Professor Discovers New Information in the Understanding of Autism and Genetics

Research out of the George Washington University (GW), published in the journal Proceedings of the National Academy of Sciences (PNAS), reveals another piece of the puzzle in a genetic developmental disorder that causes behavioral diseases such as autism. Anthony-Samuel LaMantia, Ph.D., professor of pharmacology and physiology at the GW School of Medicine and Health Sciences (SMHS) and director of the GW Institute for Neuroscience, along with post-doctoral fellow Daniel Meechan, Ph.D. and Thomas Maynard, Ph.D., associate research professor of pharmacology and physiology at GW SMHS, authored the study titled “Cxcr4 regulation of interneuron migration is disrupted in 22q11.2 deletion syndrome.”

For the past nine years, LaMantia and his colleagues have been investigating how behavioral disorders such as autism, attention deficit hyperactivity disorder (ADHD), and schizophrenia arise during early brain development. His work published in PNAS focuses specifically on the effects diminished 22q11.2 gene dosage has on cortical circuit development.

This research shows for the first time that genetic lesions known to be associated with autism and other behavioral diseases disrupt cellular and molecular mechanisms that ensure normal development of a key type of cortical neuron: the interneuron. LaMantia and his colleagues had found previously that one type of cortical neuron, the projection neuron, is not generated in appropriate numbers during development in a mouse model of 22q11 Deletion Syndrome. In the current study published in PNAS, LaMantia found that interneurons, while made in the right numbers at their birthplace outside of the cortex, are not able to move properly into the cortex where they are needed to control cortical circuit activity. The research shows that the main reason they don’t move properly is due to diminished expression of activity of a key regulatory pathway for migration, the Cxcr4 cytokine receptor.

“This gives us two pieces of the puzzle for this genetic developmental disorder,” said LaMantia. “These two pieces tell us that in very early development, those with 22q11.2 deletion syndrome do not make enough cells in one case, and do not put the other cells in the right place. This occurs not because of some degenerative change, but because the mechanisms that make these cells and put them in the right place during the first step of development have gone awry due to mutation.”

The next step in LaMantia’s research is to probe further into the molecular mechanisms that disrupt the proliferation of projection neurons and migration of interneurons. “If we understand that better and understand its consequences, we can go about fixing it,” said LaMantia. “We want to understand why cortical circuits don’t get built properly due to the genetic deletion of chromosome 22.”

LaMantia recently received the latest installment of a 10-year RO1 grant from the National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health & Human Development for his project, titled “Regulation of 22q11 Genes in Embryonic and Adult Forebrain.” This will allow him to further his research.

(Image: iStockphoto)

Mistaking OCD for ADHD Has Serious Consequences

On the surface, obsessive compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD) appear very similar, with impaired attention, memory, or behavioral control. But Prof. Reuven Dar of Tel Aviv University’s School of Psychological Sciences argues that these two neuropsychological disorders have very different roots — and there are enormous consequences if they are mistaken for each other.

Prof. Dar and fellow researcher Dr. Amitai Abramovitch, who completed his PhD under Prof. Dar’s supervision, have determined that despite appearances, OCD and ADHD are far more different than alike. While groups of both OCD and ADHD patients were found to have difficulty controlling their abnormal impulses in a laboratory setting, only the ADHD group had significant problems with these impulses in the real world.

According to Prof. Dar, this shows that while OCD and ADHD may appear similar on a behavioral level, the mechanism behind the two disorders differs greatly. People with ADHD are impulsive risk-takers, rarely reflecting on the consequences of their actions. In contrast, people with OCD are all too concerned with consequences, causing hesitancy, difficulty in decision-making, and the tendency to over-control and over-plan.

Their findings, published in the Journal of Neuropsychology, draw a clear distinction between OCD and ADHD and provide more accurate guidelines for correct diagnosis. Confusing the two threatens successful patient care, warns Prof. Dar, noting that treatment plans for the two disorders can differ dramatically. Ritalin, a psychostimulant commonly prescribed to ADHD patients, can actually exacerbate OCD behaviors, for example. Prescribed to an OCD patient, it will only worsen symptoms.

ADHD medicine affects the brain’s reward system

A group of scientists from the University of Copenhagen has created a model that shows how some types of ADHD medicine influence the brain’s reward system. The model makes it possible to understand the effect of the medicine and perhaps in the longer term to improve the development of medicine and dose determination. The new research results have been published in the Journal of Neurophysiology.

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Smoking and hyperactivity (ADHD) share common genetic risk factor

A variation of a particular gene may link the behaviours typical of childhood attention hyperactivity disorder, or ADHD for short, and those associated with smoking, suggests research published online in the Archives of Disease in Childhood (1, 2)

Childhood ADHD and subsequent smoking in adulthood frequently go hand in hand, say the authors, with people who have been diagnosed with ADHD more likely to start smoking early and to smoke twice as much as those without the condition.

The researchers focused on five variations in DNA sequences (single nucleotide polymorphisms or SNPs) in different genes that are strongly associated with different aspects of smoking behaviour, such as the number of cigarettes smoked every day, and taking up and quitting smoking.

Mayo Clinic Researchers Develop New Tools to Better Treat ADHD Patients in Early Stages

Mayo Clinic researchers are presenting new findings on the early treatment of child and adolescent attention deficit hyperactivity disorder this week at the American Academy of Childhood and Adolescent Psychiatry annual meeting in San Francisco. They include a method to get better input from parents and teachers of children who are being diagnosed with ADHD for the first time — allowing for more effective treatment upon the first consultation. Researchers also showed how a tool can help clinicians better diagnose and treat children who have both ADHD and oppositional defiance disorder.

(Image credit: Psyc3330 w11, Wikimedia Commons)

Study on ADHD, Provide New Insight Into Prevalence and Treatment Needs

Attention Deficit Hyperactivity Disorder is both under and over diagnosed.

That’s the result of one of the largest studies conducted on ADHD in the United States, published in the Journal of Attention Disorders.

A substantial number of children being treated for ADHD may not have the disorder, while many children who do have the symptoms are going untreated, according to the 10-year Project to Learn about ADHD in Youth (PLAY) study funded by the National Center on Birth Defects and Developmental Disabilities of the Centers of Disease Control and Prevention

"Childhood ADHD is a major public health problem. Many studies rely on parent reporting of an ADHD diagnosis, which is a function of both the child’s access to care in order to be diagnosed, and the parent’s perception that there is a problem," said Robert McKeown, of the University of South Carolina’s Arnold School of Public Health, who led the South Carolina portion of the study.

"Further complicating our understanding of the prevalence of ADHD and its treatment is that the diagnosis often is made by a clinician who has little experience assessing and diagnosing mental disorders. As a result, ADHD is both under and over diagnosed," said McKeown, distinguished professor emeritus in the department of epidemiology and biostatistics.

The study, conducted between 2002-2012, was a collaborative research project with the University of South Carolina’s Arnold School and School of Medicine and the University of Oklahoma’s Health Sciences Center.

"To our knowledge, this is the largest community-based epidemiologic study of ADHD to date," McKeown said.

The eyes may be windows into the soul, but following their movement also could allow doctors to make quick, accurate diagnoses for disorders like autism, schizophrenia, or attention deficit hyperactivity disorder, various research projects suggest.

Eye tracking, which records where subjects focus when watching visual displays, could diagnose brain disorders more accurately than subjective questionnaires or medical examinations do, researchers say. Exams are expensive and time-consuming, and subjective tests have been known to wrongly identify healthy people or misdiagnose disorders.

To make sense of all that people see, the brain filters huge amounts of visual information, fills in gaps and focuses on certain objects. That complex task uses many mental circuits, so differences in what people choose to look at ― differences so subtle that only a computer can spot them ― could provide unprecedented insight into common neurological problems.

A mysterious region deep in the human brain could be where we sort through the onslaught of stimuli from the outside world and focus on the information most important to our behavior and survival, Princeton University researchers have found.

The researchers report in the journal Science that an area of our brain called the pulvinar regulates communication between clusters of brain cells as our brain focuses on the people and objects that need our attention. Like a switchboard operator, the pulvinar makes sure that separate areas of the visual cortex — which processes visual information — are communicating about the same external information, explained lead author Yuri Saalmann, an associate research scholar in the Princeton Neuroscience Institute (PNI). Without guidance from the pulvinar, an important observation such as an oncoming bus as one is crossing the street could get lost in a jumble of other stimuli.

Saalmann said these findings on how the brain transmits information could lead to new ways of understanding and treating attention-related disorders, such as attention deficit hyperactivity disorder (ADHD) and schizophrenia.

More Kids Taking Antipsychotics for ADHD: Study

Use of powerful antipsychotic medications such as Abilify and Risperdal to control youngsters with attention-deficit/hyperactivity disorder (ADHD) and other behavior problems has skyrocketed in recent years, a new study finds.

Antipsychotics are approved to treat bipolar disorder, schizophrenia, other serious mental problems and irritability related to autism. But they don’t have U.S. Food and Drug Administration approval for ADHD or other childhood behavior problems, and their use for this purpose is considered “off label.”

"Only a small proportion of antipsychotic treatment of children (6 percent) and adolescents (13 percent) is for FDA-approved clinical indications," said lead researcher Dr. Mark Olfson, a professor of clinical psychiatry at Columbia University Medical Center in New York City.