About half of smokers seeking treatment for smoking cessation have a history of depression. Compared with smokers who are not depressed, those who suffer from a major depressive disorder (MDD) have greater difficulty quitting.
In a Pfizer-sponsored clinical trial to assess the effect of varenicline (Chantix®) on smoking cessation, as well as mood and anxiety levels in smokers with current or a history of depression, researchers concluded that the drug does help some of these patients to quit smoking without worsening symptoms of depression or anxiety.
The study was led by Robert Anthenelli, MD, associate chief of staff for mental health at VA San Diego Healthcare System and professor of psychiatry at UC San Diego School of Medicine, where he directs the Pacific Treatment and Research Center. It will be published September 17 in the journal Annals of Internal Medicine.
“Depression and smoking are among the leading causes of disability and death in the world, yet studies testing smoking cessation drugs generally exclude participants who are taking antidepressants, and relapse rates are high among those who do manage to quit,” said Anthenelli. “To our knowledge, this was the first randomized, controlled study of the prescription smoking-cessation drug, varenicline, which we found to help patients with depression quit smoking, without worsening their depressive symptoms.”
The study looked at 525 adult smokers with stable current or past major depression, from 38 centers in eight countries. The study participants smoked at least 10 cigarettes a day, and were motivated to quit smoking. They took either varenicline or a placebo twice daily for 12 weeks; after treatment ended, researchers followed them for an additional 40 weeks.
Illustration courtesy of Bani Chaudhary, Saltman Quarterly
Many causative factors have linked to the eating disorder anorexia nervosa – culture, stress, puberty, social networks, among them – but the largest influence may be genetic.
In a new paper published in the journal Molecular Psychiatry, an international team of scientists, including researchers at The Scripps Research Institute and UC San Diego School of Medicine, report that a variant of the EPHX2 gene that codes for an enzyme involved in regulating cholesterol metabolism occurs more frequently in people with anorexia.
“When we saw that, we thought that we might be onto something, because nobody else had reported this gene as having a pronounced role in anorexia,” said principal investigator Nicholas J. Schork, PhD, a professor at TSRI and professor of psychiatry at UC San Diego.
The study was the largest effort yet to probe the genetic underpinnings of anorexia, studying the DNA sequences of more than 1,200 patients and almost 2,000 non-anorexic controls.
Cholesterol is a waxy, fat-like substance that is essential to life. It’s a critical structural component of cellular membranes and a precursor molecule necessary to many biochemical processes. The human body makes it, but also derives additional amounts from diet – excessively so when it comes to most modern, high-fat Western diets.
A number of serious health conditions and diseases are associated with abnormal or dysfunctional regulation of cholesterol, most notably heart disease and obesity. Researchers say it’s not clear yet how abnormal cholesterol metabolism caused by EPHX2 variants is linked to anorexia, but they note people with anorexia often exhibit unhealthily high blood cholesterol levels, even when severely malnourished.
Anorexia is primarily an affliction of women. The gender ratio is almost 10:1, with girls and young women particularly affected. Anorexics severely restrict eating and become emaciated, yet view themselves as fat and overweight. Study co-author Walter Kaye, MD, director of the UC San Diego Eating Disorders Center for Treatment and Research, said people with anorexia tend to be anxious, depressed and obsessive.
The consequences can be deadly. The mortality rate for anorexia is estimated to be more than 10 percent, making it perhaps the deadliest of psychiatric illnesses.
Read the full TSRI news release here.
A patient wears a cap holding in place electrodes for an EEG recording. Wikimedia.
The diagnosis and treatment of serious mental illness has always been a daunting affair.
“For the past 100 years, diagnoses have largely relied upon clinicians interviewing patients and making inferences about the patients’ inner experiences and the underlying neural systems impacted by a disorder,” said Gregory Light, PhD, associate professor of Psychiatry at UC San Diego.
The mind that mattered most was the mind of the clinician, charged with identifying both condition and treatment based almost entirely upon perceived symptoms, observed behaviors, and past experience.
That leaves a lot of room for differing and perhaps incorrect conclusions: What is normal and what is not? What’s the difference between deep grief and clinical depression? Where does quirkiness end and disease begin? Are we studying and treating schizophrenia correctly?
In a commentary published online this week in PNAS Early Edition with co-author Risto Naatanen, a noted Finnish psychologist and neuroscientist, Light argues that the time is ripe for clinical psychiatry to begin making use of empirical biomarkers that can not only identify specific mental illnesses with unprecedented precision, but guide treatments and perhaps predict the likelihood of disease.
“We’ve witnessed dazzling advances in neuroscience over the past 20 years,” he said, “and yet those advances have not made it into the clinic. We currently have few, if any, laboratory tests or biomarkers that can inform diagnosis, guide treatment decisions or offer any predictive value.”
One new tool Light has specifically in mind is called mismatch negativity, a measure of the functioning of the auditory processing system in the brain discovered by Naatanen in 1978. MMN is an index of cerebral responses to violations of a rule established by a sequence of sensory stimuli, typically auditory.
In other words, if you hear a steady hum that is interrupted by irrelevant “oddball” sounds, MMN reflects your brain’s ability to make automatic comparisons between the different sounds and evaluate their meaning and context.
MMN, it turns out, has significant relevance to at least some mental dysfunctions.
Exercise helps with better brain functioning in HIV-infected adults
Regular exercise is not only good for health, but can give people living with HIV a significant mental boost. This is according to a study by David J. Moore, PhD, associate professor of psychiatry and colleagues at UC San Diego School of Medicine, published recently in the Journal of NeuroVirology, who found that HIV-infected adults who exercise suffered significantly less neurocognitive impairment than patients who do not exercise.
Despite recent advances in antiretroviral treatment, impaired brain functioning is a reality faced by nearly half of all people living with HIV. Such impairment may be asymptomatic, or include deficits that interfere with a patient’s daily functioning, such as problems with financial management, driving or adhering to their medications.
Moore and his team found that HIV-infected adults who exercise were approximately half as likely to show signs of neurocognitive impairment as those who do not. They also had better working memory and could process information more rapidly than patients who follow a sedentary lifestyle.
The major benefit of exercise to the brain seems to be the reduction of neurocognitive risk factors, such as high blood pressure and abnormally high levels of lipids in the blood. Metabolic syndrome associated with the use of antiretroviral treatment is also linked to an increase in cerebrovascular risk factors, such as diabetes, hypertension and obesity – risk factors that may be mitigated by exercise.
In the study, 335 community-dwelling HIV-infected people were asked how much exercise they undertook during the previous 72 hours, and persons were classified into those who engaged in significant exercise (e.g., activities that make the heart beat rapidly) and those who did not. Seven cognitive areas commonly affected by HIV were tested, including verbal fluency, working memory, speed of information processing, learning, recall, executive function and motor function.
“Exercise as a modifiable lifestyle behavior may reduce or potentially prevent neurocognitive impairment in HIV-infected persons,” says Moore. “Physical exercise, together with other modifiable lifestyle factors such as education, social engagement, cognitive stimulation and diet, could be fruitful interventions to support people living with HIV.
These photomicrographs depict comparative stained sections of a healthy brain (top) and of patient EP, in which significant structures in the medial temporal lobe are heavily damaged or missing. The letters identify specific brain structures, such as EC and PRC for entorhinal cortex and perirhinal cortex, respectively, both important to memory formation and function.
Gone, But Not Forgotten
UC San Diego scientists recall EP, perhaps the world’s second-most famous amnesiac
An international team of neuroscientists has described for the first time in exhaustive detail the underlying neurobiology of an amnesiac who suffered from profound memory loss after damage to key portions of his brain.
Writing in this week’s Online Early Edition of PNAS, principal investigator Larry R. Squire, PhD, professor in the departments of Neurosciences, Psychiatry and Psychology at the University of California, San Diego School of Medicine and Veteran Affairs San Diego Healthcare System (VASDHS) – with colleagues at UC Davis and the University of Castilla-La Mancha in Spain – recount the case of EP, a man who suffered radical memory loss and dysfunction following a bout of viral encephalitis.
EP’s story is strikingly similar to the more famous case of HM, who also suffered permanent, dramatic memory loss after small portions of his medial temporal lobes were removed by doctors in 1953 to relieve severe epileptic seizures. The surgery was successful, but left HM unable to form new memories or recall people, places or events post-operation.
HM (later identified as Henry Gustav Molaison) was the subject of intense scientific scrutiny and study for the remainder of his life. When he died in 2008 at the age of 82, he was popularized as “the world’s most famous amnesiac.” His brain was removed and digitally preserved at The Brain Observatory, a UC San Diego-based lab headed by Jacopo Annese, PhD, an assistant adjunct professor in the Department of Radiology and a co-author of the PNAS paper.
Like Molaison, EP was also something of a scientific celebrity, albeit purposefully anonymous. In 1992, at the age of 70, he was diagnosed with viral encephalitis. He recovered, but the illness resulted in devastating neurological loss, both physiologically and psychologically.
Not only did he also lose the ability to form new memories, EP suffered a modest impairment in his semantic knowledge – the knowledge of things like words and the names of objects. Between 1994, when he moved to San Diego County, and his death 14 years later, EP was a subject of continued study, which included hundreds of different assessments of cognitive function.
“The work was long-term,” said Squire, a Career Research Scientist at the VASDHS. “We probably visited his house 200 times. We knew his family.” In a 2000 paper, Squire and colleagues described EP as a 6-foot-2, 192-pound affable fellow with a fascination for the computers used in his testing. He was always agreeable and pleasant. “He had a sense of humor,” said Squire.
Effects of Alcoholism: a Q & A with Marc Schuckit, Distinguished Professor of Psychiatry
The overconsumption of alcohol kills 2.5 million people each year around the globe, according to the World Health Organization. It is a major factor in many neuropsychiatric disorders and a risk factor for cardiovascular diseases, cirrhosis of the liver and various cancers.
The effects of alcohol abuse are felt far beyond the physical and psychological effects of the drinker. From drunk driving fatalities to booze-fueled violence and other behavioral disorders, alcohol abuse leaves a lasting, damaging mark on individuals and society.
Marc Schuckit, MD, is a Distinguished Professor of psychiatry at the University of California, San Diego School of Medicine and editor of the Journal of Studies on Alcohol and Drugs. He has spent his career studying the causes and effects of alcohol use and abuse. We asked for a status report.
Q: Where do you rate alcohol consumption as a social and public health problem? Is it trending up or down? Where do you see the most cause for alarm?
A: It’s close to number one. It’s a worldwide problem. Alcohol use is one of the leading risk factors in the overall burden of disease, especially among men age 15 to 60. The U.S. has an average consumption rate per person per year somewhere between eight and 10 liters of absolute alcohol. That’s somewhere in the middle among countries worldwide, but it’s still one heck of a lot of booze. Alcohol use disorders, such as dependence and the problems associated with these conditions, are much more common than, say, illicit drug disorders, as important as they are.Whether the problem is trending up or down depends upon who you’re reading. Excessive alcohol consumption has been a bad problem for decades. Not a lot has changed. It remains a bad problem.
Q: To what degree can abuse and dependence on alcohol, or alcoholism, be attributed to genetics? Does a biological predisposition outweigh all other factors?
A: If you use the general definition of alcohol abuse and dependence, this basically reflects severe repetitive problems with alcohol. The condition is roughly 60 percent genetic. Nonetheless, that still means the environment and environmental interaction with genetics is almost half the picture.The fact that researchers are now finding some genes related to the disease can help with identifying it and people at higher risk. This knowledge can help start early prevention. It’s also possible that understanding something about the genetics will help with treatment, though not always.
Q: One of your major studies concluded that sensitivity to the effects of alcohol strongly influences risk of alcohol dependence. Can you elaborate?
A: One of the characteristics through which the genes for alcohol abuse and dependence operate is the ability to consume fairly large amounts of alcohol, but have relatively little effect. This is associated with a probability of drinking a lot more per occasion than some other people and carries a higher risk for alcohol problems in the long run. Depending upon a range of factors, including their genetic make-up, other people experience a lot of effects after a few drinks, which means they have a higher sensitivity per drink, a characteristic often related to a lower alcoholism risk.We think we’ve found some of the genes that are associated with the low alcohol sensitivity (or low effect per drink) and that we may be able to use this information to identify people at greater risk and educate them. This would be very useful when working with, say, adolescents.
Q: In your opinion, what has been the most interesting or surprising discovery in alcohol research over the last decade or so?
A: For me, it’s the findings about alcohol sensitivity, which are the opposite of what we initially thought. We had hypothesized that the people at high risk for alcohol abuse and dependence were those with a higher effects, but that’s not what we found. People who can drink a lot without obvious effect tend to drink a lot and they hang out with other people who drink a lot.
Using imaging research, it looks like this low sensitivity to alcohol may be related to how the brain is processing information. People who have a low sensitivity process some kinds of information with a little bit less efficiency than others. They’re as smart as anybody else, it’s just a different intensity in the way the brain is working. That, in turn, might interfere with their ability to recognize effects of more moderate doses of alcohol.
Presently, there are about 40 million Americans over the age of 65, with the fastest-growing segment of the population over 80 years old. Traditionally, aging has been viewed as a period of progressive decline in physical, cognitive and psychosocial functioning, and aging is viewed by many as the “number one public health problem” facing Americans today.
But this negative view of aging contrasts with results of a comprehensive study of 1,006 older adults in San Diego by researchers from the University of California, San Diego School of Medicine and Stanford University. Results of the Successful Aging Evaluation (SAGE) study – comprising a 25-minute phone interview, followed by a comprehensive mail-in survey – will be published in the December 7 online issue of the American Journal of Psychiatry.
“While there is a growing public health interest in understanding and promoting successful aging, until now little published research has combined measures of physical health with cognitive and psychological assessments, in a large and randomly selected sample,” said principal investigator Dilip V. Jeste, MD, Estelle and Edgar Levi Chair in Aging, Distinguished Professor of Psychiatry and Neurosciences, and director of UC San Diego’s Stein Institute for Research on Aging, and the current President of the American Psychiatric Association (which was not involved in this study).
The SAGE study included adults between the ages of 50 and 99 years, with a mean age of just over 77 years. In addition to measures which assessed rates of chronic disease and disability, the survey looked at more subjective criteria such as social engagement and participants’ self-assessment of their overall health.
“Sometimes the most relevant outcomes are from the perspective of the subjects themselves,” said Jeste.
The study concludes that resilience and depression have significant bearing on how individuals self-rate successful aging, with effects that are comparable to that of physical health. “Even though older age was closely associated with worse physical and cognitive functioning, it was also related to better mental functioning,“ said co-author Colin Depp, PhD, associate professor of psychiatry at UC San Diego School of Medicine.