Tag Archives: Research

The Burned Out State of Mind

April 10, 2015Mind MattersBurnout, Depersonalization, Exhaustion, ICD10, Mind, Peer Reviewed Studies, psychology, ResearchESNP Educational Consulting Services

Let’s say you watch a movie in a theater where the protagonist is caught in what we would consider an abusive situation. Specifically, the hero is required to work through two situations: one bad, the other worse. Neither situation is a choice that will make the hero better, however there doesn’t seem to be any immediate relief aside from choosing between the two options. Because neither situation is optimal, our hero chooses the the lesser evil and proceeds to believe it’s the only option. The constant exposure to an abusive situation leads to his resignation of his fate, an uncaring despot, until the climax of the movie saves the day.

Ultimately our lives are far less condensed in drama, however the phenomenon of burnout is more common in our modern lives than we recognize or give it credit for.

The term ‘burnout’ was initiated in the United States about 35 years ago. The psychoanalyst Freudenberger, for example, published one of the first scientific descriptions of the burnout syndrome as psychiatric and physical breakdown. According to one of the first more extensive characterizations by Susan E. Jackson and Christina Maslach, burnout is the result of chronic stress (at the workplace) which has not been successfully dealt with. It is characterized by exhaustion and depersonalization (negativism/cynicism) and is found predominantly in caring and social professions (e.g. social workers, teachers, nurses, doctors, dentists). A later definition based on the MBI and which is in widespread use today, describes exhaustion, depersonalization, and reduced satisfaction in performance as the decisive elements of burnout syndrome.

Contrary to earlier observations regarding the epidemiology of burnout, it has been noted that the syndrome is not associated with certain workplaces, circumstances, sex or age. The occurrence of burnout syndrome has been described in diverse occupations, e.g. in social workers, advisors, teachers, nurses, laboratory workers, speech therapists, ergo therapists, doctors and dentists, police and prison officers, stewardesses, managers, and even in housewives, students and unemployed people. Psychological explanations assume that in most of these occupations the combination of caring, advising, healing or protecting, coupled with the demands of showing that one cares, is of central importance.

In the 10th revision of the International Classification of Diseases (ICD 10) the term ‘burnout’ was described in Problems related to life management difficulty under Z.73.0 as ‘Burnout-state of total exhaustion‘. In addition to the question of a uniform, generally accepted definition, etiological and pathogenetic aspects are the subjects of much controversy. It is generally believed today that ‘negative stress’ (distress) probably represents a key phenomenon in the etiopathogenesis of burnout. Other important pathogenetic factors are thought to be ‘being swamped by daily routine’ and ‘disappointed expectations’. Most of the theories and models for the development of burnout syndrome are published in the psychological, psychosomatic and psychiatric literature.

A. Weber and A. Jaekel-Reinhard discuss in their paper on burnout that depending on the duration and severity of the burnout, there are often further negative social consequences. These include, from the point of view of the individual, withdrawal at the workplace (so called ‘inner resignation’) or effects on private life (partner/ sexual problems, social isolation). From the perspective of society, there is an increased risk of repeated or long periods of absence from work and early invalidity.

The Burnout Phenomenon is so prevalent that it has warranted its own branch of research. This research is being carried out in many countries around the world, so it is clear that burnout has global significance. Recently, there has been a growing interest in developing interventions to reduce burnout, from government agencies and organizations in both the public and private sectors. Without a doubt, burnout poses a major challenge for society. Given the ongoing importance of the burnout phenomenon, and the rising interest in making real progress in alleviating it, there is a need for a primary venue for the many research contributions being made.

To highlight further importance on the alarming rates of burnout, the scientific community came together in April 2015 and created the Burnout Research Journal. This is a peer-reviewed international journal aimed at presenting basic, translational and clinical high-quality research related to the phenomenon of burnout. As the first journal dedicated to understanding the causes of burnout and potential solutions to the problem, Burnout Research welcomes original research articles, review articles, case reports, and opinion pieces. The goal of the journal is to publish the top research in three major areas: Cutting-edge research that lays out new directions for the burnout field, including new research paradigms and measures, new theoretical models, and new collaborations between researchers and practitioners. Critical reviews that provide comprehensive and integrative analyses of key themes (such as cultural or occupational differences in burnout), or meta-analyses of major datasets. Translational research studies that assess promising interventions for preventing burnout and building engagement.

From an educational perspective, the days when academia was a low-stress working environment are over, with “burnout” levels now comparable with those in other service sectors, according to a 2011 study, “Burnout in university teaching staff: a systematic literature review.” This study was published in the journal Educational Research and was led by Noelle Robertson, senior lecturer in clinical psychology at the University of Leicester, and a master’s student there, Jenny Watts. The researchers, who describe their work as the first survey of the extent of burnout among full-time, non-medical university teaching staff, report that younger staff appeared more vulnerable, suffering from greater “emotional exhaustion.”

The analysis is based on 12 peer-reviewed studies in the United States, Britain, Canada, South Africa, Spain, Turkey and the Netherlands, and likens levels of burnout among those who teach in higher education to those of schoolteachers and health professionals. The authors also attempt to pinpoint the key factors that push some academics into a state characterized by “the depletion of emotional reserves (emotional exhaustion), an increasingly cynical and negative approach towards others (depersonalization) and a growing feeling of work-related dissatisfaction.”

These results could also be because younger staff have more contact with students, but also because more experienced colleagues have developed better coping strategies.Gender seemed to have most impact on the way burnout revealed itself, the study suggests. Male lecturers typically had higher depersonalization scores, for example, while their female peers tended to suffer more emotional exhaustion.This probably reflected, the authors suggest, the draining effect on women who were having to “juggle multiple roles at work and at home,” on the one hand, and their reluctance to adopt “a distant, indifferent professional persona” on the other.

The research indicated that “staff exposure to high numbers of students, especially tuition of postgraduates, strongly predicts the experience of burnout.” However, they suggest that lecturers with qualities that might make them particularly suited to the job suffered more than their less engaged colleagues. The quality of “openness” may “make appealing tutors, encouraging greater interaction with students,” but it also appeared to “predispose teachers to burnout,” the paper says.

In a separate analysis of professional burnout among professors in the United States, a Texas Woman’s University Ph.D. candidate found tenure track professors had more significant symptoms of workplace frustration than their tenured and non-tenure track faculty counterparts.

Janie Crosmer, who conducted the survey of more than 400 full-time faculty across the U.S. in December 2008, said she was unsurprised that the high stresses of pursuing academia’s most coveted status led to burnout. She utilized the Maslach Burnout Inventory in her survey, which measures burnout in three categories. A faculty survey found professors, on average, fell within the average burnout range. See the Inventory Table Results Below:

Emotional Exhaustion (Range 0-54)
• < 13: Low Degree of Burnout
• 14-23: Average Degree of Burnout
• > 24: High Degree of Burnout
• Full Faculty Survey Sample: 20.1

Depersonalization (Range 0-30)
• < 2: Low Degree of Burnout
• 3-8: Average degree of burnout
• > 9: High Degree of Burnout
• Full Faculty Survey Sample: 6.3

Personal Accomplishment (Range 0-48)
• > 43: Low Degree of Burnout
• 36-42: Average Degree of Burnout
• < 35: High Degree of Burnout
• Full Faculty Survey: 35.99

Crosmer said she was struck by the candor and, at times, negativity manifested in faculty comments. Professors complained about massive red tape, inflexible mandates for holding office hours, low morale, health concerns and insufficient travel funds. And while Crosmer would still like to land a faculty position in the future, she was disheartened by what she heard.

“By reading that, you were [thinking] do I really want to teach ever? Some of the comments were, oh my goodness.”

As with just about any industry, professors also said they felt they should earn more money. One respondent opined, “We are the most highly educated people in the country and among the worst paid.”

Learning’s Many Costs, First Quarter 2015 Edition

March 31, 2015Brain BitsAmygdala, brain function, Children's Hospital Los Angeles, Columbia University Medical Center, Educare, Preschool, Research, socio-econonomic, socio-psychological, UNC, University of GeorgiaESNP Educational Consulting Services

Flipping channels, Dr. Phil comes onto the main screen and has a mother and daughter in opposite angles to him. The problems seemed to be typical psychological, reality-show formula: mom is overprotective of her teenage daughter, teenage daughter ‘rebels’ and begins a long distance relationship with a man 10 years her senior (who also happens to be a drug dealer still serving time), and the conflicts between them become unbearable. Dr. Phil in his infinite wisdom brought out his objectivity to the mother, and then to the daughter. It is however the explanation to the daughter that resonates with her: “Now remember, it is the Neocortex that develops last in the brain, and that means right now, you’re not able yet to have complete insight to all of the consequences of your actions. This is why you would need guidance with some of your decisions, including starting a relationship with a currently jailed drug dealer.”

Most of us have a familiarity with family drama played out on television. Whether the purpose is to entertain or to educate, the family’s dysfunctional dynamic from one to the next seem to be rooted deep into social, educational and economic factors. How then is the brain development affected? Is Dr. Phil’s approach by combining the brain science with family dynamics warranted?

In the early online edition of the journal Nature Neuroscience (March 30, 2015), investigators from nine universities across the country reports correlative links between family income and brain structure. Relationships between the brain and family income were strongest in the lowest end of the economic range, thus suggesting that interventional policies aimed at these children may have the largest societal impact. The study, led by researchers at The Saban Research Institute of Children’s Hospital Los Angeles and Columbia University Medical Center.

In the largest study of its kind to date, the researchers looked at 1,099 typically developing individuals between the ages of 3 and 20 years as part of the multi-site Pediatric Imaging, Neurocognition and Genetics (PING) study. Associations between socioeconomic factors (including parent education and family income) and measurements of surface area of the brain were drawn from demographic and developmental history questionnaires, as well as high-resolution brain MRIs. Statistics (controlled for education, age and genetic ancestry) showed that income was nonlinearly associated with brain surface area, and that income was more strongly associated with the brain than was parental educational attainment.

First author Kimberly G. Noble, MD, PhD says, “Specifically, among children from the lowest-income families, small differences in income were associated with relatively large differences in surface area in a number of regions of the brain associated with skills important for academic success. ” Dr. Noble is an assistant professor of pediatrics and director of the Neurocognition, Early Experience and Development (NEED) Lab of Columbia University Medical Center. She is also an associate professor of Neuroscience and Education at Teachers College, Columbia University.

Conversely, among children from higher-income families, incremental increases in income level were associated with much smaller differences in surface area. Higher income was also associated with better performance in certain cognitive skills; cognitive differences that could be accounted for by greater brain surface area.

“While in no way implying that a child’s socioeconomic circumstances lead to immutable changes in brain development or cognition, our data suggest that wider access to resources likely afforded by the more affluent may lead to differences in a child’s brain structure,” said Elizabeth Sowell, PhD, director of the Developmental Cognitive Neuroimaging Laboratory, part of the Institute for the Developing Mind at CHLA. “Family income is linked to factors such as nutrition, health care, schools, play areas and, sometimes, air quality,” added Dr. Sowell, indicating that everything going on in the environment shapes the developing brain. “Future research may address the question of whether changing a child’s environment — for instance, through social policies aimed at reducing family poverty — could change the trajectory of brain development and cognition for the better.”

From the socio-economic factors, we take a look at socio-psychological factors, some of which affect our ability to create meaningful connections. A recent study from the University of Georgia shows differences in brain structure according to how trusting people are of others.

The team of researchers used two measures to determine the trust levels of 82 study participants. The participants filled out a self-reported questionnaire about their tendency to trust others. They also were shown pictures of faces with neutral facial expressions, and were asked to evaluate how trustworthy they found each person in the picture. This gave researchers a metric, on a spectrum, of how trusting each participant was of others.

Researchers then took MRI scans of the participants’ brains to determine how brain structure is associated with the tendency to be more trusting of others. What researchers found were differences in two areas of the brain.

“The most important finding was that the grey matter volume was greater in the ventral medial prefrontal cortex, which is the brain region that serves to evaluate social rewards, in people that tended to be more trusting of others,” said the study’s lead author Brian Haas, an assistant professor in the department of psychology.

“Another finding that we observed was for a brain region called the amygdala. The volume of this area of the brain, which codes for emotional saliency, was greater in those that were both most trusting and least trusting of others. If something is emotionally important to us, the amygdala helps us code and remember it.”

The long term hope for the research may have implications for future treatments of psychological conditions such as autism. Future studies may focus on how, and if, trust can be improved and whether the brain is malleable according to the type of communication someone has with another. “There are conditions, like autism, that are characterized by deficits in being able to process the world socially, one of which is the ability to trust people,” Dr. Haas said. “Here we have converging evidence that these brain regions are important for trust; and if we can understand how these differences relate to specific social processes, then we may be able to develop more targeted treatment techniques for people who have deficits in social cognition.”

So what can we do as a community with fragile families who have young children in such a fast-paced, competitive, and digitally plugged world? Begin the developmental awareness young for a firmer foundation with research-backed programs.

Supporting this is new research from UNC’s Frank Porter Graham Child Development Institute (FPG) revealing high-quality early education is especially advantageous for children when they start younger and continue longer. Not only does more high-quality early education significantly boost the language skills of children from low-income families, children whose first language is not English benefit even more.

“These findings show that more high-quality early education and care can narrow the achievement gap before children reach kindergarten,” said Noreen M. Yazejian, principal investigator of FPG’s Educare Learning Network Implementation Study. “Children from low-income families can improve their standing relative to their middle class peers.”

Ms. Yazejian said previous research has shown language skills are most malleable for children before age 4, which in large part explains high-quality early education’s powerful effects. Her study examined children’s receptive language skills–the ability to hear and understand words–because these particular skills are an excellent predictor of later academic success.

According to Yazejian, Educare classrooms offered the chance to study children enrolled in high-quality early education and care from the earliest ages. Educare is an enhanced Early Head Start and Head Start program for low-income, high-needs children from 6 weeks old until entry into kindergarten. The model has been replicated in 20 schools nationwide over the last 15 years.

“Educare’s comprehensive approach to early childhood education aims to level the playing field for children living in poverty,” said Portia Kennel, executive director of the Educare Learning Network. “This new study confirms that we need to include the earliest years of life as part of our nation’s education system. Quality early education prepares vulnerable children for success by preventing the achievement gap that appears long before kindergarten.”

Many people traditionally have viewed early care for infants primarily as a support for mothers who want to work and not as an essential component of early schooling. However, findings from the FPG study add to a growing body of research revealing better outcomes for children from low-income families who start high-quality education earlier and stay in it longer.

Earlier research has shown the English language skills that dual-language learners develop prior to kindergarten can predict educational achievement through eighth grade, but keeping skills in the home language also is beneficial. Home language skills are related to long-term social, emotional, cognitive, and academic outcomes.

“Most dual-language learners in this study were in classrooms where English was the primary instructional language but in which one staff member could use their home language as needed to support learning,” Ms. Yazejian explained. “It’s not surprising our findings show they quickly acquired skills in English. That’s why it’s reassuring that our study found that the acquisition of English language skills in Educare classrooms does not come at the expense of Spanish skills.”

The number of young children who speak a language other than English at home is growing, and this study contributes valuable new information to the field. “It’s encouraging to see that dual-language learners are making strides that form the critical foundation for later learning,” according to Ms. Kennel.

Ms.Yazejian encourages the thinking that more than one year of high quality early care and education brings greater benefits for children. “The differences we found in this study, extrapolated to thousands of children–especially dual-language learners–could add up to lasting effects and lower public education costs.”

The Balancing Act Homework and Extracurricular Lives in School-Aged Children

February 26, 2015NeuropedagogyAcademic Achievement, children, Extra-Curricular Activities, Harris Cooper, Harris Poll, Homework, National Educational Association, Parents, Research, Stanford Graduate School of Education, Student life, United States Department of Education, University of MichiganESNP Educational Consulting Services

For every generation of parents who have school age children, there is a theme that binds parents from the past to present: either there is too much homework, or too many extracurricular activities. Modern life has sped up the pace incredibly, especially in metropolitan cities around the world, making the demands after the school day on the family become even more stressful.

And it isn’t actually an unusual complaint or observation from a parent. The perception that homework has increased in recent years is supported by the results of a research study from the University of Michigan in 2000. The Institute for Social Research at the University of Michigan found that time spent on home study by 6- to 8-year-old children more than doubled between 1981 and 1997 (Hofferth & Sandberg, 2000). Their results found a 146% increase between 1981 and 1997 in the time that six- to eight-year-old children (generally in grades K-3) spent on home study. In 1981, time diaries that were used to record homework times indicated that primary-grade children spent an average of 52 minutes studying per week; this figure increased to 128 minutes per week in 1997 (Hofferth & Sandberg, 2000). The proportional increase seemed very large because the baseline measurement—time spent on study in 1981—was very small. Moreover, the ISR study found no substantial increase in home study time over the same period for nine to twelve-year-old children (generally third to sixth graders). Their average weekly home study time was 3:22 in 1981 and 3:41 in 1997— a difference that was not large enough to achieve statistical significance.(Hofferth & Sandberg, 2000)

In 2003, The Journal of Educational Evaluation and Policy Analysis published a study by Brian P. Gill and Steven L. Schlossman entitled, “A Nation at Rest: The American Way of Homework.” The researchers found that the great majority of American children at all grade levels then spent less than one hour studying on a typical day—an amount that has not changed substantially in at least 20 years. High school students in the late 1940s and early 1950s studied no more than their counterparts did in the 1970s, 1980s, and 1990s.

Gill and Schlossman have also concluded that changes in educational opinion on homework over the last half century prior to 2003 have had little effect on student behavior, with only two notable exceptions: a temporary increase in homework time in the decade following Sputnik, and a new willingness in the two decades before the 2000’s to assign small amounts to primary-grade students. Does this signify then that homework is dictated by current events and/or standings of students when ranked side by side their peers from other countries?

As a standard, homework recommendations from the National Education Association conclude that, “The National PTA recommendations fall in line with general guidelines suggested by researcher Harris Cooper: 10-20 minutes per night in the first grade, and an additional 10 minutes per grade level thereafter (e.g., 20 minutes for second grade, 120 minutes for twelfth). High school students may sometimes do more, depending on what classes they take.”

They also cite that homework usually falls into one of three categories: practice, preparation, or extension; the purpose usually varies by grade. Individualized assignments that tap into students’ existing skills or interests can be motivating. At the elementary school level, homework can help students develop study skills and habits and can keep families informed about their child’s learning. At the secondary school level, student homework is associated with greater academic achievement. (Review of Educational Research, 2006).

The Review of Educational Research published a comprehensive survey of all the studies on homework and achievement performed between 1987 and 2003. A strong connection was found between the two particularly in high school. In elementary grades, homework helps youngsters establish healthy study habits and keeps parents connected to what their children are doing at school. Homework in high school also lead to higher scholastic success. However, more recently in 2014, a Stanford researcher found that too much homework can negatively affect kids, especially their lives away from school, where family, friends and activities matter. The researchers used survey data to examine perceptions about homework, student well-being and behavioral engagement in a sample of 4,317 students from 10 high-performing high schools in upper-middle-class California communities. Students in these schools average about 3.1 hours of homework each night.

Denise Pope, a senior lecturer at the Stanford Graduate School of Education co-authored a study published in the Journal of Experimental Education with Mollie Galloway and Jerusha Conner, found that too much homework is associated with:

• Greater stress: 56 percent of the students considered homework a primary source of stress. Forty-three percent viewed tests as a primary stressor, while 33 percent put the pressure to get good grades in that category. Less than 1 percent of the students said homework was not a stressor.

• Reductions in health: In their open-ended answers, many students said their homework load led to sleep deprivation and other health problems.

• Less time for friends, family and extracurricular pursuits: Both the survey data and student responses indicated that spending too much time on homework meant that students were “not meeting their developmental needs or cultivating other critical life skills,” according to the researchers. Students were more likely to drop activities, not see friends or family, and not pursue hobbies they enjoy.

In places where students attend high-performing schools, too much homework can reduce their time to foster skills in the area of personal responsibility, the researchers concluded. “Young people are spending more time alone,” they wrote, “which means less time for family and fewer opportunities to engage in their communities.”

On the flipside, there are students who value time to engage in their interests and communities via extracurricular activities on top of homework. Participation in activities such as sports, clubs, private lessons, and religious activities enrich students’ lives by supporting social skills. Several studies emphasize the benefits of extracurricular activities and homework, while others focus on the negative consequences of each. Overscheduled children may not have as much time to complete homework assignments, leading to a decline in academic achievement. According to the critics too much involvement in extracurricular activities takes away from time that could be spent studying or completing homework. On the other hand there were many students who also felt forced or obligated to choose homework over developing other talents or skills.

A bit of history on the extracurricular path into student lives. Extracurricular activities began in the United States in the 19th century. At first they were just an additional part to the normal academic schedule for the year and usually had some practical or vocational interest that was included into the activities. The first extracurricular activities that were well known in schools started at Harvard and Yale University. They were literacy clubs that consisted of different debate clubs and Greek systems such as fraternities and sororities.

Students in American schools were the first to initiate athletic clubs which soon became popular while literacy clubs began to decline. Around the time of World War I, schools started adding clubs such as journalism, and newspaper. (Casinger, J. 2011) Now these clubs have become popular and many public high schools and grade schools have clubs for all interests. In the year 2010, about 1 in 4 students participated in academic clubs. (Miller, Zittleman, 2010).

To determine the relationship between extracurricular involvement and homework performance, a research study was conducted by Rachel Johnson and Ryana Moulden entitled, “A Correlational Study of Extracurricular Involvement and Homework Performance of Third Grade Students.” Data was collected in two third grade classes for the four-week study in two elementary schools. For the first two weeks, math homework scores were recorded, and the second two weeks, language arts homework scores were recorded. No significant correlation was found between the number of hours spent in extracurricular activities and math homework performance, however the results revealed a significant negative relationship between the number of hours spent in extracurricular activities and language arts homework performance.

In his article, “Extracurricular Activities,” Fred C. Lunenburg states, “Extracurricular activities serve the same goals and functions as the required and elective courses in the curriculum. However, they provide experiences that are not included in formal courses of study. They allow students to apply the knowledge that they have learned in other classes and acquire concepts of democratic life.”(2010) The positive effects that extracurricular activities have on students’ education are behavior, better grades, school completion, positive aspects to become successful adults, and a social aspect. Higher grades and positive attitudes towards school are secondary effects that extracurricular activities have on students. Self esteem can be a predictor of academic performance. Students who don’t like school won’t do as well as the students who do like school because they are not motivated to succeed. The students who don’t like school usually feel as though they are not succeeding or that they can succeed.

A study done by the United States Department of Education revealed that, “Students who participate in extracurricular activities are three times more likely to have a grade point average of a 3.0 or higher. This is higher than students who did not participate in extracurricular activities. This is regardless of their previous background or achievement.” Students that participate in extracurricular activities also showed positive changes in students self confidence, teacher perception, and greater confidence, and then developed positive school related adult attachments. Extracurricular activities increases a students connection to school, raises their self esteem, and positive social natures.

These are some of the results of The Harris Poll of 2,241 adults (of whom 457 have school-aged children) surveyed online between June 11 and 17, 2014. With parents of K-12 students reporting their children spend an average of 38.4 hours per week on scheduled activities during the school year (including school time, extra-curricular school activities and other scheduled commitments), while maintaining an average of 19.1 hours of free time, this finds America’s school-aged children with a roughly 2:1 ratio of scheduled to free/leisure time. Perhaps not surprisingly, parents whose children have 15 or more hours per week of combined extracurricular and other “scheduled” time are much more likely than those whose children have under 15 hours to report feeling pressured to put their child in activities that other children are doing (21% <15 hours, 36% 15+ hours). They are then also more likely to worry their child is “over-programmed” (18% and 35%, respectively).

At the end of the day, it is a balance between time and aptitude between homework and extracurricular activities, as both are a part of character and brain development for students. In the Harris Poll where some adults see a crowded calendar, others see the opportunity for new experiences, and nearly two-thirds of Americans (65%) wish they had the opportunity to have as many varied experiences as children do today. This sentiment is significantly stronger among those with school-aged children (73%) than among those without (62%).

Brain Molecular Protein Connections in Neurodevelopmental Disorders: The Research

January 18, 2015Brain BitsAarhus University, ADHD, Autism, Autism Centre, Brain, corpus callosum, Epilepsy, Genetics, Genome, Language Impairment, Mayo Clinic, Minerals, Molecular Protein Connections, Neurodevelopmental Disorders, Phenome, Research, Stanford University, UCSF, VItaminsESNP Educational Consulting Services

It is not news to us in the field that researchers looking to determine causation of Neurodevelopmental Disorders have zeroed in on Molecular Proteins in the brains. To be specific, these disorders (namely Epilepsy, Intellectual Disability, Autism Spectrum Disorder, and Attention Deficit Hyperactivity Disorder) are being hailed as brain-based disorders due to the surging evidence in the last 2 years that indeed, some molecular proteins are atypical in both brain origin and development.

Let’s begin the survey in August 2013 where genetic studies were initiated in large scale. An international study on the genes involved in Epilepsy Disorder had uncovered 25 new mutations on 9 key genes behind a devastating form of epilepsy disorder during childhood. Among those were two genes never before associated with this form of epilepsy. One of these genes previously had been linked to autism and a rare neurological disorder, for which an effective therapy had previously been developed. With the findings of this research, the direction for developing genome-wide diagnostic screens for newborns to identify who is at risk for epilepsy improves potentially development of precise therapies for the condition.

“The limitations of what we currently can do for epilepsy patients are completely overwhelming,” said Daniel Lowenstein, MD, a UCSF neuroscientist and epilepsy expert. Along with Ruben Kuzniecky, MD from New York University, the pair was overseeing the Epilepsy Phenome/Genome Project (EPGP). “More than a third of our patients are not treatable with any medication, so the idea of finding specific drug targets, instead of a drug that just bathes the brain and may cause problems with normal brain function, is very appealing.”

“We knew there was something happening that was unique to these kids, but we had no idea what that was,” said Elliott Sherr, MD, PhD. He a pediatric neurologist at UCSF Benioff Children’s Hospital, and is the principal investigator of the Epi4K Epileptic Encephalopathy (EE) project. He was responsible for the development of this group of the target research patients within EPGP.

The team identified in in their research children with two classic forms of EE – infantile spasms and Lennox-Gastaut Syndrome – in which no other family member was affected. They excluded children who had identifiable causes of epilepsy, such as strokes at birth, which are a known risk for this group of disorders. Of the 4,000 patients whose genomes are being analyzed in the Epi4K, 264 children fit that description. The Epi4K sequencing team, led by David Goldstein, PhD from Duke University ran a genetic scan on the children and their parents. They compared their scans to thousands of people of similar heritage without epilepsy, used a cutting-edge new technique called exome sequencing. This method focuses on the exome, which is the 2 percent of our genetic code that represents active, protein-making genes. Those 25,000 genes are considered to be the code for what makes us unique, and is also responsible for disease mutations.

The genetic analysis revealed 439 new mutations in the children, with 181 of the children having at least one. Nine of the genes that hosted those mutations appeared in at least two children with EE and five of those had shown up in previous, smaller EE studies. Of the four other genes included, two may have been coincidental, the researchers found. But two new genes never before associated with EE – known scientifically as GABRB3 and ALG13 – each appeared with less than a one-in-40-billion statistical chance (p = 4.1×10-10) of being connected to EE by coincidence.

The findings implicated GABRB3, for the first time, as a single-gene cause of EE, and offered the strongest evidence to date for the gene’s role in any form of epilepsy, Sherr said. Knowing this about GABRB3, which is also involved with Angelman’s Syndrome, also offers the possibility that children with mutations only in this gene might benefit from the existing therapy for Angelman’s.

Another new gene, ALG13, is key to putting sugars on proteins, which points to a new way of thinking about the causes of and treatment for epilepsy.

‘The take-home is that a lot of these kids have genetic changes that are unique to them,” Sherr said. “Most of these genes have been implicated in these or other epilepsies – others were genes that have never been seen before – but many of the kids have one of these smoking guns.”

From GABRB3 and ALG13 genes in Epilepsy to misfiring neurons in the ADHD brain, the evidence continues to mount on how one size results do not fit all. In June 2104, Neuroscientists collaborating from the Mayo Clinic in Florida and rom Aarhus University in Denmark have shed light on why neurons in the brain’s reward system can be miswired, potentially contributing to disorders such as attention deficit hyperactivity disorder (ADHD).

In their study, scientists looked at dopaminergic neurons, which regulate pleasure, motivation, reward, and cognition, and have been implicated in development of ADHD. Together they unveiled a receptor system that is critical for correct wiring of the dopaminergic brain area during embryonic development. However they also discovered that after brain maturation, a cut in the same receptor, SorCS2, produces a two-chain receptor that induces cell death following damage to the peripheral nervous system.

It is the SorCS2 receptor that functions as a molecular switch between apparently opposing effects in proBDNF. ProBDNF is a neuronal growth factor that helps select cells that are most beneficial to the nervous system, while eliminating those that are less favorable in order to create a finely tuned neuronal network. The reserchers also found that some cells in mice deficient in SorCS2 are unresponsive to proBDNF and have dysfunctional contacts between dopaminergic neurons.

“This miswiring of dopaminergic neurons in mice results in hyperactivity and attention deficits. A number of studies have reported that ADHD patients commonly exhibit miswiring in this brain area, accompanied by altered dopaminergic function. We may now have an explanation as to why ADHD risk genes have been linked to regulation of neuronal growth,” says the study’s senior investigator, Anders Nykjaer, M.D., Ph.D., a neuroscientist at Mayo Clinic in Florida and at Aarhus University in Denmark.

On the other hand, a study published by Cell Press in the October 2014 issue of The American Journal of Human Genetics shows that Neurodevelopmental Disorders caused by distinct genetic mutations produce similar molecular effects in cells. This suggests a unique perspective in that a one-size-fits-all therapeutic approach could be effective for conditions, ranging from seizures to attention-deficit hyperactivity disorder.

“Neurodevelopmental disorders are rare, meaning trying to treat them is not efficient,” says senior study author Carl Ernst of McGill University. “Once we fully define the major common pathways involved, targeting these pathways for treatment becomes a viable option that can affect the largest number of people.”

Ernst and his team used human fetal brain cells to study the molecular effects of reducing the activity of genes that are mutated in two distinct autism-spectrum disorders. Changes in transcription factor 4 (TCF4) cause 18q21 deletion syndrome, which is characterized by intellectual disability and psychiatric problems. Mutations in euchromatic histone methyltransferase 1 (EHMT1) cause similar symptoms in a condition known as 9q34 deletion syndrome. “Our study suggests that one fundamental cause of disease is that neural stem cells choose to become full brain cells too early. This could affect how they incorporate into cellular networks, for example, leading to the clinical symptoms that we see in kids with these diseases,” Ernst says.

So far, we have learned about breakthroughs in genetic studies in Epilepsy, discoveries of misfiring of neurons in ADHD and in long lasting effects of mutations of certain brain cells leading to Intellectual Disability or psychiatric problems. Now let’s take a closer look at Austism Spectrum Disorder. Would we find some molecular or genetic aberration? Stanford University researchers in December 2014 mapped an entire molecular network of crucial protein interactions that contribute to autism.

While “much work remains to be done,” Dr. Charles Auffray of Université de Lyon who collaborated with the researchers, states this is “a bold attempt to leverage a number of rich sources of data and knowledge and to complement them with relevant additional measurements to unravel the molecular networks of ASD.”

Though further research is needed to fully understand autism’s origins, this study “contributes to the development of an openly shared methodological framework and tools for data analysis and integration that can be used to explore the complexity underlying many other rare or common diseases,” Auffray said.

In this current study of autism, the scientists did not just look at genes, they also looked at gene expression — the protein interactions — in patients with autism. After they had identified a “protein interaction module,” the researchers sequenced the genomes of 25 patients to confirm its involvement in autism. They then validated these findings with data from 500 additional patients. In the next step, the team examined gene expression within the module, partly by using the Allen Human Brain Atlas.

It was in this stage that the researchers discovered the brain’s corpus callosum and oligodendrocyte cells made important contributions to ASD. Developmentally, the oligodendrocyte cells help form myelin, the insulating sheath of brain cells necessary for high velocity nerve conduction. And for patients with autism, for instance, these cells exhibited extensive gene mis‐expression in the corpus callosum, the bundle of nerve fibers connecting left and right brain hemispheres.

The findings from the Stanford University study were not only supported in 2014 by the Heidelberg University but also given more specificity in the mutations not only for those with ASD, but for neurodevelopmental disorders in general. These German Researchers posited that generally, these disorders are multi-faceted and can lead to intellectual disability, autism spectrum disorder and language impairment. Mutations in the Forkhead box FOXP1 gene have been linked to all these disorders, suggesting that it may play a central role in various cognitive and social processes.

Dysfunction of motor, social, sensory and cognitive aspects play a major role in autism spectrum disorder (ASD) and intellectual disability (ID). A high comorbidity is often observed between these disorders, suggesting that mutations in critical genes can cause a spectrum of neuropsychiatric phenotypes. The Forkhead box transcription factor FOXP1, for example, has been linked to various cognitive disorders. FOXP1-specific deletions, mutations and chromosomal breakpoints interrupting the gene have been reported in patients with Intellectual Disability, Autism Spectrum Disorder, speech and language deficits, and motor development delay.

They were interested to examine the behavioral phenotype of our Foxp1 KO mice, as FOXP1 mutations are associated with various behavioral deficits in humans, including social unattainability, hyperactivity, altered learning and memory, and specific obsessions.Results showed: Foxp1 KO mice have a reduced ability for short-term recognition memory and memory for spatial contexts, which have been described before in ASD patients and in mouse models of ASD. The effect on spatial memory may be explained by the CA1 hippocampal deficits we observed in Foxp1 KO as the hippocampus is important for spatial memory. The disruption of the striatal region in Foxp1 KO mice may also contribute to the deficits in learning and memory. It has been shown that striatal lesions and infusion of the striatum with a dopaminergic antagonist results in impaired performance in spatial learning tests, while object recognition is impaired by administration of glutamate antagonists to the striatum. Interestingly, the striatum has previously been associated with the pathology of ASD in both mice and humans.

Foxp1 KO mice also displayed a higher occurrence of repetitive behaviours, in accordance with previous findings in mouse models of autism. Repetitive motor behavior is associated with abnormal activation of dopaminergic cortical-basal ganglia circuitry and therefore might partially be explained by the morphological disruption we observed in the striatal region.

They also recorded a striking reduction of social interest in Foxp1 KO mice. Difficulties communicating and interacting with other people is a key feature of human ASD, and reduced social interaction as well as hyperactivity has been reported in mouse models of ASD before. A strong PPI deficit was observed in Foxp1 KO mice, indicating impaired abilities for sensorimotor integration. Reduced PPI has been previously reported in ASD patients. This effect on PPI in Foxp1 KO mice may be partly explained by the reduction in the striatal region as a cortico-limbic-striatopallidal circuit is involved in the circuit regulating PPI.

Excitatory and inhibitory imbalance is a hallmark brain feature of Autism Spectrum Disorder. Several studies have reported that ASD-related mutations selectively impact glutamatergic or GABAergic synapses without affecting the other, leading to an imbalance of excitatory and inhibitory inputs. WIth their research, they have ultimately shown that the amplitude of miniature excitatory postsynaptic currents but not miniature inhibitory postsynaptic currents is larger in Foxp1 KO CA1 hippocampal neurons. This suggests that Foxp1 KO neurons receive a disproportionate magnitude of excitatory to inhibitory input. In addition, excitability of CA1 pyramidal cells was reduced in Foxp1 KO mice.

With all this information, it is possible to hypothesize that treatment protocol will also change to a more direct, molecular level based on the genetic misfiring or aberration. In the next post, we will discuss the current therapeutic interventions available for these disorders.