Biological Psychology Links

By MATTHEW PERRONE WASHINGTON — Andrew White returned from a nine-month tour in Iraq beset with signs of post-traumatic stress disorder: insomnia, nightmares, constant restlessness. Doctors tried to ease his symptoms using three psychiatric drugs, including a potent anti-psychotic called Seroquel. Thousands of soldiers suffering from PTSD have received the same medication over the last nine years, helping to make Seroquel one of the Veteran Affairs Department's top drug expenditures and the No. 5 best-selling drug in the nation. Several soldiers and veterans have died while taking the pills, raising concerns among some military families that the government is not being up front about the drug's risks. They want Congress to investigate. In White's case, the nightmares persisted. So doctors recommended progressively larger doses of Seroquel. At one point, the 23-year-old Marine corporal was prescribed more than 1,600 milligrams per day — more than double the maximum dose recommended for schizophrenia patients. A short time later, White died in his sleep. "He was told if he had trouble sleeping he could take another (Seroquel) pill," said his father, Stan White, a retired high school principal. An investigation by the Veterans Affairs Department concluded that White died from a rare drug interaction. He was also taking an antidepressant and an anti-anxiety pill, as well as a painkiller for which he did not have a prescription. Inspectors concluded he received the "standard of care" for his condition. Copyright 2010 The Associated Press.

By Jim Nash Treatment of severe depression with magnetic stimulation is moving beyond large mental health centers and into private practices nationwide, following more than two decades of research on the treatment. Yet even as concern about its efficacy fades, one potential side effect—seizures—continues to shadow the technology. Called repetitive transcranial magnetic stimulation (rTMS), the noninvasive technique uses electromagnets to create localized electrical currents in the brain. The gentle jolts activate certain neurons, reducing symptoms in some patients. Eight psychiatrists contacted for this article, all of whom use rTMS to treat depression, say it is the most significant development in the field since the advent of antidepressant medications. The prevailing theory is that people with depression do not produce enough of certain neurotransmitters, which include serotonin and dopamine. Electricity (administered in combination with antidepressants) stimulates production of those neurotransmitters. A National Institute of Mental Health (NIMH) study released this spring shows that 14 percent of patients with drug-resistant major depressive disorder experience a remission of symptoms after rTMS treatment compared with a control group, which reported a 5 percent rate of remission. Physicians and researchers say those results are similar to the success rate of antidepressants. No notable side effects occurred during the study, according to its authors, who include Mark George, an early rTMS researcher and a professor of psychiatry, radiology and neurosciences at the Medical University of South Carolina in Charleston. They have suggested that higher levels of electrical stimulation might attain better results. © 2010 Scientific American,

Jerome Burne Sixty years ago, the philosopher Gilbert Ryle published his famous attack on Cartesian dualism, The Concept of Mind, which claimed to find a logical flaw in the popular notion that mental life has a parallel but separate existence from the physical body. Among other effects it provided sophisticated support for the psychological behaviourists, then in the ascendant, who asserted that since we could not objectively observe mental activity it was not really a fit subject for scientific investigation. Nowhere was the notion of banning mental states taken up more enthusiastically than by the emerging discipline of neuropsychiatry. If consciousness and all its manifestations were "merely" the firing of neurons and the release of chemicals in the brain, what need was there to focus on mental states? Once the physical brain was right, the rest would follow. It was an approach that has spawned a vast pharmaceutical industry to treat any pathological psychological state – anxiety, shyness, depression, psychosis – with a variety of pills. The underlying promise is that scientifically adjusting the levels of various brain chemicals will bring relief and a return to normality. The biggest-selling class of these drugs are the anti-depressant SSRIs – brands include Prozac, Seroxat and Lustral. A recent report revealed that they were the most widely prescribed drugs in America, with an estimated global market value of over $20 billion. However, as is set out calmly and clearly in Irving Kirsch’s The Emperor’s New Drugs, it would seem that the whole golden edifice is based on a lie. © Times Newspapers Ltd 2010

by Martin Enserink There's a new twist in the ongoing battle over whether a virus is linked to chronic fatigue syndrome (CFS). After the journal held it for 2 months, a study supporting a link between a mouse retrovirus and CFS was published today in the Proceedings of the National Academy of Science (PNAS). Many are still doubtful of the link, but they're impressed by the authors' efforts to ensure accuracy. In the new study, conducted by scientists at the National Institutes of Health (NIH), the U.S. Food and Drug Administration (FDA), and Harvard University, researchers scanned for traces of a virus known as XMRV in samples taken from 37 CFS patients, collected by Harvard Medical School CFS specialist Anthony Komaroff in the mid-1990s. They found evidence for the virus in 32 (87%) of the patients, but in only three out of 44 healthy controls (6.8%). It remains to be seen whether the infection causes the disease or vice versa, says NIH virologist and co-author Harvey Alter—but he's "confident" that the findings are correct. XMRV—less succinctly known as xenotropic murine leukemia virus-related virus—was first implicated for its potential involvement in prostate cancer, a link that's still under intense debate. Then, in a Science paper published last year, a team led by retrovirologist Judy Mikovits of the Whittemore Peterson Institute for Neuro-Immune Disease (WPI) in Reno, Nevada, found evidence of infection in 67% of CFS patients, compared with just 3.4% of healthy controls. But since then, four other papers failed to find the link, or any evidence of XMRV infection in humans at all. The last of the four, by researchers at the U.S. Centers for Disease Control and Prevention (CDC), was also held for a while, at the researchers' request, while they tried to figure out how government labs could come to such opposite conclusions. The CDC paper was eventually published on 1 July in Retrovirology. © 2010 American Association for the Advancement of Science.

By David Biello Ketamine—a powerful anesthetic for humans and animals that lists hallucinations among its side effects and therefore is often abused under the name Special K—delivers rapid relief to chronically depressed patients, and researchers may now have discovered why. In fact, the latest evidence reinforces the idea that the psychedelic drug could be the first new drug in decades to lift the fog of depression. "We were trying to figure out what ketamine was doing to produce this rapid response," which can take as little as two hours to begin to act, says neuroscientist Ron Duman of the Yale University School of Medicine. So Duman and his colleagues gave a small amount of ketamine (10 milligrams per kilogram of body weight) to rats and watched the drug literally transform the animals' brains. "Ketamine… can induce a rapid increase in connections in the brain, the synapses by which neurons interact and communicate with each other, " Duman says. "You can visually see this response that occurs in response to ketamine." More specifically, as the researchers report in the August 20 issue of Science, ketamine seems to stimulate a biochemical pathway in the brain (known as mTOR) to strengthen synapses in a rat's prefrontal cortex—the region of the brain associated with thinking and personality in humans. And the ketamine helped rats cope with the depression analog experience brought on by forcing the rodents to swim or exposing them to inescapable stress. "Preclinical and clinical studies show that repeated stress or depression can cause a decrease in connections and an atrophy of connections in the same region of the brain," Duman explains, noting that magnetic resonance imaging shows that some depressed patients have a smaller prefrontal cortex as a result. "Ketamine has the opposite effect and can oppose or reverse the effects of depression" for roughly seven days per dose. © 2010 Scientific American

By Jordan Lite Despite kids’ protests, enforcing early bedtimes may be good for their mental health. Teens who are allowed to go to bed later are more likely to suffer from depression—probably for the simple reason that they are not getting enough sleep, a recent study suggests. Columbia University scientists found that depression was 24 percent more common in teens whose parents let them go to bed at midnight or later than in kids whose moms and dads required them to hit the pillow by 10 p.m. The night owls were also 20 percent more likely to have suicidal thoughts. Teens with bedtimes of midnight or later got an average of seven and a half hours of sleep, whereas those with a lights-out of 10 p.m. or earlier got an average of eight hours and 10 minutes. Although the association between later bedtimes and depression was greater before controlling for parents’ marital status and poverty level, it remained statistically significant after taking those things into account—as well as teens’ perceptions of how much their parents cared about them. The researchers looked at parent-enforced bedtimes—as opposed to simply logging hours slept—to rule out the possibility that depression was causing some kids to sleep less, rather than the other way around. Earlier work supports the idea that too little sleep may lead to depression. Research at the University of London showed that children who suffer from insomnia are at increased risk of developing depression in their tweens and teens. © 2010 Scientific American

By Caroline Parkinson A new form of brain disease, similar to Creutzfeld-Jakob Disease, could affect more people than previously thought, researchers in the US say. It had been thought that only people with one genetic profile were vulnerable to the prion disease VPSPr. But in an Annals of Neurology study, Case Western Reserve University experts found people with all three possible gene patterns are affected by VPSPr. They say the findings could help with the treatment of prion diseases. Although it is a prion disease like vCJD, VPSPr is not linked to eating infected meat. However, like CJD, the new condition happens sporadically. It was first identified because of the fast-advancing form of dementia seen in those affected. They were also unable to speak or move. But tests for CJD proved negative. Further molecular examination showed VPSPr was a prion disease, but one which looked very different to those already known. The human prion protein gene comes in three variants, depending on which amino acid the prion proteins contain - valine (V) or methionine (M). People can be VV, MM or MV. The first clutch of cases identified all had the VV variant. However, these latest cases included people with the other variants too. Despite extensive research, a relatively large group of neurodegenerative diseases associated with dementia remain undefined. (C)BBC

By NICHOLAS BAKALAR A new study suggests that a 50-year-old drug commonly used as an anesthetic for humans and animals — and abused, as the drug called Special K — may deliver almost instant relief in some of the most troublesome cases of bipolar depression. It has been known for several years that small doses of the drug, ketamine, can relieve major depression. But this study, done by researchers at the National Institute of Mental Health, is the first to demonstrate efficacy in patients with treatment-resistant bipolar depression. Indeed, the researchers said, the effect on this group appeared to be even stronger. Although the study was small, with just 18 patients, it was conducted under the highest standards for a drug study: it was randomized, placebo-controlled and double-blinded. In bipolar disorder, sometimes called manic-depressive illness, patients cycle between periods of elation and severe depression, and the depressive phase carries a high risk of suicide. It is commonly treated with mood stabilizers, including lithium, anticonvulsants and some antipsychotics, often in complex combinations. Both mania and depression usually improve on these drugs. But when the depression remains, it is notoriously difficult to treat, so a fast-acting medicine with lasting effects would have obvious advantages. Ketamine probably acts by limiting the action of one type of brain receptor that moves nerve signals between neurons. Copyright 2010 The New York Times Company

Neuroscientists have long used EEGs to try to understand the brain.Neuroscientists have long used EEGs to try to understand the brain. (Str Old/Reuters) Psychiatrists and engineers have teamed up to help predict how people with schizophrenia will respond to a medication that can produce serious side-effects. Psychiatrists say clozapine is an effective treatment for chronic medication-resistant schizophrenia, but it can produce side-effects such as seizures, cardiac arrhythmias or bone marrow suppression and blood problems that require weekly to monthly blood tests to monitor. Now researchers at McMaster University in Hamilton have used machine learning to "train" a computer to predict whether a patient will respond to the drug based on the brainwave patterns and responses recorded on an EEG device readily available at hospitals and laboratories. "Now what we can do is predict beforehand whether the person is going to respond, so we only expose the patient to the risk if there's a very good chance the treatment will be effective," said study author James Reilly, a professor of electrical and computer engineering at McMaster. Reilly and his psychiatrist and engineering colleagues at the university were able to correctly predict whether 23 middle-aged people diagnosed with schizophrenia would respond to the drug with an accuracy of about 89 per cent, according to the study published in the current online issue of the journal Clinical Neurophysiology. © CBC 2010

By Dana Scarton Following a protocol demonstrated moments earlier, the Colorado youth pressed his bare hands against the rim of a urinal, licked each palm, then reached out to accept a Tic Tac. Before popping the mint into his mouth, Christian added a move of his own: He dropped it onto the tile floor and stomped on it. The ad lib elicited gasps, congratulatory pats on the back, and applause from onlookers crammed into the men's room on a lower level of the Hyatt Regency Crystal City. As the others took their turn at the bizarre ritual, Christian leaned on a wall outside, seeming pleased if perhaps a bit queasy. "I wanted to challenge myself," he said. Christian later told his father, Kern Low, that he would no longer struggle with paralyzing fears of contamination associated with public restrooms, a problem that had interfered with family outings for the past three years. Facing fears was the evening's objective for Christian and about 150 other people dealing with obsessive-compulsive disorder (OCD). Led by psychologist Jonathan Grayson, they were going "Virtual Camping" -- a two-hour after-dark excursion and germfest that was part of the 2010 International OCD Foundation Conference held at the Hyatt Regency last month. "What can you do in one night?" Grayson had asked as the evening began. "You can take a step toward learning how to deal with uncertainty." Then he led the participants into the steamy streets of Crystal City, where, among other things, they would be encouraged to shake the hand of a homeless man (to fight more contamination fears), to chant "Crash and burn" to passing motorists (to show that thoughts would not cause actual harm) and to touch ripe garbage with their bare hands (contamination, again). © 1996-2010 The Washington Post Company

Daniel Cressey After an epic series of experiments, a group of researchers has observed and reproduced what could be the spontaneous generation of prions — rogue misfolded proteins that have been implicated in the destruction of the central nervous system. These misfolded proteins, the culprits in Creutzfeldt–Jakob disease and scrapie, are highly infectious. Although famously transmitted by the ingestion of infected meats, prions are also thought to arise spontaneously in a tiny fraction of humans and other animals. Such de novo prion generation has previously been achieved with animal cells using a method called 'protein misfolding cyclic amplification' (PMCA), which involves repeated rounds of ultrasound and incubation. Now, a London-based team reports observing prions appearing from healthy mouse brain tissue1. (Human samples have traditionally proved less amenable to PMCA, and the misfolding of prion proteins is believed to occur at a much lower rate in humans than in mice.) "What we were doing was trying to develop a very sensitive assay for prion detection on a metal surface, so we could use that in prion decontamination," says co-author John Collinge, who heads up the Department of Neurodegenerative Disease at University College London. "It took a while before we could convince ourselves this was a real phenomenon." © 2010 Nature Publishing Group

by Linda Geddes IF YOU thought depression was caused by low serotonin levels, think again. It looks as if the brain chemistry of a depressed person is much more complex, with mounting evidence suggesting that too much serotonin in some brain regions is to blame. If correct, it might explain some of the negative side-effects associated with selective serotonin re-uptake inhibitors (SSRIs), antidepressants like Prozac which increase the amount of the neurotransmitter serotonin in some parts of the brain. The traditional view of depression was largely based on the observation that SSRIs boost mood- although why they do so is unknown. "Because antidepressants increase serotonin in some parts of the brain, people assumed that depression must be the result of low serotonin levels," says Christopher Lowry of the University of Boulder in Colorado. But the discovery of multiple types of serotonin-releasing neurons in the brain, along with high levels of serotonin recorded in people with depression, is prompting a rethink. "What's more likely is that there are subgroups of serotonin neurons that are overactive in depressed patients, rather than underactive as we have all been assuming," says Lowry. One of the first clues that something might be amiss with the traditional theory came three years ago, when Murray Esler at the Baker Heart Research Institute in Melbourne, Australia, and colleagues found that the level of serotonin in the brains of people with panic disorder was four times higher than in healthy volunteers (Stress, DOI: 10.1080/10253890701300904), and in depressed people who were not receiving treatment it was two times higher than in volunteers (Archives of General Psychiatry, vol 65, p 38). © Copyright Reed Business Information Ltd.

by Andy Coghlan NASAL sprays containing the hormone oxytocin, nicknamed the "cuddle chemical" because it helps mothers bond with their babies, have helped people with schizophrenia. Although the 15 participants used the sprays for three weeks only, most reported measurable improvements in their symptoms in this the first trial to test oxytocin in schizophrenia. "It's proof of concept that there's therapeutic potential here," says David Feifel at the University of California in San Diego, head of the team running the trial. Each participant received oxytocin or a placebo for three weeks, then the opposite treatment for three weeks with a week break in between. On the basis of two standard tests for schizophrenia, taken before and after each block of treatment, participants averaged improvements of around 8 per cent when taking the oxytocin compared with the placebo (Biological Psychiatry, DOI: 10.1016/j.biopsych.2010.04.039). The effects didn't kick in until the final week, suggesting that it takes a while for the hormone to begin acting. "Standard antipsychotic drugs increase their efficacy several weeks later too, so oxytocin fits that profile," says Feifel. Feifel thinks that oxytocin is dampening down the excessive production of the neurotransmitter dopamine, which can trigger schizophrenic symptoms such as hallucinations. © Copyright Reed Business Information Ltd.

by Linda Geddes NEXT time a sentimental movie makes you cry, blame your serotonin levels. Differences in the neurotransmitter might explain why some people are more prone to crying in emotional situations than others. Frederick van der Veen's team at the Erasmus Medical Centre in Rotterdam, the Netherlands, gave 25 female volunteers a single dose of either paroxetine - a selective serotonin reuptake inhibitor (SSRI) which briefly increases serotonin levels - or a placebo. Four hours later they were asked to watch one of two emotional movies: Brian's Song, in which the hero dies of cancer, or Once Were Warriors, about domestic violence, and to indicate if, and to what extent certain scenes had made them cry. On another day, the women watched the second film with their treatments swapped over. "It didn't matter which movie they saw, we saw a strong and consistent effect of paroxetine," says van der Veen, who presented the results at the Forum of European Neuroscience in Amsterdam last week. "Higher serotonin levels lead to less crying." Although SSRIs are used to treat depression, their mood-boosting effects do not normally show up for around six weeks. The women reported no change in mood in the current study. "We're looking at the direct effect of a single dose of paroxetine," says van der Veen, who adds that the findings might help explain why some people report blunted emotions when taking SSRIs. © Copyright Reed Business Information Ltd

By James Dao NEW YORK — The government is preparing to issue new rules that will make it substantially easier for veterans who have been found to have posttraumatic stress disorder to receive disability benefits for the illness, a change that could affect hundreds of thousands of veterans from the wars in Iraq, Afghanistan, and Vietnam. The regulations from the Department of Veterans Affairs— which will take effect as early as Monday and cost as much as $5 billion over several years, according to congressional analysts — will essentially eliminate a requirement that veterans document specific events like bomb blasts, firefights, or mortar attacks that might have caused post-traumatic stress disorder, an illness characterized by emotional numbness, irritability, and flashbacks. For decades, veterans have complained that finding such records was extremely time consuming and sometimes impossible. And in the wars in Afghanistan and Iraq, veterans groups assert, the current rules discriminate against tens of thousands of service members — many of them women — who did not serve in combat roles but nevertheless suffered traumatic experiences. Under the new rule, which applies to veterans of all wars, the department will grant compensation to those with the illness if they can simply show that they served in a war zone and in a job consistent with the events that they say caused their conditions. They would not have to prove, for instance, that they came under fire, served in a front-line unit, or saw a friend killed. © Copyright 2010 Globe Newspaper Company.

Scientists at Penn State University say they have developed a mouse that gets depressed in a similar fashion to humans, which could led to better treatment for the condition among people. Biology professor Bernhard Luscher, the project's leader, said that is because scientists will be able to test different drugs for various mental conditions and observe the mice to see the results. "A mouse can't tell us if it is feeling depressed, so we used a number of different kinds of tests to gauge ... changes ... of a type of depression that, in humans, does not respond well to some antidepressant drugs," Luscher said. Drug trials Researchers essentially created a rodent with a genetic defect that interferes with the development of a protein in the brain, called the GABA-A receptor. The lack of that protein allows the mice to mimic brain disorders among humans but lets the researchers reach different conclusions, the scientists noted. For example, a GABA-A deficiency had been linked to anxiety disorders but not directly to depression. In a paper to be published in Biology Psychiatry, however, Luscher used the genetically-modified mouse to show that the protein is in fact important to proper brain function and that whatever cerebral problems cause anxiety also have a hand in the appearance of depression. © CBC 2010

COLUMBUS, Ohio – A drug used to help control psychotic behavior in people with schizophrenia holds promise for controlling similar symptoms in the early stages of Alzheimer’s disease, a new study suggests. What sets this drug – called quetiapine – apart from its contemporary counterparts is its apparent lack of serious side effects, such as confusion, muscle stiffness and imbalance in the joints, said Douglas Scharre, a study co-author and an associate professor of clinical neurology at Ohio State University. None of the 10 subjects in the study reported any of these symptoms during a 12-week trial.

By Suzanne Elston If you're feeling a little winter weary right about now, you're not alone. It turns out that getting enough sunlight, particularly during the winter months, can be critical to our mental health. This seasonal lack of sunlight can affect the balance of chemicals in our brain, including serotonin. That's the chemical that's responsible for regulating sleep patterns and it can also affect our moods and our appetite. For most of us, the next sunny day will be enough to brighten our spirits. But for some people, lack of sunlight can cause a serious condition known as Seasonal Affective Disorder, or SAD. "Some of us don't do very well with the light that's available during the winter months." SAD sufferers can have symptoms that range from chronic fatigue and oversleeping, to overeating and subsequent weight gain. In severe cases, individuals are unable to function normally. SAD sufferers may also experience persistent physical symptoms such as headaches, digestive disorders, and chronic pain that doesn't respond to treatment. In extreme cases, SAD patients may even become suicidal. Women are four times more likely than men to suffer from SAD, but it can affect anyone at any age. SAD symptoms in children include irritability, difficulty getting out of bed and school problems. This could help explain why your child has trouble making it out of the door in time to catch the school bus during the winter months. © Straight Goods, 2000-2002. All Rights Reserved.

ORLANDO, Fla., — Pregnant or nursing women may be able to reduce their chances of developing postpartum depression and improve the neurological development of their babies by increasing their consumption of the essential fatty acid DHA, according to David Kyle, Ph.D., the U.S. director of the Mother and Child Foundation. DHA (docosahexaenoic acid) is an omega-3 fatty acid mostly found in fish like tuna and salmon and in algae. Approximately 15-20 percent of women who give birth in the United States develop postpartum depression, according to Kyle, who spoke today at the 223rd national meeting of the American Chemical Society, the world’s largest scientific society. “We believe that the high incidence of postpartum depression in the United States may be triggered by a low dietary intake of DHA,” he said. Kyle’s organization studies nutrition for mothers and its effect on their babies. While DHA has been recognized as beneficial to infants, there has been less public awareness of the apparent link between DHA and postpartum depression, according to Kyle.

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.

Chapter 16. Psychopathology: Biological Basis of Behavior Disorders