Biological Psychology Links

By Steve Connor, Science Editor A revolutionary way of screening the entire human genome for the genetic signposts of disease has produced its latest success – the first inherited link to common migraine and a possible reason for extreme headaches. The technique, which scans all 23 pairs of human chromosomes in a single sweep, has found the first genetic risk factor that predisposes someone to the common form of migraine, which affects one in six women and one in 12 men. The discovery has immediately led to a new possible cause of migraine by alerting scientists to DNA defects involved in the build-up of a substance in the nerves of sufferers that could be the trigger for their migraines. Scientists believe the findings could lead both to a better understanding as well as new treatments for the chronic and debilitating condition which is estimated to be one of the most costly brain-related disorders in society, causing countless lost working days. Scanning the entire blueprint of human DNA by genome-wide association studies (GWAS) has had a profound effect on the understanding of a range of other medical conditions over the past few years, from heart disease and obesity to bipolar disorder and testicular cancer. The study of migraine, published in the journal Nature Genetics, was an archetypal example of the new approach of medical genetics using the GWAS technique. Scientists analysed the genomes of some 5,000 people with migraine and compared their DNA to that of unaffected people to see if there were any significant differences that could be linked statistically to the condition. ©independent.co.uk

by Jon Cohen Thirty-five years ago, researchers studying chimpanzees in the wild noticed that neighboring communities had distinct grooming behaviors that could not be explained by differences in their environments. They contended that these behavioral idiosyncrasies were learned, or "cultural," and other scientists soon began noting group-specific tool uses and courting behaviors that also didn't appear to be environmental. But in a new study, researchers say some of these behaviors may be genetic after all. Before that 1975 revelation, few researchers had observed different communities of wild chimpanzees, and no one had even recognized that these behavioral differences existed. Investigators have been arguing about whether chimps truly have culture ever since. Proponents of culture published a landmark Nature paper in 1999 documenting 39 behaviors that were frequently observed in some communities and never seen in others. In the article's wake, a flood of reports began to appear about culture in other species, and the debates roiled on, with endless discussions about the meaning of the word itself. The new study, published online tomorrow in the Proceedings of the Royal Society B, examines partial sequences of the mitochondrial DNA (mtDNA) from wild chimpanzees in nine different groups. This DNA is handy because it's inherited only from mothers, and only chimp females typically move to new communities. Team members examined the links between the groups and 38 of the 39 supposed cultural variants documented in the earlier report. The study does not link behaviors to specific genes or even conclude that there is a genetic explanation. Rather, it assesses whether genetic differences can be excluded as an explanation for each behavior; it finds that they cannot more than half the time. © 2010 American Association for the Advancement of Science.

By Nicholette Zeliadt Down's syndrome (DS) is an incurable, heritable disorder affecting an estimated 400,000 people in the U.S. It is characterized by impaired cognitive ability and abnormal physical growth. Whereas scientists have long known that DS is caused by inheriting an extra copy of all or part of chromosome 21, the underlying cause of the brain defects common in Down's patients has not been fully gleaned. Now, a collaborative team of scientists working with a mouse model of DS has discovered that just two genes are responsible for the majority of the brain abnormalities present in their animals. The scientists hope that their findings will help scientists understand brain defects in humans with the disorder as well as aid in the development of drugs to treat the cognitive impairment in Down's patients. Previous studies suggest that brain defects in DS mice occur very early, while the mice are still developing embryos. These defects result from abnormalities in how brain neurons communicate with each other—either via excitatory signals, which stimulate other neurons to communicate, or inhibitory signals, which act to prevent other neurons from firing. During embryonic development, the proper ratio of excitatory and inhibitory neurons is established for optimal brain function. These electrical circuits are the basis for memory formation and learning. Human chromosome 21 has more than 300 genes on it. Some of the features of DS—including cognitive deficits, heart defects, gastrointestinal problems and poor muscle tone—could therefore result from having either an additional copy of a single gene on chromosome 21; combinations of extra genes; or from the effects some redundant genes may exert on other chromosomes' genes. This complexity has significantly slowed the pace of researchers' attempts to understand the genetic basis of how such a diverse array of symptoms and abnormalities arise. © 2010 Scientific American,

By Bruce Bower Here’s some not-so-sobering news for party people, barhoppers and clubgoers. Individuals who inherit a particular gene variant that tweaks the brain’s reward system are especially likely to drink a lot of alcohol in the company of heavy-boozing peers. That’s the preliminary indication of a new study directed by psychology graduate student Helle Larsen of Radboud University Nijmegen in the Netherlands. Adults carrying at least one copy of a long version of the dopamine D4 receptor gene, dubbed DRD4, imbibed substantially more alcohol around a heavy-drinking peer than did others who lacked that gene variant, Larsen’s group reports in a paper published online July 7 in Psychological Science. “Carriers of the long gene may be more attuned to, and influenced by, another person’s heavy drinking than noncarriers are,” Larsen says. Her study provides the first evidence that a gene influences human alcohol use in social situations. Scientists have yet to decipher the precise brain effects of DRD4’s long form. Larsen hypothesizes that in the presence of heavy drinkers, the gene variant may increase dopamine activity in brain areas that amplify alcohol’s appeal as a rewarding social activity. © Society for Science & the Public 2000 - 2010

Steve Connor Huntington’s disease is a relatively rare genetic disorder that you wouldn’t wish upon your worst enemy. If you carry a single copy of the affected gene you are destined to die a horrible death involving uncontrollable movements, psychiatric disturbances and progressive dementia. The first symptoms typically occur around the age of 40, and it takes between 10 and 15 more years for the gradual neurodegeneration to end life. Ten years after the excitement of mapping the human genome, and the revolution in the understanding of genetic disorders that the achievement has brought, it is easy to forget that some of those directly affected by inherited diseases have seen little in terms of practical benefit. The gene involved in Huntington’s disease was mapped to chromosome 4 in 1983 by a team led by Jim Gusella at Harvard Medical School in Boston, but it took another 10 years of intensive effort to isolate and clone the gene itself. This allowed scientists to find the type of changes, or mutations, that cause the disorder – the mutated gene has about two or three times the normal number of ‘GAG repeats. I remember on both occasions – in 1983 and 1993 – there were optimistic predictions that the discoveries would soon lead to a test for the carriers of the Huntington’s mutation and effective treatments – even possibly a cure – for the disease. The sad fact is that although a relatively cheap and accurate diagnostic test for the Huntington’s mutation has existed for some years, this medical advance has for the affected families arguably produced more misery than it has eradicated. For a start, there has been no accompanying revolution in treatment, largely because there are so few affected people (estimated to be about 12,000 in Britain) to make it worth the expense and effort of the drug companies to develop new therapies. ©independent.co.uk

by Bob Holmes, Eugene, Oregon EXTROVERTS are born not made - or at least, that's what they say. But what if it's more subtle than that? What if we tailor our personalities to our surroundings to make the most of our genes? Conventional comparisons between identical and fraternal twins indicate that nearly half of individual differences in personality traits have some underlying genetic cause. So people have tended to think of personality traits as largely determined by genes, says evolutionary psychologist Aaron Lukaszewski of the University of California at Santa Barbara. He felt there was a flaw in this thinking: if personality were rigidly determined, individuals could end up with the "wrong" personality type for their circumstances. Being extrovert, for instance, exposes people to social conflict. Wimpy men are more likely to suffer in such encounters, while hunkier men may benefit from putting good genes on display. To avoid mismatches, Lukaszewski reasoned, evolution must have favoured a more flexible system. To test this idea, he measured the strength of 85 male and 89 female students and asked them to rate their own attractiveness relative to their peers. Then he gave each a standard personality test to measure how extrovert they were. Sure enough, stronger and more attractive men, and more attractive women, were more extrovert, Lukaszewski reported at a June meeting of the Human Behavior and Evolution Society in Eugene, Oregon. © Copyright Reed Business Information Ltd.

Greg Miller Michael Meaney and Moshe Szyf work in the same Canadian city, but it took a chance meeting at a Spanish pub more than 15 years ago to jump-start a collaboration that helped create a new discipline. Meaney, a neuroscientist at the Douglas Mental Health University Institute in Montreal, studies how early life experiences shape behavior later in life. Across town at McGill University, Szyf is a leading expert on chemical alterations to DNA that affect gene activity. Sometime in the mid-1990s, both men attended the same meeting in Madrid and ended up at a bar talking and drinking beer. "A lot of it," Szyf recalls. Meaney told Szyf about his findings that rat pups raised by inattentive mothers tend to be more anxious as adults than pups raised by more nurturing mothers. He also described how the activity of stress-related genes was altered in the undernurtured pups. At some point in the conversation, Szyf had a flash of insight: This difference must be due to DNA methylation—the chemical alteration he had been studying in stem cells and tumor cells. The idea cut against the conventional thinking in both fields. In neuroscience, the prevailing wisdom held that long-term changes in behavior result from physical changes in neural circuits—such as when neurons build new synapses and become more sensitive to messages from their neighbors. And most scientists who studied DNA methylation thought the process was restricted to embryonic development or cancer cells. © 2010 American Association for the Advancement of Science. All Rights Reserved.

UCLA scientists have developed a fast new way to image how thousands of genes misfire proteins in a mouse model of Parkinson’s disease. The approach may provide a research blueprint for pinpointing the abnormal brain regions linked to autism and schizophrenia. The new findings are reported in the June edition of Genome Research. Last year, UCLA pharmacologist Desmond Smith developed a new method to rapidly track how genes express proteins in the human brain. Called “voxelation,” the approach involves cutting the brain into cubes, then using DNA chip technology and math to reconstruct gene expression patterns in three-dimensional images. This time, Smith used voxelation to compare gene expression in the brains of mice. Half of the mice received drugs to induce Parkinson’s disease. The UCLA team analyzed the brain cubes with DNA chips to track the expression of 9,000 genes simultaneously. They then combined the 9,000 resulting images to visualize how the genes construct the brain.

Several lines of evidence suggest that a partially genetically controlled serotonergic dysfunction is involved in the biological pathogenesis of suicide. To investigate the involvement of serotonergic dysfunction in suicide victims, Japanese scientists measured the protein level of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis, as a pre-synaptic maker. They also measured serotonin receptor 2A (5HT2A receptor) density as a post-synaptic marker in the serotonergic system in postmortem brains of 10 suicide victims and 12 controls. In addition, to clarify the genetic involvement in serotonergic function, the authors examined whether the variations of the TPH gene could affect TPH protein level, and whether those of the 5HT2A receptor gene could affect 5HT2A receptor density in 28 postmortem brain samples. No significant differences were found in TPH protein level or 5HT2A receptor density between suicide victims and controls. There was a significant negative correlation, however, between TPH protein level and 5HT2A receptor density. The variation of the TPH gene (the A218C polymorphism: a single base transition, A to C) had a significant influence on both TPH protein level and 5HT2A receptor binding. The AA genotype of the A218C polymorphism of the TPH gene showed higher TPH protein level along with lower 5HT2A receptor density than did any other genotypes in the postmortem brains of both suicide victims and controls.

Scientists at Northwestern University have discovered new clues into the chain of events that causes Alzheimer’s. As this ScienCentral News video reports, they wanted to settle the debate about plaques that form in the brain. Researchers have known for a while that plaques of protein in the brain play a role in Alzheimer's disease, the progressive, degenerative brain disease that currently devastates over 4 million Americans. These plaques are called beta-amyloid plaques, or "senile" plaques, and are thought of as the hallmark brain lesions of Alzheimer's. But brain researchers at Northwestern University's Cognitive Neurology and Alzheimer's Disease Center wanted to know if the plaque was just a symptom, or the cause of the disease. John Disterhoft, physiology professor at the Feinberg School of Medicine at Northwestern, studied this in mice. Disterhoft and his team genetically altered a strain of mice so that they would be prone to get Alzheimer's. They did this by giving the mice a human gene that causes excess formation of amyloid precursor protein, or APP. © ScienCentral, 2000-2003.

UCLA scientists report parallels between human speech and the song of a bird, findings that may contain clues to human speech disorders. The research by a team led by Stephanie White, UCLA assistant professor of physiological science, supports the theory that two genes shared by humans and songbirds, FoxP1 and FoxP2, may play a critical role in human speech, and speech disorders. The study is published March 31 in the Journal of Neuroscience. "We examined the expression of FoxP1 and FoxP2 in embryonic human brains and found a striking correspondence between bird and human expression," said White, a member of UCLA's Brain Research Institute. "The similar expression patterns suggest that songbirds can be studied to investigate neural mechanisms for vocal learning that may be parallel to those used by the human brain. "Our findings make it more likely that FoxP2 plays a critical role for learning speech and vocalization in both humans and the songbird," she said. "Understanding how FoxP1 and FoxP2 function in the songbird may reveal significant insights into human vocal learning and speech disorders."

By Jeff Wheelwright Pecos Road runs due west along the southern boundary of Phoenix. On the city side of the road, new subdivisions of retirement homes are pushing up their tile roofs like mushrooms that sprout with no rain. On the other side of the road lies the flat scrub of the Gila River Indian Community, some 600 square miles, most of it empty. The reservation shimmers out of the reach of the builders like a desert mirage. This land was no good to anyone in 1859, when it was allocated to the Pima Indians. Today it has 13,000 Native American residents, living in squat cinder-block houses in scattered, dusty hamlets; three casinos that have boosted the tribal income to $100 million annually from $4 million; irrigated cotton, alfalfa, and citrus, for Pimas were always farmers; and a hospital and two kidney-dialysis clinics, with another medical clinic in the planning stage. Kidney failure is a deadly complication of diabetes, and Pimas, so far as scientists can tell, have the world’s highest rate of type 2 diabetes. The Pimas have grown to hate this superlative perhaps more than the disease itself. Mary Thomas, the 60-year-old ex-governor of the tribe and presently its lieutenant governor, drove me around the community. A few miles south of Pecos Road, we came to the St. Johns Mission, a quiet, whitewashed church. There was once a Catholic boarding school for Indian children on the grounds. Thomas said that when she was 17 and in school here, she went for an eye test and was told she had diabetes. © 2004 The Walt Disney Company. All rights reserved

A gene that helps fruit flies develop alcohol tolerance has been found – and named “hangover”. The gene also controls the flies’ response to stress, and the researchers say that a similar pathway linking alcohol tolerance and stress probably functions in humans. The findings may explain why people who have been in a stressful situation often have a blunted response to alcohol and may drink more to feel inebriated, experts say, putting them at greater risk of becoming addicted. Ulrike Heberlein at the University of California at San Francisco, US, and Henrike Scholz from the University of W�rzburg in Germany, exposed fruit flies to ethanol vapour. Intoxicated fruit flies show similar behaviour to tipsy humans: they lack coordination and postural control and then fall asleep. It took the flies an average of 20 minutes to recover following their exposure. After four hours on the wagon, the same Drosophila were again exposed to alcohol. By now, they had developed a tolerance to alcohol and so needed more to reach the same drunkenness, and took longer to “dry out” - 28 minutes. But flies with a defective form of the hangover gene still took 20 minutes to recover from inebriation time after time - never building up a tolerance. The researchers then investigated how the gene was involved in stress responses since, in humans at least, the alcohol and stress responses appear to be linked. © Copyright Reed Business Information Ltd.

No matter how much you might hate hearing it, you know you do have you mother's eyes, or her hair, or her smile. How much you resemble your mother depends on which of her genes you inherit. But looking like her is not the only hold your mom's genes have on your life. There's mounting evidence that mom's genes may indirectly affect your weight and your health all the way into adulthood. "Not only are your genes important, and your environment — that is, how much you eat, how much dietary fat you eat — but also mom's genes are important," says geneticist Joseph Jarvis, perhaps influencing how your body is affected by what you eat. Jarvis, a researcher at Washington University School of Medicine in St. Louis, says that's because our mother's genes somehow affect how our bodies react to our prenatal and early environment (while nursing), switching certain of our genes on or off. This could have consequences throughout our lives, affecting our weight that could lead to health issues such as diabetes and high cholesterol. According to Jarvis, much of the earlier research into this effect had looked at weight gain of very young mice. This is because for "a two-week-old mouse, the only source of food they have is mother's milk. And we know that in mice, milk production has a genetic basis," he explains. "So it makes sense for the two-week weight to depend on who your mother was." © ScienCentral, 2000-2005.

Laser light has been used to remotely control gene therapy in rats. This mechanism will help make gene therapy more effective by allowing the precise time and location at which new genes are activated to be controlled, meaning specific tissues can be targeted while healthy tissues are left alone. Lasers have been used in the past to perforate cells for gene therapy in cultured cells. But the new research – activating marker genes in the eyes of rats – is more sophisticated and the first time lasers have been used for gene therapy in live animals. Kazunori Kataoka, at the University of Tokyo, Japan, and colleagues developed a photosensitive molecular complex that could be activated in rats’ eyes by irradiating them with visible light from a low power laser. The synthetic complex is designed to deliver foreign DNA by carrying it past the cell membrane – a process known as transfection. The complex consists of three components: a photosensitive anionic dendrimer, which provides the triggering mechanism, and a cationic peptide which drives the third component, its DNA payload, towards the nucleus of a cell after it has been released. The complex enters the cell by a process known as endocytosis, where the cell's plasma membrane envelops the complex at its surface and draws it into the cell. The membrane around the complex then detaches from the cell's membrane to form a bubble containing the complex within the cell. © Copyright Reed Business Information Ltd.

By NICHOLAS WADE On an animal-breeding farm in Siberia are cages housing two colonies of rats. In one colony, the rats have been bred for tameness in the hope of mimicking the mysterious process by which Neolithic farmers first domesticated an animal still kept today. When a visitor enters the room where the tame rats are kept, they poke their snouts through the bars to be petted. The other colony of rats has been bred from exactly the same stock, but for aggressiveness instead. These animals are ferocious. When a visitor appears, the rats hurl themselves screaming toward their bars. “Imagine the most evil supervillain and the nicest, sweetest cartoon animal, and that’s what these two strains of rat are like,” said Tecumseh Fitch, an animal behavior expert at the University of St. Andrews in Scotland who several years ago visited the rats at the farm, about six miles from Akademgorodok, near the Siberian city of Novosibirsk. Frank Albert, a graduate student at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, is working with both the tame and the hyperaggressive Siberian strains in the hope of understanding the genetic basis of their behavioral differences. “The ferocious rats cannot be handled,” Mr. Albert said. “They will not tolerate it. They go totally crazy if you try to pick them up.” Copyright 2006 The New York Times Company

By INGFEI CHEN Thirty years ago, Nick Patterson worked in the secret halls of the Government Communications Headquarters, the code-breaking British agency that unscrambles intercepted messages and encrypts clandestine communications. He applied his brain to “the hardest problems the British had,” said Dr. Patterson, a mathematician. Today, at 59, he is tackling perhaps the toughest code of all — the human genome. Five years ago, Dr. Patterson joined the Broad Institute, a joint research center of Harvard and the Massachusetts Institute of Technology. His dexterity with numbers has already helped uncover startling information about ancient human origins. In a study released in May, scientists at the Broad Institute scanned 20 million “letters” of genetic sequence from each of the human, chimpanzee, gorilla and macaque monkey genomes. Based on DNA differences, the researchers speculated that millions of years after an initial evolutionary split between human ancestors and chimp ancestors, the two lineages might have interbred again before diverging for good. The controversial theory was built on the strength of rigorous statistical and mathematical modeling calculations on computers running complex algorithms. That is where Dr. Patterson contributed, working with the study’s leader, David Reich, who is a population geneticist, and others. Their findings were published in Nature. Copyright 2006 The New York Times Company

A part of the brain first affected by Alzheimer’s disease (http://www.nia.nih.gov/Alzheimers/) is thinner in youth with a risk gene for the disorder, a brain imaging study by researchers at the National Institute of Mental Health (NIMH), one of the National Institutes of Health (NIH), has found. A thinner entorhinal cortex, a structure in the lower middle part of the brain’s outer mantle, may render these youth more susceptible to degenerative changes and mental decline later in life, propose Drs. Philip Shaw, Judith Rapoport, Jay Giedd, and NIMH and McGill University colleagues. They report on how variation in the gene for apoliproprotein (ApoE), which plays a critical role in repair of brain cells, affects development of this learning and memory hub in the June, 2007 Lancet Neurology. “People with the Alzheimer’s-related variant of the ApoE gene might not be able to sustain much aging-related tissue loss in the entorhinal cortex before they cross a critical threshold,” explained Shaw. “But the early thinning appears to be a harmless genetic variation rather than a disease-related change, as it did not affect youths’ intellectual ability. Only long-term brain imaging studies of healthy aging adults will confirm whether this anatomical signature detectible in childhood predisposes for Alzheimer’s.” It was already known that adults destined to develop Alzheimer’s disease tend to have a smaller and less active entorhinal cortex (http://www.nia.nih.gov/Alzheimers/ResearchInformation/NewsReleases/Archives/PR2000/PR20000329MRI.htm). This structure is the first to shrink in volume and to develop the neurofibrillary tangles (http://www.nia.nih.gov/Alzheimers/Publications/UnravelingTheMystery/Part1/Hallmarks.htm) characteristic of the disorder.

By Linda Carroll Janine Geredes is the kind of person many of us love to hate. No matter how much the Northern California woman eats, she never gets fat. While the rest of us obsess over every morsel passing through our lips, convinced we’ll pack on the pounds if we let our guard down for just one moment, Geredes worries she’ll become unappealingly bony if she doesn’t eat enough. “I’ve always had to work to keep weight on,” says Geredes, 43, who is 5 feet 6 inches tall and weighs 118 pounds. “When I was a growing up I was teased for being so thin. But now, people are always saying, ‘I wish I could eat like you. You stay so thin. You must work out a ton.’ I don’t. My son and daughter are the same way. I’ve always figured it was genetic.” As it turns out, Geredes may be right. Scientists now say they have discovered the “skinny” gene. And they’ve found this lucky batch of DNA in a variety of animals, according to a report published Tuesday in the journal Cell Metabolism. "This gene is in every organism from worms to humans," says the study’s senior author, Dr. Jonathan Graff, an associate professor of developmental biology and internal medicine at the University of Texas Southwestern Medical Center. "We all have it. It's very striking." © 2007 MSNBC.com © 2007 Microsoft

By BENEDICT CAREY BY age 2 it was clear that the boy had a sensibility all his own, affectionate and distant at the same time, often more focused on patterns and objects than the people around him. He was neither naturally social like his mother, nor an early and gifted reader like his father. Quirky, curious, exuberant, he would leap up and dance across the floor after solving a problem or winning a game, duck walking like an N.F.L. receiver posing for a highlight film. Yet after Phil and Susan Schwarz received a diagnosis for their son, Jeremy, of high functioning autism, they began to think carefully about their own behaviors and histories. Mr. Schwarz, a software developer in Framingham, Mass., found in his son’s diagnosis a new language to understand his own life. His sensitivities when growing up to loud noises and bright light, his own diffidence through school, his parents’ and grandparents’ special intellectual skills — all echoed through his and Jeremy’s behavior, like some ancient rhythm. His son’s diagnosis, Mr. Schwarz said, “provided a frame in which a whole bunch of seemingly unrelated aspects of my own life growing up fit together for the first time.” Researchers have long known that many psychiatric disorders and developmental problems run in families. Children born to parents with bipolar disorder, in which moods cycle between euphoria and depression, run about eight times the normal risk for developing a mood problem. Those born to parents with depression run three times the usual risk. Attention and developmental disorders like autism also have a genetic component. Copyright 2007 The New York Times Company

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