This blog was started as the primary means of reporting information on a disease that we chose to "support" through grid-computation. The grid we joined in order to support research about schizophrenia was the GPUgrid (go to their website). Since January 25, 2012, we have contributed 3,219 total credits to the grid! We have also had great success with our blog, with 828 page views as of 7:50 pm on April 26, 2012.

This will be our last blog post before the three of us become college graduates (hooray!). We want to extend a big thanks to everyone who has helped make our blogging and grid-computing experiences fun and successful adventures!

--Rachel, Caitlyn, Ryan

Here are the responses to questions posted by our professor regarding the article in the last post.

--Rachel, Caitlyn, Ryan

1.      The introduction states that the heritability of Schizophrenia is 85-90%. What type of trait is this? Does VE or VG contribute more to the variance in this phenotype? Draw and/or describe the linear regression scatterplot that would indicate this level of narrow-sense heritability.

a.       “Genetic factors and gene-environment interactions together contribute over 80% of the liability for developing schizophrenia and a number of chromosomal regions and genes have been “linked” to the risk for developing the disease.”—from original source that stated 85-90% heritability, http://www.schres-journal.com/article/S0920-9964(08)00168-0/abstract. Thus, this is a quantitative trait. VE (environmental variation) and VG (genetic variation=VA+VD) are both factors that contribute to the development of schizophrenia, but I think that VG plays a larger role in the phenotypic variation because it incorporates both additive genetic variation (genes from parents) and the dominance genetic variation (interactions between genes). Environment can cause the disease to appear, but variation is due to genetics (I think). The linear regression would contain a line with a slope of 0.85-0.9 (85-90% genetic/heritable).

2.      The paper asserts that Schizophrenia is at the low, negative end of the “fitness indicator” spectrum. How does this concept relate to the “good-genes hypothesis” described in class and your book?

a.       The good genes hypothesis is analogous to the sexy son hypothesis. These hypotheses state that females prefer certain traits in males and thus mate with those males. This passes on the preference and the trait to future generations, ensuring a preferential trait in the offspring, and thus increasing the offspring’s fitness. The fitness indicator, similarly, asserts that animals have traits “that reveal to potential mates an individual’s underlying genetic quality” (article). In schizophrenia’s case, these traits are negative and thus indicate poor fitness, decreasing the individual’s chances of mating.

3.      The author claims that mutation-selection balance maintains Schizophrenia in the population. Use your text to define this term. Schizotypy is said to be maintained by sexual selection and kin selection. Explain how each of these two mechanisms maintains this trait.

a.       Mutation-selection balance, according to our text, “describes an equilibrium in the frequency of an allele that occurs because new copies of the allele are created by mutation at exactly the same rat that old copies of the allele are eliminated by natural selection.” Sexual selection maintains schizotypy because it initially increases “‘verbal courtship’ traits including creativity, emotional sensitivity, and expressiveness” (article). Kin selection increases schizotypy because individuals with high schizotypy have a higher fitness than non-schizotypal individuals. The offspring are thus more likely to be highly schizotypal and kin—no matter the level of schizotypy—will ensure their maturation to a reproductive age. This will allow the highly schizotypal individuals to continue reproducing at a higher rate than the low schizotypy individuals and increase indirect fitness. Furthermore, a highly schizotypal individual is more likely to mate with a non-schizotypy or high-schizotypy individual.

4.      The author uses a mathematical model to show that the SSM model, plus under-reporting of male fitness, explains how the Schizophrenia genes stay in the population. Do you buy this hypothesis and his empirical data, and why or why not?

a.       No—for several reasons. First of all, he admits there are many potential problems with the model. Secondly, there were no empirical studies conducted by the author—he simply created a mathematical model. Thirdly, the author does not define “fitness” or how it is measured. Fourthly, he states that much research is only partially consistent with the SSM. Lastly, he asserts that the SSM model will only be effective if all of his postulates are met and upheld.

Bonus: Find the typo on the first page of this article
"Schzotypy” is printed instead of “schizotypy” in the seventh line of the abstract’s background section.

Paper on Schizophrenia and Sexual Selection

Here is a link to a paper discussing the connection between schizophrenia and what we have learned so far in our Evolution class this semester!

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012205/?tool=pubmed

Here are the responses from Caitlyn and I regarding our interview with Dr. Saz Madison--Enjoy!
      -Ryan and Caitlyn

1) Describe your feelings about or response to the interview.

Ryan: The amount of knowledge and insight Dr. Madison had on our questions was absolutely astounding. He brought up things I never even knew about or even thought about (like Schizophrenia being induced in Chimpanzees). It was a great learning experience and I found myself wanting to hear more. I liked his response to my question about the evolution of schizophrenia, in particular.

Caitlyn: After the interview, I not only felt like I had a much better understanding of schizophrenia as a whole, but I also felt more optimistic about finding a way to not only treat schizophrenia, but also finding a way to prevent it from occurring.

2) What changes occurred for you as a result from the interview?

Ryan: The main change that I underwent was the idea to be more open about causes of certain diseases and reasons for them sprouting up or being so harmful. I always have a very biological approach—“it’s gotta be genetic!” is a frequent saying of mine. Dr. Madison was able to open my eyes and show me there are other possibilities and the environment is a strong force in diseases like Schizophrenia. Openness is always an important attribute to have as a scientist, I feel.

Caitlyn: The biggest change was that I got a different perspective about how our grid project could be helpful as well as hurtful to furthering the research for schizophrenia. Going into the interview I had a very positive, one-sided view of the grid project and how helpful it could be, but after talking to Dr. Madison, I started to understand that it may not take into consideration all of the variables that go into a disease like schizophrenia.

3) Did anything about it disturb you?

Ryan: Nothing about it disturbed me, honestly. It was a pleasant interview and I learned more in 40 minutes about Schizophrenia than I could learn in an entire semester, I feel.

Caitlyn: There was nothing in the interview that bothered me, it actually had the complete opposite effect.  I came in thinking that there wasn't a whole lot that could be done for the disease, and I left believing that one day the brain will be able to get rid of the disease on its own, however far fetched that idea may be. 

4) Describe the connections you found between the interview and your class work/research.

Ryan: I purposefully asked a question about the evolution of Schizophrenia, just to see what his attitude on it was. It was clear he wasn’t convinced the disease is evolving or can evolve-it is possible he says, but he feels the brain is evolving to be a better machine over time. This is a huge connection, obviously, because we are in this class. Another connection is the causes of schizophrenia. In genetics, my research, and other biology classes, the cause of diseases is always discussed as either genetic or environmental. Dr. Madison was able to further show the importance of looking at bother of these factors when looking at disease causation and that is something I will take home. It’s not always a genetic cause, as we learned in Genetics class with obesity, for example, and I kind of lost sight of that. Connections were abound.

Caitlyn: What I learned in the interview had a lot of connections with the research that we have done.  I've found that no two cases of schizophrenia are the same, and Dr. Madison reiterated that by saying that they all must be treated in different ways, through behavior treatments in coordination with antipsychotics. Also the idea that even though schizophrenia is known to have some kind of genetic component, there must be some kind of traumatic event to cause the disease to manifest in anyone.  Just because you have the genetic component does not always mean that you are going to get the disease.

Below are my responses to some questions about the interview we conducted with Dr. Saz Madison.

Enjoy!

-Rachel

Describe your feelings about/in response to the interview.

I hold Dr. Madison in very high esteem and the interview we conducted with him only raised my regard for him. I felt that the professor’s responses to our questions—which were by no means simple to answer—were educated, realistic and well-said. Dr. Madison made the interview very efficient and enlightening while still maintaining a fun atmosphere!

What changes occurred for you as a result of the interview?

As my knowledge of psychological (specifically, behavioral) phenomena grows, so does my preference for these methods of research and development. Dr. Madison reinforced the idea that humans are bio-psycho-social beings and our behaviors are largely enforced by our environment (just as evolution is).

Did anything about the interview disturb or bother you?

Nothing about the interview disturbed or bothered me. It was interesting to note, however, the empirical data suggesting that our brains really aren’t that much different from other organism’s brains when approached in a percentage-based way. (For example, the human brain stem takes up the same percent of the human brain as a lizard brain stem takes up in the lizard brain.)

Describe the connections you found between the interview and your research and classwork.

Dr. Madison inferred in his interview that the phenotypic expression of schizophrenia has a widely varying range due to its “umbrella-like” nature. This corresponds to the multiple “types” of schizophrenia I discovered while researching the topic. Furthermore, the genetic and environmental components expanded upon by the professor also correlate with my research, which indicated that schizophrenia researchers are unsure of the factors that definitely cause schizophrenia.

Below is our group’s interview with Dr. Saz Madison. Enjoy!

What are the physical causes of schizophrenia? Do you think schizophrenia has a definite genetic component, as there is some debate?

There is some debate and some debate for good reasons. So of course when we start talking about genetic/physiological components of psychological disorders in our field one thing that we pay the most attention to is pedigree studies. What happens if you have a disorder occur in a family and then all of a sudden you notice that the frequency with which the disorder occurs multiplies within families? We find a much higher rate within a family than we do in the general population. Well, it’s kind of hard to argue against some biological component then! Of course, there are alternative explanations, which is why there is still debate. It could have something to do with environmental factors. So if you consider the fact that many theories suggest we are born with a biological predisposition, then not everyone within a family with a biological predisposition will develop the disorder. Perhaps they encounter environmental stimuli later in life that trigger the onset of the disorder. But for many people it doesn’t develop at all; they could go their entire lives and never experience symptomology. So I think this debate will go on for quite awhile… even if we identify a gene that it occurs on, it’s still likely not to be definitive. This is because we know that you can find where it occurs in a family but its not going to occur in every family. So trying to decide which one is more important [whether it is genetic or not] will be important for treatment purposes if you want to do preventative types of work, but otherwise it doesn’t really have a significant impact on treatment (which, of course, is my perspective). This is what I do- I’m a clinician! I think, “What do we do once it manifests?”

What are the ABA (Applied Behavior Analysis) treatments for schizophrenia, and how effective are they? Are there pharmacological treatments that are equally effective?

Let’s start with the pharmacological approaches. Most of these approaches available to us—like the antipsychotic medications—are fantastic (from a certain perspective). Why? Because we are most effective at treating the positive symptoms of schizophrenia with antipsychotics. The positive symptoms of schizophrenia are those symptoms that you develop as a result of the onset of the disorder. Positive refers to things which you administer, so positive punishment (for example) would be administering a punishment. So then negative would be removing something. Well the positive and negative symptoms of schizophrenia are similar… Positive symptoms are those about which the disorder says, “Here, this is a gift for you! You will now have delusions and hallucinations!” Negative symptoms are things we lose as a result of the onset of the disorder. For example, I would lose tonality in my speech, I would no longer have emotional variability—we see flat affects in speech and less social reciprocity. Antipsychotics are great at treating the positive symptoms. They’re pretty darn good, in fact! But those negative symptoms are the ones patients don’t do so well with. That’s when we see behavioral interventions. Things like ABA come into play—usually very specific things like social skills training-oriented things. Usually we see someone with schizophrenia who is so poor at interacting socially that they cannot function well in daily life. We sit down and we develop a behavioral intervention—a behavioral training program—that’s based on increasing their social functionality (for example), or increasing the likelihood that they’ll engage in activities of daily living. So just like most of the talk-based therapies, ABA would really focus on building those skills and behaviors that are observable, measurable, and repeatable. You would start out with asking yourself questions such as, “What are the important activities of daily living for this individual? Are they living alone or are they living in a treatment setting? Are they capable of getting, establishing and maintaining gainful employment?” All of our ABA approaches would be focused on those questions and increasing the likelihood of doing those things.

So would you say you need both types of treatments (pharmacological and behavioral) to make progress?

Absolutely. In fact, I have this mantra when I teach about schizophrenia in a few of my classes: everything that is psychological is also biological. This makes sense, seeing as the parent fields of psychology are biology and philosophy. It makes you think about the age old question, “Nature or nurture?” …Sure, like yes or no? Black or white? (What about all the fantastic primary colors?) Is it all nature—biological? Or, is it all nurture—psychogenic? The likelihood that it’s one or the other is incredibly low. So our interventions should also be targeted at both the biological and psychological components. Another mantra that I teach is that we are bio-psycho-social beings. It all relates! What makes us rich, sophisticated human beings is that we are biological, psychological beings who function in social settings.

What are your opinions on grid-computing, specifically in regards to neural disorders?

I think that any opportunity to further the research on schizophrenia is an excellent idea! This is a new and different component to research that’s humanitarian. There are a couple components that I find interesting to this. Taking this particular approach—trying to understand the etiology and then develop an intervention to neurological and psychological disorders like schizophrenia—is a great idea. Trying to address all the different components of this disorder—actually, this set of disorders (disorders when occurring together constitute schizophrenia)—will make it difficult to develop a singular treatment. Does this decrease the value of a grid-computing project like this? No, I do not believe that it does! I think that there is certainly value in it. However, when I think about all the aspects of this class of disorders and I ask myself if I had to do a factorial approach and ask, “What might these symptoms be attributable?” over and over again, its likely that I would likely make a list of symptoms and start to bifurcate the symptoms list into things that, for instance, might be dopaminergically oriented. Then it’s likely that there are symptoms that are purely psychological in nature. This purely psychological list may be impacted by the purely physiological symptoms, though. Eventually, I hope we can intervene at the neurological level, at the neurotransmitter level, right at the synapse with some agonist or antagonist molecule that will address all the symptoms of schizophrenia. I’d be thrilled! But do I anticipate that? I do not. I think that one major problem that we face is that research in the physiological, genetic, physical realms and research in the psychogenic realms—even if on the same subject—occur in vacuums, almost. While we all recognize that we are bio-psycho-social beings we still research our disorders separately and talk about them separately and develop interventions separately! If we deal with one realm, we deal with the other realm too! Grid-computing is a fantastic project—does it have utility?—yes. Likely very good things come out of it—yes. Would it help to incorporate research from all over?—yes. But this seems very unlikely due to competition between pharmaceutical companies, etc. We should recognize that we are bio-psycho-social beings and could integrate research from all these perspectives to come up with useful, novel, diverse responses and solutions! Responses will be stunted without all perspectives.

Can you see any evolutionary advancement of schizophrenia? For example, has the overall severity of the disease increased over time? Does the overall increase in brain size of humans allows for more errors in development/physiology, such as diseases like schizophrenia?

Really?! That’s a long question! Here’s what I think, and I could be wrong, as I’m not a neuroscientist, and it’s just an opinion. What makes us human is the amazing cortex we have—this wonderful expanse of association areas. In similar animals you notice differences in development and growth of the brain, which separates us. Where is the development and growth taking place? The cortex! Yes, it is definitely likely all these disorders are changing over time. Does increasing cortex size increase risk of developing disorders? I don’t think that’s the case—it’s very simplistic to me. It’s possible, but I’m not convinced. Before we even called schizophrenia, schizophrenia, going back to the Middle Ages, Demonology was the main treatment of the diseases. We used a priest to treat our symptoms. That was 500-600 years ago. This shows our entire psychological field is in its infancy—we’re talking 20^th century when we started identifying schizophrenia as a disease. I am, personally, still not convinced it’s gotten worse. Changed? Yes. Worse? I don’t know. We’re continually developing neurologically, at least in our cortex; hopefully that means we are able to compute ourselves better and think about this better. I really do believe the more our brains develop the more effectively we will function as a whole, and not allow for greater opportunity for disease. Will these disorders spontaneously go away? I don’t know. I’m a Romanticist!

Do you know of any other species that can get schizophrenia or other neural disorders?

Why do we do research on animals? Because a lot of those underlying processes—a majority of them—work just like they work in our brains. So, I know for certain, that we can induce schizophrenia-like symptoms in chimpanzees and other species similar to humans. I believe if we can induce those, can they occur spontaneously? Yes. Because of the similar processes, I would have an expectation that those dysfunctions (neurological disorders) can occur. The psychogenic symptoms may manifest differently since humans function a bit differently psychologically than other animals. If we work from a standpoint of biological predisposition in related species resulting in a manifestation of schizophrenia, what is particular to us that chimpanzees may not have/experience? There are things we do that can predispose us to stress, which may be an underlying cause of manifestation. Chimpanzees don’t have the iPhone 4s! Other species have very similar biological or genetic components, but don’t experience this in the same frequency as humans. They have stress, sure, but is it the same level we experience? Probably not. We create blatantly challenging environments that cause stress. This is all just a matter of opinion, but I believe, to answer your question in one phrase, yes, it can occur.

Thanks for reading!

-Rachel and Ryan

Since our grid-computing project is on schizophrenia, our group determined a very reliable and excellent source to interview would be Dr. Saz Madison, Associate Professor of Psychology at Rockhurst University, and a clinical psychologist. His focus, in class and in research, is on abnormal psychology and psychotherapy, making him a credible candidate for an interview. You can view Dr. Madison's Rockhurst University webpage here. We hope you enjoy our next blog post, which will feature questions posed by Caitlyn, Ryan, and Rachel, and Dr. Madison’s enlightening and intriguing responses!

-Ryan