Posts tagged science

April 5th, 2012

Discovery of key link between circadian rhythms and metabolism may lead to new therapies for sleep disorders and diabetes.

The discovery of a major gear in the biological clock that tells the body when to sleep and metabolize food may lead to new drugs to treat sleep problems and metabolic disorders, including diabetes.

Scientists at the Salk Institute for Biological Studies, led by Ronald M. Evans, a professor in Salk’s Gene Expression Laboratory, showed that two cellular switches found on the nucleus of mouse cells, known as REV-ERB-α and REV-ERB-β, are essential for maintaining normal sleeping and eating cycles and for metabolism of nutrients from food.

The findings, reported March 29 in Nature, describe a powerful link between circadian rhythms and metabolism and suggest a new avenue for treating disorders of both systems, including jet lag, sleep disorders, obesity and diabetes.

“This fundamentally changes our knowledge about the workings of the circadian clock and how it orchestrates our sleep-wake cycles, when we eat and even the times our bodies metabolize nutrients,” says Evans. “Nuclear receptors can be targeted with drugs, which suggests we might be able to target REV-ERB-α and β to treat disorders of sleep and metabolism.”

Nurses, emergency personnel and others who work shifts that alter the normal 24-hour cycle of waking and sleeping are at much higher risk for a number of diseases, including metabolic disorders such as diabetes. To address this, scientists are trying to understand precisely how the biological clock works and uncover possible targets for drugs that could adjust the circadian rhythm in people with sleep disorders and circadian-associated metabolic disorders.

In mammals, the circadian timing system is orchestrated by a central clock in the brain and subsidiary clocks in most other organs. The master clock in the brain is set by light and determines the overall diurnal or nocturnal preference of an animal, including sleep-wake cycles and feeding behavior.

Scientists knew that two genes, BMAL1 and CLOCK, worked together at the core of the clock’s molecular machinery to activate the network of circadian genes. In this way, BMAL1 acts like the accelerator on a car, activating genes to rev up our physiology each morning so that we are alert, hungry and physically active.

Prior to this work REV-ERB-α and β were thought to play only a minor role in these cycles, possibly working together to slow CLOCK-BMAL1 activity to make minor adjustments to keep the clock running on time.

However, genetic studies of two genes with similar functions can be very difficult and thus the real importance of REV-ERB-α and β remained mysterious.

The Salk scientists got around this hurdle by developing mice in which both genes could be turned off in the liver at any point by giving them an estrogen derivative called tamoxifen. Now mice could develop normally to adulthood, at which point the scientists could turn off REV-ERB-α and REV-ERB-β in their livers—an organ crucial to maintaining the correct balance of sugar and fat in blood—to see what effects it had on circadian rhythms and metabolism.

“When we turned off both receptors, the animal’s biological clocks went haywire,” says Han Cho, first author on the paper and a postdoctoral researcher in Evan’s laboratory. “The mice started running on their exercise wheels when they should have been resting. This suggested REV-ERB-α and REV-ERB-β aren’t an auxiliary system that makes minor adjustments, but an integral part of the clock’s core mechanism. Without them, the clock can’t function properly.”

Digging more deeply into the clockworks, the Salk scientists mapped out the genes that the REV-ERBs control to keep the body operating on the right schedule, finding that they overlap with hundreds of the same genes controlled by CLOCK and BMAL1. This and other findings suggested that the REV-ERBs, act as a break on the genes BMAL1 activates.

“We thought that the core of the clock was an accelerator, and that all REV-ERB-α and REV-ERB-β did was to pull the foot off that pedal,” says Evans. “What we’ve shown is that these receptors act directly as a break to slow clock activity. Now we’ve got a accelerator and a break, each equally important in creating the daily rhythm of the clock.”

The scientists also found that the REV-ERBs control the activity of hundreds of genes involved metabolism, including those responsible for controlling levels of fats and bile. The mice in which REV-ERB-α and REV-ERB-β were turned off had high levels of fat and sugar in their blood—common problems in people with metabolic disorders.

“This explains how our cellular metabolism is tied to daylight cycles determined by the movements of the sun and the earth,” says Satchidananda Panda, an associate professor in Salk’s Regulatory Biology Laboratory and co-author on the paper. “Now we want to find ways of leveraging this mechanism to fix a person’s metabolic rhythms when they are disrupted by travel, shift work or sleep disorders.”

Source: Neuroscience News

April 5th, 2012

Yale researchers show in detail how three genes within human embryonic stem cells regulate development, a finding that increases understanding of how to grow these cells for therapeutic purposes.

This process, described in the April 6 issue of the journal Cell Stem Cell, is different in humans than in mice, highlighting the importance of research using human embryonic stem cells.

“It is difficult to deduce from the mouse how these cells work in humans,” said Natalia Ivanova, assistant professor of genetics in the Yale Stem Cell Center and senior author of the study. “Human networks organize themselves quite differently.”

Embryonic stem cells form soon after conception and are special because each cell can become any type of cell in the body. Cells become increasingly specialized as development progresses, losing the ability to become other cell types — except for the renewal of a few new stem cells. Scientists want to understand the processes of self-renewal and differentiation in order to treat a host of diseases characterized by damaged cells such as Parkinson’s disease, spinal cord injury, heart disease, and Alzheimer’s.

Scientists have identified three genes active in early development — Nanog, Oct 4, and Sox 2 — as essential to maintaining the stem cell’s ability to self-renew and prevent premature differentiation into the “wrong” type of cells. Because of restrictions on the use of human embryonic stem cells, much of the investigation into how these genes work has been done in mice.

The new study shows that human embryonic cells operate in fundamentally different ways in humans than in mouse cells. In humans, for instance, Nanog pairs with Oct 4 to regulate differentiation of so-called neuro-ectoderm cells, a lineage that gives rise to neurons and other central nervous system cells. Sox 2, by contrast, inhibits the differentiation of mesoderm — a lineage that gives rise to muscles and many other tissue types. Oct 4 cooperates with the other genes and is crucial in the regulation of all four early cell lineages: ectoderm, mesoderm, and endoderm — which gives rise to gut and glands such as liver and pancreas — as well as the creation of new stem cells. The self-renewal of stem cells has been implicated in several forms of cancer.

Ivanova stresses that many other genes must be involved in regulation of these early developmental changes, and her lab is investigating that question now.

Source: Neuroscience News

April 4, 2012

Brain pacemakers have a long-term effect in patients with the most severe depression. This has now been proven by scientists from the Bonn University Medical Center. Eleven patients took part in the study over a period of two to five years. A lasting reduction in symptoms of more than 50 percent was seen in nearly half of the subjects. The results are now being presented in the current edition of the journal Neuropsychopharmacology.

People with severe depression are constantly despondent, lacking in drive, withdrawn and no longer feel joy. Most suffer from anxiety and the desire to take their own life. Approximately one out of every five people in Germany suffers from depression in the course of his/her life – sometimes resulting in suicide. People with depression are frequently treated with psychotherapy and medication. “However, many patients are not helped by any therapy,” says Prof. Dr. Thomas E. Schläpfer from the Bonn University Medical Center for Psychiatry and Psychotherapy. “Many spend more than ten years in bed – not because they are tired, but because they have no drive at all and they are unable to get up.”

One possible alternative is “deep brain stimulation,” in which electrodes are implanted in the patient’s brain. The target point is the nucleus accumbens - an area of the brain known as the gratification center. There, a weak electrical current stimulates the nerve cells. Brain pacemakers of this type are often used today by neurosurgeons and neurologists to treat ongoing muscle tremors in Parkinson’s disease.

A 2009 study proved an antidepressive effect

In 2009, the Bonn scientists were able to establish that brain pacemakers also demonstrate an effect in the most severely depressed patients. Ten subjects who underwent implantation of electrodes in the nucleus accumbens all experienced relief of symptoms. Half of the subjects had a particularly noticeable response to the stimulation by the electrodes.

"In the current study, we investigated whether these effects last over the long term or whether the effects of the deep brain stimulation gradually weaken in patients," says Prof. Schläpfer. There are always relapses in the case of psychotherapy or drug treatment. Many patients had already undergone up to 60 treatments with psychotherapy, medications and electroconvulsive therapy, to no avail. "By contrast, in the case of deep brain stimulation, the clinical improvement continues steadily for many years." The scientists observed a total of eleven patients over a period of two to five years. "Those who initially responded to the deep brain stimulation are still responding to it even today," says the Bonn psychiatrist, summarizing the results. During the study, one patient committed suicide. "That is very unfortunate," says Prof. Schläpfer. "However, this cannot always be prevented in the case of patients with very severe depression."

he current study shows that the positive effects last for years

Even after a short amount of time, the study participants demonstrated an improvement in symptoms. “The intensity of the anxiety symptoms decreased and the subjects’ drive improved,” reports the psychiatrist. “After many years of illness, some were even able to work again.” With the current publication, the scientists have now demonstrated that the positive effects do not decrease over a longer period of time. “An improvement in symptoms was recorded for all subjects; for nearly half of the subjects, the extent of the symptoms was more than 50 percent below that of the baseline, even years after the start of treatment,” says Prof. Schläpfer. “There were no serious adverse effects of the therapy recorded.”

The long-term effect is now confirmed with the current study. How precisely the electrical stimulation is able to alter the function of the nucleus accumbens is not yet known. “Research is still needed in this area,” says Prof. Schläpfer. “Using imaging techniques, it was proven that the electrodes actually activate the nucleus accumbens.” The deep brain stimulation method may signify hope for people who suffer from the most severe forms of depressive diseases. “However, it will still take quite a bit of time before this therapeutic method becomes a part of standard clinical practice,” says the Bonn scientist.

Provided by University of Bonn 

Source: medicalxpress.com

April 4, 2012

Awakening from anesthesia is often associated with an initial phase of delirious struggle before the full restoration of awareness and orientation to one’s surroundings. Scientists now know why this may occur: primitive consciousness emerges first. Using brain imaging techniques in healthy volunteers, a team of scientists led by Adjunct Professor Harry Scheinin, M.D. from the University of Turku, Finland in collaboration with investigators from the University of California, Irvine, have now imaged the process of returning consciousness after general anesthesia. The emergence of consciousness was found to be associated with activations of deep, primitive brain structures rather than the evolutionary younger neocortex.

This image shows one returning from oblivion — imaging the neural core of consciousness. Positron emission tomography (PET) findings show that the emergence of consciousness after anesthesia is associated with activation of deep, phylogenetically old brain structures rather than the neocortex. Left: Sagittal (top) and axial (bottom) sections show activation in the anterior cingulate cortex (i), thalamus (ii) and the brainstem (iii) locus coeruleus/parabrachial area overlaid on magnetic resonance image (MRI) slices. Right: Cortical renderings show no evident activations. Credit: Turku PET Center

These results may represent an important step forward in the scientific explanation of human consciousness.

"We expected to see the outer bits of brain, the cerebral cortex (often thought to be the seat of higher human consciousness), would turn back on when consciousness was restored following anesthesia. Surprisingly, that is not what the images showed us. In fact, the central core structures of the more primitive brain structures including the thalamus and parts of the limbic system appeared to become functional first, suggesting that a foundational primitive conscious state must be restored before higher order conscious activity can occur" Scheinin said.

Twenty young healthy volunteers were put under anesthesia in a brain scanner using either dexme-detomidine or propofol anesthetic drugs. The subjects were then woken up while brain activity pictures were being taken. Dexmedetomidine is used as a sedative in the intensive care unit setting and propofol is widely used for induction and maintenance of general anesthesia. Dexmedetomidineinduced unconsciousness has a close resemblance to normal physiological sleep, as it can be reversed with mild physical stimulation or loud voices without requiring any change in the dosing of the drug. This unique property was critical to the study design, as it enabled the investigators to separate the brain activity changes associated with the changing level of consciousness from the drugrelated effects on the brain. The staterelated changes in brain activity were imaged with positron emission tomography (PET).

The emergence of consciousness, as assessed with a motor response to a spoken command, was associated with the activation of a core network involving subcortical and limbic regions that became functionally coupled with parts of frontal and inferior parietal cortices upon awakening from dexme-detomidine-induced unconsciousness. This network thus enabled the subjective awareness of the external world and the capacity to behaviorally express the contents of consciousness through voluntary responses.

Interestingly, the same deep brain structures, i.e. the brain stem, thalamus, hypothalamus and the anterior cingulate cortex, were activated also upon emergence from propofol anesthesia, suggesting a common, drugindependent mechanism of arousal. For both drugs, activations seen upon regaining consciousness were thus mostly localized in deep, phylogenetically old brain structures rather than in the neocortex.

The researchers speculate that because current depth-of-anesthesia monitoring technology is based on cortical electroencephalography (EEG) measurement (i.e., measuring electrical signals on the sur-face of the scalp that arise from the brain’s cortical surface), their results help to explain why these devices fail in differentiating the conscious and unconscious states and why patient awareness during general anesthesia may not always be detected. The results presented here also add to the current understanding of anesthesia mechanisms and form the foundation for developing more reliable depth-of-anesthesia technology.

The anesthetized brain provides new views into the emergence of consciousness. Anesthetic agents are clinically useful for their remarkable property of being able to manipulate the state of consciousness. When given a sufficient dose of an anesthetic, a person will lose the precious but mysterious capacity of being aware of one’s own self and the surrounding world, and will sink into a state of oblivion. Conversely, when the dose is lightened or wears off, the brain almost magically recreates a subjective sense of being as experience and awareness returns. The ultimate nature of consciousness remains a mystery, but anesthesia offers a unique window for imaging internal brain activity when the subjective phenomenon of consciousness first vanishes and then re-emerges. This study was designed to give the clearest picture so far of the internal brain processes involved in this phenomenon.

The results may also have broader implications. The demonstration of which brain mechanisms are involved in the emergence of the conscious state is an important step forward in the scientific explanation of consciousness. Yet, much harder questions remain. How and why do these neural mechanisms create the subjective feeling of being, the awareness of self and environment the state of being conscious?

Provided by Academy of Finland

Source: medicalxpress.com

ScienceDaily (Apr. 4, 2012) — University of Oregon scientists collaborating with an Oregon company that synthesizes antisense Morpholinos for genetic research have developed a UV light-activated on-off switch for the vital gene-blocking molecule. Based on initial testing in zebra-fish embryos, the enhanced molecule promises to deliver new insights for developmental biologists and brain researchers.

The seven-member team describes the advancement in an open-access paper published in the May issue of the journal Development. UO neuroscientist Philip Washbourne, a professor of biology, says the paper is a “proof-of-concept” on an idea he began discussing with scientists at Gene Tools LLC in Philomath, Ore., about four years ago. Gene Tools was founded in the 1980s by James Summerton, who first invented Morpholino oligos. The company holds the exclusive license to distribute these molecules to researchers around the world.

Morpholinos are short-chain, artificially produced oligomers that bind to RNA in cells and block protein synthesis. For a decade, biologists have used them in zebra fish, mice and African clawed toads to study development, but they remained in the active, or on, position. Gene Tools created and introduced a light-sensitive linker, allowing researchers to control the molecule — even leaving one on in one cell and off in an adjacent cell — with a pinpoint UV laser beam.

Researchers in Washbourne’s lab — led by neuroscience research associate Alexandra Tallafuss — were challenged to give the new molecules a test run. They applied them to their work in zebra fish. “Now we can turn them on and off,” Washbourne said. “You can insert them and then manipulate them to learn just when a gene is important, and we learned two things right away.”

Researchers have known that if a gene known as “no tail” is blocked in development, zebra fish fail to grow tails. They now know that the no-tail gene does not need to produce protein for tail formation until about 10 hours, or very late, into an embryo’s development.

Secondly, the researchers looked at the gene sox10, which is vital in the formation of neural crest cells, which give rise to dorsal root ganglion cells — neurons that migrate out of the spinal cord — and pigment cells. “Again, we found that sox10 is not needed as early in development as theorized,” Washbourne said.

"These light-sensitive molecules significantly expand the power and precision of molecular genetic studies in zebrafish," said Robert Riddle, a program director at the National Institute of Neurological Disorders and Stroke (NINDS). "Researchers from many fields will be able to use these tools to explore the function of different genes in embryonic regions, specific cell types and at precise times in an animal’s lifespan."

The NINDS and National Institute of Child Health and Human Development, both at the National Institutes of Health, supported the research through grants to Washbourne and Eisen.

"This successful collaboration between our scientists and this Oregon-based company shows that commercial innovation can come quickly by jointly addressing common needs," said Kimberly Andrews Espy, vice president for research and innovation at the UO. "This is a remarkable example of turning a concept into a working tool that likely will benefit many researchers around the world."

Source: Science Daily

April 3rd, 2012

Working in mice, scientists at Washington University School of Medicine in St. Louis have devised a treatment that prevents the optic nerve injury that occurs in glaucoma, a neurodegenerative disease that is a leading cause of blindness.

Researchers increased the resistance of optic nerve cells to damage by repeatedly exposing the mice to low levels of oxygen similar to those found at high altitudes. The stress of the intermittent low-oxygen environment induces a protective response called tolerance that makes nerve cells — including those in the eye — less vulnerable to harm.

The study, published online in Molecular Medicine, is the first to show that tolerance induced by preconditioning can protect against a neurodegenerative disease.

Stress is typically thought of as a negative phenomenon, but senior author Jeffrey M. Gidday, PhD, associate professor of neurological surgery and ophthalmology, and others have previously shown that the right kinds of stress, such as exercise and low-oxygen environments, can precondition cells and induce changes that make them more resistant to injury and disease.

Scientists previously thought tolerance in the central nervous system only lasted for a few days. But last year Gidday developed a preconditioning protocol that extended the effects of tolerance from days to months. By exposing mice to hypoxia, or low oxygen concentrations, several times over a two-week period, Gidday and colleagues triggered an extended period of tolerance. After preconditioning ended, the brain was protected from stroke damage for at least 8 weeks.

“Once we discovered tolerance could be extended, we wondered whether this protracted period of injury resistance could also protect against the slow, progressive loss of neurons that characterizes neurodegenerative diseases,” Gidday says.

To find out, Gidday turned to an animal model of glaucoma, a condition linked to increases in the pressure of the fluid that fills the eye. The only treatments for glaucoma are drugs that reduce this pressure; there are no therapies designed to protect the retina and optic nerves from harm.

Scientists classify glaucoma as a neurodegenerative disease based on how slowly and progressively it kills retinal ganglion cells. The bodies of these cells are located in the retina of the eye; their branches or axons come together in bundles and form the optic nerves. Scientists don’t know if damage begins in the bodies or axons of the cells, but as more and more retinal ganglion cells die, patients experience peripheral vision loss and eventually become blind.

For the new study, Yanli Zhu, MD, research instructor in neurosurgery, induced glaucoma in mice by tying off vessels that normally allow fluid to drain from the eye. This causes pressure in the eye to increase. Zhu then assessed how many cell bodies and axons of retinal ganglion cells were intact after three or 10 weeks.

The investigators found that normal mice lost an average of 30 percent of their retinal ganglion cell bodies after 10 weeks of glaucoma. But mice that received the preconditioning before glaucoma-inducing surgery lost only 3 percent of retinal ganglion cell bodies.

“We also showed that preconditioned mice lost significantly fewer retinal ganglion cell axons,” Zhu says.

Gidday is currently investigating which genes are activated or repressed by preconditioning. He hopes to identify the changes in gene activity that make cells resistant to damage.

“Previous research has shown that there are literally hundreds of survival genes built into our DNA that are normally inactive,” Gidday says. “When these genes are activated, the proteins they encode can make cells much less vulnerable to a variety of injuries.”

Identifying specific survival genes should help scientists develop drugs that can activate them, according to Gidday.

Neurologists are currently conducting clinical trials to see if stress-induced tolerance can reduce brain damage after acute injuries like stroke, subarachnoid hemorrhage or trauma.

Gidday hopes his new finding will promote studies of tolerance’s potential usefulness in animal models of Parkinson’s disease, Alzheimer’s disease and other neurodegenerative conditions.

“Neurons in the central nervous system appear to be hard-wired for survival,” Gidday says. “This is one of the first steps in establishing a framework for how we can take advantage of that metaphorical wiring and use positive stress to help treat a variety of neurological diseases.”

Source: Neuroscience News

April 3, 2012

Researchers at the University of Montreal’s Sainte-Justine Hospital have identified how neural cells like those in our bodies are able to build up resistance to opioid pain drugs within hours. Humans have known about the usefulness of opioids, which are often harvested from poppy plants, for centuries, but we have very little insight into how they lose their effectiveness in the hours, days and weeks following the first dose.

"Our study revealed cellular and molecular mechanisms within our bodies that enables us to develop resistance to this medication, or what scientists call drug tolerance," lead author Dr. Graciela Pineyro explained. "A better understanding of these mechanisms will enable us to design drugs that avoid tolerance and produce longer therapeutic responses."

The research team looked at how drug molecules would interact with molecules called “receptors” that exist in every cell in our body. Receptors, as the name would suggest, receive “signals” from the chemicals that they come into contact with, and the signals then cause the various cells to react in different ways. They sit on the cell wall, and wait for corresponding chemicals known as receptor ligands to interact with them. “Until now, scientists have believed that ligands acted as ‘on- off’ switches for these receptors, all of them producing the same kind of effect with variations in the magnitude of the response they elicit,” Pineyro explained. “We now know that drugs that activate the same receptor do not always produce the same kind of effects in the body, as receptors do not always recognize drugs in the same way. Receptors will configure different drugs into specific signals that will have different effects on the body.”

Pineyro is attempting to tease the “painkilling” function of opioids from the part that triggers mechanisms that enable tolerance to build up. “My laboratory and my work are mostly structured around rational drug design, and trying to define how drugs produce their desired and non desired effects, so as to avoid the second, Pineyro said. “If we can understand the chemical mechanisms by which drugs produce therapeutic and undesired side effects, we will be able to design better drugs.”

Once activated by a drug, receptors move from the surface of the cell to its interior, and once they have completed this ‘journey’, they can either be destroyed or return to the surface and used again through a process known as “receptor recycling.” By comparing two types of opioids – DPDPE and SNC-80 – the researchers found that the ligands that encouraged recycling produced less analgesic tolerance than those that didn’t. “We propose that the development of opioid ligands that favour recycling could be away of producing longer-acting opioid analgesics,” Pineyro said.

Provided by University of Montreal

Source: medicalxpress.com

April 3, 2012

Epilepsy affects 50 million people worldwide, but in a third of these cases, medication cannot keep seizures from occurring. One solution is to shoot a short pulse of electricity to the brain to stamp out the seizure just as it begins to erupt. But brain implants designed to do this have run into a stubborn problem: too many false alarms, triggering unneeded treatment. To solve this, Johns Hopkins biomedical engineers have devised new seizure detection software that, in early testing, significantly cuts the number of unneeded pulses of current that an epilepsy patient would receive.

Sridevi Sarma’s research focuses on a system with three components: electrodes implanted in the brain, which are connected by wires to a neurostimulator or battery pack, and a sensing device, also located in the brain implant, which detects when a seizure is starting and activates the current to stop it. Credit: Greg Stanley/JHU

Sridevi V. Sarma, an assistant professor of biomedical engineering, is leading this effort to improve anti-seizure technology that sends small amounts of current into the brain to control seizures.

"These devices use algorithms — a series of mathematical steps —to figure out when to administer the treatment," Sarma said. "They’re very good at detecting when a seizure is about to happen, but they also produce lots of false positives, sometimes hundreds in one day. If you introduce electric current to the brain too often, we don’t know what the health impacts might be. Also, too many false alarms can shorten the life of the battery that powers the device, which must be replaced surgically."

Her new software was tested on real-time brain activity recordings collected from four patients with drug-resistant epilepsy who experienced seizures while being monitored. In a study published recently in the journal Epilepsy & Behavior, Sarma’s team reported that its system yielded superior results, including flawless detection of actual seizures and up to 80 percent fewer alarms when a seizure was not occurring. Although the testing was not conducted on patients in a clinical setting, the results were promising.

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ScienceDaily (Apr. 3, 2012) — Depressed individuals with a tendency to ruminate on negative thoughts, i.e. to repeatedly think about particular negative thoughts or memories, show different patterns of brain network activation compared to healthy individuals, report scientists of a new study in Biological Psychiatry.

The risk for depression is increased in individuals with a tendency towards negative ruminations, but patterns of autobiographic memory also may be predictive of depression.

When asked to recall specific events, some individuals have a tendency to recall broader categories of events instead of specific events. This is termed overgeneral memory and, like those who tend to ruminate, these individuals also have a higher risk of developing depression.

These self-referential activities engage a network of brain regions called the default mode network, or DMN. Prior studies using imaging techniques have already shown that the DMN activates abnormally in individuals with depression, but the relationship between DMN activity and depressive ruminations was not clear.

In this new report, Dr. Shuqiao Yao of Central South University in Hunan, China and colleagues evaluated DMN functional connectivity in untreated young adults experiencing their first episode of major depression and healthy volunteers. Each participant underwent a brain scan and completed tests to measure their levels of rumination and overgeneral memory.

As expected, the depressed patients exhibited higher levels of rumination and overgeneral memory than did the control subjects. They also observed increased functional connectivity in the anterior medial cortex regions and decreased functional connectivity in the posterior medial cortex regions in depressed patients compared with control subjects.

Among the depressed subjects, an interesting pattern of dissociation emerged. The increased connectivity in anterior regions was positively associated with rumination, while the decreased connectivity in posterior regions was negatively associated with overgeneral memory.

Dr. Yao commented on the importance of these findings: “In the future, resting-state network activity in the brain will provide useful models for investigating network features of cognitive dysfunction in psychopathology.”

"As we dig deeper in brain imaging studies, we are becoming increasingly interested in the activity of brain circuits rather than single brain regions," said Dr. John Krystal, Editor of Biological Psychiatry. “Although it is a more complicated process, studying brain circuits may provide greater insight into symptoms, such as depressive ruminations. The current study nicely illustrates how altered activity at different sites within a brain network may be related to different features of depression.”

Source: Science Daily