Schizophrenia Research Article & Questions

This is a link to the research article used in the discussion questions below: http://schizophreniabulletin.oxfordjournals.org/content/34/4/722.full

Questions and Answers:

1. Is schizophrenia a qualitative or quantitative trait?  What is the estimated heritability of this phenotype? (You may have to use other sources to determine this).               Schizophrenia is a quantitative trait meaning that there is a range of differences that exist for the disease among different individuals. Schizophrenia is polygenic or coded for by more than one gene and there is a genetic and environmental factor for the disease. This is why there can sometimes be incomplete penetrance of the disease and why some people have worse schizophrenia than others. One percent of people worldwide are affected by schizophrenia. The heritability of this disorder is around 83% for genetic factors and 17% due to environmental factors found in a research article on Pub Med (http://www.ncbi.nlm.nih.gov/pubmed/9435762). Lastly, men have higher lifetime prevalence than women do for the disorder, which was found in the same article listed in the previous sentence.

2. For the next few questions, I will pose some of the same ones asked and addressed in the paper.  Please provide a summary to answer each:
1. What kind of inheritance explains the observed patterns seen in schizophrenia?   
   There is not one particular gene that is considered to cause schizophrenia itself, but instead many different aspects within genes that contribute to it. Certain neurodevelopmental errors or normal single nucleotide polymorphisms (SNPs), copy number variants (CNVs), or insertions/deletions all aid in morphing certain genes. When expressed separately, many of these changes are not considered bad, some are even beneficial. However, when many of these changed genes are expressed together, that is what greatly increases the cause of disease such as schizophrenia.
               Due to these genes being considered “normal” when expressed separately, they tend to be “below the radar” of selection and are not able to be selected against. It is thought that in certain circumstances or environments, changes in genes like this can be utilized in beneficial ways, adding another reason to why they are not selected against.
2. Why do schizophrenia risk genes persist in evolution?                             Schizophrenia is a quantitative trait, meaning it is polygenic. Each gene by itself has a small effect on the individual, but with the wrong combination of the multiple genes, schizophrenia can manifest. The genes could each have variations within their normal range. These genes still persist in evolution because some of them are either neutral or advantageous to the population. In other words, there is a selection for the advantageous alleles, and there is not selection against the neutral alleles. Chance, assortive mating, and other mechanisms can cause the wrong combination of genes that result in schizophrenia.
3. What are the possible heterozygote advantages associated with schizophrenia?  Do you agree?                                                                                                              Balancing selection could be a possible advantage meaning that the alleles sometimes increase fitness. The idea of increased fitness for schizophrenia is not plausible because in most cultures today it is seen as a dysfunction. The heterozygote advantage tends to favor environmental adaptations (no heritability) or high-frequency alleles (which have been found through psychiatric genetics). The susceptible alleles can give hidden benefits to patients with schizophrenia or to their first-degree relatives that might explain its persistent existence. These benefits include increased intelligence or creativity in relatives and shamanism in patients with schizophrenia. Shamanism is the most ancient form of healing. It involves a change of consciousness to request healing and advice from the spiritual world. Some say that behavioral traits such as paranoia could have been beneficial in environments that were under attack by nonhuman predators, but overall the heterozygote advantage is not very beneficial. Today, schizophrenia is associated with decreased fertility, reduced survival, and reduced attractiveness for mating, lower marriage rates and even reduced fertility once married.

3. If heterosis is acting on the schizophrenia alleles, what might you expect will happen to these alleles over the long term? (Think fitness tables...)                                                    Over the long term if heterosis were to occur, the highest frequency would be the heterozygote, Aa for example. There would be equilibrium of alleles and neither fixation or extinction would occur for either allele. Variation would be maintained at the locus.

4. This paper, and much of evolutionary psychology, is panselectionist or ultradarwinist.  What does that mean?  What other mechanisms of evolution might be at play here? 
   Panselectionism (or ultradarwinism) is the idea that all changes in genes are either beneficial or detrimental to an organism, meaning that there are no neutral changes. Therefore, every trait with a genetic origin must have some adaptive value and has evolved solely through natural selection. This thinking tends to rule out other evolutionary processes such as genetic drift, which is simply the chance changes in the genetic structure of a population, and gene flow, which is the exchange of alleles between or among conspecific populations. In all likelihood, gene flow probably played a major role in this disorder because it is prevalent in many areas of the world. A mechanism that also plays a role is mutation. When coupled with natural selection, mutation can be a potent force of evolution, and may play a role in schizophrenia. Because it is believed that there is an environmental component of the onset of schizophrenia, it can be assumed that there is some sort of epigenetic component of this disorder as well.