1. Researchers identify how inflammation spreads through the brain after injury

    March 26, 2017 by Ashley

    From the University of Maryland School of Medicine press release:

    Researchers have identified a new mechanism by which inflammation can spread throughout the brain after injury. This mechanism may explain the widespread and long-lasting inflammation that occurs after traumatic brain injury, and may play a role in other neurodegenerative diseases.

    The findings were published today in a study in the Journal of Neuroinflammation.

    This new understanding has the potential to transform how brain inflammation is understood, and, ultimately, how it is treated. The researchers showed that microparticles derived from brain inflammatory cells are markedly increased in both the brain and the blood following experimental traumatic brain injury (TBI). These microparticles carry pro-inflammatory factors that can activate normal immune cells, making them potentially toxic to brain neurons. Injecting such microparticles into the brains of uninjured animals creates progressive inflammation at both the injection site and eventually in more distant sites.

    Research has found that neuroinflammation often goes on for years after TBI, causing chronic brain damage. The researchers say that the microparticles may play a key role in this process.

    Chronic inflammation has been increasingly implicated in the progressive cell loss and neurological changes that occur after TBI. These inflammatory microparticles may be a key mechanism for chronic, progressive brain inflammation and may represent a new target for treating brain injury.

    The researchers on the paper include four University of Maryland School of Medicine researchers: Alan Faden, Stephen R. Thom, Bogdan A. Stoica, and David Loane.

    “These results potentially provide a new conceptual framework for understanding brain inflammation and its relationship to brain cell loss and neurological deficits after head injury, and may be relevant for other neurodegenerative disorders such as Alzheimer disease in which neuroinflammation may also play a role,” said Dr. Faden. “The idea that brain inflammation can trigger more inflammation at a distance through the release of microparticles may offer novel treatment targets for a number of important brain diseases.”

    The researchers studied mice, and found that in animals who had a traumatic brain injury, levels of microparticles in the blood were much higher. Because each kind of cell in the body has a distinct fingerprint, the researchers could track exactly where the microparticles came from. The microparticles they looked at in this study are released from cells known as microglia, immune cells that are common in the brain. After an injury, these cells often go into overdrive in an attempt to fix the injury. But this outsized response can change protective inflammatory responses to chronic destructive ones.

    The findings have important potential clinical implications. The researchers say that microparticles in the blood have the potential to be used as a biomarker — a way to determine how serious a brain injury may be. This could help guide treatment of the injuries, whose severity is often difficult to gauge.

    They also found that exposing the inflammatory microparticles to a compound called PEG-TB could neutralize them. This opens up the possibility of using that compound or others to treat TBI, and perhaps even other neurodegenerative diseases.


  2. Major research project provides new clues to schizophrenia

    by Ashley

    From the Karolinska Institutet press release:

    Researchers at Karolinska Institutet collaborating in the large-scale Karolinska Schizophrenia Project are taking an integrative approach to unravel the disease mechanisms of schizophrenia. In the very first results now presented in the scientific journal Molecular Psychiatry, the researchers show that patients with schizophrenia have lower levels of the vital neurotransmitter GABA as well as changes in the brain’s immune cells.

    Schizophrenia is one of the most disabling psychiatric diseases and affects approximately one per cent of the population. It commonly onsets in late adolescence and is often a life-long condition with symptoms such as delusions, hallucinations, and anxiety. The disease mechanisms are largely unknown, which has hampered the development of new drugs. The drugs currently available are designed to alleviate the symptoms, but are only partly successful, as only 20 per cent of the patients become symptom-free.

    The Karolinska Schizophrenia Project (KaSP) brings together researchers from a number of different scientific disciplines to build up a comprehensive picture of the disease mechanisms and to discover new targets for drug therapy. Patients with an acute first-episode psychosis are recruited and undergo extensive tests and investigations. Cognitive function, genetic variation, biochemical anomalies as well as brain structure and function are analysed using the latest techniques and then compared with healthy peers.

    The first results from the project are now presented in two studies published in the journal Molecular Psychiatry. One of the studies shows that patients with newly debuted schizophrenia have lower levels of the neurotransmitter GABA in their cerebrospinal fluid than healthy people and that the lower the concentration of GABA the more serious their symptoms are.

    GABA is involved in most brain functions and along with glutamate it accounts for almost 90 per cent of all signal transmission. While glutamate stimulates brain activity, GABA inhibits it, and the two neurotransmitters interact with each other.

    “Over the years, animal studies have suggested a link between decreased levels of GABA and schizophrenia,” says Professor Göran Engberg at Karolinska Institutet’s Department of Physiology and Pharmacology. “Our results are important because they clinically substantiate this hypothesis.”

    The other study used the imaging technique of positron emission tomography (PET) to show that patients with untreated schizophrenia have lower levels of TSPO (translocator protein), which is expressed on immune cells such as microglia and astrocytes.

    “Our interpretation of the results is an altered function of immune cells in the brain in early-stage schizophrenia,” says Senior lecturer Simon Cervenka at Karolinska Institutet’s Department of Clinical Neuroscience.

    The results of the two studies provide new clues to the pathological mechanisms of schizophrenia, but it is unclear if the changes are the cause or the result of the disease. Follow-up studies are now underway to examine what causes the anomalies and how these biological processes can be influenced to change the progression of the disease.

    KaSP is a collaboration between clinical and preclinical research groups at Karolinska Institutet and four psychiatric clinics under Stockholm County Council.


  3. Brain cells show teamwork in short-term memory

    March 23, 2017 by Ashley

    From the University of Western Ontario press release:

    Nerve cells in our brains work together in harmony to store and retrieve short-term memory, and are not solo artists as previously thought, Western-led brain research has determined.

    The research turns on its head decades of studies assuming that single neurons independently encode information in our working memories.

    “These findings suggest that even neurons we previously thought were ‘useless’ because they didn’t individually encode information have a purpose when working in concert with other neurons,” said researcher Julio Martinez-Trujillo, based at the Robarts Research Institute and the Brain and Mind Institute at Western University.

    “Knowing they work together helps us better understand the circuits in the brain that can either improve or hamper executive function. And that in turn may have implications for how we work though brain-health issues where short-term memory is a problem, including Alzheimer disease, schizophrenia, autism, depression and attention deficit disorder.”

    Working memory is the ability to learn, retain and retrieve bits of information we all need in the short term: items on a grocery list or driving directions, for example. Working memory deteriorates faster in people with dementia or other disorders of the brain and mind.

    In the past, researchers have believed this executive function was the job of single neurons acting independently from one another — the brain’s version of a crowd of people in a large room all singing different songs in different rhythms and different keys. An outsider trying to decipher any tune in all that white noise would have an extraordinarily difficult task.

    This research, however, suggests many in the neuron throng are singing from the same songbook, in essence creating chords to strengthen the collective voice of memory. With neural prosthetic technology — microchips that can “listen” to many neurons at the same time — researchers are able to find correlations between the activity of many nerve cells. “Using that same choir analogy, you can start perceiving some sounds that have a rhythm, a tune and chords that are related to each other: in sum, short-term memories,” said Martinez-Trujillo, who is also an associate professor at Western’s Schulich School of Medicine & Dentistry.

    And while the ramifications of this discovery are still being explored, “this gives us good material to work with as we move forward in brain research. It provides us with the necessary knowledge to find ways to manipulate brain circuits and improve short term memory in affected individuals,” Martinez-Trujillo said.

    “The microchip technology also allows us to extract signals from the brain in order to reverse-engineer brain circuitry and decode the information that is in the subject’s mind. In the near future, we could use this information to allow cognitive control of neural prosthetics in patients with ALS or severe cervical spinal cord injury,” said Adam Sachs, neurosurgeon and associate scientist at The Ottawa Hospital and assistant professor at the University of Ottawa Brain and Mind Research Institute.


  4. Sound waves boost older adults’ memory, deep sleep

    by Ashley

    From the Northwestern University press release:

    IF

    Gentle sound stimulation — such as the rush of a waterfall — synchronized to the rhythm of brain waves significantly enhanced deep sleep in older adults and improved their ability to recall words, reports a new Northwestern Medicine study.

    Deep sleep is critical for memory consolidation. But beginning in middle age, deep sleep decreases substantially, which scientists believe contributes to memory loss in aging.

    The sound stimulation significantly enhanced deep sleep in participants and their scores on a memory test.

    “This is an innovative, simple and safe non-medication approach that may help improve brain health,” said senior author Dr. Phyllis Zee, professor of neurology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine sleep specialist. “This is a potential tool for enhancing memory in older populations and attenuating normal age-related memory decline.”

    The study will be published March 8 in Frontiers in Human Neuroscience.

    In the study, 13 participants 60 and older received one night of acoustic stimulation and one night of sham stimulation. The sham stimulation procedure was identical to the acoustic one, but participants did not hear any noise during sleep. For both the sham and acoustic stimulation sessions, the individuals took a memory test at night and again the next morning. Recall ability after the sham stimulation generally improved on the morning test by a few percent. However, the average improvement was three times larger after pink-noise stimulation.

    The older adults were recruited from the Cognitive Neurology and Alzheimer’s Disease Center at Northwestern.

    The degree of slow wave sleep enhancement was related to the degree of memory improvement, suggesting slow wave sleep remains important for memory, even in old age.

    Although the Northwestern scientists have not yet studied the effect of repeated nights of stimulation, this method could be a viable intervention for longer-term use in the home, Zee said.

    Previous research showed acoustic simulation played during deep sleep could improve memory consolidation in young people. But it has not been tested in older adults.

    The new study targeted older individuals — who have much more to gain memory-wise from enhanced deep sleep — and used a novel sound system that increased the effectiveness of the sound stimulation in older populations.

    The study used a new approach, which reads an individual’s brain waves in real time and locks in the gentle sound stimulation during a precise moment of neuron communication during deep sleep, which varies for each person.

    During deep sleep, each brain wave or oscillation slows to about one per second compared to 10 oscillations per second during wakefulness.

    Giovanni Santostasi, a study coauthor, developed an algorithm that delivers the sound during the rising portion of slow wave oscillations. This stimulation enhances synchronization of the neurons’ activity.

    After the sound stimulation, the older participants’ slow waves increased during sleep.

    Larger studies are needed to confirm the efficacy of this method and then “the idea is to be able to offer this for people to use at home,” said first author Nelly Papalambros, a Ph.D. student in neuroscience working in Zee’s lab. “We want to move this to long-term, at-home studies.”

    Northwestern scientists, under the direction of Dr. Roneil Malkani, assistant professor of neurology at Feinberg and a Northwestern Medicine sleep specialist, are currently testing the acoustic stimulation in overnight sleep studies in patients with memory complaints. The goal is to determine whether acoustic stimulation can enhance memory in adults with mild cognitive impairment.

    Previous studies conducted in individuals with mild cognitive impairment in collaboration with Ken Paller, professor of psychology at the Weinberg College of Arts and Sciences at Northwestern, have demonstrated a possible link between their sleep and their memory impairments.


  5. Head injuries can alter hundreds of genes and lead to serious brain diseases

    by Ashley

    From the UCLA press release:

    Head injuries can harm hundreds of genes in the brain in a way that increases people’s risk for a wide range of neurological and psychiatric disorders, UCLA life scientists report.

    The researchers identified for the first time master genes that they believe control hundreds of other genes which are linked to Alzheimer’s disease, Parkinson’s disease, post-traumatic stress disorder, stroke, attention deficit hyperactivity disorder, autism, depression, schizophrenia and other disorders.

    Knowing what the master genes are could give scientists targets for new pharmaceuticals to treat brain diseases. Eventually, scientists might even be able to learn how to re-modify damaged genes to reduce the risk for diseases, and the finding could help researchers identify chemical compounds and foods that fight disease by repairing those genes.

    “We believe these master genes are responsible for traumatic brain injury adversely triggering changes in many other genes,” said Xia Yang, a senior author of the study and a UCLA associate professor of integrative biology and physiology.

    Genes have the potential to become any of several types of proteins, and traumatic brain injury can damage the master genes, which can then lead to damage of other genes.

    That process can happen in a couple of ways, said Yang, who is a member of UCLA’s Institute for Quantitative and Computational Biosciences. One is that the injury can ultimately lead the genes to produce proteins of irregular forms. Another is to change the number of expressed copies of a gene in each cell. Either change can prevent a gene from working properly. If a gene turns into the wrong form of protein, it could lead to Alzheimer’s disease, for example.

    “Very little is known about how people with brain trauma — like football players and soldiers — develop neurological disorders later in life,” said Fernando Gomez-Pinilla, a UCLA professor of neurosurgery and of integrative biology and physiology, and co-senior author of the new study. “We hope to learn much more about how this occurs.”

    The research appears in EBioMedicine, a journal published by Cell and The Lancet.

    The researchers trained 20 rats to escape from a maze. They then used a fluid to produce a concussion-like brain injury in 10 of the rats; the 10 others did not receive brain injuries. When the rats were placed in the maze again, those that had been injured took approximately 25 percent longer than the non-injured rats to solve it.

    To learn how the rats’ genes had changed in response to the brain injury, the researchers analyzed genes from five animals in each group. Specifically, they drew RNA from the hippocampus, which is the part of the brain that helps regulate learning and memory, and from leukocytes, white blood cells that play a key role in the immune system.

    In the rats that had sustained brain injuries, there was a core group of 268 genes in the hippocampus that the researchers found had been altered, and a core group of 1,215 genes in the leukocytes that they found to have been changed.

    “A surprise was how many major changes occurred to genes in the blood cells,” Yang said. “The changes in the brain were less surprising. It’s such a critical region, so it makes sense that when it’s damaged, it signals to the body that it’s under attack.”

    Nearly two dozen of the altered genes are present in both the hippocampus and the blood, which presents the possibility that scientists could develop a gene-based blood test to determine whether a brain injury has occurred, and that measuring some of those genes could help doctors predict whether a person is likely to develop Alzheimer’s or other disorders. The research could also lead to a better way to diagnose mild traumatic brain injury.

    More than 100 of the genes that changed after the brain injury have counterparts in humans that have been linked to neurological and psychiatric disorders, the researchers report. For example, 16 of the genes affected in the rats have analogs in humans, and those genes are linked to a predisposition for Alzheimer’s, the study reports. The researchers also found that four of the affected genes in the hippocampus and one in leukocytes are similar to genes in humans that are linked to PTSD.

    Yang said the study not only indicated which genes are affected by traumatic brain injury and linked to serious disease, but also might point to the genes that govern metabolism, cell communication and inflammation — which might make them the best targets for new treatments for brain disorders.

    The researchers now are studying some of the master genes to determine whether modifying them also causes changes in large numbers of other genes. If so, the master genes would be even more promising as targets for new treatments. They also plan to study the phenomenon in people who have suffered traumatic brain injury.

    In a 2016 study, Yang, Gomez-Pinilla and colleagues reported that hundreds of genes can be damaged by fructose and that an omega-3 fatty acid called docosahexaenoic acid, or DHA, seems to reverse the harmful changes produced by fructose. One of the genes they identified in that study, Fmod, also was among the master regulator genes identified in the new research.

    Not everyone with traumatic brain injuries develops the same diseases, but more severe injuries can damage more genes, said Gomez-Pinilla, who also is a member of UCLA’s Brain Injury Research Center.

     


  6. Brain architecture alters to compensate for depression

    March 22, 2017 by Ashley

    From the Children’s Hospital Los Angeles press release:

    A study led by Ravi Bansal, PhD, and Bradley S. Peterson, MD, of The Saban Research Institute of Children’s Hospital Los Angeles, has found structural differences in the cerebral cortex of patients with depression and that these differences normalize with appropriate medication. The study, published in Molecular Psychiatry on March 7, is the first to report within the context of a randomized, controlled trial, the presence of structural changes in the cerebral cortex during medication treatment for depression and the first to provide in vivo evidence for the presence of anatomical neuroplasticity in human brain.

    “Our findings suggest that thickening of the cerebral cortex is a compensatory, neuroplastic response that helps to reduce the severity of depressive symptoms,” said Peterson, director of the Institute of the Developing Mind at CHLA and professor of pediatrics and psychiatry at the Keck School of Medicine of the University of Southern California. “Patients off medication have a thickened cortex, and the thicker it is, the fewer the symptoms they have. Treatment with medication then reduces the severity of symptoms, which in turn reduces the need for biological compensation in the brain — so that their cortex becomes thinner, reaching thickness values similar to those in healthy volunteers.”

    The investigators acquired anatomical brain scans at baseline and again at the end of the 10-week study period for 41 patients with chronic depression, while 39 healthy volunteers were scanned once. This study was conducted with adult patients treated at Columbia University, when Peterson and Bansal were faculty members.

    Patients were randomized to receive active medication duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, or placebo. During the trial, patients receiving medication experienced significant improvement of symptoms compared with patients receiving placebo. In medication-treated patients, cortical thickness declined toward values found in healthy volunteers while placebo-treated patients showed a slight thickening of the cortex. According to Bansal, a researcher at CHLA and professor of pediatrics at the Keck School of Medicine of USC, this finding suggests that placebo-treated patients continue to require compensation for their ongoing symptoms.

    “Although this study was conducted in adults, the methodology developed — pairing a randomized controlled trial with MRI scanning — can be applied to many other populations in both children and adults,” said Bansal. “Also, our observations of neuroplasticity suggest new biological targets for treatment of persons with neuropsychiatric disorders.”


  7. Blueberry concentrate improves brain function in older people

    March 20, 2017 by Ashley

    From the University of Exeter press release:

    Blueberries

    Drinking concentrated blueberry juice improves brain function in older people, according to research by the University of Exeter.

    In the study, healthy people aged 65-77 who drank concentrated blueberry juice every day showed improvements in cognitive function, blood flow to the brain and activation of the brain while carrying out cognitive tests.

    There was also evidence suggesting improvement in working memory.

    Blueberries are rich in flavonoids, which possess antioxidant and anti-inflammatory properties.

    Dr Joanna Bowtell, head of Sport and Health Sciences at the University of Exeter, said: “Our cognitive function tends to decline as we get older, but previous research has shown that cognitive function is better preserved in healthy older adults with a diet rich in plant-based foods.

    “In this study we have shown that with just 12 weeks of consuming 30ml of concentrated blueberry juice every day, brain blood flow, brain activation and some aspects of working memory were improved in this group of healthy older adults.”

    Of the 26 healthy adults in the study, 12 were given concentrated blueberry juice — providing the equivalent of 230g of blueberries — once a day, while 14 received a placebo.

    Before and after the 12-week period, participants took a range of cognitive tests while an MRI scanner monitored their brain function and resting brain blood flow was measured.

    Compared to the placebo group, those who took the blueberry supplement showed significant increases in brain activity in brain areas related to the tests.

    The study excluded anyone who said they consumed more than five portions of fruit and vegetables per day, and all participants were told to stick to their normal diet throughout.

    Previous research has shown that risk of dementia is reduced by higher fruit and vegetable intake, and cognitive function is better preserved in healthy older adults with a diet rich in plant-based foods.

    Flavonoids, which are abundant in plants, are likely to be an important component in causing these effects.


  8. New risk factors for anxiety disorders

    by Ashley

    From the University of Würzburg press release:

    Mental, social and inherited factors all play a role in anxiety disorders. In the journal Molecular Psychiatry, a research team from Julius-Maximilians-Universität Würzburg (JMU) in Bavaria, Germany, describes a hitherto unknown genetic pathway for developing such diseases: They pinpointed at least four variants of the GLRB gene (glycine receptor B) as risk factors for anxiety and panic disorders. More than 5000 voluntary participants and 500 patients afflicted by panic disorder took part in the study that delivered these results.

    In Germany, around 15 percent of adults suffer from anxiety and panic disorders. Some people may have an extreme fear of spiders or other objects while others have breathing difficulties and accelerated heart beat in small rooms or large gatherings of people. With some afflicted persons, the anxiety attacks occur for no apparent cause. Many patients suffer from the detrimental impacts on their everyday lives — they often have problems at work and withdraw from social contacts.

    How are fear and anxiety triggered? How do anxiety disorders arise and evolve?

    Scientists from Münster, Hamburg and Würzburg have looked into these questions within the scope of Collaborative Research Center (CRC) TR 58 funded by Deutsche Forschungsgemeinschaft. Their goal is to develop new therapies that are better tailored to the individual patients. Anxiety disorders can be treated with drugs and behaviour therapy for instance.

    Gene triggers hyperekplexia

    The discovery that different variants of the GLRB gene are associated with anxiety disorders might also contribute to the development of improved therapies. The gene had been known to the researchers for some time, albeit only in connection with a different disease:

    “Some mutations of the gene cause a rare neurological disorder called hyperekplexia,” explains Professor Jürgen Deckert, member of the CRC and Director of the Department of Psychiatry at the JMU University Hospital. The patients are permanently hypertonic and show pronounced startle responses, which may even cause sufferers to fall involuntarily. Similar to persons suffering from anxiety disorders, these patients develop behaviour to avoid potentially frightening situations.

    The “fear network” in the brain is activated

    But the GLRB gene variants that have recently been associated with anxiety and panic disorders for the first time are different from the ones described above. They occur more frequently and presumably entail less severe consequences. But they, too, trigger overshooting startle responses, and as a result may excessively activate the brain’s “fear network.” High-resolution images of the brain activities of study participants provided the clues for the Würzburg scientists.

    “The results point to a hitherto unknown pathway of developing an anxiety disorder,” Deckert says. He believes that further investigations are now necessary to determine whether these findings can be harnessed to develop new or individual therapies. For example, it is conceivable to bring the “fear network” that is misregulated by the GLRB gene back on track by administering drugs.


  9. Even after treatment, brains of anorexia nervosa patients not fully recovered

    March 19, 2017 by Ashley

    From the University of Colorado Anschutz Medical Campus press release:

    Even after weeks of treatment and considerable weight gain, the brains of adolescent patients with anorexia nervosa remain altered, putting them at risk for possible relapse, according to researchers at the University of Colorado Anschutz Medical Campus.

    The study, published last week in the American Journal of Psychiatry, examined 21 female adolescents before and after treatment for anorexia and found that their brains still had an elevated reward system compared to 21 participants without the eating disorder.

    “That means they are not cured,” said Guido Frank, MD, senior author of the study and associate professor of psychiatry and neuroscience at the University of Colorado School of Medicine. “This disease fundamentally changes the brain response to stimuli in our environment. The brain has to normalize and that takes time.”

    Brain scans of anorexia nervosa patients have implicated central reward circuits that govern appetite and food intake in the disease. This study showed that the reward system was elevated when the patients were underweight and remained so once weight was restored.

    The neurotransmitter dopamine might be the key, researchers said.

    Dopamine mediates reward learning and is suspected of playing a major role in the pathology of anorexia nervosa. Animal studies have shown that food restriction or weight loss enhances dopamine response to rewards.

    With that in mind, Frank, an expert in eating disorders, and his colleagues wanted to see if this heightened brain activity would normalize once the patient regained weight. Study participants, adolescent girls who were between 15 and 16 years old, underwent a series of reward-learning taste tests while their brains were being scanned.

    The results showed that reward responses were higher in adolescents with anorexia nervosa than in those without it. This normalized somewhat after weight gain but still remained elevated.

    At the same time, the study showed that those with anorexia had widespread changes to parts of the brain like the insula, which processes taste along with a number of other functions including body self-awareness.

    The more severely altered the brain, the harder it was to treat the illness, or in other words, the more severely altered the brain, the more difficult it was for the patients to gain weight in treatment.

    Generalized sensitization of brain reward responsiveness may last long into recovery,” the study said. “Whether individuals with anorexia nervosa have a genetic predisposition for such sensitization requires further study.”

    Frank said more studies are also needed to determine if the continued elevated brain response is due to a heightened dopamine reaction to starvation and whether it signals a severe form of anorexia among adolescents that is more resistant to treatment.

    In either case, Frank said the biological markers discovered here could be used to help determine the likelihood of treatment success. They could also point the way toward using drugs that target the dopamine reward system.

    “Anorexia nervosa is hard to treat. It is the third most common chronic illness among teenage girls with a mortality rate 12 times higher than the death rate for all causes of death for females 15-24 years old,” Frank said. “But with studies like this we are learning more and more about what is actually happening in the brain. And if we understand the system, we can develop better strategies to treat the disease.”


  10. OCD-like behavior linked to genetic mutation

    by Ashley

    From the Northwestern University press release:

    A new Northwestern Medicine study found evidence suggesting how neural dysfunction in a certain region of the brain can lead to obsessive and repetitive behaviors much like obsessive-compulsive disorder (OCD).

    Both in humans and in mice, there is a circuit in the brain called the corticostriatal connection that regulates habitual and repetitive actions. The study found certain synaptic receptors are important for the development of this brain circuit. If these receptors are eliminated in mice, they exhibit obsessive behavior, such as over-grooming.

    This is the first strong evidence that supports the biological basis for how these genes that code for these receptors might affect obsessive or compulsive behaviors in humans. By demonstrating that these receptors have this role in development, researchers down the line will have a target to develop treatments for obsessive-compulsive behavior.

    “Variations in these receptor genes are associated with human neurodevelopmental disorders, such as autism and neuropsychiatric disorders such as OCD,” said lead author Anis Contractor, associate professor of physiology at Northwestern University Feinberg School of Medicine. “People with OCD are known to have abnormalities in function of corticostriatal circuits.”

    The study was published February 21 in the journal Cell Reports. The findings shed light on the importance of these receptors in the formation of the corticostriatal circuits, Contractor said.

    “A number of studies have found mutations in the kainate receptor genes that are associated with OCD or other neuropsychiatric and neurodevelopmental disorders in humans,” said Contractor, who also is an associate professor of neurobiology at the Weinberg College of Arts and Sciences at Northwestern. “I believe our study, which found that a mouse with targeted mutations in these genes exhibited OCD-like behaviors, helps support the current genetic studies on neuropsychiatric and neurodevelopmental disorders in humans.”

    The traits of OCD the mice in the study exhibited included over-grooming, continuously digging in their bedding and consistently failing a simple alternating-choice test in a maze.