Air Pollution Exposure in Early Life Linked to Hyperactivity

Early-life exposure to traffic-related air pollution was significantly associated with higher hyperactivity scores at age 7, according to new research from the University of Cincinnati (UC) and Cincinnati Children’s Hospital Medical Center.

The research is detailed in a study being published Tuesday, May 21, in Environmental Health Perspectives, a peer-reviewed open access journal published by the National Institute of Environmental Health Sciences (NIEHS), an institute within the National Institutes of Health (NIH). 

The research was conducted by faculty members from the UC College of Medicine’s Department of Environmental Health in collaboration with Cincinnati Children’s. Nicholas Newman, DO, director of the Pediatric Environmental Health and Lead Clinic at Cincinnati Children’s and an assistant professor of pediatrics at UC, was the study’s first author.

"There is increasing concern about the potential effects of traffic-related air pollution on the developing brain,” Newman says. "This impact is not fully understood due to limited epidemiological studies.

"To our knowledge, this is the largest prospective cohort with the longest follow-up investigating early life exposure to traffic-related air pollution and neurobehavioral outcomes at school age.” Scientists believe that early life exposures to a variety of toxic substances are important in the development of problems later in life.

Newman and his colleagues collected data on traffic-related air pollution (TRAP) from the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), a long-term epidemiological study examining the effects of traffic particulates on childhood respiratory health and allergy development.  Funded by the National Institute of Environmental Health Sciences, CCAAPS is led by Grace LeMasters, PhD, of the environmental health department. Study participants—newborns in the Cincinnati metropolitan area from 2001 through 2003—were chosen based on family history and their residence being either near or far from a major highway or bus route.

Children were followed from infancy to age 7, when parents completed the Behavioral Assessment System for Children, 2nd Edition (BASC-2), assessing attention deficit hyperactivity disorder (ADHD) and related symptoms including attention problems, aggression, conduct problems and atypical behavior. Of the 762 children initially enrolled in the study, 576 were included in the final analysis at 7 years of age.  

Results showed that children who were exposed to the highest third amount of TRAP during the first year of life were more likely to have hyperactivity scores in the "at risk” range when they were 7 years old. The "at risk” range for hyperactivity in children means that they need to be monitored carefully because they are at risk for developing clinically important symptoms.

"Several biological mechanisms could explain the association between hyperactive behaviors and traffic-related air pollution,” Newman says, including narrowed blood vessels in the body and toxicity in the brain’s frontal cortex.

Newman notes that the higher air pollution exposure was associated with a significant increase in hyperactivity only among those children whose mothers had greater than a high school education. Mothers with higher education may expect higher achievement, he says, affecting the parental report of behavioral concerns.

"The observed association between traffic-related air pollution and hyperactivity may have far-reaching implications for public health,” Newman says, noting that studies have shown that approximately 11 percent of the U.S. population lives within 100 meters of a four-lane highway and that 40 percent of children attend school within 400 meters of a major highway.

"Traffic-related air pollution is one of many factors associated with changes in neurodevelopment, but it is one that is potentially preventable.”  

LeMasters, Patrick Ryan, PhD, Linda Levin, PhD, David Bernstein, MD, Gurjit Khurana Hershey, MD, PhD,  James Lockey, PhD, Manuel Villareal, MD, Tiina Reponen, PhD, Sergey Grinshpun, PhD, Heidi Sucharew, PhD, and Kim Dietrich, PhD, were co-authors of the study.

A New Precise Method of Performing Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is the most effective acute treatment for severe major depression. However, even with newer forms of ECT, there remains a significant risk of adverse cognitive effects, particularly memory problems.

Current theories hold that the regions that need to be stimulated to treat the depression (the cortex) are different and separate from the regions that result in memory problems (the hippocampus and temporal lobes). Theoretically, a more precise form of ECT could have all of the efficacy and few or none of the adverse cognitive side effects.

A new study published in Brain Stimulation now reports the initial clinical results of a novel form of precise ECT called FEAST (Focal Electrically Applied Seizure Therapy). This clinical trial in 17 depressed adults builds on earlier design work and animal testing done at Columbia University in NY. This new form of ECT uses pulsed direct current stimulation, with the bulk of the electrical charge being delivered directly under one electrode placed on the right orbital cortex, about 1 inch above the right eye. Traditional ECT uses alternating current, which flows in both directions and is thus harder to direct and target.

”We found, in this feasibility study, that FEAST produced clinically meaningful antidepressant improvements,” said Dr. Ziad Nahas, first author of the research conducted jointly at the Medical University of South Carolina and Columbia University (NY). Dr. Nahas is now Department Chair at the America University in Beirut, Lebanon. “Importantly, the time it took for patients to be fully reoriented after the treatment was just 5 minutes from when they first opened their eyes. This orientation time traditionally corresponds to the cognitive side effects. This is much quicker than any other form of ECT, where the orientation time is much greater, sometimes up to or exceeding an hour.”

Overall, the group had their depression symptoms almost reduced by half, after an average of 10 sessions over 4 weeks. Eight individual patients had at least a 50% reduction in their symptoms, and 5 remitted, meaning they were largely symptom free.

This was the first human use of FEAST, and the group is continuing to refine the method and test how it works using advanced brain imaging and electroencephalography (EEG).

Dr. Harold Sackeim, Professor of Psychiatry and Radiology at Columbia University and the early developer of the FEAST technique, commented, “These initial encouraging results suggest that one can perfect and refine ECT with a more focal delivery system like FEAST. These are exciting confirmatory data in depressed patients building on what we found in earlier work.”

“Further work is needed to see if we can improve the titration schedule, refine the dose, and make this into another, better, method of performing ECT,” said Nahas.

Heavier Babies at Greater Risk of Autism

It is the first time that a clear link has been made between babies who grow to above average size at birth and risk of Autism Spectrum Disorder and follows from a study of more than 40,000 child health records in Sweden.

The research, led by The University of Manchester, also confirms earlier research which reported that premature and poorly grown, low weight babies appear more susceptible to the condition.

Autism affects how individuals interact with the world and with other people and there is no known cure. One child in 100 has the condition in the UK according to NHS figures. Researchers believe it has origins in both genetic and environmental causes.

Professor Kathryn Abel, from the University’s Centre for Women’s Mental Health and Institute of Brain, Behaviour and Mental Health, led the research published in The American Journal of Psychiatry this month.

Professor Abel said: “The processes that leads to ASD probably begin during fetal life; signs of the disorder can occur as early as three years of age. Fetal growth is influenced by genetic and non-genetic factors. A detailed understanding of how fetal growth is controlled and the ways in which it is associated with ASD are therefore important if we are to advance the search for cures.

“To our knowledge, this is the first large prospective population-based study to describe the association between the degree of deviance in fetal growth from the normal average in a population of children and risk of ASD with and without intellectual disability. We have shown for the first time categorically that abnormal fetal growth in both directions increases risk of autism spectrum disorder.”

Researchers looked at data from the Stockholm Youth Cohort in Sweden, where early ultrasound dating provides detailed weights of the baby’s progression in pregnancy. Infants and children then also take part in structured clinical assessments of their social, motor, language and cognitive abilities.

The cohort contained records of 589,114 children aged 0-17 in Sweden between 2001 and 2007. Certain child data was removed, including children too young to have a diagnosis for ASD, adopted children and non Swedish or Stockholm County residents, children not born in Sweden and twins.

From the remaining available data, researchers found 4,283 young people with autism and 36,588 who did not have the condition and who acted as the control.

The study found that bigger babies who were born weighing over 4.5kg (or 9lb 14) showed a higher incidence of autism, as did smaller infants who were born weighing less than 2.5kg (5.5lb). A baby who had poor fetal growth would therefore have a 63% greater risk of developing autism compared to normally grown babies. A baby who was large at birth would have a 60% greater risk. This effect was independent of whether or not the baby was born pre or post term.

Professor Abel added: “We think that this increase in risk associated with extreme abnormal growth of the fetus shows that something is going wrong during development, possibly with the function of the placenta.

“Anything which encourages abnormalities of development and growth is likely to also affect development of the baby’s brain. Risk appeared particularly high in those babies where they were growing poorly and continued in utero until after 40 weeks. This may be because these infants were exposed the longest to unhealthy conditions within the mother’s womb.

“We now need more research into fetal growth, how it is controlled by the placenta and how this affects how the brain develops. One of the key areas to research is maternal condition and healthy growth.”

The study was also unique as it was big enough to be able to look at the differences between children who developed ASD with and those without intellectual disability as well as differences between children born pre and post-term (after 40 weeks).

Anxiety from a Neurogenesis perspective

Although an influence of adult neurogenesis in mediating some of the effects of antidepressants has received considerable attention in recent years, much less is known about how alterations in this form of plasticity may contribute to psychiatric disorders such as anxiety and depression.

One way to begin to address this question is to link the functions of adult-born hippocampal neurons with specific endophenotypes of these disorders.

Recent studies have implicated adult-born hippocampal neurons in pattern separation, a process by which similar experiences or events are transformed into discrete, non-overlapping representations.

Here we propose that impaired pattern separation underlies the overgeneralization often seen in anxiety disorders, specifically post-traumatic stress disorder and panic disorder, and therefore represents an endophenotype for these disorders.

The development of new, pro-neurogenic compounds may therefore have therapeutic potential for patients who display pattern separation deficits.