May 5, 2016
University of Texas at Austin
New research indicates that slow-motion earthquakes or ‘slow-slip events’ can rupture the shallow portion of a fault that also moves in large, tsunami-generating earthquakes. The finding has important implications for assessing tsunami hazards. The discovery was made by conducting the first-ever detailed investigation of centimeter-level seafloor movement at an offshore subduction zone.
Research published in the May 6 edition of Science indicates that slow-motion earthquakes or “slow-slip events” can rupture the shallow portion of a fault that also moves in large, tsunami-generating earthquakes. The finding has important implications for assessing tsunami hazards. The discovery was made by conducting the first-ever detailed investigation of centimeter-level seafloor movement at an offshore subduction zone.
“These data have revealed the true extent of slow-motion earthquakes at an offshore subduction zone for the first time,” said Laura Wallace, a research scientist at The University of Texas at Austin’s Institute for Geophysics who led the study.
An international team of researchers from the U.S., Japan and New Zealand collaborated on the research. The Institute for Geophysics is a research unit of The University of Texas Jackson School of Geosciences.
The world’s most devastating tsunamis are generated by earthquakes that occur near the trenches of subduction zones, places where one tectonic plate begins to dive or “subduct” beneath another. Using a network of highly sensitive seafloor pressure recorders, the team detected a slow-slip event in September 2014 off the east coast of New Zealand. The study was undertaken at the Hikurangi subduction zone, where the Pacific Plate subducts beneath New Zealand’s North Island.
The slow-slip event lasted two weeks, resulting in 15-20 centimeters of movement along the fault that lies between New Zealand and the Pacific Plate, a distance equivalent to three to four years of background plate motion. If the movement had occurred suddenly, rather than slowly, it would have resulted in a magnitude 6.8 earthquake. The seafloor sensors recorded up to 5.5 centimeters of upward movement of the seafloor during the event.
Slow-slip events are similar to earthquakes, but instead of releasing strain between two tectonic plates in seconds, they do it over days to weeks, creating quiet, centimeter-sized shifts in the landscape. In a few cases, these small shifts have been associated with setting off destructive earthquakes, such as the magnitude 9.0 Tohoku-Oki earthquake that occurred off the coast of Japan in 2011 and generated a tsunami that caused the Fukushima Daiichi nuclear power plant disaster.
The slow-slip event that the team studied occurred in the same location as a magnitude 7.2 earthquake in 1947 that generated a large tsunami. The finding increases the understanding of the relationship between slow slip and normal earthquakes by showing that the two types of seismic events can occur on the same part of a plate boundary.
The link has been difficult to document in the past because most slow-slip monitoring networks are land-based and are located far from the trenches that host tsunami-generating earthquakes, Wallace said. The data for this study was recorded by HOBITSS, a temporary underwater network that monitored slow-slip events by recording vertical movement of the seafloor. HOBITSS stands for “Hikurangi Ocean Bottom Investigation of Tremor and Slow Slip.”
“Our results clearly show that shallow, slow-slip event source areas are also capable of hosting seismic rupture and generating tsunamis,” said Yoshihiro Ito, a professor at Kyoto University and study co-author. “This increases the need to continuously monitor shallow, offshore slow-slip events at subduction zones, using permanent monitoring networks similar to those that have been established offshore of Japan.”
Professor Spahr Webb, a co-author from Columbia University’s Lamont-Doherty Earth Observatory agreed.
“Our New Zealand experiment results demonstrate the great potential for using offshore monitoring systems at subduction zones in the Pacific Northwest for tsunami and earthquake early warning,” said Webb.
Earthquakes are unpredictable events, Wallace said, but the linkage between slow-slip events and earthquakes could eventually help in forecasting the likelihood of damaging earthquakes.
“To do that we will have to understand the links between slow-slip events and earthquakes much better than we currently do,” Wallace said.
The research team installed the HOBITSS network in May 2014, which consisted of 24 seafloor pressure gauges, and 15 ocean bottom seismometers. The team collected the devices and data in June 2015.
“The project findings add to critical information for anticipating potentially life-threatening earthquakes and tsunamis,” said Maurice Tivey, program director of the National Science Foundation’s Division of Ocean Sciences.
Additional participants included scientists from the University of Tokyo, Tohoku University, GNS Science, the University of California at Santa Cruz and the University of Colorado Boulder.
The research was funded by the National Science Foundation; the Japan Society for Promotion of Science; Japan’s Ministry of Education, Culture, Sports, Science and Technology; and grants from participating universities and research institutions.
- Laura M. Wallace, Spahr C. Webb, Yoshihiro Ito, Kimihiro Mochizuki, Ryota Hino, Stuart Henrys, Susan Y. Schwartz, Anne F. Sheehan. Slow slip near the trench at the Hikurangi subduction zone, New Zealand. Science, 2016 DOI: 10.1126/science.aaf2349
Source: University of Texas at Austin. “Tsunami risk: World’s shallowest slow-motion earthquakes detected offshore of New Zealand.” ScienceDaily. ScienceDaily, 5 May 2016. <www.sciencedaily.com/releases/2016/05/160505144723.htm>.
Candida infections also more common among those with memory loss
May 4, 2016
Johns Hopkins Medicine
In a study prompted in part by suggestions from people with mental illness, researchers found that a history of Candida yeast infections was more common in a group of men with schizophrenia or bipolar disorder than in those without these disorders, and that women with schizophrenia or bipolar disorder who tested positive for Candida performed worse on a standard memory test than women with schizophrenia or bipolar disorder who had no evidence of past infection.
In a study prompted in part by suggestions from people with mental illness, Johns Hopkins researchers found that a history of Candida yeast infections was more common in a group of men with schizophrenia or bipolar disorder than in those without these disorders, and that women with schizophrenia or bipolar disorder who tested positive forCandida performed worse on a standard memory test than women with schizophrenia or bipolar disorder who had no evidence of past infection.
The researchers caution that their findings, described online on May 4 in npj Schizophrenia — a new publication from Nature Publishing Group — do not establish a cause-and-effect relationship between mental illness and yeast infections but may support a more detailed examination into the role of lifestyle, immune system weaknesses and gut-brain connections as contributing factors to the risk of psychiatric disorders and memory impairment.
“It’s far too early to single out Candida infection as a cause of mental illness or vice versa,” says Emily Severance, Ph.D., assistant professor of pediatrics and member of the Stanley Division of Developmental Neurovirology at the Johns Hopkins University School of Medicine. “However, most Candidainfections can be treated in their early stages, and clinicians should make it a point to look out for these infections in their patients with mental illness.” She adds that Candida infections can also be prevented by decreased sugar intake and other dietary modifications, avoidance of unnecessary antibiotics, and improvement of hygiene.
Candidaalbicans is a yeastlike fungus naturally found in small amounts in human digestive tracts, but its overgrowth in warm, moist environments causes burning, itching symptoms, thrush (rashes in the throat or mouth) in infants and those with weakened immune systems, and sexually transmittable genital yeast infections in men and women. In its more serious forms, it can enter the bloodstream. In most people, the body’s own healthy bacteria and functioning immune system prevent its overgrowth.
Severance says she and her team focused on a possible association betweenCandida susceptibility and mental illness in the wake of new evidence suggesting that schizophrenia may be related to problems with the immune system, and because some people with weakened immune systems are more susceptible to fungal infections.
Also, she says, patients and parents of patients had shared personal stories and testimonials with the researchers about their experience with yeast infections, and these discussions prompted the investigation into possible links between mental illness and the microbiome — the body’s natural collection of bacteria. The researchers, she adds, chose to focus on Candidabecause it is one of the most common types of yeast in the body.
For the study, colleagues from the Sheppard Pratt Health System took blood samples from a group of 808 people between the ages of 18 and 65. This group was composed of 277 controls without a history of mental disorder, 261 individuals with schizophrenia and 270 people with bipolar disorder. The researchers used the blood samples to quantify the amount of IgG class antibodies to Candida, which indicates a past infection with the yeast. After accounting for factors like age, race, medications and socioeconomic status, which could skew the results, they looked for patterns that suggested links between mental illness and infection rates.
Significantly, the team says, it found no connection between the presence ofCandida antibodies and mental illness overall in the total group. But when the investigators looked only at men, they found 26 percent of those with schizophrenia had Candida antibodies, compared to 14 percent of the control males. There wasn’t any difference found in infection rate between women with schizophrenia (31.3 percent) and controls (29.4 percent). The higher infection rate percentages in women over men likely reflects an increased susceptibility for this type of infection in all women.
Men with bipolar disorder had clear increases in Candida as well, with a 26.4 percent infection rate, compared to only 14 percent in male controls. But, after accounting for additional variables related to lifestyle, the researchers found that the association between men with bipolar disorder and Candidainfection could likely be attributed to homelessness. However, the link between men with schizophrenia and Candida infection persisted and could not be explained by homelessness or other environmental factors. Many people who are homeless are subjected to unpredictable changes in stress, sanitation and diet, which can lead to infections like those caused byCandida.
Severance says the data add support to the idea that environmental exposures related to lifestyle and immune system factors may be linked to schizophrenia and bipolar disorder, and that those factors may be different for each illness. Similarly, specific mental illnesses and related symptoms may be very different in men versus women.
This Johns Hopkins research group, led by Robert Yolken, M.D., director of the Stanley Division of Developmental Neurovirology, had previously shown that toxoplasmosis infection could trigger schizophrenia, and this could lead to neurocognitive problems. The organism that causes toxoplasmosis is a parasite that uses cats as its primary host, but it can also infect humans and other mammals.
To determine whether infection with Candida affected any neurological responses, all participants in the new study took a 30-minute assessment of cognitive tasks to measure immediate memory, delayed memory, attention skills, use of language and visual-spatial skills.
Each of the five skills tests are scored based on an adjusted 100-point system. Results showed that control men and women with and without priorCandida infection had no measureable differences in scores in the five neurological responses. However, the researchers noticed that women with schizophrenia and bipolar disorder who had a history of Candida infection had lower scores on the memory portions of this test compared to those women with no prior infection. For example, women with schizophrenia and the highest Candida antibody levels scored about an average of 11 points lower on the test for immediate memory than the controls, from a score of 68.5 without infection to 57.4 with infection. And the women with schizophrenia and the highest Candida antibody levels scored almost 15 points lower on the test for delayed memory, from a score of 71.4 without infection to 56.2 with infection. The effect of Candida infection in women with bipolar disorder on memory test scores was smaller than that seen in women with schizophrenia but was still measureable.
“Although we cannot demonstrate a direct link between Candida infection and physiological brain processes, our data show that some factor associated withCandida infection, and possibly the organism itself, plays a role in affecting the memory of women with schizophrenia and bipolar disorder, and this is an avenue that needs to be further explored,” says Severance. “BecauseCandida is a natural component of the human body microbiome, yeast overgrowth or infection in the digestive tract, for example, may disrupt the gut-brain axis. This disruption in conjunction with an abnormally functioning immune system could collectively disturb those brain processes that are important for memory.”
Severance says they plan to take their studies of the gut-brain connection into mouse models to test for a cause-and effect-relationship with Candidaand memory deficits.
The researchers emphasized that the current study design had limitations. For example, they were unable to tell where in the body the infection was located and whether or not participants had a current or past infection ofCandida. The researchers were also not able to account for every possible lifestyle variable that might contribute to these results.
The researchers in the Stanley Division of Developmental Neurovirology are investigating whether pathogens, such as bacteria or viruses, may contribute or trigger certain mental disorders.
According to the National Institute of Mental Health, about 1 percent of people in the U.S. have schizophrenia and about 2 percent have bipolar disorder. Although these diseases have a genetic component, there is evidence that they may also be triggered by environmental factors and stress.
Additional authors on the study include Kristin Gressitt of Johns Hopkins Medicine; Catherine Stallings, Emily Katsafanas, Lucy Schweinfurth, Christina Savage, Maria Adamos, Kevin Sweeney, Andrea Origoni, Sunil Khushalani and Faith Dickerson of Sheppard Pratt Health System; and F. Markus Leweke of Heidelberg University.
The study was supported by a research grant from the National Institute of Mental Health (MH-94268) and a grant from the Stanley Medical Research Institute.
The authors also thank the individuals with psychiatric disorders and their families who originally suggested this line of research.
- Emily G Severance, Kristin L Gressitt, Catherine R Stallings, Emily Katsafanas, Lucy A Schweinfurth, Christina L Savage, Maria B Adamos, Kevin M Sweeney, Andrea E Origoni, Sunil Khushalani, F Markus Leweke, Faith B Dickerson, Robert H Yolken. Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder. npj Schizophrenia, 2016; 2: 16018 DOI:10.1038/npjschz.2016.18
Source: Johns Hopkins Medicine. “Yeast infection linked to mental illness: Candida infections also more common among those with memory loss.” ScienceDaily. ScienceDaily, 4 May 2016. <www.sciencedaily.com/releases/2016/05/160504121327.htm>.
May 3, 2016
University of North Carolina at Chapel Hill
The southeastern United States should, by all means, be relatively quiet in terms of seismic activity. It’s located in the interior of the North American Plate, far away from plate boundaries where earthquakes usually occur. But the area has seen some notable seismic events — most recently, the 2011 magnitude-5.8 earthquake near Mineral, Virginia that shook the nation’s capital.
The southeastern United States should, by all means, be relatively quiet in terms of seismic activity. It’s located in the interior of the North American Plate, far away from plate boundaries where earthquakes usually occur. But the area has seen some notable seismic events — most recently, the 2011 magnitude-5.8 earthquake near Mineral, Virginia that shook the nation’s capital.
Now scientists report in a new study a likely explanation for this unusual activity: pieces of the mantle under this region have been periodically breaking off and sinking down into the Earth. This thins and weakens the remaining plate, making it more prone to slipping that causes earthquakes. The study authors conclude this process is ongoing and likely to produce more earthquakes in the future.
“Our idea supports the view that this seismicity will continue due to unbalanced stresses in the plate,” said Berk Biryol, a seismologist at the University of North Carolina at Chapel Hill and lead author of the new study. “The [seismic] zones that are active will continue to be active for some time.” The study was published today in the Journal of Geophysical Research — Solid Earth, a journal of the American Geophysical Union.
Compared to earthquakes near plate boundaries, earthquakes in the middle of plates are not well understood and the hazards they pose are difficult to quantify. The new findings could help scientists better understand the dangers these earthquakes present.
Old plates and earthquakes
Tectonic plates are composed of Earth’s crust and the uppermost portion of the mantle. Below is the asthenosphere: the warm, viscous conveyor belt of rock on which tectonic plates ride.
Earthquakes typically occur at the boundaries of tectonic plates, where one plate dips below another, thrusts another upward, or where plate edges scrape alongside each other. Earthquakes rarely occur in the middle of plates, but they can happen when ancient faults or rifts far below the surface reactivate. These areas are relatively weak compared to the surrounding plate, and can easily slip and cause an earthquake.
Today, the southeastern U.S. is more than 1,056 miles from the nearest edge of the North American Plate, which covers all of North America, Greenland and parts of the Atlantic and Arctic oceans. But the region was built over the past billion years by periods of accretion, when new material is added to a plate, and rifting, when plates split apart. Biryol and colleagues suspected ancient fault lines or pieces of old plates extending deep in the mantle following episodes of accretion and rifting could be responsible for earthquakes in the area.
“This region has not been active for a long time,” Biryol said. “We were intrigued by what was going on and how we can link these activities to structures in deeper parts of the Earth.”
A CAT scan of the Earth
To find out what was happening deep below the surface, the researchers created 3D images of the mantle portion of the North American Plate. Just as doctors image internal organs by tracing the paths of x-rays through human bodies, seismologists image the interior of the Earth by tracing the paths of seismic waves created by earthquakes as they move through the ground. These waves travel faster through colder, stiffer, denser rocks and slower through warmer, more elastic rocks. Rocks cool and harden as they age, so the faster seismic waves travel, the older the rocks.
The researchers used tremors caused by earthquakes more than 2,200 miles away to create a 3D map of the mantle underlying the U.S. east of the Mississippi River and south of the Ohio River. They found plate thickness in the southeast U.S. to be fairly uneven — they saw thick areas of dense, older rock stretching downward and thin areas of less dense, younger rock.
“This was an interesting finding because everybody thought that this is a stable region, and we would expect regular plate thickness,” Biryol said.
At first, they thought the thick, old rocks could be remnants of ancient tectonic plates. But the shapes and locations of the thick and thin regions suggested a different explanation: through past rifting and accretion, areas of the North American Plate have become more dense and were pulled downward into the mantle through gravity. At certain times, the densest parts broke off from the plate and sank into the warm asthenosphere below. The asthenosphere, being lighter and more buoyant, surged in to fill the void created by the missing pieces of mantle, eventually cooling to become the thin, young rock in the images.
The researchers concluded this process is likely what causes earthquakes in this otherwise stable region: when the pieces of the mantle break off, the plate above them becomes thinner and more prone to slip along ancient fault lines. Typically, the thicker the plate, the stronger it is, and the less likely to produce earthquakes.
According to Biryol, pieces of the mantle have most likely been breaking off from underneath the plate since at least 65 million years ago. Because the researchers found fragments of hard rocks at shallow depths, this process is still ongoing and likely to continue into the future, potentially leading to more earthquakes in the region, he said.
The above post is reprinted from materials provided by University of North Carolina at Chapel Hill. The original item was written by Lauren Lipuma.Note: Materials may be edited for content and length.
- C. Berk Biryol, Lara S. Wagner, Karen M. Fischer, Robert B. Hawman.Relationship Between Observed Upper Mantle Structures and Recent Tectonic Activity Across the Southeastern United States.Journal of Geophysical Research: Solid Earth, 2016; DOI:10.1002/2015JB012698
Source: University of North Carolina at Chapel Hill. “Likely cause for recent southeast US earthquakes: Underside of the North American Plate peeling off.” ScienceDaily. ScienceDaily, 3 May 2016. <www.sciencedaily.com/releases/2016/05/160503130840.htm>.
Part of the Middle East and North Africa may become uninhabitable due to climate change
May 2, 2016
Part of the Middle East and North Africa may become uninhabitable due to climate change.
More than 500 million people live in the Middle East and North Africa — a region which is very hot in summer and where climate change is already evident. The number of extremely hot days has doubled since 1970. “In future, the climate in large parts of the Middle East and North Africa could change in such a manner that the very existence of its inhabitants is in jeopardy,” says Jos Lelieveld, Director at the Max Planck Institute for Chemistry and Professor at the Cyprus Institute.
Lelieveld and his colleagues have investigated how temperatures will develop in the Middle East and North Africa over the course of the 21st century. The result is deeply alarming: Even if Earth’s temperature were to increase on average only by two degrees Celsius compared to pre-industrial times, the temperature in summer in these regions will increase more than twofold. By mid-century, during the warmest periods, temperatures will not fall below 30 degrees at night, and during daytime they could rise to 46 degrees Celsius (approximately 114 degrees Fahrenheit). By the end of the century, midday temperatures on hot days could even climb to 50 degrees Celsius (approximately 122 degrees Fahrenheit). Another finding: Heat waves could occur ten times more often than they do now.
By mid-century, 80 instead of 16 extremely hot days
In addition, the duration of heat waves in North Africa and the Middle East will prolong dramatically. Between 1986 and 2005, it was very hot for an average period of about 16 days, by mid-century it will be unusually hot for 80 days per year. At the end of the century, up to 118 days could be unusually hot, even if greenhouse gas emissions decline again after 2040. “If humankind continues to release carbon dioxide as it does now, people living in the Middle East and North Africa will have to expect about 200 unusually hot days, according to the model projections,” says Panos Hadjinicolaou, Associate Professor at the Cyprus Institute and climate change expert.
Atmospheric researcher Jos Lelieveld is convinced that climate change will have a major impact on the environment and the health of people in these regions. “Climate change will significantly worsen the living conditions in the Middle East and in North Africa. Prolonged heat waves and desert dust storms can render some regions uninhabitable, which will surely contribute to the pressure to migrate,” says Jos Lelieveld.
The research team recently also published findings on the increase of fine particulate air pollution in the Middle East. It was found that desert dust in the atmosphere over Saudi Arabia, Iraq and in Syria has increased by up to 70 percent since the beginning of this century. This is mainly attributable to an increase of sand storms as a result of prolonged droughts. It is expected that climate change will contribute to further increases, which will worsen environmental conditions in the area.
In the now published study, Lelieveld and his colleagues first compared climate data from 1986 to 2005 with predictions from 26 climate models over the same time period. It was shown that the measurement data and model predictions corresponded extremely well, which is why the scientists used these models to project climate conditions for the period from 2046 to 2065 and the period from 2081 to 2100.
Largest temperature increase in already hot summers
The researchers based their calculations on two future scenarios: The first scenario, called RCP4.5, assumes that the global emissions of greenhouse gases will start decreasing by 2040 and that the Earth will be subjected to warming by 4.5 Watt per square meter by the end of the century. The RCP4.5 scenario roughly corresponds to the target set at the most recent UN climate summit, which means that global warming should be limited to less than two degrees Celsius.
The second scenario (RCP8.5) is based on the assumption that greenhouse gases will continue to increase without further limitations. It is therefore called the “business-as-usual scenario.” According to this scenario, the mean surface temperature of the Earth will increase by more than four degrees Celsius compared to pre-industrial times.
In both scenarios, the strongest rise in temperature in the Middle East and North Africa is expected during summer, when it is already very hot, and not during winter, which is more common in other parts of the globe. This is primarily attributed to a desert warming amplification in regions such as the Sahara. Deserts do not buffer heat well, which means that the hot and dry surface cannot cool by the evaporation of ground water. Since the surface energy balance is controlled by heat radiation, the greenhouse effect by gases such as carbon dioxide and water vapor will increase disproportionately.
Regardless of which climate change scenario will become reality: both Lelieveld and Hadjinicolaou agree that climate change can result in a significant deterioration of living conditions for people living in North Africa and the Middle East, and consequently, sooner or later, many people may have to leave the region.
- J. Lelieveld, Y. Proestos, P. Hadjinicolaou, M. Tanarhte, E. Tyrlis, G. Zittis.Strongly increasing heat extremes in the Middle East and North Africa (MENA) in the 21st century. Climatic Change, 2016; DOI:10.1007/s10584-016-1665-6
- Klaus Klingmüller, Andrea Pozzer, Swen Metzger, Georgiy L. Stenchikov, Jos Lelieveld. Aerosol optical depth trend over the Middle East.Atmospheric Chemistry and Physics, 2016; 16 (8): 5063 DOI:10.5194/acp-16-5063-2016
Source: Max-Planck-Gesellschaft. “Climate-exodus expected in the Middle East and North Africa: Part of the Middle East and North Africa may become uninhabitable due to climate change.” ScienceDaily. ScienceDaily, 2 May 2016. <www.sciencedaily.com/releases/2016/05/160502131421.htm>.
eSource Meeting in Philadelphia
CBI is running its 3rd meeting addressing eSource Data in Clinical Investigations. Industry leaders will be there and it should be a highly productive experience for all. Dr. Mitchel will be presenting Target Health’s experience of the first FDA product approval where direct data entry occurred at the time of the clinic visit. Using results and experiences during the clinical development of an FDA-cleared de novo 510(k) device, as well as an NDA currently under FDA review, the presentation will take a deep-dive into the processes that were used, including how to:
1. Involve regulators as partners
2. Educate and train the clinical research sites
3. Integrate eSource processes with risk-based monitoring
4. Evaluate the impact on the clinical research enterprise
Spring Time in NY
Yes, nature is alive in the Big Apple.
On the way to the theatre down Park Avenue on a lovely Spring day. ©Target Health 2016
ON TARGET is the newsletter of Target Health Inc., a NYC – based, full – service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services to the pharmaceutical and device industries, including the paperless clinical trial.
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
Autism Spectrum Disorder (ASD)
The puzzle ribbon is an often used symbol for the autism spectrum, as it represents the diversity of conditions and people within it. Source Wikipedia Commons
Autism spectrum or autistic spectrum describes a range of conditions classified as neurodevelopmental disorders in the fifth revision of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5). The DSM-5, published in 2013, redefined the autism spectrum to encompass the previous (DSM-IV-TR) diagnoses of autism, Asperger syndrome, pervasive developmental disorder not otherwise specified (PDD-NOS), and childhood disintegrative disorder. Features of these disorders include social deficits and communication difficulties, stereotyped or repetitive behaviors and interests, sensory issues, and in some cases, cognitive delays. Compared with the DSM-4 diagnosis of autistic disorder, the DSM-5 diagnosis of ASD no longer includes communication as a separate criterion, and has merged social interaction and communication into one category. Rather than categorizing these diagnoses, the DSM-5 has adopted a dimensional approach to diagnosing disorders that fall underneath the autism 1) ___ umbrella. Some have proposed that individuals on the autism spectrum may be better represented as a single diagnostic category. Within this category, the DSM-5 has proposed a framework of differentiating each individual by dimensions of severity, as well as associated features (i.e., known genetic disorders, and intellectual disability).
Autism forms the core of the autism spectrum disorders. Asperger syndrome is closest to autism in signs and likely causes; unlike autism, people with Asperger syndrome have no significant delay in language development, according to the older DSM-4 criteria. PDD-NOS is diagnosed when the criteria are not met for a more specific disorder. Some sources also include Rett syndrome and childhood disintegrative disorder, which share several signs with autism but may have unrelated causes; other sources differentiate them from ASD, but group all of the above conditions into the pervasive developmental disorders. Under the DSM-5, autism is characterized by persistent deficits in social communication and interaction across multiple contexts, as well as restricted, repetitive patterns of behavior, interests, or activities. These deficits are present in early childhood, and lead to clinically significant functional impairment. There is also a unique form of 2) ___ called autistic savantism, where a child can display outstanding skills in music, art, and numbers with no practice.
Asperger syndrome was distinguished from autism in the DSM-4 by the lack of delay or deviance in early language development. Additionally, individuals diagnosed with Asperger syndrome did not have significant cognitive delays. PDD-NOS was considered subthreshold autism and atypical autism because it was often characterized by milder symptoms of autism or symptoms in only one domain (such as social difficulties). In the DSM-5, both Asperger syndrome and PDD-NOS have been incorporated into autism spectrum 3) ___. CDC’s most recent estimate is that 1 out of every 68 children, or 14.7 per 1,000, have some form of ASD as of 2010. Reviews tend to estimate a prevalence of 6 per 1,000 for autism spectrum disorders as a whole, although prevalence rates vary for each of the developmental disorders in the spectrum. Autism prevalence has been estimated at 1-2 per 1,000, Asperger syndrome at roughly 6 per 1,000, childhood disintegrative disorder at 0.02 per 1,000, and PDD-NOS at 3.7 per 1,000. These rates are consistent across cultures and ethnic groups, as autism is considered a 4) ___ disorder. While rates of autism spectrum disorders are consistent across cultures, they vary greatly by gender, with boys affected far more frequently than girls. The average male-to-female ratio for ASDs is 4.2:1, affecting 1 in 70 males, but only 1 in 315 females. Females, however, are more likely to have associated cognitive impairment. Among those with an ASD and intellectual disability, the gender ratio may be closer to 2:1. Prevalence differences may be a result of gender differences in expression of clinical symptoms, with autistic females showing less atypical behaviors and, therefore, less likely to receive an ASD diagnosis.
Autism spectrum disorders are thought to follow two possible developmental courses, although most parents report that symptom onset occurred within the first 5) ___ of life. One course of development is more gradual in nature, in which parents report concerns in development over the first two years of life and diagnosis is made around 3-4 years of age. Some of the early signs of ASDs in this course include decreased looking at faces, failure to turn when name is called, failure to show interests by showing or pointing, and delayed pretend play. A second course of development is characterized by normal or near-normal development followed by loss of skills or regression in the first 2-3 years. Regression may occur in a variety of domains, including communication, social, cognitive, and self-help skills; however, the most common regression is loss of 6) ___. There continues to be a debate over the differential outcomes based on these two developmental courses. Some studies suggest that regression is associated with poorer outcomes and others report no differences between those with early gradual onset and those who experience a regression period. While there is conflicting evidence surrounding language outcomes in ASD, some studies have shown that cognitive and language abilities at age 2 1/2 may help predict language proficiency and production after age 5. Overall, the literature stresses the importance of early intervention in achieving positive longitudinal outcomes.
While specific causes of autism spectrum disorders have yet to be found, many risk factors have been identified in the research literature that may contribute to their development. These 7) ___ factors include genetics, prenatal and perinatal factors, neuroanatomical abnormalities, and environmental factors. It is possible to identify general risk factors, but much more difficult to pinpoint specific factors. In the current state of knowledge, prediction can only be of a global nature and therefore requires the use of general markers. Transcranial magnetic stimulation (TMS) has become increasingly popular as a treatment for autism in children, but it’s unclear how effective it is or how long the treatment might last. The basic premise is this: When a powerful magnet generates a magnetic field near the head, the field travels a few centimeters through the scalp and skull, changing the electrical activity of neurons in those locations. The result is a temporary reorganization in the way brain cells communicate with one another. Unlike electroconvulsive therapy, in which electrodes are placed directly on the scalp in order to trigger a seizure, TMS can be targeted to one brain region, and allows for more precise alterations of brain function. It also seems to be gentler than the brutal images associated with the early years of electroconvulsive therapy: TMS is not painful and doesn’t seem to cause amnesia or cognitive problems. The side effects seem limited to headaches and some muscular discomfort, though a few people have had seizures during therapy. TMS can stimulate neurons’ activity or change the signaling patterns of cells that are already active. Given its capacity to do both noninvasively, from the start it offered the promise of a powerful treatment for a range of neuropsychiatric disorders that seem to involve dysfunctions in brain circuits, such as depression, schizophrenia, epilepsy and obsessive-compulsive disorder.
In the mid-1990s, researchers began treating depression with repetitive TMS, administering treatment in regular sessions over weeks or months. Initial trials suggested the technique was effective at least some of the time, and in 2007 the U.S. 8) ___ and ___ ___,(FDA) approved it to treat depression in people who don’t respond to medication and talk therapy. It has since also been used to treat chronic pain and to aid recovery from stroke. The University of Louisville has been at the forefront of some of the research on TMS. In typical brains, neurons engage in a perpetual balancing act between excitation and inhibition in response to the endless flow of stimulation that comes their way. Too much inhibition can lead to depression, and too much excitation to both autism and epilepsy. (The latter may explain why many people with autism have seizures and show extreme sensitivity to touch and sound.)
Different cells specialize in one activity or the other – stirring up networks or calming things down – and work together to maintain the balance. Research suggests that some of the abnormality in autism brains occurs in mini-columns, vertical networks of cells that work together to process information. Pyramidal cells at the center of these columns are excitatory. Clustered around them, other types of cells, particularly double bouquet cells, turn down the signals so that only the most important information gets through. When this shower curtain of inhibition – a phrase coined by Hungarian scientist Janos Szentagothai – doesn’t work as it should, the signals spill out, drenching the nearby networks in stimulation. In autism, the thinking is that TMS could correct the imbalance between 9) ___ and inhibition. The small currents created by TMS change neurons’ electrical charge and cause them to release chemical messengers, sending a ripple of activity to distant areas of the brain. High-frequency stimulation is thought to increase excitatory activity and a low frequency to increase inhibition. Preliminary results from research with monkeys suggest that people with autism may benefit, for example, from applying TMS to increase excitation in an area of the brain associated with sociability. Because the region is close to the brain’s surface, it is easily accessible to TMS, but is also well connected to the rest of the brain: As a result, any changes there, may have beneficial effects in many other areas. Several of the studies required the participants to perform a visual illusion task designed to trigger a high-frequency brain wave called gamma. Gamma waves are involved in high-level attention processing and have been found to be abnormal in the 10) ___ of people with autism, often responding too strongly to distractions. Studies have found that after repeated bouts of TMS, people with autism process visual information more efficiently, making fewer errors in the illusion task. They are also less irritable and hyperactive and show fewer repetitive behaviors, at least for a while, than before the treatment. The effect is akin to rebooting a computer – something you eventually have to repeat. At its best, TMS can produce dramatic changes.
ANSWERS: 1) spectrum; 2) autism; 3) disorder; 4) universal; 5) year; 6) language; 7) risk; 8) Food and Drug Administration; 9) excitation; 10) brains
The word autism, comes from the Greek word autos, meaning self. The term describes conditions in which a person is removed from social interaction — hence, an isolated self. A few examples of autistic symptoms and treatments were described long before autism was named. The Table Talk of Martin Luther**, compiled by his note taker, Mathesius, contains the story of a 12-year-old boy who may have been severely autistic. Luther reportedly thought the boy was a soulless mass of flesh possessed by the devil, and suggested that he be suffocated, although a later critic has cast doubt on the veracity of this report. The earliest well-documented case of autism is that of Hugh Blair of Borgue, as detailed in a 1747 court case in which his brother successfully petitioned to annul Blair’s marriage to gain Blair’s inheritance. The Wild Boy of Aveyron, a feral child caught in 1798, showed several signs of autism; the medical student Jean Itard treated him with a behavioral program designed to help him form social attachments and to induce speech via imitation.
The New Latin word autismus (English translation autism) was coined by the Swiss psychiatrist Eugen Bleuler in 1910 as he was defining symptoms of schizophrenia. He derived it from the Greek word autos (meaning self), and used it to mean morbid self-admiration, referring to autistic withdrawal of the patient to his fantasies, against which any influence from outside becomes an intolerable disturbance. The word autism first took its modern sense in 1938 when Hans Asperger of the Vienna University Hospital adopted Bleuler’s terminology autistic psychopaths in a lecture in German about child psychology. Asperger was investigating an ASD now known as Asperger syndrome, though for various reasons it was not widely recognized as a separate diagnosis until 1981. Leo Kanner, an American physician, at the Johns Hopkins Hospital first used autism in its modern sense in English when he introduced the label early infantile autism in a 1943 report of 11 children with striking behavioral similarities. Almost all the characteristics described in Kanner’s first paper on the subject, notably autistic aloneness and insistence on sameness, are still regarded as typical of the autistic spectrum of disorders. It is not known whether Kanner derived the term independently of Asperger.
Kanner’s reuse of autism led to decades of confused terminology like infantile schizophrenia, and child psychiatry’s focus on maternal deprivation led to misconceptions of autism as an infant’s response to refrigerator mothers. Starting in the late 1960s autism was established as a separate syndrome by demonstrating that it is lifelong, distinguishing it from intellectual disability and schizophrenia and from other developmental disorders, and demonstrating the benefits of involving parents in active programs of therapy. As late as the mid-1970s there was little evidence of a genetic role in autism; now it is thought to be one of the most heritable of all psychiatric conditions. Although the rise of parent organizations and the destigmatization of childhood ASD have deeply affected how we view ASD, parents continue to feel social stigma in situations where their child’s autistic behavior is perceived negatively by others, and many primary care physicians and medical specialists still express some beliefs consistent with outdated autism research.
The Internet has helped autistic individuals bypass nonverbal cues and emotional sharing that they find so hard to deal with, and has given them a way to form online communities and work remotely. Sociological and cultural aspects of autism have developed: some in the community seek a cure, while others believe that autism is simply another way of being. The emergence of the autism rights movement has served as an attempt to encourage people to be more tolerant of those with autism. Through this movement, people hope to cause others to think of autism as a difference instead of a disease. Proponents of this movement wish to seek acceptance, not cures. There have also been many worldwide events promoting autism awareness such as World Autism Awareness Day, Light It Up Blue, Autism Sunday, Autistic Pride Day, Autreat, and others. There have also been many organizations dedicated to increasing the awareness of autism and the effects that autism has on someone’s life. These organizations include Autism Speaks, Autism National Committee, Autism Society of America, and many others. Social-science scholars have had an increased focused on studying those with autism in hopes to learn more about autism as a culture, transcultural comparisons and research on social movements. Media has had an influence on how the public perceives those with autism. Rain Man, a film that won 4 Oscars, depicts a character with autism who has incredible talents and abilities. While many autistics don’t have these special abilities, there are some autistic individuals who have been successful in their fields.
**Martin Luther’s Table Talk (German: Tischreden) is a collection of his sayings around the dinner table at the Black Cloister, Luther’s home, but also at other times and locations, such as walks in the garden or notes taken while on journeys. It is based on notes taken by various students of Luther between 1531 and 1544. It was compiled by Johannes Mathesius, J. Aurifaber, V. Dietrich, Ernst Kroker, and several others, and published at Eisleben in 1566. Mathesius spoke enthusiastically of the privilege of eating with Luther and hearing him converse. Earlier note takers had written down only the serious remarks of Luther, but Mathesius also wrote down the facetious or even damaging remarks, a sign of the increasing reverence in which Luther was held.
Patients with Rosacea Have Increased Risk of Dementia
Rosacea is a common chronic inflammatory skin disorder where upregulation of matrix metalloproteinases (MMPs) and antimicrobial peptides (AMPs) is observed. Notably, inflammation, MMPs, and AMPs are also involved in the etiopathogenesis of neurodegenerative disorders including certain forms of dementia such as Alzheimer disease (AD). As a result, a study published in the Annals of Neurology (28 April 2016), was performed to investigate the association between rosacea and dementia, including AD in Danish registers.
For the study, all Danish citizens aged >18 years between January 1, 1997 and December 31, 2012 were linked at the individual level through administrative registers. When this was done, the study was able to identify a total of 5,591,718 individuals, including 82,439 patients with rosacea. Of these individuals, a total of 99,040 developed dementia (any form) during the study period, and 29,193 were diagnosed with AD. The adjusted hazards ratios HRs) of dementia and AD were 1.07 and 1.25, respectively, in patients with rosacea. Stratified by gender, the HRs of AD were 1.28 and 1.16 in women and men, respectively. When results were stratified by age at study entry, the risk of AD was only significantly increased in individuals >60 years old (adjusted HR = 1.20). When analyses were limited to patients with a hospital dermatologist diagnosis of rosacea only, the adjusted HRs of dementia and AD were 1.42 and 1.92, respectively.
According to the authors, rosacea is significantly associated with dementia, particularly AD, and that increased focus on symptoms of cognitive dysfunction in older patients with rosacea may be relevant.
Trigeminal Nerve Stimulation (TNS) For Treating Major Depression
The trigeminal nerve (the fifth cranial nerve, or simply CN V) is a nerve responsible for sensation in the face and motor functions such as biting and chewing. The largest of the cranial nerves, its name (trigeminal = tri-, or three and -geminus, or twin; thrice-twinned) derives from the fact that each trigeminal nerve (one on each side of the pons) has three major branches: the ophthalmic nerve (V1), the maxillary nerve (V2), and the mandibular nerve (V3). The ophthalmic and maxillary nerves are purely sensory, and the mandibular nerve has sensory (or cutaneous) and motor functions.
Major depressive disorder (MDD), often simply called depression, is a mental disorder characterized by a pervasive and persistent low mood that is accompanied by low self-esteem and by a loss of interest or pleasure in normally enjoyable activities. MDD is a disabling condition that adversely affects a person’s family, work or school life, sleeping and eating habits, and general health. In the United States, around 3.4% of people with major depression die by suicide, and up to 60% of people who die by suicide had depression or another mood disorder.
According to an article published online in Epilepsy and Behavior (23 August 2014), an open-label proof-of-concept trial using Trigeminal Nerve Stimulation (TNS) for MDD was performed that according to the authors was the first study that evaluated a TNS interventional protocol for the treatment of MDD. For the study, a total of 11 patients (10F; 1M) were studied, with a mean age of 50.36 years (range of 30 to 60). Results showed that there was a reduction of depressive symptoms with a mean score of 5.72 (p<0.001) on the original 17-item Hamilton Depression Rating Scale (HDRS-17). All patients presented clinical response defined as a reduction of scores of at least 50%. Only one patient did not reach a remission score (defined as an HDRS score lower than 8).
The authors concluded that the data analysis provided significant support to use TNS in ameliorating depressive symptoms of patients with moderate or severe depressive episode, but that further controlled studies will contribute to establish the clinical relevance of this new strategy for MDD.
As a followup, a study was presented at the American Society of Clinical Psychopharmacology (ASPC) 2015 Annual Meeting where results were presented that showed, in a sham treatment controlled study that TNS may be a useful adjunctive treatment for patients with MDD that is not adequately controlled by antidepressant medication. The study included 43 adults aged 23 to 65 years with nonpsychotic unipolar MDD who were unresponsive to more than 6 weeks of treatment with at least one antidepressant. Participants were randomly assigned to receive active stimulation or control sham stimulation for 6 weeks. They self-stimulated the trigeminal nerve for 8 hours each night at home using patch electrodes placed on the forehead.
Clinical outcomes were assessed using the Beck Depression Inventory (BDI), the Inventory of Depressive Symptomology (IDS-SR), and the Hamilton Depression Rating Scale (HDRS-17). Results showed that patients receiving active stimulation had significantly greater symptom improvement at week 6 than patients receiving the control condition on the BDI, and they approached significance on the IDS-SR.
Table. Symptom Improvement With TNS vs Sham
However, symptom severity for all scales improved significantly for patients receiving active stimulation. The mean score on the BDI fell from 24.6 at baseline to 14.2 at week 6 (P <0.00001; the mean score on the IDS-SR fell from 38.3 to 26.1 (P >0.00001), and the HDRS-17 score fell from 19.4 to 12.1 (P < .0001).
Drug Approved to Treat Hallucinations/Delusions Associated with Parkinson’s Disease
According to the National Institutes of Health, an estimated 50,000 Americans are diagnosed with Parkinson’s disease (PD) each year, and about one million Americans have the condition. The neurological disorder typically occurs in people over age 60, when cells in the brain that produce a chemical called dopamine become impaired or die. Dopamine helps transmit signals between the areas of the brain that produce smooth, purposeful movement — like eating, writing and shaving. Early symptoms of the disease are subtle and occur gradually. In some people PD progresses more quickly than in others. As the disease progresses, the shaking, or tremor, which affects the majority of people with PD, may begin to interfere with daily activities. Other symptoms may include depression and other emotional changes; hallucinations and delusions; difficulty in swallowing, chewing, and speaking; urinary problems or constipation; skin problems; and sleep disruptions.
Hallucinations or delusions can occur in as many as 50% of patients with PD at some time during the course of their illness. People who experience them see or hear things that are not there (hallucinations) and/or have false beliefs (delusions). The hallucinations and delusions experienced with PD are serious symptoms, and can lead to thinking and emotions that are so impaired that the people experiencing them may not relate to loved ones well or take appropriate care of themselves.
The FDA has approved Nuplazid (pimavanserin) tablets, the first drug approved to treat hallucinations and delusions associated with psychosis experienced by some people with PD. The effectiveness of Nuplazid was shown in a six-week clinical trial of 199 participants. Nuplazid was shown to be superior to placebo in decreasing the frequency and/or severity of hallucinations and delusions without worsening the primary motor symptoms of PD. As with other atypical antipsychotic drugs, Nuplazid has a Boxed Warning alerting health care professionals about an increased risk of death associated with the use of these drugs to treat older people with dementia-related psychosis. No drug in this class is approved to treat patients with dementia-related psychosis. In clinical trials, the most common side effects reported by participants taking Nuplazid were: swelling, usually of the ankles, legs, and feet due to the accumulation of excessive fluid in the tissue (peripheral edema); nausea; and abnormal state of mind (confused state).
Nuplazid was granted breakthrough therapy designation for the treatment of hallucinations and delusions associated with PD. Breakthrough therapy designation is a program designed to expedite the development and review of drugs that are intended to treat a serious condition and where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint. The drug was also granted a priority review. The FDA’spriority review program provides for an expedited review of drugs that offer a significant improvement in the safety or effectiveness for the treatment, prevention, or diagnosis of a serious condition.
Nuplazid is marketed by Acadia Pharmaceuticals Inc. of San Diego, California.