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.
Card 10 in Hermann Rorschach’s original inkblot series. You can see the entire series and how Nazi leaders Adolph Eichmann, Hermann Goering and Albert Speer interpreted the images here, courtesy of Cabinet magazine
Judgments after Nuremberg
As a young professor of psychiatry in the 1970s, Joel E. Dimsdale studied concentration camp survivors – and their families – in the years after World War II. What were the psychological consequences of their suffering and trauma? What mechanisms did they use to cope?
One day a man came to visit Dimsdale at his Boston office. He had heard the professor speak and believed Dimsdale should study another group as well: the Nazi perpetrators who had conceived and implemented the camps that resulted in the murder of millions.
The man said he had met some of Nazi leaders.
The man had killed some of them.
“He was one of the executioners at the Nuremberg trials,” recalled Dimsdale, now a professor emeritus in the UC San Diego School of Medicine.
The trials, of course, were a series of highly publicized, history-making military tribunals held by Allied victors to judge and punish the surviving remnants of Nazi German leadership after the war. Scores of political, military and public officials were tried, most notably 22 defendants in the Bavarian city of Nuremberg over several months in 1945 and 1946.
These were some of Nazi Germany’s most notorious leaders: Field Marshall Hermann Goering, deputy Fuhrer Rudolf Hess, army head Wilhelm Keitel, SS leader Ernst Kaltenbrunner, and interior minister Wilhelm Frick, who had co-authored the Nazi’s anti-Semitic Race Laws introduced in 1935 in, ironically, Nuremberg.
Though Dimsdale continued and expanded his psychiatric research, ultimately conducting hundreds of studies about stress, sleep and how patients cope with severe illness over a long and distinguished career, he took the advice of the Nuremberg executioner and eventually wrote a book about the trials and efforts to better understand the psychology of the accused.
“One of the great questions of psychology is the anatomy of malice,” said Dimsdale, “and nowhere is that subject more compelling than in trying to explain the behavior of the accused war criminals at Nuremberg. Were they inherently depraved monsters or ordinary men corrupted by power and circumstances? Were they somewhere on a continuum of human behavior or distinctly different? How did they get that way?”
Image courtesy of Dan Anderson www.danandersonphoto.com
Using Biomarkers to Identify and Treat Schizophrenia
Researchers say lab-based tests may be boon to both clinicians and researchers
In the current online issue of PLoS ONE, researchers at the University of California, San Diego School of Medicine say they have identified a set of laboratory-based biomarkers that can be useful for understanding brain-based abnormalities in schizophrenia. The measurements, known as endophenotypes, could ultimately be a boon to clinicians who sometimes struggle to recognize and treat the complex and confounding mental disorder.
“A major problem in psychiatry is that there are currently no laboratory tests that aid in diagnosis, guide treatment decisions or help predict treatment response or outcomes,” said Gregory A. Light, PhD, associate professor of psychiatry and the study’s first author. “Diagnoses are currently based on a clinician’s ability to make inferences about patients’ inner experiences.”
Diagnosing and treating schizophrenia is a particularly troubling challenge. The disorder, which affects about 1 percent of the U.S. population or roughly 3 million people, is characterized by a breakdown of normal thought processes and erratic, sometimes dangerous or harmful, behaviors.
“Schizophrenia is among the most severe and disabling conditions across all categories of medicine,” said Light, who also directs the Mental Illness, Research, Education and Clinical Center at the San Diego VA Healthcare System.
The precise cause or causes of schizophrenia are not known, though there is a clear genetic component, with the disorder more common in some families.
Clinicians typically diagnose schizophrenia based upon inferences drawn from the patient’s inner experiences. That is, their ability to describe what’s happening inside their minds.