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Bipolar Disorder Basic Biology

Scientists know there is a strong genetic component to bipolar disorder, but they have had an extremely difficult time identifying the genes that cause it. So, in an effort to better understand the illness's genetic causes, researchers at UCLA tried a new approach.
Instead of only using a standard clinical interview to determine whether individuals met the criteria for a clinical diagnosis of bipolar disorder, the researchers combined the results from brain imaging, cognitive testing, and an array of temperament and behavior measures. Using the new method, UCLA investigators -- working with collaborators from UC San Francisco, Colombia's University of Antioquia and the University of Costa Rica -- identified about 50 brain and behavioral measures that are both under strong genetic control and associated with bipolar disorder. Their discoveries could be a major step toward identifying the specific genes that contribute to the illness.
The results are published in the Feb. 12 edition of the Journal JAMA Psychiatry.
A severe mental illness that affects about 1 to 2 percent of the population, bipolar disorder causes unusual shifts in mood and energy, and it interferes with the ability to carry out everyday tasks. Those with the disorder can experience tremendous highs and extreme lows -- to the point of not wanting to get out of bed when they're feeling down. The genetic causes of bipolar disorder are highly complex and likely involve many different genes, said Carrie Bearden, a senior author of the study and an associate professor of psychiatry and psychology at the UCLA Semel Institute for Neuroscience and Human Behavior.
"The field of psychiatric genetics has long struggled to find an effective approach to begin dissecting the genetic basis of bipolar disorder," Bearden said. "This is an innovative approach to identifying genetically influenced brain and behavioral measures that are more closely tied to the underlying biology of bipolar disorder than the clinical symptoms alone are."
The researchers assessed 738 adults, 181 of whom have severe bipolar disorder. They used high-resolution 3-D images of the brain, questionnaires evaluating temperament and personality traits of individuals diagnosed with bipolar disorder and their non-bipolar relatives, and an extensive battery of cognitive tests assessing long-term memory, attention, inhibitory control and other neurocognitive abilities.
Approximately 50 of these measures showed strong evidence of being influenced by genetics. Particularly interesting was the discovery that the thickness of the gray matter in the brain's temporal and prefrontal regions -- the structures that are critical for language and for higher-order cognitive functions like self-control and problem-solving -- were the most promising candidate traits for genetic mapping, based on both their strong genetic basis and association with the disease.
"These findings are really just the first step in getting us a little closer to the roots of bipolar disorder," Bearden said. "What was really exciting about this project was that we were able to collect the most extensive set of traits associated with bipolar disorder ever assessed within any study sample. These data will be a really valuable resource for the field."
The individuals assessed in this study are members of large families living in Costa Rica's central valley and Antioquia, Colombia. The families were founded by European and native Amerindian populations about 400 years ago and have a very high incidence of bipolar disorder. The groups were chosen because they have remained fairly isolated since their founding and their genetics are therefore simpler for scientists to study than those of general populations.
The fact that the findings aligned so closely with those of previous, smaller studies in other populations was surprising even to the scientists, given the subjects' unique genetic background and living environments.
"This suggests that even if the specific genetic variants we identify may be unique to this population, the biological pathways they disrupt are likely to also influence disease risk in other populations," Bearden said.
The researchers' next step is to use the genomic data they collected from the families -- including full genome sequences and gene expression data -- to begin identifying the specific genes that contribute to risk for bipolar disorder. The researchers also plan to extend their investigation into the children and teens in these families. They hypothesize that many of the bipolar-related brain and behavioral differences found in adults with bipolar disorder had their origins in adolescent neurodevelopment.

Journal Reference:
  1. Scott C. Fears, Susan K. Service, Barbara Kremeyer, Carmen Araya, Xinia Araya, Julio Bejarano, Margarita Ramirez, Gabriel Castrillón, Juliana Gomez-Franco, Maria C. Lopez, Gabriel Montoya, Patricia Montoya, Ileana Aldana, Terri M. Teshiba, Zvart Abaryan, Noor B. Al-Sharif, Marissa Ericson, Maria Jalbrzikowski, Jurjen J. Luykx, Linda Navarro, Todd A. Tishler, Lori Altshuler, George Bartzokis, Javier Escobar, David C. Glahn, Jorge Ospina-Duque, Neil Risch, Andrés Ruiz-Linares, Paul M. Thompson, Rita M. Cantor, Carlos Lopez-Jaramillo, Gabriel Macaya, Julio Molina, Victor I. Reus, Chiara Sabatti, Nelson B. Freimer, Carrie E. Bearden. Multisystem Component Phenotypes of Bipolar Disorder for Genetic Investigations of Extended PedigreesJAMA Psychiatry, 2014; DOI: 10.1001/jamapsychiatry.2013.4100

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MitoQ Significantly Reverses Multiple Sclerosis-like Disease in Mice

Researchers at Oregon Health & Science University have discovered that an antioxidant designed by scientists more than a dozen years ago to fight damage within human cells significantly helps symptoms in mice that have a multiple sclerosis-like disease.

The antioxidant -- called MitoQ -- has shown some promise in fighting neurodegenerative diseases. But this is the first time it has been shown to significantly reverse an MS-like disease in an animal. The discovery could lead to an entirely new way to treat multiple sclerosis, which affects more than 2.3 million people worldwide. Multiple sclerosis occurs when the body's immune system attacks the myelin, or the protective sheath, surrounding nerve fibers of the central nervous system. Some underlying nerve fibers are destroyed. Resulting symptoms can include blurred vision and blindness, loss of balance, slurred speech, tremors, numbness and problems with memory and concentration.
The antioxidant research was published in the December edition of Biochimica et Biophysica Acta Molecular Basis of Disease. The research team was led by P. Hemachandra Reddy, Ph.D., an associate scientist in the Division of Neuroscience at OHSU's Oregon National Primate Research Center. To conduct their study, the researchers induced mice to contract a disease called experimental autoimmune encephalomyelitis, or EAE, which is very similar to MS in humans. They separated mice into four groups: a group with EAE only; a group that was given the EAE, then treated with the MitoQ; a third group that was given the MitoQ first, then given the EAE; and a fourth "control" group of mice without EAE and without any other treatment. After 14 days, the EAE mice that had been treated with the MitoQ exhibited reduced inflammatory markers and increased neuronal activity in the spinal cord -- an affected brain region in MS -- that showed their EAE symptoms were being improved by the treatment. The mice also showed reduced loss of axons, or nerve fibers and reduced neurological disabilities associated with the EAE. The mice that had been pre-treated with the MitoQ showed the least problems. The mice that had been treated with MitoQ after EAE also showed many fewer problems than mice who were just induced to get the EAE and then given no treatment.
"The MitoQ also significantly reduced inflammation of the neurons and reduced demyelination," Reddy said. "These results are really exciting. This could be a new front in the fight against MS."
Even if the treatment continues to show promise, testing in humans would be years away. The next steps for Reddy's team will be to understand the mechanisms of MitoQ neuroprotection in different regions of the brain, and how MitoQ protects mitochondria within the brain cells of the EAE mice. Mitochondria, components within all human cells, convert energy into forms that are usable by the cell. There is a built-in advantage with MitoQ. Unlike many new drugs, MitoQ has been tested for safety in numerous clinical trails with humans. Since its development in the late 1990s, researchers have tested MitoQ's ability to decrease oxidative damage in mitochondria.
"It appears that MitoQ enters neuronal mitochondria quickly, scavenges free radicals, reduces oxidative insults produced by elevated inflammation, and maintains or even boosts neuronal energy in affected cells," said Reddy. The hope has been that MitoQ might help treat neurodegenerative diseases like Alzheimer's and Parkinson's. Studies evaluating its helpfulness in treating those diseases are ongoing.
Journal Reference:
  1. Peizhong Mao, Maria Manczak, Ulziibat P. Shirendeb, P. Hemachandra Reddy. MitoQ, a mitochondria-targeted antioxidant, delays disease progression and alleviates pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis.Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2013; 1832 (12): 2322 DOI:10.1016/j.bbadis.2013.09.005


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New Technological Tools For Autism

Researchers in Georgia Tech's Center for Behavior Imaging have developed two new technological tools that automatically measure relevant behaviors of children, and promise to have significant impact on the understanding of behavioral disorders such as autism.
One of the tools -- a system that uses special gaze-tracking glasses and facial-analysis software to identify when a child makes eye contact with the glasses-wearer -- was created by combining two existing technologies to develop a novel capability of automatic detection of eye contact. The other is a wearable system that uses accelerometers to monitor and categorize problem behaviors in children with behavioral disorders.
Both technologies already are being deployed in the Center for Behavior Imaging's (CBI) ongoing work to apply computational methods to screening, measurement and understanding of autism and other behavioral disorders.
Children at risk for autism often display distinct behavioral markers from a very young age. One such marker is a reluctance to make frequent or prolonged eye contact with other people. Discovering an automated way to detect this and other telltale behavioral markers would be a significant step toward scaling autism screening up to much larger populations than are currently reached. This is one goal of the five-year, $10 million "Expeditions" project, funded in fall 2010 by the National Science Foundation under principal investigator and CBI Director Jim Rehg, also a professor in Georgia Tech's School of Interactive Computing.
The eye-contact tracking system begins with a commercially available pair of glasses that can record the focal point of their wearer's gaze. Researchers took video of a child captured by a front-facing camera on the glasses, worn by an adult who was interacting with the child. The video was then processed using facial recognition software available from a second manufacturer. Combine the glasses' hard-wired ability to detect wearer gaze with the facial-recognition software's ability to detect the child's gaze direction, and the result is a system able to detect eye contact in a test interaction with a 22-month-old with 80 percent accuracy. The study was conducted in Georgia Tech's Child Study Lab (CSL), a child-friendly experimental facility richly equipped with cameras, microphones and other sensors.
"Eye gaze has been a tricky thing to measure in laboratory settings, and typically it's very labor-intensive, involving hours and hours of looking at frames of video to pinpoint moments of eye contact," Rehg said. "The exciting thing about our method is that it can produce these measures automatically and could be used in the future to measure eye contact outside the laboratory setting. We call these results preliminary because they were obtained from a single subject, but all humans' eyes work pretty much the same way, so we're confident the successful results will be replicated with future subjects."
The other new system, developed in collaboration with the Marcus Autism Center in Atlanta and Dr. Thomas Ploetz of Newcastle University in the United Kingdom, is a package of sensors, worn via straps on the wrists and ankles, that uses accelerometers to detect movement by the wearer. Algorithms developed by the team analyze the sensor data to automatically detect episodes of problem behavior and classify them as aggressive, self-injurious or disruptive (e.g., throwing objects).
Researchers first developed the algorithms by putting the sensors on four Marcus clinic staff members who together performed some 1,200 different behavior instances, and the system detected "problem" behaviors with 95 percent accuracy and classified all behaviors with 80 percent accuracy. They then used the sensors with a child diagnosed along the autism spectrum, and the system detected the child's problem-behavior episodes with 81 percent accuracy and classified them with 70 percent accuracy.
"These results are very promising in leading the way toward more accurate and reliable measurement of problem behavior, which is important in determining whether treatments targeting these behaviors are working," said CSL Director Agata Rozga, a research scientist in the School of Interactive Computing and co-investigator on the Expeditions award. "Our ultimate goal with this wearable sensing system is to be able to gather data on the child's behavior beyond the clinic, in settings where the child spends most of their time, such as their home or school. In this way, parents, teachers and others who care for the child can be potentially alerted to times and situations when problem behaviors occur so that they can address them immediately."
"What these tools show is that computational methods and technologies have great promise and potential impact on the lives of many children and their parents and caregivers," said Gregory Abowd, Regents' Professor in the School of Interactive Computing and a prominent researcher in technology and autism. "These technologies we are developing, and others developed and explored elsewhere, aim to bring more effective early-childhood screening to millions of children nationwide, as well as enhance care for those children already diagnosed on the autism spectrum."
Both technologies were presented in early September at the 14th ACM International Conference on Ubiquitous Computing (Ubicomp 2012). Among the other devices under study at CSL are a camera/software system that can track children's facial expressions and customized speech analysis software to detect vocalization patterns.

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Mechanism Underlying Common Non-familial Parkinson's Disease

Researchers in the Taub Institute at Columbia University Medical Center (CUMC) have identified a mechanism that appears to underlie the common sporadic (non-familial) form of Parkinson's disease, the progressive movement disorder. The discovery highlights potential new therapeutic targets for Parkinson's and could lead to a blood test for the disease. The study, based mainly on analysis of human brain tissue, was published September 25 in the online edition of Nature Communications.
Studies of rare, familial (heritable) forms of Parkinson's show that a protein called alpha-synuclein plays a role in the development of the disease. People who have extra copies of the alpha-synuclein gene produce excess alpha-synuclein protein, which can damage neurons. The effect is most pronounced in dopamine neurons, a population of brain cells in the substantia nigra that plays a key role in controlling normal movement and is lost in Parkinson's. Another key feature of Parkinson's is the presence of excess alpha-synuclein aggregates in the brain.
As the vast majority of patients with Parkinson's do not carry rare familial mutations, a key question has been why these individuals with common sporadic Parkinson's nonetheless acquire excess alpha-synuclein protein and lose critical dopamine neurons, leading to the disease.
Using a variety of techniques, including gene-expression analysis and gene-network mapping, the CUMC researchers discovered how common forms of alpha-synuclein contribute to sporadic Parkinson's. "It turns out multiple different alpha-synuclein transcript forms are generated during the initial step in making the disease protein; our study implicates the longer transcript forms as the major culprits," said study leader Asa Abeliovich, MD, PhD, associate professor of pathology and neurology at CUMC. "Some very common genetic variants in the alpha-synuclein gene, present in many people, are known to impact the likelihood that an individual will suffer from sporadic Parkinson's. In our study, we show that people with 'bad' variants of the gene make more of the elongated alpha-synuclein transcript forms. This ultimately means that more of the disease protein is made and may accumulate in the brain."
"An unusual aspect of our study is that it is based largely on detailed analysis of actual patient tissue, rather than solely on animal models," said Dr. Abeliovich. "In fact, the longer forms of alpha-synuclein are human-specific, as are the disease-associated genetic variants. Animal models don't really get Parkinson's, which underscores the importance of including the analysis of human brain tissue."
"Furthermore, we found that exposure to toxins associated with Parkinson's can increase the abundance of this longer transcript form of alpha-synuclein. Thus, this mechanism may represent a common pathway by which environmental and genetic factors impact the disease," said Dr. Abeliovich.
The findings suggest that drugs that reduce the accumulation of elongated alpha-synuclein transcripts in the brain might have therapeutic value in the treatment of Parkinson's. The CUMC team is currently searching for drug candidates and has identified several possibilities.
The study also found elevated levels of the alpha-synuclein elongated transcripts in the blood of a group of patients with sporadic Parkinson's, compared with unaffected controls. This would suggest that a test for alpha-synuclein may serve as a biomarker for the disease. "There is a tremendous need for a biomarker for Parkinson's, which now can be diagnosed only on the basis of clinical symptoms. The finding is particularly intriguing, but needs to be validated in additional patient groups," said Dr. Abeliovich. A biomarker could also speed clinical trials by giving researchers a more timely measure of a drug's effectiveness.
The study was supported by the grants from the Michael J. Fox Foundation, the National Institutes of Health, and the National Institute of Neurological Disorders and Stroke (RO1NS064433).
Journal Reference:
  1. Herve Rhinn, Liang Qiang, Toru Yamashita, David Rhee, Ari Zolin, William Vanti, Asa Abeliovich. Alternative α-synuclein transcript usage as a convergent mechanism in Parkinson's disease pathologyNature Communications, 2012; 3: 1084 DOI: 10.1038/ncomms2032


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Cataracts and Alzheimer's Share Common Etiological Factors

In a recent study, investigators at Boston University Schools of Medicine (BUSM) and Public Health (BUSPH) identified a gene linking age-related cataracts and Alzheimer's disease. The findings, published online in PLoS ONE, contribute to the growing body of evidence showing that these two diseases, both associated with increasing age, may share common etiologic factors. 
Gyungah Jun, PhD, from the departments of medicine, ophthalmology and biostatistics at BUSM and BUSPH, served as the study's lead author. Lindsay A. Farrer, PhD, professor of medicine, neurology, ophthalmology, genetics & genomics, epidemiology and biostatistics and chief of the Biomedical Genetics Section at BUSM, was the study's senior author. 

Using the Framingham Offspring Eye Study cohort, investigators looked at brain MRI findings on or after 10 years from the original eye exam and concluded that there was a significant correlation between a quantitative measure of cortical cataract and several Alzheimer's disease-related measures of brain degeneration, in particular volume of the temporal horn which is a brain structure that is progressively enlarged in patients with Alzheimer's disease. Another strong correlation in these same individuals, between cortical cataract formation and poorer performance on several cognitive tests administered at the time of the MRI scan, further supports this link. 

With such a link not confounded by age or sex, the investigators then performed a genome-wide association study looking at nearly 190,000 single-nucleotide polymorphisms (SNPs), or DNA sequence variations. Three intronic (non-coding) SNPs in the gene encoding δ-catenin came to the fore. This protein is a key component in cell adherence and formation of cell junctional structures. Previously, δ-catenin was also implicated in brain and eye development, but not directly in either cataracts or Alzheimer's disease. To establish a more direct link of δ-catenin to Alzheimer's disease, the researchers transfected into neuronal cells δ-catenin bearing a mutation near the location of the top-associated SNPs and observed a significant and specific increase in the toxic form of amyloid β, the protein that aggregates in Alzheimer brains and thought to be central to development of the disorder. In addition, the researchers found increased deposits of δ-catenin in lens tissue obtained from autopsy-confirmed Alzheimer's cases but not from subjects lacking Alzheimer's-associated neuropathology. 

"Though much work remains to be done, a link between cataracts and Alzheimer's disease supports the idea of a systemic rather than brain-limited focus for processes leading to Alzheimer's disease," said Farrer. "This study gives hope that we are moving toward earlier diagnosis and new treatment targets for this debilitating disease." 

Juliet Moncaster, PhD, from the department of psychiatry; Sudha Seshadri, MD from department of neurology and associate professor of the Framingham Heart Study; Jacqueline Buros, BS, from the department of medicine; Ann C. McKee, MD, from the departments of neurology, pathology and laboratory medicine, the Boston University Alzheimer's Disease Center, and the Bedford Veterans Administration Hospital; and Phillip A. Wolf, MD, of the departments of neurology, epidemiology and professor of the Framingham Heart Study of BUSM and BUSPH, contributed to this paper. Researchers from the University of Toronto, the Bedford Veterans Administration Hospital, the Universití Laval and the University of Cambridge also collaborated on this study. 

This study was supported by grants from the National Institute on Aging for investigated-initiated projects (R01-AG025259, R01-AG33193, R01-AG081220, R01-AG16495, and R01-AG033040) and the Boston University Alzheimer Disease Center (P30-AG13846), National Institute of General Medical Science (R01-GM75986), Wellcome Trust, Medical Research Council, Canadian Institutes of Health Research, Alzheimer Society of Ontario, and Ontario Research Fund. 

Reference: 

Gyungah Jun, Juliet A. Moncaster, Carolina Koutras, Sudha Seshadri, Jacqueline Buros, Ann C. McKee, Georges Levesque, Philip A. Wolf, Peter St. George-Hyslop, Lee E. Goldstein, Lindsay A. Farrer. δ-Catenin Is Genetically and Biologically Associated with Cortical Cataract and Future Alzheimer-Related Structural and Functional Brain Changes. PLoS ONE, 2012; 7 (9): e43728 DOI: 10.1371/journal.pone.0043728

Boston University Medical Center.

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Dementia Associated With Low Vitamin C and Beta-carotene

Forgetfulness, lack of orientation, cognitive decline ... these are among the symptoms of Alzheimer's disease (AD). Now researchers from the University of Ulm, among them the Epidemiologist Professor Gabriele Nagel and the Neurologist Professor Christine von Arnim, have discovered that the serum-concentration of the antioxidants vitamin C and beta-carotene are significantly lower in patients with mild dementia than in control persons. It might thus be possible to influence the pathogenesis of AD by a person's diet or dietary antioxidants. 
A total of 74 AD-patients and 158 healthy controls were examined for the study that has been published in the Journal of Alzheimer's Disease (JAD). AD is a neurodegenerative disease: Alterations in the brain caused by amyloid-beta-plaques, degeneration of fibrillae and a loss of synapses are held responsible for the characteristic symptoms. Oxidative stress, which constrains the exploitation of oxygen in the human body, is suspected to promote the development of AD. Whereas so called antioxidants might protect against neurodegeneration. 

In their study, the researchers have investigated whether the serum-levels of vitamin C, vitamin E, beta-carotene as well as lycopene and coenzyme Q10 are significantly lower in the blood of AD-patients. "In order to possibly influence the onset and development of Alzheimer's disease, we need to be aware of potential risk factors," says Gabriele Nagel. Participants were recruited from the cross-sectional study IMCA ActiFE (Activity and Function in the Elderly in Ulm) for which a representative population-based sample of about 1,500 senior citizens has been examined. The 65 to 90 years old seniors from Ulm and the surrounding area underwent neuropsychological testing and answered questions regarding their lifestyle. What is more, their blood has been examined and their body mass index (BMI) was calculated. 

For the present study, scientists have compared 74 patients with mild dementia (average age 78.9 years) with a control group consisting of 158 healthy, gender-matched persons of the same age. Results are quite interesting: The concentration of vitamin C and beta-carotene in the serum of AD-patients was significantly lower than in the blood of control subjects. Whereas no such difference between the groups could be found for the other antioxidants (vitamin E, lycopene, coenzyme Q10). Potential confounding factors such as education, civil status, BMI, consumption of alcohol and tobacco have been considered in the statistical analysis. Nevertheless, additional parameters such as the storage and preparation of food as well as stressors in the life of participants might have influenced the findings. 

Therefore, results need to be confirmed in prospective surveys. "Longitudinal studies with more participants are necessary to confirm the result that vitamin C and beta-carotene might prevent the onset and development of Alzheimer's disease," says Gabriele Nagel. Vitamin C can for example be found in citrus fruits; beta-carotene in carrots, spinach or apricots. 

Source:
Christine A.F. von Arnim, Florian Herbolsheimer, Thorsten Nikolaus, Richard Peter,Hans K. Biesalski, Albert C. Ludolph, Matthias Riepe, Gabriele Nagel, and the ActiFE Ulm study group. Dietary Antioxidants and Dementia in a Population-Based Case-Control Study among Older People in South Germany. Journal of Alzheimer’s disease, 2012 DOI: 10.3233/JAD-2012-120634

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Low Dopamine in Frontal Cortex Blamed For Impulsivity

 Raising levels of the neurotransmitter dopamine in the frontal cortex of the brain significantly decreased impulsivity in healthy adults, in a study conducted by researchers at the Ernest Gallo Clinic and Research Center at the University of California, San Francisco.


"Impulsivity is a risk factor for addiction to many substances, and it has been suggested that people with lower dopamine levels in the frontal cortex tend to be more impulsive," said lead author Andrew Kayser, PhD, an investigator at Gallo and an assistant professor of neurology at UCSF. "We wanted to see if we could decrease impulsivity by raising dopamine, and it seems as if we can."
The study was published on July 4 in the Journal of Neuroscience.

In a double-blinded, placebo-controlled study, 23 adult research participants were given either tolcapone, a medication approved by the Food and Drug Administration (FDA) that inhibits a dopamine-degrading enzyme, or a placebo. The researchers then gave the participants a task that measured impulsivity, asking them to make a hypothetical choice between receiving a smaller amount of money immediately ("smaller sooner") or a larger amount at a later time ("larger later"). Each participant was tested twice, once with tolcapone and once with placebo.

Participants -- especially those who were more impulsive at baseline -- were more likely to choose the less impulsive "larger later" option after taking tolcapone than they were after taking the placebo. Magnetic resonance imaging conducted while the participants were taking the test confirmed that regions of the frontal cortex associated with decision-making were more active in the presence of tolcapone than in the presence of placebo.

"To our knowledge, this is the first study to use tolcapone to look for an effect on impulsivity," said Kayser. The study was not designed to investigate the reasons that reduced dopamine is linked with impulsivity. However, explained Kayser, scientists believe that impulsivity is associated with an imbalance in dopamine between the frontal cortex, which governs executive functions such as cognitive control and self-regulation, and the striatum, which is thought to be involved in the planning and modification of more habitual behaviors.

"Most, if not all, drugs of abuse, such as cocaine and amphetamine, directly or indirectly involve the dopamine system," said Kayser. "They tend to increase dopamine in the striatum, which in turn may reward impulsive behavior. In a very simplistic fashion, the striatum is saying 'go,' and the frontal cortex is saying 'stop.' If you take cocaine, you're increasing the 'go' signal, and the 'stop' signal is not adequate to counteract it."

Kayser and his research team plan a follow-up study of the effects of tolcapone on drinking behavior. "Once we determine whether drinkers can safely tolerate this medication, we will see if it has any effect on how much they drink while they're taking it," said Kayser.
Tolcapone is approved as a medication for Parkinson's disease, in which a chronic deficit of dopamine inhibits movement.

Co-authors of the paper are Daicia C. Allen, BS, Ana Navarro-Cebrian, PhD, Jennifer M. Mitchell, PhD and senior author Howard L. Fields, MD, PhD, of the Gallo Center and UCSF.
The study was supported by funds from the Wheeler Center for the Neurobiology of Addiction, the U.S. Army Telemedicine and Advanced Technology Research Center, the Alcoholic Beverage Medical Research Foundation/The Foundation for Alcohol Research and the State of California.



Journal Reference:
  1. Andrew S. Kayser, Daicia C. Allen, Ana Navarro-Cebrian, Jennifer M. Mitchell, and Howard L. Fields. Dopamine, Corticostriatal Connectivity, and Intertemporal Choice.The Journal of Neuroscience, 4 July 2012, 32(27):9402-9409 DOI: 10.1523/JNEUROSCI.1180-12.2012


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Actual Risk of Using Ecstasy

There has been significant debate in policy circles about whether governments have over-reacted to ecstasy by issuing warnings against its use and making it illegal. In the UK, David Nutt said ecstasy was less dangerous than horseback riding, which led to him being fired as the government's chief drug advisor. Others have argued that ecstasy is dangerous if you use it a lot, but brief use is safe.


New research published online July 25 by the scientific journal Addiction, gives some of the first information available on the actual risk of using ecstasy. It shows that even in recreational amounts over a relatively short time period, ecstasy users risk specific memory impairments. Further, as the nature of the impairments may not be immediately obvious to the user, it is possible people wouldn't get the signs that they are being damaged by drug use until it is too late.

New ecstasy users who took ten or more ecstasy pills over their first year of use showed decreased function of their immediate and short-term memory compared with their pre-ecstasy performance. These findings are associated with damage of the hippocampus, the area of the brain that oversees memory function and navigation. Interestingly, hippocampal damage is one of the first signs of Alzheimer's disease, resulting in memory loss and disorientation. (Credit: © James Steidl / Fotolia)

According to the study, new ecstasy users who took ten or more ecstasy pills over their first year of use showed decreased function of their immediate and short-term memory compared with their pre-ecstasy performance. These findings are associated with damage of the hippocampus, the area of the brain that oversees memory function and navigation. Interestingly, hippocampal damage is one of the first signs of Alzheimer's disease, resulting in memory loss and disorientation.

The study participants took an average of 32 pills each over the course of the year, or about two and a half pills per month. Some participants took as few as ten pills over the year and still showed signs of memory impairments.

Lead author Dr. Daniel Wagner says: "This study was designed to minimize the methodological limitations of earlier research, in which it was not possible to say whether cognitive impairments seen among ecstasy users were in place before drug use began. By measuring the cognitive function of people with no history of ecstasy use and, one year later, identifying those who had used ecstasy at least ten times and remeasuring their performance, we have been able to start isolating the precise cognitive effects of this drug."

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