Evolution’s Relation to Schizophrenia

Schizophrenia is not something new to humanity, but rather a mental illness that has affected individuals throughout history. It is characterized by a loss of reality through severely distorted beliefs, perceptions, and thought processes that typically develop in early adulthood.  Schizophrenia is found in all cultures across the world and occurs in about 1% of the population, suggesting its heritability, as its occurrence is much greater than mutation can explain. The disorder undoubtedly causes great disadvantage to individuals who exhibit its symptoms, from reduced social aptitude to anxiety-driven behavior. Not only does it affect behavior, but also reproductive ability, which is reduced to 50% in male Schizophrenic individuals. The puzzling question about schizophrenia is then: how has it persisted throughout time if it has had such disadvantageous effects on those affected?

Evolutionary theories have proposed several potent explanations of how genes associated with schizophrenic individuals have remained in the human gene pool. Deleterious alleles have been shown to survive as a result of heterozygote advantage, genetic polymorphism, and pleitropy (when deleterious genes are associated with other advantageous genes). Studies have shown that these three evolutionary concepts do indeed pose strong explanations for the persistence of schizophrenia.

As in the case of Sickle-Cell Anemia, where heterozygous genotyped individuals experienced increased resistance to malaria causing their reproductive advantage, schizophrenia could exhibit the same effect. Studies have revealed that schizophrenic females experience increased fecundity. Their male offspring had a higher rate of survival in their first year of life compared to male offspring of non-schizophrenic females. Further, female offspring of schizophrenic mothers had a higher rate of survival for the first fifteen years of life, suggesting that heterozygosity in offspring causes an advantage over homozygosity in offspring. It has also been discovered that immediate relatives of schizophrenic individuals have lower rates of viral infections, lower rates of accidents, and increased fertility (Brune 2003). This again suggests that genes associated with schizophrenia cause a greater survival and reproductive advantage, directly tying in with the evolutionary theory of natural selection. 

Apart from heterozygote advantage, schizophrenia may also be a result of the evolution of sociability. Although schizophrenic behavior is not typically seen as particularly pro-social or progressive, it could have been beneficial to our early ancestors’ development. For example, the over-protective nature of schizophrenic mothers would have certainly caused a greater likelihood of survival of her offspring. Additionally, in evolutionary scenarios where establishing territoriality would be more important than pro-social behavior, individuals with Schizophrenic alleles would have an advantage over more socially adapt individuals (Brune 2003). More recently, studies have shown that relatives of schizophrenic individuals exhibit higher levels of creativity, a characteristic key to survival and progression. This would certainly cause a greater chance that schizophrenic alleles would be passed on.

The fact that schizophrenia is not particularly beneficial to individuals yet it has persisted through time suggests that evolutionary principles could very well be at work. Heterozygote advantage has been found in several other cases where deleterious alleles remain in a gene pool and evidence strongly suggests that this is the case for schizophrenia-coding genes. Furthermore, behavior associated with schizophrenia seems to have been beneficial in certain situations where pro-social behavior was not favorable. Lastly, genes associated with schizophrenia have been linked to survival and reproductive advantage time and again, supporting gene polymorphism and pleitropy. Evidently, evolutionary principles provide a convincing explanation for the presence of schizophrenia in populations throughout todays world.  

Sarah Bakhiet 

Word Count: 535

Work Cited

Brune, Martin. "Schizophrenia—an Evolutionary Enigma?" Neuroscience and Biobehavioral Reviews 28 (2004) 41–53. Sunburst.usd.edu. Web. 23 Oct. 2003. 

The Unpredictable Evolution of the Infamous Flu Virus…H1N1, H5N1, H?N?

The flu has been dangerously prominent in the Western hemisphere in the recent winter months, and the notion that the situation could grow worse troubles scientists and other people around the world. There are several types of flu viruses, ranging from H1N1 to H15N9, depending on the various surface proteins. Avian flu begins in birds and infects others of the same species. Every now and then, a viral strain evolves to where it is able to attach to cells of a different species. H5N1 (hemagglutinin and neuraminidase), the most widespread and deadliest known avian flu virus, is one that has spread to humans but is unable to spread amongst the human species.  Even though it has been roaming in mostly Egypt and Asian nations (Figure 1), H5N1’s evolutionary ability brings the possibility of a global H5N1 pandemic.

How bad is H5N1? How will the infamous virus evolve in the future? H5N1’s paradoxical traits have kept questions like these in constant debate.  Although widespread in about 63 countries, among birds and many other animal populations, the viral disease is difficult to detect. In spite of being fatal in at least half of the people infected, about 364 out of 615 people since 2003, the virus has also been of no consequence to thousands of people in the virus’s presence. Despite continuous evolution since the late 1990’s, H5N1 is not yet capable of airborne transmission…

Concerns about the future evolution of H5N1 led two scientific teams to conduct research on how H5N1 would behave in ferrets and the effects of the strain’s mutations. The research led by Dr. Ron A. M. Fouchier and his colleagues in the Erasmus Medical Center was carried out by introducing three mutations and transferring the virus through ten generations of ferrets by means of nasal infection. “The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets. None of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses” (Herfst et al., 2012). On the other hand, Dr. Yoshihiro Kawaoka’s experiment in the University of Wisconsin-Madison utilized the H5N1 spike gene and inserted it into H1N1 from the 2009 swine flu. A viral strain with four mutations infected but did not kill the ferrets that breathed it in. The results from both research groups indicated that H5N1 lost its lethality as it became more contagious but shockingly proved how mutations could evolve and render H5N1 airborne transmissible.

Obviously, natural selection plays a large and significant role in “molding” H5N1’s functional characteristics. How the virus will mutate to form a fair tradeoff between replication speed and infection rate (Figure 2 – more deadly viruses are usually located farther down the respiratory tract and thus spread to new hosts more slowly) is something we can only predict and hope for the best. Still, with our prior flu experiences and our own evolutionary capabilities, we can stand our guard and prepare for the fight against the evolution of H5N1, no matter how it turns out.

 

Figure 1. Map of Asia, Europe, Africa, and Australia from the World Health Organization reports the areas where H5N1 have been found.

 

Figure 2. Two images of human respiratory system compare the effects of H1N1 to those of H5N1. Source: wpclipart.com

San-Pei Lee

Word Count: 552

Works Cited:

 S. Herfst et al., “Transmission of influenza A/H5N1 virus via aerosol or respiratory droplets between ferrets”. Science. 336, 1534-1541 (22 June 2012). Web. 18 February 2013.

Yong, Ed. “Influenza: Five Questions on H1N1”. Nature. 486, 456–458 (28 June 2012). Web. 19 February 2013.

Zimmer, Carl. “The Future Evolution of Bird Flu”. Phenomena: The Loom, 7 February 2013. Web. 17 February 2013.  

PANDAS: How do we classify it?

Over the course of history, "tics and obsessive-compulsive symptoms occur so frequently together in the same patient or in different members of the same family that they are now considered by some investigators to be alternate manifestations of the same neuropsychiatric disorder" (Garvey, Giedd and Swedo 1998). This neuropsychiatric disorder has come to be known as pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections, or PANDAS, which has come to puzzle scientists and doctors alike over recent decades. PANDAS is a disorder that is characterized by the sudden onset of symptoms similar to those seen in tic and obsessive-compulsive disorders (OCD). A child is only diagnosed with PANDAS when there is a clinical history of having a streptococcal infection prior to the sudden onset of these symptoms. These children make up a subgroup of children that have been diagnosed with Sydenham’s chorea, which is a disease that has been found to be closely related to OCD and tic disorders, therefore suggesting that PANDAS is also a part of this group.

Issues that have arisen can in part be attributed to the small sample sizes used for testing, which do not provide scientists samples that will allow them to look at all of the possibilities that may play a role into the sudden onset of these disorders. However, a connection was found between streptococcal infections and PANDAS, but is debated as to whether this streptococcal infection causes the onset of PANDAS and in result the onset of OCD and tic disorders. According to Dr. Edward L. Kaplan, current research is not evident enough to identify a causative relationship. Kaplan mentions that not all children show the symptoms of a streptococcal infection, and are therefore simply carriers, resulting in a lack of clinical records of a streptococcal infection that were being used to previously diagnose children with PANDAS.

Currently, the etiology of the disease is unknown, and scientists agree that more research needs to be done in order to come to a definitive classification of this disorder. This disorder is one in which it is debated as to whether the streptococcal infection is what is causing the disorder or if it is just coincidence. However, evidence that has been presented thus far supports the hypothesis that the onset of PANDAS and tic and obsessive-compulsive disorders are causative as more research is revealing the two disorders being present together in many individuals. However, in order to fully understand the etiopathogenesis of PANDAS, we would first need to fully understand the etiopathogenesis of the disorders closely related to it, starting with Syndenham’s chorea, which currently serves as the medical model for PANDAS. Whether or not the onset of PANDAS is due to an evolutionary advance of streptococcus or just coincidence is a question that must be answered by the use of genetically similar disease to piece together the current enigma that is PANDAS. 

Works Cited:

Garvey, M., Giedd, J., & Swedo, S. (1998). PANDAS: the search for environmental triggers of pediatric neuropsychiatric disorders. Lessons from rheumatic fever. Journal Of Child Neurology, 13(9), 413-423.

PANDAS to CANS: Evolution of a controversial disorder | Infectious Diseases in Children. (n.d.). Healio: Medical Specialty News, Journals, and Free CME. Retrieved from http://www.healio.com/pediatrics/news/print/infectious-diseases-in-children/%7BCAFAB629-3452-44AF-BA2D-4D99A8012DFC%7D/PANDAS-to-CANS-Evolution-of-a-controversial-disorder

                Snider, L., & Swedo, S. (n.d). PANDAS: current status and directions for research. Molecular Psychiatry, 9(10), 900-907.


Word Count: 479

Melissa Martinez

The Evolution of Depression

               We’re all familiar with depression; with its characteristic symptoms of sadness, low self-esteem, loss of interest in sex, decreased appetite, and suicidal tendencies, depression has prevailed in humanity as far back as recorded history. Even the father of evolutionary biology, Charles Darwin, suffered from depression. As if suffering from depression hadn’t caused enough misery for Darwin, the continued prevalence of the disorder in mankind presents a challenge to Darwin’s theory of evolution: if this heritable disease has effects of decreasing biological fitness by hindering reproduction (due to decreased sex drive) and survival (due to suicidal thoughts), why isn’t it selected against as predicted by Darwin’s theory of natural selection? Coming to Darwin’s rescue in their paper, “The Bright Side of Being Blue: Depression as an Adaptation for Analyzing Complex Problems”, published in Psychological Review in 2009, psychiatrists Dr. Paul W. Andrews and Dr. J. Anderson Thomson, Jr., introduce their hypothesis that depression is in fact an evolutionary adaptation for analyzing and solving complex problems, and that the net benefits of depression account for its prevalence.

                
                 To solve our problems, we must devote time to analyzing them, and in order to devote the appropriate amount of time, there should be minimal disruption of the problem-solving process. Depressive rumination, or the process of devoting significant cognitive effort to analyzing depression-triggering problems, is a time consuming process that has negative consequences on biological fitness by drawing attention away from sex, food, and social interactions. However, Andrews and Thomson observed in their experiment comparing accuracy on cognitive laboratory tasks that depressed people tended to outperform the non-depressed people in certain cognitive exercises. Statistically, in the results of the experiment, lower moods positively correlated with higher intelligence scores. From this study, it was apparent to Andrews and Thomson that depressive rumination facilitates the problem-solving process by sustaining the mind’s analysis of the problem, and by minimizing any disruption in the process. Furthermore, according to recent studies, the ability to execute depressive rumination is rooted in the biology of the brain.

            The ability to focus with high intensity is controlled by the left ventrolateral prefrontal cortex (VLPFC). Several studies have found that in depressed people, activity of the VLPFC is much higher than in non-depressed people, with the neurons in the VLPFC firing continuously in order to keep maximum attention focused on complex problems. Andrews and Thomson interpret this high activity in the VLPFC as the biological basis of depressive rumination, enabling people to stay focused on their predicaments. Moreover, they explain that the sadness that follows depressive rumination is part of a coordinated system with the activation of the VLPFC. From these studies, it seems that if depression did not exist, perhaps humans would not be as well equipped to solve complex dilemmas.

            
            Andrews and Thomson’s analytical rumination hypothesis has three facets: first, that depression is provoked by analytically difficult problems that impact biological-fitness related goals; second, that depression systematizes the body to promote persistent analysis of the triggering problem, an act known as depressive rumination; and third, that to solve these difficult problems, depression makes tradeoffs with other goals to spur analysis of the triggering problem. According to epidemiological evidence, the ‘triggering problem’ that initiates depression is usually an avoidable stressor rather unavoidable, and depressed people tend to apply significant cognitive strain to understand how the stressor could have been avoided.

           Now the question arises: what triggered the evolution of depression in humans? To this, Andrews and Thomson have no clear answer; however, they have logical theories. Throughout the course of human evolution, humans are believed to have lived in groups. Living in groups is a beneficial practice in terms of biological fitness because of the benefits of sharing food, protection from predators, raising children, and close proximity to mates. However, introducing a social aspect into human interactions requires that humans develop the ability to cooperate with one another as well. Therefore, humans that had the ability to solve the complex social dilemmas that their fitness depended on (while still effectively competing for resources and mates) were the ones that were repeatedly selected over evolutionary time. Therefore, the development of emotions and problem-solving processes can be thought of as adaptations that gradually accumulated, giving humans the best chance for survival and reproduction. Additionally, Andrews and Thomson believe depressed individuals were also able to elicit sympathy and support from group members, an advantageous trait when conflict arose against other individuals.

             Another theory that Andrews and Thomson propose is that depressive rumination is the optimum analytical tool that natural selection could produce to prevent the recurrence of suffering from avoidable stressors. For example, in the alternative problem-solving process of operant conditioning, organisms learn to avoid certain negative outcomes by associating those outcomes with environmental stimuli and using that information to avoid the causes of the detrimental outcomes. However, multiple exposures to the negative outcomes required by operant conditioning are risky if those outcomes are deadly. Therefore, it is likely that natural selection favored the more complex way of thinking (depressive rumination) that enabled humans to foresee avoidable stressors, allowing them to take the appropriate preventative measures.

            Depressive rumination is a process that serves as a beneficial adaptation because it allows people to solve the problems that trigger depression in an effective way. Although depression comes with its trade-offs of low mood and sexual disinterest, the benefit of depressive rumination serves the higher goal of solving complex social dilemmas which impact biological fitness. Although no concrete evidence has proven the evolutionary basis behind the prevalence of depression, Dr. Andrews and Dr. Thomson’s work provides a stepping-stone for future research in the science of behavioral evolution.

Iyza Baig

Word Count: 934

Andrews, Paul W., and J. Anderson Thomson. "The Bright Side of Being Blue: Depression as an Adaptation for Analyzing Complex Problems." Psychological Review 116.3 (2009): 620-54. American Psychological Association. Web. 13 Feb. 2013. <http://psycnet.apa.org/journals/rev/116/3/620.pdf>.

Lehrer, John. "Depression’s Upside: Is There an Evolutionary Purpose to Feeling Really Sad?" The New York Times. The New York Times, 25 Feb. 2010. Web. 13 Feb. 2013. <http://www.nytimes.com/2010/02/28/magazine/28depression-t.html>.

Evolution of Drug Resistance in Malaria

With only a limited number of drugs currently available to treat or prevent malaria, antimalarial drug resistance has rapidly become the greatest challenge in malaria control today. Resistance typically develops through “spontaneous mutations that confer reduced sensitivity to a given drug” (Bloland 2001). While multiple mutations are required to confer resistance against some drugs, a single point mutation can suffice for others. Malaria infections have been found with widely variable drug susceptibility, ranging from highly resistant to completely sensitive. If the resistance is able to perpetuate, it can become quickly established in a population.

In the 1950s, the drug chloroquine was introduced and heralded as a “miracle cure” against Plasmodium falciparum, the most deadly type of malaria (Fuller 2009). However shortly thereafter, the first resistant strains were reported along the Panama-Colombian and Thai-Cambodian borders, and by the early 1990s, chloroquine was considered ineffective in many parts of the world, including sub-Saharan Africa (Plowe 2008). A number of factors can contribute to the spread of resistance, including vector and parasite biology. Evidence has suggested that certain combinations of drug-resistant parasites and vector species have higher rates of drug resistance transmission than others. In addition, because many antimalarial drugs have similarities in chemical structure, development of resistance to one oftentimes allows for development of further resistance to other drugs, leading to multiple drug resistant (MDR) strains (Bloland 2001).

New treatments incorporating the drug artemisinin has seen promising success in recent malaria treatment, but there is now growing concern that artemisinin is losing its potency (Fuller 2009). Malaria experts have identified early signs of resistance to artemisinin in the same area “around the Thai-Cambodian border” which “appears to have been a starting point” for other drug-resistant strains of malaria, including that of the drug chloroquine. The World Health Organization posits three current viable methods of combating drug resistance in malaria: reducing overall drug pressure with improvements in diagnoses and more rigid prescribing practices, implementation of directly observed therapy (DOT) techniques and other close follow-up approaches to ensure optimal drug use, and combination therapies with a variety of antimalarial drugs.

Bloland, Peter B. "Drug Resistance in Malaria." World Health Organization, 2001. Web. 21 Feb. 2013.

Fuller, Thomas. "Spread of Malaria Feared as Drug Loses Potency." The New York Times. N.p., 27 Jan. 2009. Web. 21 Feb. 2013.

Plowe, Christopher V. "The Evolution of Drug-resistant Malaria." National Center for Biotechnology Information. US National Library of Medicine National Institutes of Health, 12 Dec. 2008. Web. 21 Feb. 2013.

Word count: 352

Sean Kim

Sickle-Cell Selection

Sickle-cell disease (SCD) is a genetic blood disorder in red blood cells. The disease is autosomal recessive, and it turns the erythrocytes into a sickle shape instead of the normal rod-shaped. The new shape is caused by a mutation in a hemoglobin gene. People with SCD can have a variety of complications ranging from anemia to a stroke. The interesting part about sickle-cell disease is its prevalence in sub-tropical sub-Saharan regions. These regions are also known to have high cases of malaria, which is a disease caused by protists of the genus Plasmodium. People with the autosomal recessive disease, or people who carry the sickle cell trait, are known to be resistant to the Plasmodium falciparum. Therefore, natural selection takes place in these areas with high cases of malaria, and the sickle cell trait gets passed on.

Researchers have studied the role of the sickle cell hemoglobin (HbS) in sub-Saharan Africa where “moderate-to-intense malaria transmission” is present (Terlouw). A lot of the children there tended to have the sickle cell trait, which is why researchers decided to study the effect of a particular antimalarial drug on young children. More specifically, they were trying to determine the effect of sulfadoxine-pyrimethamine to clear P. falciparum parasites. They found that those children with the sickle cell trait reacted to the drug a lot better than those without the trait (Terlouw). Natural selection acts again. The sickle cell trait outcompeted the dominant trait when trying to survive in the presence of the drug. This cannot be due to random selection because the sickle cell trait remained in high quantity among the children, which further demonstrated that natural selection took place. If we continue to make drugs to cure diseases, it is important that we take evolution into account because it will give us a better understanding of how to fight off these different diseases such as malaria. 

Word Count: 313 

Source

Feiko O. ter Kuile, et al. "Increased Efficacy Of Sulfadoxine-Pyrimethamine In The Treatment Of Uncomplicated Falciparum Malaria Among Children With Sickle Cell Trait In Western Kenya." The Journal Of Infectious Diseases 11 (2002): 1661. JSTOR Life Sciences. Web. 18 Feb. 2013.

Alyssa Thomas 

Evolutionary Biology as a Stepping Stone for the Development of Anti-Cancer Treatments

One of the most promising areas for the application of evolutionary principles in the fight against disease seems to be cancer treatment. Cancer itself is a disease rooted in one of the most fundamental principles of evolution; mutation. The NIH defines cancer as the "uncontrolled growth of abnormal cells in the body." (Dugdale 2012) These cells are abnormal because they reproduce at an increased rate or stop the process of apoptosis (programmed cell death). These abnormalities are genetic, caused by mutations in oncogenes. There are numerous genes which regulate cell growth and death and thus even cancers originating from the same organs can have very different genotypes and respond differently to treatment. This is what makes cancer such a pernicious disease. Unlike atherosclerosis (treated by regulating blood pressure and lowering LDL levels) or diabetes (treated relatively effectively with well regulated insulin injections) there is no “one size fits all” treatment for cancer. Therefore, it seems, an understanding of everyone’s cancer cell genome will be exceedingly helpful in tailoring a treatment specific to their disease. This type of individualized treatment has become much more viable as the cost of genotyping cells has declined. Knowledge of the cancer’s genome allows oncologists to employ more targeted treatments rather than the broad brushed “forms of cytotoxic chemotherapy and radiation therapy” (Hannun 1997) that are in most cases still the standard of care.

However, even with the knowledge of a cancer’s genome oncologists are still battling the forces of natural selection. They may be successful in eliminating the most aggressive or most prevalent strain of cancer, but may leave behind mutant cancer strains which then go on to fill the niche emptied by the cancer treatment. A new treatment is required because “tumors that are intrinsically resistant to chemotherapy are unable to activate the apoptotic machinery and may therefore be fundamentally resistant to chemotherapeutic cell death” (Hannun 1997). Furthermore, the selectivity of current chemotherapy treatments for cancer cells is limited and these treatments are usually accompanied by debilitating side effects. Cancer cells “may preferentially undergo cell cycle arrest or other nonapoptotic responses to damaging insults” and therefore “selectivity over normal cells may not be achievable”(Hannun 1997). Doctors have therefore begun to look towards the immune system for effective treatment options. The merit of a treatment utilizing our own immune machinery is that the immune cells could, in theory, adapt to the mutations in cancer cells and therefore treat multiple related cancer strains much more effectively than a targeted therapy.

Researchers have discovered a dendritic immune cell (DC) which is believed to influence which foreign matter is attacked by the immune system and which is left alone. While “B and T lymphocytes are the mediators of immunity…their function is under the control of dendritic cells” (Banchereau & Steinman 1998). The DCs “display many fine dendrites” (Banchereau & Steinman 1998) which are used to capture potential antigens. DCs exist in the “skin, airways and lymphoid organs” (Banchereau & Steinman 1998) in their immature form. When exposed to pathogens however the DCs undergo a transformation during which “antigen-capturing devices disappear, and T-cell stimulatory functions increase” (Banchereau & Steinman 1998) thereby allowing the DCs to communicate with T-cells and confer information about the new pathogen. Researchers believe that they can use these cells to induce the immune system to attack cancer cells as well as to treat other diseases such as HIV or TB. (Engber 2012) Vaccines have been synthesized with cancer markers and activators which attract DCs, but cancer response to these treatments has been limited and, like other treatments, variable from patient to patient. Researchers believe that large tumors that have become prolific enough to affect a patient’s health have mutated in such a fashion so as to be ignored by T-cells so immunotherapy treatments must be tailored to bypass these disguises. Hopefully, through an increased understanding of evolution, biology and chemistry a breakthrough in customized immune therapy is not that far off.

Works Cited

Banchereau, Jacques, and Ralph M. Steinman. "Dendritic Cells and the Control of Immunity." Nature 392 (1998): 245-52. Print. 

Dugdale, David C. "Cancer." Cancer. U.S. National Library of Medicine, 3 Sept. 2012. 

           Web. 16 Feb. 2013.

Engber, Daniel. "Is the Cure for Cancer Inside You?" NY Times. N.p., 21 Dec. 2012. 

           Web. 16 Feb. 2013.

Hannun, Yusuf A. "Apoptosis and the Dilemma of Cancer Chemotherapy." Bloodjournal.hematologylibrary.org. The Journal of the American Society of Hematology, 15 Mar. 1997.Web. 16 Feb. 2013.

word count: 656
Ben Kirby