In Rats and Men, Nicotine Withdrawal Casts Similar PallReduced reward response in brains helps explain why it’s so hard to quit smoking
Efforts to quit smoking tend to end in failure. Almost half of smokers attempt to quit each year, but only 4 to 7 percent succeed on any given attempt without medicines or assistance, according to the American Cancer Society, and less than 25 percent of smokers who use medicines remain smoke-free for more than six months. Relapse is especially common within 48 hours of quitting when nicotine withdrawal symptoms are most acute.
In a set of novel experiments involving both humans and rats, researchers at the University of California, San Diego School of Medicine, Florida Atlantic University (FAU), University of Pittsburgh, Washington University and Harvard Medical School report that the brain’s response to reward – its ability to recognize and derive pleasure from natural stimuli such as food, money or sex – is measurably reduced after nicotine withdrawal.
The findings, published this week online in JAMA Psychiatry, suggest that nicotine withdrawal significantly impacts the ability to modulate behavioral choices based on the expectancy of reward. This deficit is seen often in people who suffer from depression.
“What we saw in both humans and rats was decreased responsiveness to reward,” said Athina Markou, PhD, professor and vice-chair of research in the Department of Psychiatry at UC San Diego. “During acute nicotine withdrawal, both people and animals attended less to positive rewards. That’s a hallmark of depression. And there is evidence that people who already express depressive symptoms and quit smoking are more likely to become clinically depressed and stay that way. These findings have an obvious bearing on how we approach cessation treatment.” 
The study authors say the breadth of the findings involving similar results in two different species offer a strong translational framework for future studies that will allow development of clinical treatments focusing on reward responsiveness during early nicotine withdrawal.
“The fact that the effect was similar across species using this translational task not only provides us with a ready framework to proceed with additional research to better understand the mechanisms underlying withdrawal of nicotine, and potentially new treatment development, but it also makes us feel more confident that we are actually studying the same behavior in humans and rats as the studies move forward,” said Michele Pergadia, PhD, associate professor of clinical biomedical science in the Charles E. Schmidt College of Medicine at FAU. 
The experiments reported in JAMA Psychiatry assessed reward responsiveness based upon the propensity to modulate behavior according to prior experience. In human testing, conducted at Washington University, participants were asked to repeat a computer task, with “correct” responses earning a modest financial reward. In testing at UC San Diego, rats were trained to press a lever upon hearing a specific tone to earn a food reward.
Results were similar. Human participants who were smokers but who had abstained from smoking for 24 hours prior to testing and rats chronically exposed to nicotine but deprived for 24 hours also prior to testing both performed less effectively than non-smokers and rats with no nicotine experience. That is, both humans and rats withdrawing from nicotine failed to display a bias toward maximizing their rewards. 
Markou’s team, which included co-authors Andre Der-Avakian, PhD, and Manoranjan D’Souza, MD, PhD, subsequently re-exposed rats to nicotine and re-tested them. This time, the animals showed a heightened reward response, stronger than before.
“This finding indicates that after the initial withdrawal, if a relapse occurs, it will produce a more pleasurable effect. That’s why smokers who have a single cigarette after quitting often find it triggers a full relapse and they’re soon back to smoking as much as before.”
Markou and Pergadia say the findings open up two avenues of future research: Studying the neurobiology of the reward response phenomenon to pinpoint where in the brain it occurs and which circuits or neurons are involved; and assessing potential medications on rats during reward response testing. Promising drugs, if approved by the FDA for human administration, could then be tested on humans in similar experiments – an approach that could provide both new insights and speed the drug development process.

In Rats and Men, Nicotine Withdrawal Casts Similar Pall
Reduced reward response in brains helps explain why it’s so hard to quit smoking

Efforts to quit smoking tend to end in failure. Almost half of smokers attempt to quit each year, but only 4 to 7 percent succeed on any given attempt without medicines or assistance, according to the American Cancer Society, and less than 25 percent of smokers who use medicines remain smoke-free for more than six months. Relapse is especially common within 48 hours of quitting when nicotine withdrawal symptoms are most acute.

In a set of novel experiments involving both humans and rats, researchers at the University of California, San Diego School of Medicine, Florida Atlantic University (FAU), University of Pittsburgh, Washington University and Harvard Medical School report that the brain’s response to reward – its ability to recognize and derive pleasure from natural stimuli such as food, money or sex – is measurably reduced after nicotine withdrawal.

The findings, published this week online in JAMA Psychiatry, suggest that nicotine withdrawal significantly impacts the ability to modulate behavioral choices based on the expectancy of reward. This deficit is seen often in people who suffer from depression.

“What we saw in both humans and rats was decreased responsiveness to reward,” said Athina Markou, PhD, professor and vice-chair of research in the Department of Psychiatry at UC San Diego. “During acute nicotine withdrawal, both people and animals attended less to positive rewards. That’s a hallmark of depression. And there is evidence that people who already express depressive symptoms and quit smoking are more likely to become clinically depressed and stay that way. These findings have an obvious bearing on how we approach cessation treatment.” 

The study authors say the breadth of the findings involving similar results in two different species offer a strong translational framework for future studies that will allow development of clinical treatments focusing on reward responsiveness during early nicotine withdrawal.

“The fact that the effect was similar across species using this translational task not only provides us with a ready framework to proceed with additional research to better understand the mechanisms underlying withdrawal of nicotine, and potentially new treatment development, but it also makes us feel more confident that we are actually studying the same behavior in humans and rats as the studies move forward,” said Michele Pergadia, PhD, associate professor of clinical biomedical science in the Charles E. Schmidt College of Medicine at FAU. 

The experiments reported in JAMA Psychiatry assessed reward responsiveness based upon the propensity to modulate behavior according to prior experience. In human testing, conducted at Washington University, participants were asked to repeat a computer task, with “correct” responses earning a modest financial reward. In testing at UC San Diego, rats were trained to press a lever upon hearing a specific tone to earn a food reward.

Results were similar. Human participants who were smokers but who had abstained from smoking for 24 hours prior to testing and rats chronically exposed to nicotine but deprived for 24 hours also prior to testing both performed less effectively than non-smokers and rats with no nicotine experience. That is, both humans and rats withdrawing from nicotine failed to display a bias toward maximizing their rewards. 

Markou’s team, which included co-authors Andre Der-Avakian, PhD, and Manoranjan D’Souza, MD, PhD, subsequently re-exposed rats to nicotine and re-tested them. This time, the animals showed a heightened reward response, stronger than before.

“This finding indicates that after the initial withdrawal, if a relapse occurs, it will produce a more pleasurable effect. That’s why smokers who have a single cigarette after quitting often find it triggers a full relapse and they’re soon back to smoking as much as before.”

Markou and Pergadia say the findings open up two avenues of future research: Studying the neurobiology of the reward response phenomenon to pinpoint where in the brain it occurs and which circuits or neurons are involved; and assessing potential medications on rats during reward response testing. Promising drugs, if approved by the FDA for human administration, could then be tested on humans in similar experiments – an approach that could provide both new insights and speed the drug development process.

Happiness in SchizophreniaResearch suggests mental illness doesn’t preclude enjoying life
Schizophrenia is among the most severe forms of mental illness, yet some people with the disease are as happy as those in good physical and mental health according to a study led by researchers at the University of California, San Diego School of Medicine.
The study is published online this week in the journal Schizophrenia Research.
“People tend to think that happiness in schizophrenia is an oxymoron,” said senior author Dilip V. Jeste, MD, Distinguished Professor of Psychiatry and Neurosciences.
“Without discounting the suffering this disease inflicts on people, our study shows that happiness is an attainable goal for at least some schizophrenia patients,” said Jeste, who is also the Estelle and Edgar Levi Chair in Aging and director of the Sam and Rose Stein Institute for Research on Aging at UC San Diego. “This means we can help make these individuals’ lives happier.”
In a survey of people with the disease, researchers found that 37 percent of patients reported being happy all or most of the time.
Of clinical significance in terms of helping people with mental illness, the patients’ happiness was unrelated to the severity or duration of their illness, to cognitive or physical function or to socioeconomic factors such as age and education, which among healthy adults have been linked to a greater sense of well-being.
Instead, the study shows that happiness among those with chronic forms of schizophrenia is associated with positive psychological and social attributes such as resilience, optimism and lower perceived stress.
The researchers believe that these positive psychosocial attributes could be taught through behavioral modification and mindfulness training techniques.
The study is based on a survey of 72 English-speaking outpatients with schizophrenia in the San Diego area. At the time of the survey, all but nine of the patients were on at least one anti-psychotic medication and 59 percent were residents in assisted-living facilities.
The comparison group for the study included 64 healthy men and women who were part of an ongoing study on successful aging. These participants were not currently using alcohol or illicit substances and did not have diagnoses of dementia or other neurological problems. Participants ranged in age from 23 to 70 years old; the mean age for both groups was 50 years.
The survey probed respondents’ happiness during the previous week, asking them to rate statements such as “I was happy” and “I enjoyed life” on a scale from “never or rarely” to “all or most of the time.”
Responses suggest that about 37 percent of schizophrenia patients were happy most or all of the time, compared with about 83 percent for those in the comparison group.
Approximately 15 percent of schizophrenia patients reported being never or rarely happy. By contrast, none of in the comparison group reported such a low level of happiness for the week prior.
People’s self-reported happiness was then examined in relation to other factors, such as age, gender, education, living situation, medication status, anxiety levels and other mental health metrics, as well as physical health, cognitive function, and a list of “psychosocial factors” that included perceived stress, attitude toward aging, spirituality, optimism, resilience and personal mastery.
“People with schizophrenia are clearly less happy than those in the general population at large, but this is not surprising,” said lead author Barton W. Palmer, PhD, professor in the UC San Diego Department of Psychiatry. “What is impressive is that almost 40 percent of these patients are reporting happiness and that their happiness is associated with positive psychosocial attributes that can be potentially enhanced.”
Image source: happyologist

Happiness in Schizophrenia
Research suggests mental illness doesn’t preclude enjoying life

Schizophrenia is among the most severe forms of mental illness, yet some people with the disease are as happy as those in good physical and mental health according to a study led by researchers at the University of California, San Diego School of Medicine.

The study is published online this week in the journal Schizophrenia Research.

“People tend to think that happiness in schizophrenia is an oxymoron,” said senior author Dilip V. Jeste, MD, Distinguished Professor of Psychiatry and Neurosciences.

“Without discounting the suffering this disease inflicts on people, our study shows that happiness is an attainable goal for at least some schizophrenia patients,” said Jeste, who is also the Estelle and Edgar Levi Chair in Aging and director of the Sam and Rose Stein Institute for Research on Aging at UC San Diego. “This means we can help make these individuals’ lives happier.”

In a survey of people with the disease, researchers found that 37 percent of patients reported being happy all or most of the time.

Of clinical significance in terms of helping people with mental illness, the patients’ happiness was unrelated to the severity or duration of their illness, to cognitive or physical function or to socioeconomic factors such as age and education, which among healthy adults have been linked to a greater sense of well-being.

Instead, the study shows that happiness among those with chronic forms of schizophrenia is associated with positive psychological and social attributes such as resilience, optimism and lower perceived stress.

The researchers believe that these positive psychosocial attributes could be taught through behavioral modification and mindfulness training techniques.

The study is based on a survey of 72 English-speaking outpatients with schizophrenia in the San Diego area. At the time of the survey, all but nine of the patients were on at least one anti-psychotic medication and 59 percent were residents in assisted-living facilities.

The comparison group for the study included 64 healthy men and women who were part of an ongoing study on successful aging. These participants were not currently using alcohol or illicit substances and did not have diagnoses of dementia or other neurological problems. Participants ranged in age from 23 to 70 years old; the mean age for both groups was 50 years.

The survey probed respondents’ happiness during the previous week, asking them to rate statements such as “I was happy” and “I enjoyed life” on a scale from “never or rarely” to “all or most of the time.”

Responses suggest that about 37 percent of schizophrenia patients were happy most or all of the time, compared with about 83 percent for those in the comparison group.

Approximately 15 percent of schizophrenia patients reported being never or rarely happy. By contrast, none of in the comparison group reported such a low level of happiness for the week prior.

People’s self-reported happiness was then examined in relation to other factors, such as age, gender, education, living situation, medication status, anxiety levels and other mental health metrics, as well as physical health, cognitive function, and a list of “psychosocial factors” that included perceived stress, attitude toward aging, spirituality, optimism, resilience and personal mastery.

“People with schizophrenia are clearly less happy than those in the general population at large, but this is not surprising,” said lead author Barton W. Palmer, PhD, professor in the UC San Diego Department of Psychiatry. “What is impressive is that almost 40 percent of these patients are reporting happiness and that their happiness is associated with positive psychosocial attributes that can be potentially enhanced.”

Image source: happyologist

War and Peace (of Mind) Meditation training may help reduce stress disorders among U.S. military personnel
Researchers from the University of California, San Diego School of Medicine and Naval Health Research Center have found that mindfulness training – a combination of meditation and body awareness exercises – can help U.S. Marine Corps personnel prepare for and recover from stressful combat situations.
The study, published in the May 16, 2014 online issue of the American Journal of Psychiatry, suggests that incorporating meditative practices into pre-deployment training might be a way to help the U.S. military reduce rising rates of stress-related health conditions, including PTSD, depression and anxiety, within its ranks.
“Mindfulness training won’t make combat easier,” said Martin Paulus, MD, professor of psychiatry and senior author. “But we think it can help Marines recover from stress and return to baseline functioning more quickly.”
Scientists describe mindfulness as a mental state characterized by “full attention to the present moment without elaboration, judgment or emotional reactivity.”  Mindfulness training, traditionally practiced through sitting meditation, attempts to cultivate this mental state by quieting the mind of extraneous thoughts.
In the study, Marine infantrymen in four platoons at Marine Corps Base Camp Pendleton took an eight-week course in mindfulness, tailored for individuals operating in highly stressful environments.
The course included classroom instruction on meditation and homework exercises, as well as training on interoception – the ability to help the body regulate its overall physical equilibrium (homeostasis) by becoming aware of bodily sensations, such as tightness in the stomach, heart rate and tingling of the skin.
“If you become aware of tightness in your stomach, your brain will automatically work to correct that tightness,” Paulus explained.
Participating Marines, along with others who had not undergone mindfulness training, then spent a day in mock immersive combat at a 32,000-square-foot training facility staged to resemble a rural Middle Eastern village. During the day’s exercises, Marines patrolled the village, met village leadership and responded to a highly realistic ambush.
The scientists found that the heart and breathing rates of those who had received mindfulness training returned to their normal, baseline levels faster than those who had not received the mindfulness training. Blood levels of a tell-tale neuropeptide suggested that the mindfulness-trained Marines experienced improved immune function, as well.
Subsequent magnetic resonance imaging scans revealed that the mindfulness-trained Marines had reduced activity patterns in regions of the brain responsible for integrating emotional reactivity, cognition and interoception. Lori Haase, a postdoctoral fellow in Paulus’ lab and a co-author of the study, said similar brain activity patterns had been observed in high performance athletes and Navy seals. High-activity levels in these areas of the brain, she noted, are associated with anxiety and mood disorders. The scientists hypothesize that reduced brain activity in the anterior insula and anterior cingulate may be characteristic of elite performers in general.
“That we can re-regulate the activity in these areas with so little training is this study’s most significant finding,” Paulus said. “Mindfulness helps the body optimize its response to stress by helping the body interpret stressful events as bodily sensations. The brain adds less emotional affect to experiences and this helps with stress recovery.”

War and Peace (of Mind)
Meditation training may help reduce stress disorders among U.S. military personnel

Researchers from the University of California, San Diego School of Medicine and Naval Health Research Center have found that mindfulness training – a combination of meditation and body awareness exercises – can help U.S. Marine Corps personnel prepare for and recover from stressful combat situations.

The study, published in the May 16, 2014 online issue of the American Journal of Psychiatry, suggests that incorporating meditative practices into pre-deployment training might be a way to help the U.S. military reduce rising rates of stress-related health conditions, including PTSD, depression and anxiety, within its ranks.

“Mindfulness training won’t make combat easier,” said Martin Paulus, MD, professor of psychiatry and senior author. “But we think it can help Marines recover from stress and return to baseline functioning more quickly.”

Scientists describe mindfulness as a mental state characterized by “full attention to the present moment without elaboration, judgment or emotional reactivity.”  Mindfulness training, traditionally practiced through sitting meditation, attempts to cultivate this mental state by quieting the mind of extraneous thoughts.

In the study, Marine infantrymen in four platoons at Marine Corps Base Camp Pendleton took an eight-week course in mindfulness, tailored for individuals operating in highly stressful environments.

The course included classroom instruction on meditation and homework exercises, as well as training on interoception – the ability to help the body regulate its overall physical equilibrium (homeostasis) by becoming aware of bodily sensations, such as tightness in the stomach, heart rate and tingling of the skin.

“If you become aware of tightness in your stomach, your brain will automatically work to correct that tightness,” Paulus explained.

Participating Marines, along with others who had not undergone mindfulness training, then spent a day in mock immersive combat at a 32,000-square-foot training facility staged to resemble a rural Middle Eastern village. During the day’s exercises, Marines patrolled the village, met village leadership and responded to a highly realistic ambush.

The scientists found that the heart and breathing rates of those who had received mindfulness training returned to their normal, baseline levels faster than those who had not received the mindfulness training. Blood levels of a tell-tale neuropeptide suggested that the mindfulness-trained Marines experienced improved immune function, as well.

Subsequent magnetic resonance imaging scans revealed that the mindfulness-trained Marines had reduced activity patterns in regions of the brain responsible for integrating emotional reactivity, cognition and interoception. Lori Haase, a postdoctoral fellow in Paulus’ lab and a co-author of the study, said similar brain activity patterns had been observed in high performance athletes and Navy seals. High-activity levels in these areas of the brain, she noted, are associated with anxiety and mood disorders. The scientists hypothesize that reduced brain activity in the anterior insula and anterior cingulate may be characteristic of elite performers in general.

“That we can re-regulate the activity in these areas with so little training is this study’s most significant finding,” Paulus said. “Mindfulness helps the body optimize its response to stress by helping the body interpret stressful events as bodily sensations. The brain adds less emotional affect to experiences and this helps with stress recovery.”

Igor Grant Named Chair of UC San Diego Department of Psychiatry

Igor Grant, MD, FRCP(C), an internationally recognized neuropsychiatrist, whose research interests have ranged from the neurobiology of HIV/AIDS and substance abuse, psychobiology of stress, to the therapeutic potential of medicinal cannabis, has been named the new Chair of the Department of Psychiatry at the University of California, San Diego School of Medicine.

“Dr. Grant embodies the extraordinary scope and depth of research in the Department of Psychiatry. Indeed, he has been fundamental to its rise and enduring excellence,” said David Brenner, MD, vice chancellor for Health Sciences and dean of the School of Medicine. “Dr. Grant has always been at the forefront of his science, pushing for answers to questions in new and sometimes controversial or difficult areas. I have no doubt that the Department of Psychiatry will continue to excel under his leadership.”

More here

The Ilk of Human KindnessOlder women with gumption score high on compassion
Researchers at the University of California, San Diego School of Medicine report that older women, plucky individuals and those who have suffered a recent major loss are more likely to be compassionate toward strangers than other older adults.
The study is published in this month’s issue of the International Journal of Geriatric Psychiatry.
Because compassionate behaviors are associated with better health and well-being as we age, the research findings offer insights into ways to improve the outcomes of individuals whose deficits in compassion put them at risk for becoming lonely and isolated later in life.
“We are interested in anything that can help older people age more successfully,” said Lisa Eyler, PhD, a professor of psychiatry and co-author. “We know that social connections are important to health and well-being, and we know that people who want to be kind to others garner greater social support. If we can foster compassion in people, we can improve their health and well-being, and maybe even longevity.”
The study, based on a survey of 1,006 randomly selected adults in San Diego County, aged 50 and over, with a mean age of 77, identified three factors that were predictive of a person’s self-reported compassion: gender, recent suffering and high mental resiliency.
Women, independent of their age, income, education, race, marital status or mental health status, scored higher on the compassion test, on average, than men. Higher levels of compassion were also observed among both men and women who had “walked a mile in another person’s shoes” and experienced a personal loss, such as a death in the family or illness, in the last year.
Those who reported higher confidence in their ability to bounce back from hard times also reported more empathy toward strangers and joy from helping those in need.
“What is exciting is that we are identifying aspects of successful aging that we can foster in both men and women,” said co-author Dilip Jeste, MD, Distinguished Professor of Psychiatry and Neurosciences, and director of the Sam and Rose Stein Institute for Research on Aging. “Mental resiliency can be developed through meditation, mindfulness and stress reduction practices. We can also teach people that the silver lining to adversity is an opportunity for personal growth.”

The Ilk of Human Kindness
Older women with gumption score high on compassion

Researchers at the University of California, San Diego School of Medicine report that older women, plucky individuals and those who have suffered a recent major loss are more likely to be compassionate toward strangers than other older adults.

The study is published in this month’s issue of the International Journal of Geriatric Psychiatry.

Because compassionate behaviors are associated with better health and well-being as we age, the research findings offer insights into ways to improve the outcomes of individuals whose deficits in compassion put them at risk for becoming lonely and isolated later in life.

“We are interested in anything that can help older people age more successfully,” said Lisa Eyler, PhD, a professor of psychiatry and co-author. “We know that social connections are important to health and well-being, and we know that people who want to be kind to others garner greater social support. If we can foster compassion in people, we can improve their health and well-being, and maybe even longevity.”

The study, based on a survey of 1,006 randomly selected adults in San Diego County, aged 50 and over, with a mean age of 77, identified three factors that were predictive of a person’s self-reported compassion: gender, recent suffering and high mental resiliency.

Women, independent of their age, income, education, race, marital status or mental health status, scored higher on the compassion test, on average, than men. Higher levels of compassion were also observed among both men and women who had “walked a mile in another person’s shoes” and experienced a personal loss, such as a death in the family or illness, in the last year.

Those who reported higher confidence in their ability to bounce back from hard times also reported more empathy toward strangers and joy from helping those in need.

“What is exciting is that we are identifying aspects of successful aging that we can foster in both men and women,” said co-author Dilip Jeste, MD, Distinguished Professor of Psychiatry and Neurosciences, and director of the Sam and Rose Stein Institute for Research on Aging. “Mental resiliency can be developed through meditation, mindfulness and stress reduction practices. We can also teach people that the silver lining to adversity is an opportunity for personal growth.”

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