite parents, teachers as well as all healthcare professionals for the purpose of helping children win the battle against behavioral challenges.

Many assessments help determine the cause of ADHD symptoms. Learn how bio-assessments for reactive hypoglycemia, diabetes, the brain-gut connection, cervical spinal alignment, exercise, whole food nutrition, brainwave optimization, and nutritional enzyme supplementation may reverse ADHD symptoms.

And now, ladies and gentlemen, we begin our final descent into woo. ADHD symptoms cannot be reversed by any of these things, and. . .OMG, this whole thing is an advertisement for. . .wait for it. . .a book co-authored by Frank J. Granett! It’s so good that he had to cite himself! And real medical terms weren’t sufficient, so we have to make up some that sound really sciency, like “differential diagnosing,” and “reclaim their behavioral and mental health,” and “bio-assesment” so we can sell ineffective treatments to gullible patients. Blood sugar problems can be diagnosed and treated without ADHD medications. The “brain-gut connection” has no supportive research except in patients with full-blown Celiac Disease. Cervical Spinal Alignment is Chiropractic’s uglier younger brother, even less useful than regular Chiropractic for treating anything, much less neurological conditions. “Brainwave Optimization,” don’t even get me started. As for the rest, we already touched on how none of these things are causative, so they are not going to be curative.

But this is what it usually comes down to, isn’t it? The voices that protest the loudest that ADHD is a fake disease created to make money by the pharmaceutical industries tend to end up thinking that it’s real enough to be treated by whatever they themselves are selling. If only there were an all-natural cure for hypocrisy. . .