Posts tagged psychiatric disorders
Articles and news from the latest research reports.
Marijuana use in adolescence may cause permanent brain abnormalities
Regular marijuana use in adolescence, but not adulthood, may permanently impair brain function and cognition, and may increase the risk of developing serious psychiatric disorders such as schizophrenia, according to a recent study from the University of Maryland School of Medicine. Researchers hope that the study, published in Neuropsychopharmacology — a publication of the journal Nature – will help to shed light on the potential long-term effects of marijuana use, particularly as lawmakers in Maryland and elsewhere contemplate legalizing the drug.
"Over the past 20 years, there has been a major controversy about the long-term effects of marijuana, with some evidence that use in adolescence could be damaging," says the study’s senior author Asaf Keller, Ph.D., Professor of Anatomy and Neurobiology at the University of Maryland School of Medicine. "Previous research has shown that children who started using marijuana before the age of 16 are at greater risk of permanent cognitive deficits, and have a significantly higher incidence of psychiatric disorders such as schizophrenia. There likely is a genetic susceptibility, and then you add marijuana during adolescence and it becomes the trigger."
"Adolescence is the critical period during which marijuana use can be damaging," says the study’s lead author, Sylvina Mullins Raver, a Ph.D. candidate in the Program in Neuroscience in the Department of Anatomy and Neurobiology at the University of Maryland School of Medicine. "We wanted to identify the biological underpinnings and determine whether there is a real, permanent health risk to marijuana use."
The scientists — including co-author Sarah Paige Haughwout, a research technician in Dr. Keller’s laboratory — began by examining cortical oscillations in mice. Cortical oscillations are patterns of the activity of neurons in the brain and are believed to underlie the brain’s various functions. These oscillations are very abnormal in schizophrenia and in other psychiatric disorders. The scientists exposed young mice to very low doses of the active ingredient in marijuana for 20 days, and then allowed them to return to their siblings and develop normally.
"In the adult mice exposed to marijuana ingredients in adolescence, we found that cortical oscillations were grossly altered, and they exhibited impaired cognitive abilities," says Ms. Raver. "We also found impaired cognitive behavioral performance in those mice. The striking finding is that, even though the mice were exposed to very low drug doses, and only for a brief period during adolescence, their brain abnormalities persisted into adulthood."
The scientists repeated the experiment, this time administering marijuana ingredients to adult mice that had never been exposed to the drug before. Their cortical oscillations and ability to perform cognitive behavioral tasks remained normal, indicating that it was only drug exposure during the critical period of adolescence that impaired cognition through this mechanism. The researchers took the next step in their studies, trying to pinpoint the mechanisms underlying these changes and the time period in which they occur.
"We looked at the different regions of the brain," says Dr. Keller. "The back of the brain develops first, and the frontal parts of the brain develop during adolescence. We found that the frontal cortex is much more affected by the drugs during adolescence. This is the area of the brain controls executive functions such as planning and impulse control. It is also the area most affected in schizophrenia."
Dr. Keller’s team believes that the results have indications for humans as well. They will continue to study the underlying mechanisms that cause these changes in cortical oscillations. “The purpose of studying these mechanisms is to see whether we can reverse these effects,” says Dr. Keller. “We are hoping we will learn more about schizophrenia and other psychiatric disorders, which are complicated conditions. These cognitive symptoms are not affected by medication, but they might be affected by controlling these cortical oscillations.”
Imagination can change what we hear and see
A study from Karolinska Institutet shows, that our imagination may affect how we experience the world more than we perhaps think. What we imagine hearing or seeing ‘in our head’ can change our actual perception. The study, which is published in the scientific journal Current Biology, sheds new light on a classic question in psychology and neuroscience - about how our brains combine information from the different senses.
"We often think about the things we imagine and the things we perceive as being clearly dissociable," says Christopher Berger, doctoral student at the Department of Neuroscience and lead author of the study. "However, what this study shows is that our imagination of a sound or a shape changes how we perceive the world around us in the same way actually hearing that sound or seeing that shape does. Specifically, we found that what we imagine hearing can change what we actually see, and what we imagine seeing can change what we actually hear."
The study consists of a series of experiments that make use of illusions in which sensory information from one sense changes or distorts one’s perception of another sense. Ninety-six healthy volunteers participated in total. In the first experiment, participants experienced the illusion that two passing objects collided rather than passed by one-another when they imagined a sound at the moment the two objects met. In a second experiment, the participants’ spatial perception of a sound was biased towards a location where they imagined seeing the brief appearance of a white circle. In the third experiment, the participants’ perception of what a person was saying was changed by their imagination of a particular sound.
According to the scientists, the results of the current study may be useful in understanding the mechanisms by which the brain fails to distinguish between thought and reality in certain psychiatric disorders such as schizophrenia. Another area of use could be research on brain computer interfaces, where paralyzed individuals’ imagination is used to control virtual and artificial devices.
"This is the first set of experiments to definitively establish that the sensory signals generated by one’s imagination are strong enough to change one’s real-world perception of a different sensory modality", says Professor Henrik Ehrsson, the principle investigator behind the study.
(Source: ki.se)
Psychiatric disorders linked to a protein involved in the formation of long-term memories
Researchers have discovered a pathway by which the brain controls a molecule critical to forming long-term memories and connected with bipolar disorder and schizophrenia.
The discovery was made by a team of scientists led by Alexei Morozov, an assistant professor at the Virginia Tech Carilion Research Institute.
The mechanism – a protein called Rap1 – controls L-type calcium channels, which participate in the formation of long-term memories. Previous studies have also linked alterations in these ion channels to certain psychiatric disorders. The discovery of the channels’ regulation by Rap1 could help scientists understand the physiological genesis of bipolar disorder and schizophrenia.
"People with genetic mutations affecting L-type calcium channels have higher rates of bipolar disorder and schizophrenia," said Morozov. "This suggests that there might be a relationship between the activation of L-type calcium channels and these psychiatric disorders. Understanding how these ion channels are controlled is the first step to determining how their functioning or malfunctioning affects mental health."
A single neuron in the brain can have thousands of synapses, each of which can grow, strengthen, weaken, and change structurally in response to learning new information. Electric signals traveling from neuron to neuron jump across these synapses through chemical neurotransmitters. The release of these chemicals is caused by the flow of electrically charged atoms through a particular subset of ion channels known as voltage-gated calcium channels.
Previous studies have shown that blocking these ion channels inhibits the formation of long-term memories. Although it was known that L-type calcium channels are activated in response to learning, how they are controlled was a mystery.
In the experiment, Morozov and colleagues knocked out the gene responsible for coding the enzyme Rap1, which he suspected played a role in activating L-type calcium channels. The researchers then used live imaging techniques to monitor the release of neurotransmitters and electron microscopy to visualize L-type channels at synapses. They discovered that, without Rap1, the L-type calcium channels were more active and more abundant at synapses all the time, increasing the release of neurotransmitters. The results showed that Rap1 is responsible for suppressing L-type calcium channels, allowing them to activate only at the proper moments, possibly during long-term memory formation.
"Our next step is to determine whether this new signaling pathway is altered in cases of mental disease," said Morozov. "If so, it could help us gain a better understanding of the molecular underpinnings of channel-related psychiatric disorders, such as bipolar disorder and schizophrenia. Such knowledge would go a long way toward developing new therapeutic methods."
(Source: eurekalert.org)
Scientists discover the origin of a giant synapse
Humans and most mammals can determine the spatial origin of sounds with remarkable acuity. We use this ability all the time—crossing the street; locating an invisible ringing cell phone in a cluttered bedroom. To accomplish this small daily miracle, the brain has developed a circuit that’s rapid enough to detect the tiny lag that occurs between the moment the auditory information reaches one of our ears, and the moment it reaches the other. The mastermind of this circuit is the “Calyx of Held,” the largest known synapse in the brain. EPFL scientists have revealed the role that a certain protein plays in initiating the growth of these giant synapses.
The discovery, published in Nature Neuroscience, could also help shed light on a number of neuropsychiatric disorders.
Enormous synapses enable faster communication
Ordinarily, neurons have thousands of contact points – known as synapses - with neighboring neurons. Within a given time frame, a neuron has to receive several signals from its neighbors in order to be able to fire its own signal in response. Because of this, information passes from neuron to neuron in a relatively random manner.
In the auditory part of the brain, this is not the case. Synapses often grow to extremely large sizes, and these behemoths are known as “Calyx of Held” synapses. Because they have hundreds of contact points, they are capable of transmitting a signal singlehandedly to a neighboring neuron. “It’s almost like peer-to-peer communication between neurons,” explains EPFL professor Ralf Schneggenburger, who led the study. The result is that information is processed extremely quickly, in a few fractions of a millisecond, instead of the slower pace of more than 10 milliseconds that occurs in most other neuronal circuits.
Identifying the protein
To isolate the protein responsible for controlling the growth of this gigantic synapse, the scientists had to perform painstaking research. Using methods for analyzing gene expression in mice, they identified several members of the “BMP” family of proteins from among more than 20,000 possible candidates.
To verify that they had truly identified the right protein, the researchers disabled BMP protein receptors in the auditory part of a mouse brain. “The resulting electrophysiological signal of the Calyx of Held was significantly altered,” explains Le Xiao, first author on the study. “This would suggest a large anatomical difference.”
The scientists then reconstructed the synapses in three dimensions from slices that were observed under an electron microscope. Instead of a single, massive Calyx of Held, which would encompass nearly half the neuron, the 3D image of the neuron clearly shows several, smaller synapses. “This shows that the process involving the BMP protein not only causes that one synapse to grow, but also performs a selection, by eliminating the others,” says Schneggenburger.
Synaptic connectivity, the key to many psychiatric puzzles
The impact of this study will go well beyond increasing our understanding of the auditory system. The results suggest that the BMP protein plays an important role in developing connectivity in the brain. Schneggenburger and his colleagues are currently investigating its role elsewhere in the brain. “Some neuropsychiatric disorders, such as schizophrenia and autism, are characterized by the abnormal development of synaptic connectivity in certain key parts of the brain,” explains Schneggenburger. By identifying and explaining the role of various proteins in this process, the scientists hope to be able to shed more light on these poorly understood disorders.
Scientists unpack testosterone’s role in schizophrenia
Testosterone may trigger a brain chemical process linked to schizophrenia but the same sex hormone can also improve cognitive thinking skills in men with the disorder, two new studies show.
Scientists have long suspected testosterone plays an important role in schizophrenia, which affects more men than women. Men are also more likely to develop psychosis in adolescence, previous research has shown.
A new study on lab rodents by researchers from Neuroscience Research Australia analysed the impact increased testosterone had on levels of dopamine, a brain chemical linked to psychotic symptoms of schizophrenia.
The researchers found that testosterone boosted dopamine sensitivity in adolescent male rodents.
“From these rodent studies, we hypothesise that adolescent increases in circulating testosterone may be a driver of increased dopamine activity in the brains of individuals susceptible to psychosis and schizophrenia,” said senior Neuroscience Research Australia researcher and author of the study, Dr Tertia Purves-Tyson, who is presenting her work at the International Congress on Schizophrenia Research in Florida this week.
Dr Philip Mitchell, Scientia Professor and Head of the School of Psychiatry at the University of NSW, said the research was very interesting.
“The relationship between sex steroids, such as testosterone, and psychiatric disorders has long intrigued researchers. For example, we have known for many years that schizophrenia presents earlier in males than females, but the biological mechanism for this has been poorly understood,” said Dr Mitchell, who was not involved in the study.
“The rodent study by Professor Shannon Weickert from the School of Psychiatry at UNSW and NeuRA is therefore of particular interest. This study suggests an important interplay between circulating testosterone levels and the brain’s sensitivity to dopamine – a neurochemical which has been long implicated in the cause of schizophrenia,” said Dr Mitchell.
“This study suggests that it is the interplay between testosterone and dopamine which is critical. This is an important observation which may very well throw an important light on solving the puzzle of the biological causes of schizophrenia.”
Cognitive thinking
A separate study by Dr Thomas Weickert at Neuroscience Research Australia examined the role testosterone plays in the cognitive thinking skills of men with schizophrenia.
The researchers examined testosterone levels in a group of 29 chronically ill men with schizophrenia or schizoaffective disorder, and a control group of 20 healthy men and asked both groups to take a series of cognition tests.
“Circulating testosterone levels significantly predicted performance on verbal memory, processing speed, and working memory in men with schizophrenia … such that increased normal levels of testosterone were beneficial to thought processing in men with schizophrenia but circulating sex steroid levels did not appear to be related to cognitive function in healthy men,” the researchers reported.
“The results suggest that circulating sex steroids may influence thought processes in men with schizophrenia.”
Dr Melanie McDowall, a researcher at the University of Adelaide’s Robinson Institute, said the study added to a large body of evidence demonstrating a link between testosterone and schizophrenia.
“This is not surprising, given the link between testosterone and dopamine,” she said, adding that symptoms of schizophrenia predominantly began after puberty.
“However, as with most endocrine and mental illnesses, schizophrenia is multifaceted (genetic, environmental etc.), hence this may not be the be all and end.”
(Source: theconversation.com)
Decision Making: From Neuroscience to Psychiatry
Adaptive behaviors increase the likelihood of survival and reproduction and improve the quality of life. However, it is often difficult to identify optimal behaviors in real life due to the complexity of the decision maker’s environment and social dynamics. As a result, although many different brain areas and circuits are involved in decision making, evolutionary and learning solutions adopted by individual decision makers sometimes produce suboptimal outcomes. Although these problems are exacerbated in numerous neurological and psychiatric disorders, their underlying neurobiological causes remain incompletely understood. In this review, theoretical frameworks in economics and machine learning and their applications in recent behavioral and neurobiological studies are summarized. Examples of such applications in clinical domains are also discussed for substance abuse, Parkinson’s disease, attention-deficit/hyperactivity disorder, schizophrenia, mood disorders, and autism. Findings from these studies have begun to lay the foundations necessary to improve diagnostics and treatment for various neurological and psychiatric disorders.
Surprisingly, yes.
The modern lobotomy originated in the 1930s, when doctors realized that by severing fiber tracts connected to the frontal lobe, they could help patients overcome certain psychiatric problems, such as intractable depression and anxiety. Over the next two decades, the procedure would become simple and popular, completed by poking a sharpened tool above the eyeball. According to one study, about two thirds of patients showed improvement after surgery.
Unfortunately, not all lobotomy practition-ers were responsible, and the technique left some patients with severe side effects, including seizures, lethargy, changes in personality, and incontinence. In response, doctors refined their techniques. They replaced the lobotomy with more specialized approaches: the cingulotomy, the anterior capsulotomy, and the subcaudate tractotomy. Studies of these procedures found evidence of benefit for at least one fourth of patients suffering from problems such as OCD and depression.
Even with the risk of side effects, those in the field still say the procedures were by and large successful. “I feel that the principle behind ablative surgery was somewhat exonerated by the research findings, which showed that it worked for very specific indications,” says Konstantin Slavin, president of the American Society for Stereotactic and Functional Neurosurgery, and professor at the University of Illinois at Chicago.
By the 1980s, lobotomies had fallen out of fashion. “In general, the entire functional neurosurgery field moved away from destruction—from ablative surgery,” Slavin says. A then-new technique called deep-brain stimulation made ablative surgery obsolete. In the procedure, a surgeon drills holes in the head and inserts electrodes into the neural tissue. When current passes through the leads, they activate or inactivate patches of the brain. “The attractive part is that we don’t destroy the tissue,” Slavin says. Doctors can also adjust treatment if a patient suffers side effects. They can turn the current down or suspend it altogether—so as to “give the brain a holiday,” as Slavin calls it.
Most deep-brain stimulation is now used to treat movement disorders such as Parkinson’s Disease. The surgical treatment of patients with OCD is FDA-approved but reserved only for extreme cases. Slavin and his colleagues have been examining broader uses in an ongoing study. “Within the next five years, we hope we’ll have a definitive answer of whether or not it works.”
New Genetic Evidence Suggests a Continuum Among Neurodevelopmental and Psychiatric Disorders
A paper published this month in the prestigious medical journal The Lancet Neurology suggests that a broad spectrum of developmental and psychiatric disorders, ranging from autism and intellectual disability to schizophrenia, should be conceptualized as different manifestations of a common underlying denominator, “developmental brain dysfunction,” rather than completely independent conditions with distinct causes.
In “Developmental Brain Dysfunction: Revival and Expansion of Old Concepts Based on New Genetic Evidence,” the authors make two key points:
- Developmental disorders (such as autism and intellectual disability) and psychiatric disorders (such as schizophrenia and bipolar disorder), while considered clinically distinct, actually share many of the same underlying genetic causes. This is an example of “variable expressivity:” the same genetic variant results in different clinical signs and symptoms in different individuals.
- When quantitative measures of neuropsychological and neurobehavioral traits are studied instead of categorical diagnoses (which are either present or absent) and individuals are compared to their unaffected family members, it is possible to more accurately demonstrate the impact of genetic variants.
According to Andres Moreno De Luca, M.D., research scientist at the Autism and Developmental Medicine Institute at Geisinger Health System and article co-author, “Recent genetic studies conducted in thousands of individuals have shown that identical genetic mutations are shared among neurodevelopmental disorders that are thought to be clinically distinct. What we have seen over the past few years is that genetic mutations that were initially found in individuals with one disorder, such as intellectual disability or autism, are then identified in people with an apparently different condition like schizophrenia, epilepsy, or bipolar disorder.”
“It turns out that the genes don’t respect our diagnostic classification boundaries, but that really isn’t surprising given the overlapping symptoms and frequent co-existence of neurodevelopmental disorders,” said Scott M. Myers, M.D., autism specialist at Geisinger Health System and article co-author.
“We believe this study supports use of the term ‘developmental brain dysfunction’ or DBD, which would encompass the broad spectrum of neurodevelopmental and neuropsychiatric disorders,” said David H. Ledbetter, Ph.D., executive vice president and chief scientific officer at Geisinger Health System, and article co-author. “Additionally, it is clear that diagnostic tools such as whole genome analysis for both children and their families are essential when diagnosing and treating these disorders in order to ensure the most personalized treatment.”
An example used in the study was analysis of intelligence quotient (IQ) scores. The average IQ score in the general population is 100. Historically, the medical community has defined intellectual disability as an IQ of less than 70 (with concurrent deficits in adaptive functioning). But according to Dr. Ledbetter, there is little difference in the function of a child with an IQ of 69 versus 71, yet one may be diagnosed with a disability and the other may not.
“We know a variety of factors contribute to IQ score, including genetics, as a child’s IQ is highly correlated with that of his or her parents and siblings. Therefore, an important factor to take into consideration when interpreting IQ is family background,” said Dr. Ledbetter. “Imagine if we have a child with a genetic abnormality, but the child’s IQ is 85. Technically, we would not diagnose this child with a disability. However, if the family of this child has IQs around 130, we could consider that this child’s genetic anomaly has ‘cost’ him or her 45 IQ points – a very substantial difference.”
According to Dr. Myers, “One implication of this concept is that studies designed to investigate the causes and mechanisms of developmental brain dysfunction should focus on measurement of quantifiable neuropsychological and neurobehavioral traits across groups of individuals with different clinical diagnoses. Another is that whenever possible, individuals with a particular genetic variant or other risk factor should be compared to their unaffected family members, not just to population norms.”
Frontiers publishes systematic review on the effects of yoga on major psychiatric disorders
Yoga has positive effects on mild depression and sleep complaints, even in the absence of drug treatments, and improves symptoms associated with schizophrenia and ADHD in patients on medication, according to a systematic review of the exercise on major clinical psychiatric disorders.
Published in the open-access journal, Frontiers in Psychiatry, on January 25th, 2013, the review of more than one hundred studies focusing on 16 high-quality controlled studies looked at the effects of yoga on depression, schizophrenia, ADHD, sleep complaints, eating disorders and cognition problems.
(Image: Corbis)
Changes in Nerve Cells Caused by Social Isolation May Contribute to the Development of Mental Illness
Reduced production of myelin, a type of protective nerve fiber that is lost in diseases like multiple sclerosis, may also play a role in the development of mental illness, according to researchers at the Graduate School of Biomedical Sciences at Mount Sinai School of Medicine. The study is published in the journal Nature Neuroscience.
Myelin is an insulating material that wraps around the axon, the threadlike part of a nerve cell through which the cell sends impulses to other nerve cells. New myelin is produced by nerve cells called oligodendrocytes both during development and in adulthood to repair damage in the brain of people with diseases such as multiple sclerosis (MS).
A new study led by Patrizia Casaccia, MD, PhD, Professor of Neuroscience, Genetics and Genomics; and Neurology at Mount Sinai, determined that depriving mice of social contact reduced myelin production, demonstrating that the formation of new oligodendrocytes is affected by environmental changes. This research provides further support to earlier evidence of abnormal myelin in a wide range of psychiatric disorders, including autism, anxiety, schizophrenia and depression.
“We knew that a lack of social interaction early in life impacted myelination in young animals but were unsure if these changes would persist in adulthood,” said Dr. Casaccia, who is also Chief of the Center of Excellence for Myelin Repair at the Friedman Brain Institute at Mount Sinai School of Medicine. “Social isolation of adult mice causes behavioral and structural changes in neurons, but this is the first study to show that it causes myelin dysfunction as well.”
Dr. Casaccia’s team isolated adult mice to determine whether new myelin formation was compromised. After eight weeks, they found that the isolated mice showed signs of social withdrawal. Subsequent brain tissue analyses indicated that the socially isolated mice had lower-than-normal levels of myelin-forming oligodendrocytes in the prefrontal cortex, but not in other areas of the brain. The prefrontal cortex controls complex emotional and cognitive behavior.
The researchers also found changes in chromatin, the packing material for DNA. As a result, the DNA from the new oligodendrocytes was unavailable for gene expression.
After observing the reduction in myelin production in socially-isolated mice, Dr. Casaccia’s team then re-introduced these mice into a social group. After four weeks, the social withdrawal symptoms and the gene expression changes were reversed.
“Our study demonstrates that oligodendrocytes generate new myelin as a way to respond to environmental stimuli, and that myelin production is significantly reduced in social isolation,” said Dr. Casaccia. “Abnormalities occur in people with psychiatric conditions characterized by social withdrawal. Other disorders characterized by myelin loss, such as MS, often are associated with depression. Our research emphasizes the importance of maintaining a socially stimulating environment in these instances.”
At Mount Sinai, Dr. Casaccia’s laboratory is studying oligodendrocyte formation to identify therapeutic targets for myelin repair. They are screening newly-developed pharmacological compounds in brain cells from rodents and humans for their ability to form new myelin.
(Source: newswise.com)