Sunday, January 26, 2020

Genetic Manipulation: Advantages and Disadvantages

Genetic Manipulation: Advantages and Disadvantages Science on the other hand, fills my brain with questions and answers the knowledge that I crave. The theory of evolution does not dismiss there is a God. It is a theory trying to explain the beginning of life, how we evolved. The Old Testament professes to do the same thing, however, the stories are symbolic in their meaning. I am a Roman Catholic, and our dear Pope John Paul II acknowledged evolution as more than a hypotheses. Only the divine soul is untouched by evolution (Jurmain et al. 2010:44). The fact that some fossils are not preserved does not disprove evolution. Many species might not have left fossils. Some organisms just do not fossilize well. The geological record is not perfect. The fossils are not laid out perfectly waiting to be discovered by paleontologists. Chances are it is highly unlikely that an organisms remains will become fossilized, rather than decomposed. For the remains that do become fossilized, their preservation is unlikely due to erosion, earthquakes, volcanic eruptions , etc; Evolution continues to be rejected by some religious conservatives and fundamentalists. A lot of them believe that evolutionary biology ignores that God exists. They state that it does not account for how the world was really created according to the scriptures in the Bible. There have been numerous efforts to block teaching of evolution in U.S. public schools since 1968. The US Supreme Court overturned the first case in Arkansas stating that there could be no law barring the teaching of evolution on the grounds that it breached the separation of church and state as stated in the U.S. Constitution. Fourteen years later the federal courts rejected a statute to teach both creation science and evolution in the public schools. The courts stated that creation science was not actually a science. To try and get around the law of separation of church and state, evolution opponents began to propose the teaching of intelligent design. They stated that it was non religious, and a scientific alternative to evolution. Intelligent design claims that the living world was too intricate to have been made by the workings of natural selection. That some living things were too complex to have been developed by evolution and could have only have been created by an intelligent designer. But, they did not identify this intelligent designer. This presentation again was blocked by a federal district judge who found intelligent design was not a science (Jurmain et al. 2010:44). What can be done to correct this controversy, or should it be corrected? Why? Although I dont agree with the Christian fundamentalists opinion, my answer is, no. Why? It is called the First Amendment. Describe and evaluate some of the positive and negative consequences of genetic manipulation Genetic engineering entails the manipulation of DNA. The tools in this process are very important for the restriction of so called enzymes, which are produce by various species of bacteria. A particular sequence of a chain of nucleotide bases, can be recognized by restriction enzymes. The nucleotide bases that make up the DNA molecule; cut the DNA at that location. Parts of DNA formed in this way are joined using enzymes called ligases(joining of two enzyme molecules to form a covalent bond, accompanied by the hydrolysis of ATP(adenosine triphosphate)) Positive side of genetic manipulation Genetic therapy entails supplying a particular function to a gene, and in turn to cells that are lacking that function. The intention is to correct a genetic disorder or an acquired disease. One type of gene therapy used today is, somatic cell therapy. It is similar to an organ transplant. One or more specific tissues are targeted for treatment by therapeutic genes from the lab or the tissue is removed and replaced with the treated cells and given back to the patient. Researchers have had success with somatic cell gene therapy for the treatment of blood, lung, liver disorders and cancer. Another positive side to genetic manipulation also involves the health industry. The manufacturing of recombinant factor VIII, a blood clotting agent missing in patients with hemophilia A. Practically all of the hemophiliacs who were treated with factor VIII before the mid 1980s contracted AIDS or hepatitis C from viral contaminants in the blood that were used to make the product. Now donor blood is screened for the presence of HIV and the hepatitis C virus. The process now includes inactivating the viruses if they prove to be present. The possibility of a virus contamination is eliminated completely by the use of recombinant factor VIII. Negative side of genetic manipulation Explanation of Cloning: A technique that is a process of several stages. An egg is taken from a donor animal The nucleus is then removed from the egg. The nucleus containing the DNA is taken from the tissue cell of the animal being cloned. The nucleus is inserted into the donor egg cell. The fused egg is then placed in the uterus of a surrogate mother. When that mother eventually gives birth, if all goes well, the baby is genetically identical to the animal that provided the tissue cells that contained the DNA. I understand the potential benefits that genetic engineering has for the future of this world, however, the thought of it getting into the wrong hands terrifies me. My main area of concern is cloning. From the beginning, back in 1997 when I heard on the news about the sheep, Dolly, being cloned in Scotland, my heart sank. There is even talk of people ordering what type of children they want, as if they were ordering from a dinner menu. I knew eventually that people would be cloned. There is evidence they have already. People are desperately waiting for transplants. Why are we not using the clones vital organs? This is something would like answered. Would you agree with your textbook authors when they say: Indeed it would not be an exaggeration to say that this is the most exciting time in the history of evolutionary biology since Darwin published On the Origins of Species? Would you agree or disagree with this statement? Why? Please provide some detailed examples? Yes, I would agree. In my younger days, I worked as a chemotherapy technician in Childrens Hospital, Boston. I worked closely with one little girl who was born without a stomach, preparing parenteral nutrition for her daily basis. Children also dying at a very young age of diabetes. But due to the amazing research done in genetics, and recombinant DNA technology, children have a much better chance of reaching adulthood and leading normal lives. Regarding the field of anthropology, the sequencing of human genes in the Human Genome Project. The progress being made in comparative genomics is terribly exciting. Personally, I cant wait to hear the DNA comparison results of the Neanderthal, modern human, and nonhuman primate. What is natural selection? The theory of Natural selection is actually the key to evolution. It is based on the following processes that include: Biological variation within all species Individuals within a species that have favorable traits are more likely to survive in their environment and produce offspring. The environment of the species determines whether or not a trait is satisfactory or not. Traits are inherited and over a period of time, favorable traits will be passed on generation to generation and become more common in the population. Isolation of a species may lead to the formation of a new species due to inhabiting a different environment and will in turn adapt to that environment. Natural selection only operates on an individual within a population, but it is the population that evolves. Why is genetic variation necessary for the process of natural selection to operate? Genetic variation plays a significant role at the microevolutionary level, producing evolutionary change. Directional evolutionary trends can only be sustained by natural selection. Individuals who carry a particular allele or a combination of alleles will produce more offspring than other individuals with different alleles. The frequency of the new allele in a population will increase slowly from generation to generation. This process is compounded over hundreds of generations for multiple loci, the result being a major evolutionary change(Jurmain et al. 2010:107). What are the sources of genetic variation? Mutations: When there is a change in the DNA molecule that means there is one type of mutation and that multiple genes occur in two or more forms called alleles. If an allele to another allele, or if the gene is altered in some way, a mutation has just occurred. Alleles are, in fact, a direct result of a mutation. The substitution of simply one DNA base for another, a point mutation, can cause a change in an allele. However, to be important to the evolutionary process, the point mutation has to occur in the sex cells. This is so the mutation can be passed on from generation to generation. Examples: No changes in phenotype due to mutations No evidence of a change on the phenotype of an organism due to mutation. Mutation occurred maybe in a stretch of DNA with no function, or perhaps the mutation occurred in a protein-coding region, but ended up not affecting the amino acid sequencing of the protein. Small change in phenotype due to mutations would for example be a single mutation like a cats ear slightly curling back. Big change in phenotype due to mutations This would create some major phenotypic changes. DDT resistance in insects are usually caused by single mutations. A single mutation can also have very strong negative effects on an organism. Mutations that would cause the death of an organism are called lethals. Gene flow Migration is used here to refer to the movement of people. This occurs when the exchange of genes between different groups of migrants interbreeding. It can also occur when an individual(s) move temporarily and produce some offspring in an entirely new population. This way they have left their genetic contribution. An example of gene flow: Happens a great deal in war. When male soldiers are stationed in remote parts of the world and impregnate the native women of that country and then the male returns to his native land. The impregnated native women in the remote country represents the gene flow. Genetic drift is known as the random factor in evolution. The population size is its entire function. Drift only occurs because a population is small. If an allele is rare in a very small population of less than 400 people, there is a very great chance that it will not be passed down to the offspring. Eventually, the allele may disappear entirely. In this instance genetic variability has been reduced drastically. Genetic drift can cause big losses of genetic variation for small populations. An example of genetic drift: The B allele was evidently not passed down to generations of Blackfoot people. There is evidence that present populations are deficient in genotypes that contain the B allele (BB, BO and AB). When the populations became greatly reduced in size, some genes may not have been passed on to the next generation. This phenomenon is referred to as a genetic bottleneck. As a result, genetic variability may have been severely reduced in succeeding generations. Founder effect is a type of genetic drift and is seen in human and non human populations. An example of the founder effect is the Baptist German religious sect that settled in Pennsylvania in the early 1700s. These families didnt marry outside their own religious sect. There has been evidence of some dramatic changes in their gene frequencies. For example; the type A blood in the sect resulted in 60 percent. United States is 42%. It is 45 percent for the sect in West Germany. They also have fewer people with certain recessive traits, such as hitchhikers thumb and attached ear lobes, compared to the U.S. population as a whole. The founder effect helps explain the high frequency of dwarfism and polydactylism (extra fingers) in the Amish of Lancaster Pennsylvania. The colony began when at least one of the individuals carried these traits. Recombination is a source of genetic variation that introduces new gene combinations into populations. For example: Siblings are never genetically identical to either of their parents or to each other (unless they are identical twins.)This is because when organisms reproduce sexually, some genetic à ¢Ãƒ ¢Ã¢â‚¬Å¡Ã‚ ¬Ãƒâ€¦Ã¢â‚¬Å"shufflingà ¢Ãƒ ¢Ã¢â‚¬Å¡Ã‚ ¬Ãƒâ€šÃ‚  occurs. This brings together a new combination of genes. How is natural selection related to environmental factors? All the evolutionary factors of mutation, genetic drift, gene flow, and recombination, interact to form genetic variation. Genes are then distributed within the populations. There isnt any long term direction to any of the above factors, but for adaptation and the evolutionary process to occur, the gene pool of the population needs to change in a certain direction.Some alleles need to consistently become more commonplace, while other become less common. Natural selection can cause a change in direction in allele frequency relative to specific environmental factors. If there is to be a change in the environment, then the selection pressures will also change, and a shift in allele frequencies is called adaptation. Now if there are long term environmental changes in the same direction, then allele frequencies would also shift very gradually over time. Example:Hemoglobin S (Hbs) which is an abnormal form of hemoglobin that is formed from a point mutation gene, produces part of the molecule of the hemoglobin. If an individual inherits this allele from both parents, he or she will have sickle cell anemia. HbS is a mutation that occurs in all populations occasionally, but the allele in generally rare. HBs, however, is more common in central Africa where it reaches 20% of the population. With the devastating effects of the HbS homozygotes, one would think that natural selection would have acted on eliminating it. But that is not the case. Natural selection has actually increased the frequency of HbS. This is because of the disease malaria. People with one HbS and one HbA allele (heterozygotes with the sickle cell trait) have red blood cells that contain hemoglobin S. Hemoglobin S is not a suitable environment for the malarial parasite. So having HbS is beneficial, because it protects that person from malaria. In this instance, malaria is the selective agent. and favors the heterozygous phenotype. In this part of the world, individuals with sickle cell anemia trait have a higher reproductive success than those with normal hemoglobin, because they are more apt to die of malaria (Jurmain et al. 2010:105). Discuss genealogy of the Blue Fugates of Kentucky. Describe Mendelian principle of inheritance as well as a phenotypic effect of an enzyme deficiency. Mendel discovered through his experiments with plants, that the inheritance of traits was not due to blending as he originally thought. He found that specific units (genes) of inheritance were passed down from generation to generation. No matter what trait Mendel selected for the second generation of the plants, it would show a ratio of 3 to 1. This meant that there were 3 dominant genes to every 1 recessive gene. Mendel realized that this 3:1 ratio occurred in later generations as well. He had found the key to understanding inheritance. Mendel came to three very important conclusions from his experiments The inheritance of each trait is determined by units(genes) that are passed on to descendents and are unchanged. An individual would inherit a gene from each parent for each trait. A trait just may not show up in an offspring but could be passed on to their offspring. Mendels observations have been summarized in to two principles: The principle of segregation and the principle of independent assortment. According to the principle of segregation two members of alleles separate from each other in the formation of sex cells (gametes) Half of the gametes carry one of the allele and the other half of the gametes carry the other allele. Principle of independent assortment-Genes for different traits are assorted independently from one another in the formation of sex cells. I feel the principle of segregation applies in the case of the blue Fugates of Kentucky. It was determined that the Fugates inherited an autosomal recessive trait. Both Martin Fugate(heterozygote) and his bride Elizabeth Fugate(heterozygote) had one recessive allele each of this disorder. Since both Martin and Elizabeth were both carriers, there was a 25% chance of their offspring being affected. There is usually a predictable phenotypic ratio of 3:1. The family would marry people who lived close by and this intermarrying continued. The community was isolated, without roads. When the railroad was completed 30 to 40 years later, roads were built and they started venturing out and marrying outside their community. The strain of the inherited blue gene began to disappear. The recessive gene was not likely to find a mate with the same recessive gene. A baby named, Benjy Stacy was born blue, 100 years later. He had the recessive gene from both his mother and fathers side. His blue color, however was only temporary. It was assumed that Benjy had just inherited one gene of the condition, and being a baby had a smaller amount of the enzyme diaphorase, and it built to normal levels as he got older (Jurmain et al. 2010:86-89) and Fugate family literature. Why do we see this rare, phenotypic deficiency? It was first seen in Alaskan Eskimos and Indians. It is a human genetic disease. The gene is located at chromosome 22. In normal people, there is a dominant, allele that is responsible for the production of the enzyme diaphoreses. Normally hemoglobin is converted into methemoglobin(a brownish compound of oxygen and hemoglobin) at a very slow rate. Diaphorase in normal blood, changes the methemoglobin back to hemoglobin. The homozygous children of the Fugate family, lacked the enzyme diaphorase. therefore this conversion could not take place. Therefore, all of their hemoglobin in their body was considered useless. Instead they had a mutant allele that produced an inert enzyme that was unable to reduce the hemoglobin. What is the nature of the evidence supporting punctuated equilibrium? The theory was advanced by two American paleontologists Eldredge and Gould. They agreed that the fossil record was incomplete, but that it could not be incomplete enough to account for the near absence of the gradualistic change from the fossil record. They said that species originate too quickly for the normal geological processes to record the event; a single bedding (a thin layer of sedimentary rock)often compresses more than tens of thousands of years into a thin slice. Speciation usually occurs when small populations cut off from the interbreeding with groups, evolving rapidly in isolation. With fewer people in an isolated population, the favorable mutations spread more readily. A small, isolated, evolving population may become extinct and may not leave a trace of a fossil record. Eldredge and Gould said that if it does remove itself from its isolation, and spread over a much wider area, its likely to be seen in the fossil record as making a punctuational appearance, fully forme d. The nature of the evidence supporting punctuated equilibrium was from the paleontologist, Cheetham. He gathered a large sample of bryzoan fossils from the Caribbean and surrounding regions. He painstakingly classified them into 17 species using 46 microscopic characteristics of their skeletons. Measured their length, dimensions of pores, and all the orifices on the fossils. He then arranged them into a family tree. He analyzed them and split a single species into several species. The abruptness in the tree, appeared more clear to him and stronger than ever. He concluded that through 15 million years of the geological record, these particular species persisted unchanged for 2-6 million years. Then in less than 160 thousand years, split off in to a new species. This new species would coexist continuously with its ancestor species. This was his punctuated result. But this was not proof The morphological differences being used to split the fossil species? What if it really did not mark a separate species, but was just another version of the species? A model of speciation was needed to recognize a new species and support any evidence of punctuated equilibrium. Several biological tests were performed and then he performed a test in genetics. Using a test of protein electrophoresis, he extracted enzymes and analyzed each of the eight morphologically defined species. In every case, the specimen from each species had very similar enzymes. This indicated they belonged to the same genetically related species. Cheetham had passed the fossil species test. His conclusion was that morphology still seems to say how evolution occurred(http://science.jrank.org/pages/5591/punctuated-Equilibrium.html)(Kerr 1995:1421). Would you agree or disagree with this? Why? Many paleontologists still say that many of these studies have their weaknesses. There is overwhelming evidence that speciation is sometimes gradual and sometimes punctuated. It is very complicated, and until there is more proof, I think I would prefer to stick to the middle ground. Theories of Psychopathy | Overview and Analysis Theories of Psychopathy | Overview and Analysis A lot of research has been conducted in the area of aggressive, antisocial, and criminal behaviour (Frick Viding, 2009). Indeed, persistent antisocial behaviour results in human suffering associated with criminal offences, and high economic costs from detaining these offenders to prevent recidivism (Loeber Farrington, 2001). What is Psychopathy? Previous findings demonstrated that over a third of incarcerated offenders have Antisocial Personality Disorder, characterized by pervasive antisocial and exploitative behaviour (Black, Gunter, Loveless, Allen, Sieleni, 2010). However, offenders with psychopathy represent an even greater danger to society. Individuals with psychopathy often use instrumental aggression for personal gain. When compared to non-psychopathic offenders, they tend to commit more serious and violent crimes (e.g. premeditated homicide), are three times more likely to reoffend, and four times more likely to recidivate by a violent offence after being released from prison (Porter, Brinke, Wilson, 2009). Psychopathy is a developmental disorder characterized by antisocial and bold disinhibited behaviours, lack of empathy and remorse, and low anxiety (Hare Neumann, 2008). Previous studies demonstrated that adults with psychopathy all display persistent antisocial behavior across the lifespan with first signs of psychopathy, such as behavioural disturbances and emotional deficits, being evident as early as childhood (Blair, 2013). While the diagnosis of psychopathy is generally applied to adults, some children present with antisocial behavior and core psychopathic traits (comparable with callous-unemotional (CU) traits) such as low empathy, lack of guilt, shallow affect, and callous use of others (Frick Viding, 2009). Although it is important not to assume that children and adolescents with psychopathic traits will exhibit psychopathy in adulthood, the assessment of psychopathic traits and antisocial behavior in youth provides considerable evidence of their persistence over time (Erme r, Cape, Nyalakanti, Calhoun, Kiehl, 2013). Psychopathic Traits in Children and Adolescents Children with conduct disorder and callous-unemotional traits show more instrumental aggression for personal gain, higher prevalence of Antisocial Personality Disorder among their parents, more frequent interactions with the police, and a greater number and variety of conduct problems than children with CD and no psychopathic traits (Herba, Hodgins, Blackwood, Kumari, Naudts, Phillips, in press). While callous-unemotional traits during childhood have been often associated with severe antisocial behavior, children with callous-unemotional traits but no antisocial behaviour frequently show higher levels of other impairments such as increased hyperactivity, low prosociality, and poor interpersonal relationships (see: Frick, Cornell, Bodin, Dane, Barry, Loney, 2003; Barker, Olivier, Viding, Salekin, Maughan, 2011; Rowe, Maughan, Moran, Ford, Briskman, Goodman, 2010). Callous and unemotional traits have been recently added as part of the diagnostic criteria for Conduct Disorder in the new version of the Diagnostic and Statistical Manual (DSM-V) (Decuyper, Caluwe, Clercq, Fruyt, 2014). Moreover, due to its high predictive validity, CU traits may have independent diagnostic value, even without the diagnosis of conduct disorder (Barker, et al., 2011; Frick, et al., 2003; Viding McCrory, 2012). Evidence of Emotional Dysfunction in Individuals with Psychopathic Traits Previous findings demonstrated that callous and unemotional children show similar emotional deficits as psychopathic adults, such as poor emotion recognition and deficits in emotional empathy (Herba, et al., in press; Blair, 2003; Pardini, Lochman, Frick, 2003). Emotional empathy represents affective reactions to emotional expressions and to verbal descriptions of the emotional states of other individuals. Empathic reactions, which can be evoked by facial expressions, voice tones, body postures, and even script, serve a communicatory function, and are processed by separate neural systems (Blair, 2013). Emotion Recognition Findings Youths and adults with psychopathic tendencies display a significant selective impairment in emotional empathy. While they normally recognize and differentiate between expressions of disgust and anger, their processing of distress cues (expressions of sadness, pain, and fear) is significantly different from healthy youths and adults without psychopathic tendencies (Blair, 2013). Studies demonstrated that distress cues inhibit antisocial behaviour in humans as well as primates by eliciting empathy in observers (Marsh Blair, 2007). Meta-analytic review of the literature shows that while having a normal processing of anger and disgust, individuals with psychopathic traits and persistent antisocial behaviour display poor recognition of certain emotional expressions, particularly fear, as well as reduced recognition of expressions of happiness and sadness, though to a lesser extent (Marsh Blair, 2007; Dawel, O’Kearney, McKone, Palermo, 2012). Blair, Collegde, Murray, and Mitchel l (2001) conducted a study looking at emotion recognition in boys with and without psychopathic tendencies (measured by a Psychopathy Screening Device). Children were shown a standardized set of six emotions (sadness, happiness, anger, disgust, fear, and surprise) morphed into different intensity levels and shown in 20 successive frames from neutral to full expression. Results demonstrated that children with psychopathic tendencies made more mistakes in recognizing expressions of fear even when they were presented at full intensity. Moreover, these children also needed more stages to be able to recognize expressions of sadness (Blair, et al. 2001). Similar impaired recognition of sad and fearful expressions is also observed using vocal tones and body poses (Stevens, Charman, Blair, 2001; Blair, Budhani, Colledge, Scott, 2005; Munoz, 2009). Psychophysiological findings A number of studies that looked at psychophysiological responsiveness of individuals with psychopathic traits provided additional evidence towards the idea that these individuals have impaired processing of expressions of distress in others. Children and adolescents with high callous-unemotional traits and psychopathic adults show reduced autonomic responses including heart rate, facial electromyographic responses, and electrodermal responses to fearful and sad expressions and distress cues in others (Blair, 1999; de Wied, van Boxtel, Matthys, Meeus, 2012; Blair, Jones, Clark, Smith, 1997). In addition, youths and adults with psychopathic tendencies also display atypical electroencephalography responses to pain in others (Blair, 2013). Functional neuroimaging findings A new study by Motzkin, Phillippi, Wolf, Baskaya, and Koenigs (2015) provided tentative evidence that the ventromedial prefrontal cortex (vmPFC) might play a significant role in regulating amygdala activity in humans. This is not surprising given the substantial amount of evidence, containing lesion studies, demonstrating that the ventromedial prefrontal cortex and amygdala play a critical role in empathic response and emotion regulation (Blair, 2008; Blair, 2013). Studies of youths with high callous-unemotional traits and conduct disorder, as well as studies of psychopathic adults, showed decreased activation of the rostral vmPFC in response to images of other individuals in pain. (Marsh, et al. 2013; Blair, 2008). Previous fMRI studies also repeatedly demonstrated reduced amygdala activation in individuals (children, youth and adults) with psychopathic traits when they are presented with images of faces expressing fear, or images of others individuals in pain (Blair, 2008; Jones, Laurens, Herba, Barker, Viding, 2009; Marsh, et al., 2007; Munoz, 2009). Moreover, studies consistently reported that lower activity in the amygdala, vmPFC, as well as the anterior insula in response to distress cues are associated with higher severity of psychopathic traits, particularly in children and adolescents (Marsh, et al., 2008; Sebastian, et al., 2012; Marsh, et al., 2013) Structural neuroimaging findings Given the amount of evidence demonstrating reduced activity in vmPFC and amygdala in youths with psychopathic traits and psychopathic adults in response to distress cues, it is worth considering whether structural abnormalities are also observed within these neural regions. A large neuroimaging study conducted by Ermer and colleagues (2013) looked at the structural brain volume in over 200 incarcerated adolescents in a maximum security facility. Their findings demonstrated volume reductions within a large brain structure that centered on the vmPFC and included the amygdala, which is associated with the emotion dysfunction component of psychopathy. Another structural neuroimaging study demonstrated an inverse relationship between the structural volume of amygdala and the severity of psychopathic traits in a large sample (N=296) of incarcerated adults (Ermer, Cope, Nyalakanti, Calhoun, Kiehl, 2012). Summary of existing findings In summary, the aforementioned findings demonstrated that individuals with psychopathy show poor recognition of, and reduced autonomic response to distress cues in others across the lifespan. Functional neuroimaging studies identified various neural structures involved in the processing of distress cues, with the most consistent evidence pointing towards the amygdala and ventromedial prefrontal cortex. fMRI studies repeatedly demonstrated reduced activity in these brain regions in children and adolescents with callous and unemotional traits, and psychopathic adults in response to facial expressions of fear and sadness. Structural neuroimaging studies provided additional evidence towards the importance of the amygdala and the vmPFC in processing of distress cues, demonstrating volume reductions in these areas in incarcerated adolescents with psychopathic traits, and a significant inverse relationship between the structural volume of the amygdala and the severity of psychopathic traits in incarcerated adult. Current Theories Given this considerable amount of evidence demonstrating emotional dysfunction in individuals with psychopathic traits across the lifespan, several models have been proposed in hopes to shed more light on this impairment. Violence Inhibition Mechanism Previous animal studies suggested that display of emotions of sadness, pain, and fear, also referred to as distress cues, serve an important evolutionary function: when displayed to a conspecific aggressor lead to the termination of the attack (Blair, 1995). Blair (1995) proposed a functionally analogous mechanism in humans referred to as violence inhibition mechanism (VIM). According to Blair, VIM represents a cognitive mechanism normally activated by non-verbal expressions of distress, which predisposes an aggressor as well as a bystander to withdraw from the situation. According to the model, moral socialization takes place through pairing of the activation of VIM by the sad and fearful expressions (Unconditioned Stimulus) of others with representations of the acts that caused this distress (Conditioned Stimulus: moral transgressions, such as an aggressive act towards an individual). As a result, representations of these moral transgressions become triggers for the VIM through classical conditioning. Thus, a normally developing child will initially find pain of others aversive, and then through socialization would learn to dislike the thoughts of acts that cause pain to others, and as a result will be less likely to engage in violent behaviour (Blair, 1995). According to Blair (1995), this mechanism is absent in individuals with psychopathy, which might be due to a specific physiological deficit or lack of early socialization experiences. Due to the absence of VIM, individuals with psychopathy are not negatively reinforced after any action (moral transgression) that results in the display of distress cues in others. Using VIM, one might predict that these individuals who were unable to form US-CS association would show emotional dysfunction, early-onset of violent behaviour, and lack of guilt or empathy post-violence, which all represent core features of psychopathy. The Response Modulation Hypothesis Another concept that has been suggested to explain the nature of emotional impairments in individuals with psychopathic traits looks at psychopathy as a disorder of attention. According to the response modulation hypothesis, individuals with psychopathy fail to recognize and process distress cues in others due to their inability to shift attention to this information when they are engaged in goal-directed behaviour. Given the amount of evidence demonstrating severe emotional processing impairments in individuals with psychopathic traits, it has been suggested that this emotional dysfunction may underpin the deficits seen in psychopathic individuals (Blair, 1995; Frick Viding, 2009). Indeed, previous studies demonstrated pronounced deficits in emotional learning and poor decision making in psychopathic adults as well as youths with psychopathic tendencies. Previous studies on decision-making behaviour in psychopathic adults demonstrated significant deficits underlying aversive conditioning, reversal learning, operant extinction, and passive avoidance learning (Blair, 2013). In an fMRI Study by Birbaumer and colleagues, a sample of ten offenders with psychopathy and ten matched controls was used to investigate the activation of neural structures, skin conductance, arousal and emotional valence in an aversive delay conditioning paradigm where neutral faces were used as conditioned stimuli and painful pressure as an unconditioned stimulus (Birbaumer, Veit, Lotze, Erb, Hermann, Grodd, Flor, 2005). Finding of this study showed inability of psychopathic individuals to learn to differentiate between conditioned stimuli, or show increased skin conductance response to the paired conditioned stimulus. Moreover, fMRI findings demonstrated reduced activity in the limbic-prefrontal circuit (combined of amygdala, orbitofrontal cortex, insula, and a nterior cingulate) in psychopathic individuals when compared to the matched controls. Another study which used a similar fear conditioning paradigm as Birbaumer and colleagues (2005) further demonstrated deficits in aversive fear conditioning in psychopathic adults (Rthermund, Ziegler, Hermann, Gruesser, Foell, Patrick, Flor, 2012). In this study, psychopathic participants showed lack of a differential startle response and lack of skin conductance towards a paired conditioned stimulus. Moreover, these results cannot be explained by differences in detection threshold of electric shock, or levels of pain tolerance, since there was no significant differences in these measures between the two groups. This study confirms previous findings of impaired ability to form associations between neutral and aversive events in adults with psychopathy. Previous studies in decision-making behaviour and the propensity to learn from punishment in youths with psychopathic traits demonstrated significant impairments in the capacity to associate outcomes (reward or punishments) with stimuli.

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