Neuroscience

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Dopamine-receptor gene variant linked to human longevity
A variant of a gene associated with active personality traits in humans seems to also be involved with living a longer life, UC Irvine and other researchers have found.
This derivative of a dopamine-receptor gene – called the DRD4 7R allele – appears in significantly higher rates in people more than 90 years old and is linked to lifespan increases in mouse studies.
Robert Moyzis, professor of biological chemistry at UC Irvine, and Dr. Nora Volkow, a psychiatrist who conducts research at the Brookhaven National Laboratory and also directs the National Institute on Drug Abuse, led a research effort that included data from the UC Irvine-led 90+ Study in Laguna Woods, Calif. Results appear online in The Journal of Neuroscience.
The variant gene is part of the dopamine system, which facilitates the transmission of signals among neurons and plays a major role in the brain network responsible for attention and reward-driven learning. The DRD4 7R allele blunts dopamine signaling, which enhances individuals’ reactivity to their environment.
People who carry this variant gene, Moyzis said, seem to be more motivated to pursue social, intellectual and physical activities. The variant is also linked to attention-deficit/hyperactivity disorder and addictive and risky behaviors.
“While the genetic variant may not directly influence longevity,” Moyzis said, “it is associated with personality traits that have been shown to be important for living a longer, healthier life. It’s been well documented that the more you’re involved with social and physical activities, the more likely you’ll live longer. It could be as simple as that.”
Numerous studies – including a number from the 90+ Study – have confirmed that being active is important for successful aging, and it may deter the advancement of neurodegenerative diseases, such as Alzheimer’s.
Prior molecular evolutionary research led by Moyzis and Chuansheng Chen, UC Irvine professor of psychology & social behavior, indicated that this “longevity allele” was selected for during the nomadic out-of-Africa human exodus more than 30,000 years ago.
In the new study, the UC Irvine team analyzed genetic samples from 310 participants in the 90+ Study. This “oldest-old” population had a 66 percent increase in individuals carrying the variant relative to a control group of 2,902 people between the ages of 7 and 45. The presence of the variant also was strongly correlated with higher levels of physical activity.
Next, Volkow, neuroscientist Panayotis Thanos and their colleagues at the Brookhaven National Laboratory found that mice without the variant had a 7 percent to 9.7 percent decrease in lifespan compared with those possessing the gene, even when raised in an enriched environment.
While it’s evident that the variant can contribute to longevity, Moyzis said further studies must take place to identify any immediate clinical benefits from the research. “However, it is clear that individuals with this gene variant are already more likely to be responding to the well-known medical adage to get more physical activity,” he added.

Dopamine-receptor gene variant linked to human longevity

A variant of a gene associated with active personality traits in humans seems to also be involved with living a longer life, UC Irvine and other researchers have found.

This derivative of a dopamine-receptor gene – called the DRD4 7R allele – appears in significantly higher rates in people more than 90 years old and is linked to lifespan increases in mouse studies.

Robert Moyzis, professor of biological chemistry at UC Irvine, and Dr. Nora Volkow, a psychiatrist who conducts research at the Brookhaven National Laboratory and also directs the National Institute on Drug Abuse, led a research effort that included data from the UC Irvine-led 90+ Study in Laguna Woods, Calif. Results appear online in The Journal of Neuroscience.

The variant gene is part of the dopamine system, which facilitates the transmission of signals among neurons and plays a major role in the brain network responsible for attention and reward-driven learning. The DRD4 7R allele blunts dopamine signaling, which enhances individuals’ reactivity to their environment.

People who carry this variant gene, Moyzis said, seem to be more motivated to pursue social, intellectual and physical activities. The variant is also linked to attention-deficit/hyperactivity disorder and addictive and risky behaviors.

“While the genetic variant may not directly influence longevity,” Moyzis said, “it is associated with personality traits that have been shown to be important for living a longer, healthier life. It’s been well documented that the more you’re involved with social and physical activities, the more likely you’ll live longer. It could be as simple as that.”

Numerous studies – including a number from the 90+ Study – have confirmed that being active is important for successful aging, and it may deter the advancement of neurodegenerative diseases, such as Alzheimer’s.

Prior molecular evolutionary research led by Moyzis and Chuansheng Chen, UC Irvine professor of psychology & social behavior, indicated that this “longevity allele” was selected for during the nomadic out-of-Africa human exodus more than 30,000 years ago.

In the new study, the UC Irvine team analyzed genetic samples from 310 participants in the 90+ Study. This “oldest-old” population had a 66 percent increase in individuals carrying the variant relative to a control group of 2,902 people between the ages of 7 and 45. The presence of the variant also was strongly correlated with higher levels of physical activity.

Next, Volkow, neuroscientist Panayotis Thanos and their colleagues at the Brookhaven National Laboratory found that mice without the variant had a 7 percent to 9.7 percent decrease in lifespan compared with those possessing the gene, even when raised in an enriched environment.

While it’s evident that the variant can contribute to longevity, Moyzis said further studies must take place to identify any immediate clinical benefits from the research. “However, it is clear that individuals with this gene variant are already more likely to be responding to the well-known medical adage to get more physical activity,” he added.

Filed under neurodegenerative diseases dopamine system gene longevity neuroscience science

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Research reveals why some teenagers more prone to binge drinking
New research helps explain why some teenagers are more prone to drinking alcohol than others. 
The study, led by King’s College London’s Institute of Psychiatry (IoP) and published in Proceedings of National Academy of Sciences (PNAS)* provides the most detailed understanding yet of the brain processes involved in teenage alcohol abuse.
Alcohol and other addictive drugs activate the dopamine system in the brain which is responsible for feelings of pleasure and reward. Recent studies from King’s IoP found that the RASGRF2 gene is a risk gene for alcohol abuse, however, the exact mechanism involved in this process has, until now, remained unknown.
Professor Gunter Schumann, from the Department of Social, Genetic and Developmental Psychiatry (SGDP) at King’s Institute of Psychiatry and lead author of the study says: “People seek out situations which fulfill their sense of reward and make them happy, so if your brain is wired to find alcohol rewarding, you will seek it out. We now understand the chain of action: how our genes shape this function in our brains and how that, in turn, leads to human behaviour. We found that the RASGRF-2 gene plays a crucial role in controlling how alcohol stimulates the brain to release dopamine, and hence trigger the feeling of reward. So, if people have a genetic variation of the RASGRF-2 gene, alcohol gives them a stronger sense of reward, making them more likely to be heavy drinkers.”

*Paper reference:  Stacey, D. et al. ‘RASGRF-2 regulates alcohol-induced reinforcement by influencing mesolimbic dopamine neurone activity and dopamine release’ Proceedings of the National Academy of Sciences (PNAS)  2012

Research reveals why some teenagers more prone to binge drinking

New research helps explain why some teenagers are more prone to drinking alcohol than others. 

The study, led by King’s College London’s Institute of Psychiatry (IoP) and published in Proceedings of National Academy of Sciences (PNAS)* provides the most detailed understanding yet of the brain processes involved in teenage alcohol abuse.

Alcohol and other addictive drugs activate the dopamine system in the brain which is responsible for feelings of pleasure and reward. Recent studies from King’s IoP found that the RASGRF2 gene is a risk gene for alcohol abuse, however, the exact mechanism involved in this process has, until now, remained unknown.

Professor Gunter Schumann, from the Department of Social, Genetic and Developmental Psychiatry (SGDP) at King’s Institute of Psychiatry and lead author of the study says: “People seek out situations which fulfill their sense of reward and make them happy, so if your brain is wired to find alcohol rewarding, you will seek it out. We now understand the chain of action: how our genes shape this function in our brains and how that, in turn, leads to human behaviour. We found that the RASGRF-2 gene plays a crucial role in controlling how alcohol stimulates the brain to release dopamine, and hence trigger the feeling of reward. So, if people have a genetic variation of the RASGRF-2 gene, alcohol gives them a stronger sense of reward, making them more likely to be heavy drinkers.”

*Paper reference:  Stacey, D. et al. ‘RASGRF-2 regulates alcohol-induced reinforcement by influencing mesolimbic dopamine neurone activity and dopamine release’ Proceedings of the National Academy of Sciences (PNAS)  2012

Filed under binge dirinking alcohol teenagers alcohol abuse dopamine system neuroscience science

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Research may explain why some people with schizophrenia do not respond to treatment

New research suggests that the molecular mechanism leading to schizophrenia may be different in patients who fail to respond to anti-psychotic medication compared to patients who do respond.

The research, from King’s College London’s Institute of Psychiatry may help explain why up to one third of patients with schizophrenia do not respond to traditional anti-psychotic medication.

Schizophrenia is known to be associated with an overactive dopamine system, meaning that the brain processes abnormally high levels of dopamine. Traditional dopamine-blocking anti-psychotic medication attempts to normalise this process. However, approximately one third of patients with schizophrenia do not respond to this treatment, and until now, no study has examined whether dopamine abnormality is present in patients resistant to antipsychotic treatment.

The study was led by Dr Arsime Demjaha, Dr Oliver Howes, Professor Shitij Kapur, Professor Sir Robin Murray and Professor Philip McGuire from King’s Institute of Psychiatry and published in the American Journal of Psychiatry

Dr Arsime Demjaha and co-authors, say: ‘Despite considerable scientific and therapeutic progress over the last 50 years, we still do not know why some patients with schizophrenia respond to treatment whilst others do not. Treatment resistance in such a disabling condition is one of the greatest clinical and therapeutic challenges to psychiatry, significantly affecting patients, their families and society in general.’

The authors conclude: ‘Our findings suggest that there may be a different molecular mechanism leading to schizophrenia in patients who do not respond to anti-psychotic medication. Identifying the precise molecular pathway particularly in these patients is of utmost importance and will help inform the development of much-needed novel treatments.’

Researchers used PET scan imaging to investigate dopamine synthesis capacity in 12 patients with schizophrenia who did not respond to treatment, 12 who did, and 12 healthy controls. They found that schizophrenia patients whose illness was resistant to antipsychotic treatment have relatively normal levels of dopamine synthesis capacity which would explain why the dopamine blocking anti-psychotic medication was not effective in this group. 

However, the authors add that the findings need to be replicated in larger samples before the research can affect clinical practice. They add that future research will need to focus on long-term prospective studies of patients who have never taken anti-psychotics to determine whether presynaptic dopamine synthesis capacity was normal in patients in the treatment-resistant group at the onset of their illness, and predates antipsychotic exposure.

(Source: kcl.ac.uk)

Filed under schizophrenia dopamine system treatment resistance treatment neuroscience science

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