Brain Trauma Raises Risk of Later PTSD in Active-Duty MarinesDeployment-related injuries are biggest predictor, but not the only factor   
In a novel study of U.S. Marines investigating the association between traumatic brain injury (TBI) and the risk of post-traumatic stress disorder (PTSD) over time, a team of scientists led by researchers from the Veterans Affairs San Diego Healthcare System and University of California, San Diego School of Medicine report that TBIs suffered during active-duty deployment to Iraq and Afghanistan were the greatest predictor for subsequent PTSD, but found pre-deployment PTSD symptoms and high combat intensity were also significant factors.
The findings are published in the December 11 online issue of JAMA Psychiatry.
The team, headed by principal investigator Dewleen G. Baker, MD, research director at the VA Center of Excellence for Stress and Mental Health, professor in the Department of Psychiatry at UC San Diego and a practicing psychiatrist in the VA San Diego Healthcare System, analyzed 1,648 active-duty Marines and Navy servicemen from four infantry battalions of the First Marine Division based at Camp Pendleton in north San Diego County. The servicemen were evaluated approximately one month before a scheduled 7-month deployment to Iraq or Afghanistan, one week after deployment had concluded, and again three and six months later.
PTSD is a psychiatric condition in which stress reactions become abnormal, chronic and may worsen over time. The condition is linked to depression, suicidal tendencies, substance abuse, memory and cognition dysfunction and other health problems.
The servicemen were assessed at each evaluation using the Clinician-Administered PTSD Scale or CAPS, a structured interview widely employed to diagnose PTSD and severity. Researchers asked about any head injuries sustained prior to joining the service and any head injuries sustained during deployment from a blast or explosion, vehicle accident, fall or head wound from a bullet or fragment.
Traumatic brain injuries are common. At least 1.7 million Americans annually sustain a TBI, with an estimated 5 million Americans living with TBI-related disabilities. More than half (56.8 percent) of the servicemen reported a TBI prior to deployment; almost a fifth (19.8 percent) reported a TBI during deployment. The vast majority of deployment-related TBIs (87.2 percent) were deemed mild, with less than 24 hours of post-traumatic amnesia. Of the 117 Marines whose TBI resulted in lost consciousness, 111 said it was less than 30 minutes.
More here

Brain Trauma Raises Risk of Later PTSD in Active-Duty Marines
Deployment-related injuries are biggest predictor, but not the only factor   

In a novel study of U.S. Marines investigating the association between traumatic brain injury (TBI) and the risk of post-traumatic stress disorder (PTSD) over time, a team of scientists led by researchers from the Veterans Affairs San Diego Healthcare System and University of California, San Diego School of Medicine report that TBIs suffered during active-duty deployment to Iraq and Afghanistan were the greatest predictor for subsequent PTSD, but found pre-deployment PTSD symptoms and high combat intensity were also significant factors.

The findings are published in the December 11 online issue of JAMA Psychiatry.

The team, headed by principal investigator Dewleen G. Baker, MD, research director at the VA Center of Excellence for Stress and Mental Health, professor in the Department of Psychiatry at UC San Diego and a practicing psychiatrist in the VA San Diego Healthcare System, analyzed 1,648 active-duty Marines and Navy servicemen from four infantry battalions of the First Marine Division based at Camp Pendleton in north San Diego County. The servicemen were evaluated approximately one month before a scheduled 7-month deployment to Iraq or Afghanistan, one week after deployment had concluded, and again three and six months later.

PTSD is a psychiatric condition in which stress reactions become abnormal, chronic and may worsen over time. The condition is linked to depression, suicidal tendencies, substance abuse, memory and cognition dysfunction and other health problems.

The servicemen were assessed at each evaluation using the Clinician-Administered PTSD Scale or CAPS, a structured interview widely employed to diagnose PTSD and severity. Researchers asked about any head injuries sustained prior to joining the service and any head injuries sustained during deployment from a blast or explosion, vehicle accident, fall or head wound from a bullet or fragment.

Traumatic brain injuries are common. At least 1.7 million Americans annually sustain a TBI, with an estimated 5 million Americans living with TBI-related disabilities. More than half (56.8 percent) of the servicemen reported a TBI prior to deployment; almost a fifth (19.8 percent) reported a TBI during deployment. The vast majority of deployment-related TBIs (87.2 percent) were deemed mild, with less than 24 hours of post-traumatic amnesia. Of the 117 Marines whose TBI resulted in lost consciousness, 111 said it was less than 30 minutes.

More here

Varenicline Helps Smokers with Depression to Quit Smoking
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.More here

Varenicline Helps Smokers with Depression to Quit Smoking

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.

More here

Illustration courtesy of Bani Chaudhary, Saltman Quarterly
Ill-fitting genes
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.

Illustration courtesy of Bani Chaudhary, Saltman Quarterly

Ill-fitting genes

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.
Opening minds
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.
[[MORE]]
“We know that many individuals with psychotic disorders have impairment in the auditory system that reflected in some of the hallmark symptoms of the illness: auditory hallucinations,” Light said. “Scientists have also found that impairment of basic brain systems that subserve auditory processing are tightly linked to cognitive impairment and cause problems for patients in real-world functioning.”
Light and Naatanen suggest that a simple electroencephalogram conducted in a doctor’s office could provide tell-tale diagnostic clues regarding MMN, including whether psychosis is looming.
“Persons at clinical high risk for developing psychosis have significantly reduced MMN comparable to those seen for schizophrenia. The amount of MMN reduction is a significant predictor of time to developing psychosis. The more severe the abnormality, the more likely the disease will develop sooner.”
Introducing the first biomarker of psychotic disorders into the clinic would seem to be a no-brainer, but actually doing so will require more research, validation and time. In clinical psychiatry, change comes neither easy nor fast.
Take, for example, the newly published fifth edition of the Diagnostic and Statistical Manual of Mental Disorders or DSM-5.
In an April news feature in Nature, David Adam wryly notes that the Catholic Church changes its pope more often than the APA publishes a new DSM. The first and second editions, published in 1952 and 1968, reflected Sigmund Freud’s notions that mental illness was a product of internal conflict. Symptoms were irrelevant to diagnosis.
Moreover, various studies revealed that psychiatric diagnoses were highly variable, even random. Different psychiatrists might offer different diagnostic conclusions for the same patient, resulting in wildly varied treatments and outcomes, a crisis in confidence described in this Annals of Internal Medicine article by Allan Frances.
The third DSM edition in 1980 attempted to be more evidence-based, reflecting advances in the neurosciences. It introduced the idea that psychotic disorders were distinct, with unique sets of symptoms and presumably unique causes. DSM-IV, which came out in 1994, fine-tuned this categorization of mental health.
But Adam argues that while neatly parsing symptoms into conditions and categories, with duly prescribed treatments, makes book-sense, it’s unworkable in clinics with real patients, most of whom present a mix of symptoms and are frequently diagnosed with multiple disorders or co-morbidities - almost none of which can be buttressed or explained at the elemental level of genes, metabolism and cells.
“The stark fact is that no one has yet agreed on how best to define and diagnose mental illness,” writes Adam.  The basic biology of virtually every mental syndrome remains a mystery.
DSM-5 sort of acknowledges the essential fuzziness of mental health and, not surprisingly, is as controversial and disputed as any of its predecessors. Even Tom Insel, MD, director of the National Institute for Mental Health, voices doubt about the efficacy of DSM-5.
“While DSM has been described as the ‘Bible’ for the field (of psychiatry), it is, at best, a dictionary, creating a set of labels and defining each,” he writes in his blog.
Insel touts the NIMH’s Research Domain Criteria, whose goal is to “transform diagnosis by incorporating genetics, imaging, cognitive science and other levels of information to lay the foundation for a new classification (of mental illnesses).”
Light and Naatanen say employing MMN in the clinic could be a significant first step toward that new foundation and future. “I can’t imagine anybody objecting to more clear-cut, reliable and empirically validated markers that provide clinicians with useful information to inform their diagnosis and treatment of complex, disabling conditions,” Light said.

A patient wears a cap holding in place electrodes for an EEG recording. Wikimedia.

Opening minds

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.

Read More

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.

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.

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