Morality and the Brain

 Radiolab episode: Morality

The issue of morality is something that has and will always be an integral component of progressive thought. Throughout history, the moral dilemma and the idea of right and wrong, has most commonly been explained through religion and philosophy. However, modern thinkers are trying to look beyond that to see where this moral sense comes from. How do we make moral decisions, and can they explained scientifically? Neurologists today, are now looking at this question through studies, which use brain imaging, on top of a number of observational techniques, to record any biological explanation of morality. This radiolab episode deals directly with this question, using four different experiments and studies. 

The Trolley Problem:

           This experimental research, performed by Joshua Greene, is centered on an idea posed by the philosophers Pilippa Foot and Judith Jarvis Thomson, called the “Trolley Problem.” This idea is comprised of two theoretical situations that spur a moral dilemma. One being the switch dilemma: A runaway trolley is hurtling down the tracks toward five people who will be killed if it proceeds on its present course. You can save these five people by diverting the trolley onto a different set of tracks, one that has only one person on it, but if you do this that person will be killed. Is it morally permissible to turn the trolley and thus prevent five deaths at the cost of one?   Most people say, "Yes."  The other is the footbridge dilemma: the trolley is headed for five people. You are standing next to a large man on a footbridge spanning the tracks. The only way to save the five people is to push this man off the footbridge and into the path of the trolley.  Is that morally permissible?  Most people say "No." The two situations lead to inquiry about why, in the switch case, it is permissible to kill one person in order to save the lives of five others, while in the footbridge case, killing the one person is completely unacceptable. Moreover, “how does everyone know (or “know”) that it is okay to turn the trolley but not okay to push the man off the footbridge?”

            Study:

In Joshua Greene’s study, brain imaging was used to record the response people had to moral dilemmas like the ones just mentioned, as well as many others. He also divided the moral dilemmas into two categories, based on difficulty, recording not only the brain activity, but also the relationship between reaction time and the difficulty of the dilemma. He hypothesized that the difference between each situation is that, one case is “up-close-and-personal” while the other is impersonal. Greene predicted that brain imaging would indicate the differentiation in brain activity when responding to a personal case as opposed to an impersonal case. The study was a preliminary attempt to understand the question “are the moral truths to which we subscribe really full blown truths, mind-independent facts about the nature of moral reality, or are they… in the mind of the beholder?” Also, in moral dilemmas such as the one mentioned, why is it horrific and outrageous to react one way and completely acceptable to act another way. Through his testing he tries to support the theory that this phenomena is less about structured moral codes enforced through experience or evolution, and more about “the way our brains are wired up.” His hypothesis also argues that in personal dilemmas, a difference in reaction times for “yes” and “no” answers would indicate that there is different brain activity allowing the person to make that judgment.

            Results:

When responding to a more personal moral dilemma, three emotional related brain regions: the posterior cingulate cortex, the medial prefrontal cortex, and the amygdala, were more active. Whereas, when a person responded to an impersonal dilemma, there was greater activity in areas associated with simple cognition: the dorsolateral prefrontal cortex, and the inferior parietal lobe. When reviewing response time, in relation to the brain images, it was shown that in cases where a person answered, “yes” to questions like the footbridge dilemma, there was intense cognitive brain activity in the dorsolateral prefrontal cortex, the inferior parietal lobe, as well as in the anterior cingulate cortex (associated with conflict), and their reaction time was extended; when a person answered “no” in cases like the footbridge dilemma, there was heightened emotional brain activity in the posterior cingulate cortex, medial prefrontal cortex, and the amygdala, and their reaction time was significantly faster.       

These results suggest that moral judgments emerge from more than one neurological system. Going even further, it appears that these emotional and cognitive systems are essentially battling with each other, striving to control and influence the outcome of a moral decision. He arrived at this conclusion by using the localization of morally driven responses in the brain to watch neural activity, while simultaneously recording the time it takes one to make a decision; from this he presumed that shorter reaction times were indicative of the emotional brain systems dominating the cognitive process, while longer reaction times mean that the cognitive systems have overpowered the impulsive emotional response.

Based on his findings, Greene believes that profound moral positions are not, as commonly perceived, invented by humans, or God given, but rather that they may somehow be embedded in brain chemistry. He thinks that morality is fundamentally a product of the interaction between neurological systems. With this theory, Greene also considers that through the evolution of humanity, we have developed a stronger cognitive response to moral dilemma, and yet the less consequentialistic (philosophical view that moral judgment is a product of evaluating the consequences of the decision) response to moral dilemma, is still, very often, overriding.

 

Kiddie Morality:

This segment looks at how young children adhere, very early, to the moral universe. Through Dr. Judith Smetana research, it is clear that moral judgment for these children is not solely realized through the rules enforced by the adults around them. In addition to what they are taught, there seems to be certain moral concepts that are understood and driven by something innate. Smetana interviews pre-school children, asking them all kinds of questions that embody complex moral ideas, but are presented simply in terms that a young child can relate to. She asks:

-Who makes the rules here?

·      The teacher.

-Can the teacher change the rules if they want to?

·      Yes. She’s the teacher; she can do whatever she wants.

-Is there a rule about hitting at your school?

·      Yes.

-Suppose the teachers agree that they don’t have a rule about hitting anymore, would it then be okay to hit?

·      No. Because that would make somebody would feel bad.

-Is there a rule about sitting during lunch? Is that a rule the teacher could change?

·      Yes. Yes, if she says okay you can stand up, you can do that... You have to listen to the teacher.

  What she found was that with certain rules, the children felt that changing or deviating from the rule would be okay, and with others, the children expressed that it would not be  okay to break them. In cases dealing with hitting, hurting, and teasing, the general consensus is that it would be wrong, even if the teacher did not see them or did not have a rule about hitting; whereas with rules like sitting in a circle during “circle time” or during lunch, the children felt that it would be acceptable if the rule was different or if there was not rule at all.

            She also addresses how young children develop this moral sense, which could be partially innate, but is also largely discovered through experience. While most young children understand a lot rules and the conditions of the rules, they still often subside and break the rules, giving in to certain intrinsic urges. Researchers think that these defiant moments could be relating to their young underdeveloped sense of empathy. In one anecdotal story, a women describes watching her four-year-old son, in his classroom, make his best friend bleed by tackling him in front of the entire class. She explained that although it was extremely difficult to intervene when she saw how mortified her son was after the incident, it was important for him understand the emotional consequences of this kind of behavior.

The next story in this segment also looked at moral development from an experiential perspective. Two adults talked about the ways in which very specific events from their childhood, where they had diverged from their moral rules, continue to resonate even after so many years. They explained how they continue to feel guilt and regret about their poor moral judgments; although, in retrospect, those experiences have heavily shaped their moral sense and ability to empathize. 

 

Controversy Surrounding the Neurological and Psychological Study of Morality

            Morality has always been, for a number of reasons, highly controversial; even before there were any kinds of scientific theories or connections made. It deals with the way we understand “right” and “wrong”, and from this very subjective perception conflict spurs. Morality is also one of the most integral components of religion. Different religions affirm different explanations as to why/how morality should be incorporated into our lives. For instance, Christianity explains morality as the 10 commandments, physically handed down from God on a tablet. In this case, neurological research is in complete opposition with Christian convictions, because it essentially proposes that morality could be, in fact, a product of brain chemistry. Because most religious perspective on morality is so heavily rooted in history, something that radically defies the common belief the way the recent scientific studies do is bound to spark significant controversy and debate. 

 

Resources

 Greene, J. D. (2007). The secret joke of Kant's soul, in Moral Psychology, Vol. 3: The Neuroscience of Morality: Emotion, Disease, and Development, W. Sinnott-Armstrong, Ed., MIT Press, Cambridge, MA

 Greene, J.D. (2003) From neural "is" to moral "ought": what are the moral implications of neuroscientific moral psychology?  Nature Reviews Neuroscience, Vol. 4, 847-850

 “Morality,” Radiolab, wnyc

Meditation and Neuroscience

WIRED- 'Buddha on the Brain'

The 'science' of meditation...?

http://www.wired.com/wired/archive/14.02/dalai.html?pg=1&topic=dalai&topic_set=

The hot new frontier of neuroscience: meditation! (Just ask the Dalai Lama.)

The Dalai Lama has a cold. He has been hacking and sniffling his way around Washington, DC, for three days, calling on President Bush and Condoleezza Rice and visiting the Booker T. Washington Public Charter School for Technical Arts. Now he's onstage at the Washington Convention Center, preparing to address 14,000 attendees at the Society for Neuroscience's annual conference.

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The mood is tense. The State Department Diplomatic Security Service has swept the hallways for explosives. Agents stand at their posts.

The 14th incarnation of the Living Buddha of Compassion approaches the podium, clears his throat, and blows his nose loudly. "So now I am releasing my stress," he says. The audience dissolves into laughte.

The Dalai Lama is here to give a speech titled "The Neuroscience of Meditation." Over the past few years, he has supplied about a dozen Tibetan Buddhist monks to Richard Davidson, a prominent neuroscience professor at the University of Wisconsin-Madison. Davidson's research created a stir among brain scientists when his results suggested that, in the course of meditating for tens of thousands of hours, the monks had actually altered the structure and function of their brains. The professor thought the Dalai Lama would make an interesting guest speaker at the Society for Neuroscience's annual meeting, and the program committee jumped at the chance. The speech also gives the Tibetan leader an opportunity to promote one of his cherished goals: an alliance between Buddhism and science.

But the invitation has sparked a noisy row within the neuroscience community. To protest the talk, some scientists set up an online petition, which was immediately hacked by the pro-Dalai Lama faction. Others are boycotting the event or withholding their conference papers. Still others have demanded - unsuccessfully - time for a rebuttal.

All of which may explain the lama's ailment. "His Holiness' cold is a manifestation of the opposition of some scientists to his coming to the conference," a young Chinese Buddhist explains to me.

The protesters complain that the Tibetan leader isn't qualified to speak about brain science. They fret that he'll draw media attention away from important findings presented at the conference. Worst of all, his presence muddles the distinction between objective inquiry and faith. "We don't want to mix science and religion in our children's classrooms," says Bai Lu, a researcher at the National Institutes of Health, "and we don't want it at a scientific meeting."

One of the petition organizers, Lu Yang Wang, is even more blunt: "Who's coming next year?" he asks. "The pope?"

Richard Davidson, 54, is at once a distinguished scientist and an avid spiritual seeker. He became fascinated with meditation in the '60s. As a graduate student at Harvard, he channeled that interest into the study of psychology and neuroscience. In his spare time, he hung out with Ram Dass, Timothy Leary's former LSD research partner turned mystic. Davidson traveled to India for a meditation retreat, then finished his doctorate in biological psychology and headed to the University of Wisconsin, where he now directs the Waisman Laboratory for Brain Imaging and Behavior.

The Dalai Lama learned of Davidson's work from other scientists and in 1992 invited him to Dharamsala, India, to interview monks with extensive meditation experience about their mental and emotional lives. Davidson recalls the "extraordinary power of compassion" he experienced in the Dalai Lama's presence.

A decade later, he got a chance to examine Tibetan Buddhists in his own lab. In June 2002, Davidson's associate Antoine Lutz positioned 128 electrodes on the head of Mattieu Ricard. A French-born monk from the Shechen Monastery in Katmandu, Ricard had racked up more than of 10,000 hours of meditation.

Lutz asked Ricard to meditate on "unconditional loving-kindness and compassion." He immediately noticed powerful gamma activity - brain waves oscillating at roughly 40 cycles per second -�indicating intensely focused thought. Gamma waves are usually weak and difficult to see. Those emanating from Ricard were easily visible, even in the raw EEG output. Moreover, oscillations from various parts of the cortex were synchronized - a phenomenon that sometimes occurs in patients under anesthesia.

The researchers had never seen anything like it. Worried that something might be wrong with their equipment or methods, they brought in more monks, as well as a control group of college students inexperienced in meditation. The monks produced gamma waves that were 30 times as strong as the students'. In addition, larger areas of the meditators' brains were active, particularly in the left prefrontal cortex, the part of the brain responsible for positive emotions.

Davidson realized that the results had important implications for ongoing research into the ability to change brain function through training. In the traditional view, the brain becomes frozen with the onset of adulthood, after which few new connections form. In the past 20 years, though, scientists have discovered that intensive training can make a difference. For instance, the portion of the brain that corresponds to a string musician's fingering hand grows larger than the part that governs the bow hand - even in musicians who start playing as adults. Davidson's work suggested this potential might extend to emotional centers.

But Davidson saw something more. The monks had responded to the request to meditate on compassion by generating remarkable brain waves. Perhaps these signals indicated that the meditators had attained an intensely compassionate state of mind. If so, then maybe compassion could be exercised like a muscle; with the right training, people could bulk up their empathy. And if meditation could enhance the brain's ability to produce "attention and affective processes" - emotions, in the technical language of Davidson's study - it might also be used to modify maladaptive emotional responses like depression.

Davidson and his team published their findings in the Proceedings of the National Academy of Sciences in November 2004. The research made The Wall Street Journal, and Davidson instantly became a celebrity scientist.

Not everyone was impressed. Yi Rao, a professor in the neurology department at Northwestern University, dismisses Davidson's study as rubbish. "The science is substandard," he says. "The motivations of both Davidson and the Dalai Lama are questionable."

As a leader of those opposing the Dalai Lama's speech, Rao criticizes Davidson for being a "politically involved scientist" who engineered the Dalai Lama's invitation to lend scientific legitimacy to Buddhism and press the Chinese government to ease up on Tibet.

But the political critique cuts both ways. Rao is Chinese, as are more than half of the 544 cosigners of the petition protesting the Dalai Lama's lecture. Many in the neuroscience community believe that Chinese opposition to the speech is fueled by the Chinese government's long-running propaganda campaign against the Tibetan leader. "It's pretty transparent," Davidson says.

Still, the broader point of Rao's argument has undeniable force: Davidson's close personal relationship with the Dalai Lama is unseemly. Scientists are supposed to maintain professional distance from individuals and organizations that support their research and have a stake in the outcome. If Davidson were receiving corporate support to study the effects of ice cream on the brain's pleasure centers, he wouldn't hang out with Ben and Jerry. Yet he's frequently seen with the Dalai Lama, whom he clearly reveres.

Davidson bristles at this charge. "I tremendously value my relationship with His Holiness and feel it has benefited my research," he says with a thin smile. "I have no intention of giving it up."

The Dalai Lama's fascination with science dates to his childhood, when young Tenzin Gyatso (his birth name) found a brass telescope that had belonged to his predecessor. For years he has been meeting with leading figures in physics and biology to broaden his understanding. He's still scratching his shaved head over quantum mechanics.

The Tibetan leader believes that Buddhism and science have much in common. Both are investigative traditions that seek to explain reality. He admires the power of the scientific method and has famously stated his willingness to jettison Buddhist doctrines shown by science to be false. However, since much of Buddhist doctrine - reincarnation, for instance - is inherently untestable, many of the Dalai Lama's beliefs remain insulated from scientific critique.

Ultimately, Buddhists and scientists hold very different views of the universe. Buddhists believe that mental and physical realms have an equal claim on reality. That is, mental constructs that science considers imaginary are, to Buddhists, objectively real and perceptible. In contrast, neuroscientists are materialists. The mind can't be separated from the physical circumstances that give rise to it. In this regard, Davidson's views hew to the scientific mainstream. "I believe mind is an emergent property of brain," he says. "Mind depends upon brain." The Dalai Lama has agreed to set this point aside for the time being.

What Buddhism has to offer science is a way to examine consciousness from the inside - though it wouldn't normally be accepted as scientific. Neuroscience approaches the brain the same way Western science views all problems: from an external, objective perspective the Dalai Lama calls "third-person." Buddhist meditation provides an introspective, first-person way to study consciousness; meditators can report their findings to scientists. "If we very precisely look at when a thought arrives, what it does … all that is very empirical," Ricard said in a 2003 radio interview. "If different meditators reproduce the same descriptions," it "has the character of science because it's experimental."

As much as the Dalai Lama enjoys dabbling in science, he has a greater purpose: to alleviate suffering. Buddhism has an extensive toolkit of techniques intended to reduce misery and perfect humanity through quieting the mind and cultivating compassion. The Dalai Lama wants to extract these methods from their religious context and ground them in the science of the brain in the hope that they will be widely adopted.

On this, Davidson and the Tibetan leader agree. Kids take PE, Davidson points out. "Wouldn't it be wonderful if they also attended a class called ME - mental education? The scientific work we're doing is providing one small piece of that larger message."

Standing onstage at the Washington Convention Center, the Dalai Lama clears his throat one last time and addresses the Society for Neuroscience.

If there is a prepared speech, he's ignoring it. For the next 30 minutes, in broken English and through his interpreter, he riffs on his childhood interest in science. "Curiosity is part of my life, part of my self. Look at this body. Some areas have more hair, some less. Why?" He stresses the importance of ethics in pursuit of scientific answers. He's especially concerned that researchers are not paying enough attention to the development of "warmheartedness." Like charity, this quality begins at home. "Come home and be with your wife, your husband, or your children," he beseeches the assembled neuroscientists, "and feel happy!"

A few minutes later, he departs in a swarm of aides and security personnel.

Opponents of the Dalai Lama's appearance fear a breach in the barrier between science and religion. For now, though, brain researchers are staying on their side of the wall. Davidson is the first to admit that his studies haven't proven that compassion is a skill to be cultivated - though clearly he believes it is. "The honest answer is, we don't know," he says, "which is why longitudinal studies are necessary."

Such research is just beginning. Experiments that will follow novices through months of intensive training - the only way to test whether meditation actually changes the brain - are starting up at UC San Francisco and UC Davis. Meditation research is blossoming at a dozen universities, including Harvard and Princeton.

Amid the flurry of Buddhist-inflected inquiry, however, there's a risk that researchers' beliefs and desires will influence the results of their experiments. Already the Mind & Life Institute, an organization cofounded by the Dalai Lama to foster dialog between researchers and mystics, sponsors summer programs that are part scientific discourse, part Buddhist retreat. These programs, Davidson says, are "producing a hybrid discipline of dharma practitioners and scientists." The scientific method is designed to counteract the bias of faith, but adulterating scientific objectivity with a first-person perspective makes it more likely that researchers will see what they want to see.

A few days before the Dalai Lama addressed the Society for Neuroscience, he stood before a similarly eminent crowd at the Mind & Life Institute's 13th annual meeting. The audience of 2,500 consisted mostly of scientists and clinicians, yet the mood was more dharma than Darwin. Sessions opened to the guttural chants of Tibetan liturgical music. Everyone stood and bowed when His Holiness entered the room.

During one presentation, Duke University professor of medicine Ralph Snyderman paused to tell His Holiness, "This is one of the most wonderful moments of my life, being here with you." It was a touching gesture. It also crystallized the dilemma. Scientists can try to test the validity of the Dalai Lama's first-person perspective. But if they allow reverence for him to cloud their judgment, they will cease to be scientists and take rebirth as something quite different: acolytes.

John Geirland (geirland@aol.com) wrote about radio telescopes in issue 12.02.

Article:

http://psyphz.psych.wisc.edu/web/pubs/2004/meditators_synchrony.pdf

BIG-HEADED with BIG BRAINS!!!

WHAT IS SELF-ESTEEM?
http://kidshealth.org/kid/feeling/emotion/self_esteem.html


DETAILS CONCERNING DR.SONIA LUPIEN'S RESEARCH
http://reporter-archive.mcgill.ca/Rep/r3016/lupien.html

DR. SONIA LUPIEN'S "STRESS, MEMORY, AND AGING" VIDEO

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Low self-esteem 'shrinks brain' By Pallab Ghosh BBC Science Correspondent Brain size was measured People with a low sense of self worth are more likely to suffer from memory loss as they get older, say researchers. The study, presented at a conference at the Royal Society in London, also found that the brains of these people were more likely to shrink compared with those who have a high sense of self esteem. Dr Sonia Lupien, of McGill University in Montreal surveyed 92 senior citizens over 15 years and studied their brain scans. She found that the brains of those with low self-worth were up to a fifth smaller than those who felt good about themselves. These people also performed worse in memory and learning tests. Retraining Dr Lupien believes that if those with a negative mind set were taught to change the way they think they could reverse their mental decline. He said: "This atrophy of the brain that we thought was irreversible is reversible - some data on animals and some data on humans shows that that if you enrich the environment if you change some factors this brain structure can come back to normal levels" Researchers are studying which psychological treatments work best. According to Dr Felicia Huppert of Cambridge University - the early signs are that fairly simple techniques can have an enormous impact: "There are interventions which talk about focusing on positive things in everyday life and savouring good moments even at times when life is difficult little tiny things may give you pleasure so there are skills involved in how to derive pleasure from the ordinary things in life". 'Reversed' According to Dr Lupien, the fear of memory loss may be a self fulfilling prophesy as anxiety leads to negative thinking which leads to mental impairment. "If you always think it's normal to lose something, then you will never work to increase it because doctors have always told you that. I'm saying that it is not normal. "So this might impact positvely on the public by saying that its possible to impact on increasing your memory performance and by saying that it is normal to have a fulfilling life, we may be able to increase self esteem among the general public - and prevent a lot of these deficits related to age". SEE ALSO: Attention drugs 'do not shrink brain' 08 Oct 02 | Health Chemical loss leads to brain decline 02 May 03 | Health Snails on trail of memory loss 24 Sep 01 | Health RELATED INTERNET LINKS: Royal Society The BBC is not responsible for the content of external internet sites TOP HEALTH STORIES US reports first swine flu death Genes 'have key role in autism' Over-40s may benefit from aspirin | News feeds

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Confidence In Memory Performance Helps Older Adults Remember

ScienceDaily (Mar. 8, 2006) — Believing that you can retain a good memory even in your twilight years is the first step to achieving that goal. Those who believe they can control their memory are more likely to employ mnemonic strategies that help keep memory fit despite the march of time. These are the conclusions of a new Brandeis study published in the Journals of Gerontology: Psychological Sciences.
See also:
Health & Medicine

* Healthy Aging
* Alzheimer's Research
* Menopause

Mind & Brain

* Memory
* Dementia
* Educational Psychology

Reference

* Memory bias
* Amnesia
* Memory
* Emotional detachment

The study demonstrates a link between actual cognitive functioning and a low sense of control, and examines whether the relationship between control beliefs and memory performance varies for young, middle-aged, and older adults and whether using mnemonic strategies influences memory performance.

"One's sense of control is both a precursor and a consequence of age-related losses in memory," says lead author Margie Lachman, professor of psychology and director of the Lifespan Lab at Brandeis University. "Our study shows that the more you believe there are things you can do to remember information, the more likely you will be to use effort and adaptive strategies and to allocate resources effectively, and the less you will worry about forgetting."

Funded by the National Institute on Aging, the study involved 335 adults, ages 21 to 83, who were asked to recall a list of 30 categorizable words, such as types of fruit and flowers. Middle-aged and older adults who perceived greater control over cognitive functioning were more likely to categorize the words and had better recall performance, Lachman notes.

"It's no surprise that age-related losses or lapses in memory can challenge our deeply embedded sense of control," says Lachman. "Thus, we find an increase with age in beliefs that memory declines are an inevitable, irreversible, and uncontrollable part of the aging process. These beliefs are detrimental because they are associated with distress, anxiety, and giving up without expending the effort or strategies needed to support memory."

In fact, even young people have problems with memory performance, though they typically chalk it up to distraction or other external factors. In contrast, older adults are more likely to judge their forgetfulness an inevitable fact of aging or even a warning sign of Alzheimer's disease, leading to anxiety and despair.

Those who don't use adaptive strategies for remembering often have the expectation that there is nothing they can do to improve memory. The study's results suggest that interventions that target conceptions of control over memory could be effective for improving strategy use and enhancing memory in middle and later adulthood.


Adapted from materials provided by Brandeis University, via EurekAlert!, a service of AAAS.
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Adaptive Evolution of Genes Underlying Schizophrenia

Bernard Crespi, Kyle Summers, Steve Dorus

The Royal Society

Biological Sciences

Nov. 2007 Vol. 274

http://rspb.royalsocietypublishing.org/content/274/1627/2801.full?sid=e8a8b351-4292-432e-9fd2-6633fa7be225#ref-39

 

Introduction

Schizophrenia afflicts close to 1% of the entire world’s human population.  Recent theories, especially in the genetics field have begun to suggest potential resolutions to this mind crippling disorder.  One evolving theory claims that “genetic liability to schizophrenia has evolved as a secondary consequence of selection for human cognitive traits”[1].  Recent studies have tested the hypothesis that certain schizophrenia-associated genes have been evolutionarily subject to positive selection.  If this hypothesis proves correct then schizophrenia would technically “represent a maladaptive byproduct of adaptive changes during human evolution”1. 

What is Schizophrenia?

When people think of this disorder, often times they think of John Nash’s disjointed conversations with invisible people about his paranoid delusions and his brilliant mathematical discoveries scribbled obsessively on dorm room windows.   We often associate schizophrenia with pure and distilled insanity that at times can breed brilliance with the heavy price of social ineptitude.  Schizophrenia literally means “split brain” which suggests a dissociation of what we consider “normally” integrated brain functions.  The disorder is characterized by somatosensory delusions including visual and auditory hallucinations.  This could include seeing things or people that aren’t there or hearing voices in one’s head or from the outside world.  Some of the symptoms of schizophrenia include a loss of coherence and cogent thought with severe damage to logical cognition especially in language and appropriate social and emotional behavior.  Though symptoms vary from case to case, the end results fall in the same category of extreme mental and social dysfunction. 

Schizophrenia has a polygenetic basis, which involves numerous genes of small effect.  “Phenotypic effects represent one end of a continuum that grades into schizotypal cognition and to normality” 1. 

On a neurological level, there has been evidence in favor of schizophrenia’s effect on neuronal pathways, especially the neurotransmitter dopamine.  “Increased dopamine activity in the mesolimbic pathway of the brain”[2] has been long associated with schizophrenia.  In most cases, treatment for this disorder involves a drug therapy that decreases dopamine activity by blocking these receptors. 

What is Positive Selection?

In the study we are reviewing it is crucial to understand what is meant by positive selection.   As we delve into the world of genetic evolution, we see that certain genes have been historically either permanently integrated or weeded out of every species genetic makeup.  When we talk about positive selection, it is referring to the fact that over a certain period of time, either spanning back to the earliest forms of sentient life or on a more recent time line specific genes have remained present, which suggests that the genes carry some adaptive quality in the furthering of the species’ evolution.  

The Study

This study involved an analysis of the molecular evolution of 76 genes.  The “criterion for inclusion of schizophrenia-linked genes was genetic association with the disorder via association studies (comparing allele frequencies or genotype distributions between cases and controls), or via family-based transmission–disequilibrium studies that test for differential inheritance of alleles between affected and non-affected siblings. We excluded all genes that were linked with schizophrenia in single studies, which were subject to failed replication attempts. The list of 76 such genes used here (electronic supplementary material) is highly congruent with that of Schmidt-Kastner et al. (2006) and was fully assembled prior to our analyses”¹.  They used two methods of measurement: a linkage disequilibrium-based method in order to test for evidence of recent selective sweeps which involves relatively large coding and non-coding genomic regions and a phylogeny-based maximum-likelihood method used for detecting positive selection based on ratio the ratio of non-synonymous to synonymous substitution rates (the evolutionary substitution of one base for another in an exon of a gene coding for a protein, such that the amino acid sequence produced is not modified[3]).  This method also takes into account the scientific philosophy that a hypothesis of any kind must reflect the most likely sequence of evolutionary events as DNA changes over time. 

As we know, Schizophrenia is directed by many genes of small effect, which complicates the detection process by requiring extremely large samples. 

Types of Analyses

Þ  HapMap Analysis:  recent positive selection is often detected through the identification of selective sweeps.  Selection for a specific allele causes a relatively large block of surrounding DNA (extended haploytpe) to increase in frequency.  A test has recently been developed that identifies selective sweeps using data from the human haplotype map.  This HapMap is based on the human genome, which aids in the discovery of human genetic variations.  In order to test for statistically higher indication of positive selection in schizophrenia-associated genes, this analysis compared the frequency of positive selection in the set of 76 genes previously selected with the same frequency in a set of 300 control genes. 

Þ   PAML Analysis:  this level of analysis used orthologous mammalian genes sequences for human subjects.  They tested codon and branch specific models (that represented periods when evolutionary changes appeared to spur the rise of schizophrenia) to identify the action of positive selection.  This branch included human, basal-primate and human-chimpanzee lineages for each gene.  For the detection of positive selection, they used Model A that identifies selection of specific codons along specific branches of the phylogenetic tree.  Model A consisted of four categories of selection on codon sites in sequence W₁=1, W₀<1.  If the maximum-likelihood resonated with a category of sites W<1 style="mso-spacerun: yes">  To test higher indication of positive selection in schizophrenia-associated genes, they compared the frequency of positive selection in the 76 genes with 120 control genes randomly chosen from the 300 from the HapMap analysis. 

Results

Þ   HapMap Analysis

14/76 genes showed significantly more signs of recent positive selection in comparison to the control genes

6/14 genes showed signs that the selection was localized specifically to the focal gene

4/14 genes showed signs of recent selection in more than one human population (the rest only in one population)

Þ   PAML Analysis

4 genes: on human lineage

7 genes: earlier in human-chimpanzee lineage

11/76 schizophrenia-associated genes showed evidence for positive selection versus 10/120 control genes

Discussion

The results of this study strongly suggest that positive selection occurs more frequently in schizophrenia-associated genes than in control genes.  Taking the maximum-likelihood method into account, it is clear that evolutionary changes are what brought this disorder into existence, and the evidence from this study suggests that it is evolution that is bolstering its genetic integration today.  No ones is going to argue that this disorder is socially or neurologically adaptive; on the surface.  Neurological research has determined that the areas of the brain that are most differentially dysregulated in schizophrenia include regions most subject to differential evolutionary change.  “Positive selection for differential expression between humans and chimpanzees are differentially dysregulated in the dorsolateral prefrontal and orbitofrontal cortices of individuals with schizophrenia”¹.  This link between genetic favoritism and neurological functioning cannot be a coincidence.  Previous studies have examined the correlations between schizophrenia-associated genes and creativity, imagination, creative and artistic skills and beneficial insight into problem solving.  It appears that alleles of several schizophrenia-associated genes have a significant effect on these faculties.  On a fundamental level, this cognitive association could begin to explain why genetically speaking, schizophrenia is adaptive. 

Limitations and Implications

Þ   The genes tested effect various other neurological, psychological and physiological conditions

Þ   Controversy about what constitutes adequate statistical demonstration of association between allelic variations of a specific gene and schizophrenia

 

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[1] http://rspb.royalsocietypublishing.org/content/274/1627/2801.full?sid=e8a8b351-4292-432e-9fd2-6633fa7be225#ref-39

 [2] http://en.wikipedia.org/wiki/Schizophrenia#Schneiderian_classification

[3] http://en.wikipedia.org/wiki/Synonymous_substitution

Willpower: A Game of Strategy

http://www.npr.org/templates/story/story.php?storyId=102728123

To the Brain, God is Just Another Guy

http://www.npr.org/templates/story/story.php?storyId=101617951


Below is the published findings of these experiments by Kapogiannis, et al:
http://www.clarin.com/diario/2009/03/10/um/estudiofereligiosa.pdf

These are just some examples of the God Experiments (this is some background material for my paper, so you do not have to read this):
http://discovermagazine.com/2006/dec/god-experiments/?searchterm=god%20experiments

Schizophrenia: The Curse That's Almost a Blessing

http://discovermagazine.com/2007/dec/schizophrenia-the-curse-thats-almost-a-blessing/?searchterm=schizophrenia