FASD: Prenatal alcohol exposure alters development of brain function

fMRI scan of working memory activation in typically-developing children. 

Credit: The Saban Research Institute

In the first study of its kind, Prapti Gautam, PhD, and colleagues from The Saban Research Institute of Children's Hospital Los Angeles found that children with fetal alcohol spectrum disorders (FASD) showed weaker brain activation during specific cognitive tasks than their unaffected counterparts.

These novel findings suggest a possible neural mechanism for the persistent attention problems seen in individuals with FASD.

The results of this study will be published in Cerebral Cortex on August 4.

"Functional magnetic resonance imaging (fMRI) has been used to observe brain activity during mental tasks in children with FASD, but we are the first to utilize these techniques to look at brain activation over time," says Gautam.

"We wanted to see if the differences in brain activation between children with FASD and their healthy peers were static, or if they changed as children got older."

FASD encompasses the broad spectrum of symptoms that are linked to in utero alcohol exposure, including cognitive impairment, deficits in intelligence and attention and central nervous system abnormalities.

These symptoms can lead to attention problems and higher societal and economic burdens common in individuals with FASD.

During the period of childhood and adolescence, brain function, working memory and attention performance all rapidly improve, suggesting that this is a crucial time for developing brain networks.

To study how prenatal alcohol exposure may alter this development, researchers observed a group of unaffected children and a group of children with FASD over two years.

They used fMRI to observe brain activation through mental tasks such as visuo-spatial attention, how we visually perceive the spatial relationships among objects in our environment, and working memory.

"We found that there were significant differences in development brain activation over time between the two groups, even though they did not differ in task performance," notes Elizabeth Sowell, PhD, director of the Developmental Cognitive Neuroimaging Laboratory at The Saban Research Institute and senior author on the manuscript.

"While the healthy control group showed an increase in signal intensity over time, the children with FASD showed a decrease in brain activation during visuo-spatial attention, especially in the frontal, temporal and parietal brain regions."

These results demonstrate that prenatal alcohol exposure can change how brain signaling develops during childhood and adolescence, long after the damaging effects of alcohol exposure in utero.

The atypical development of brain activation observed in children with FASD could explain the persistent problems in cognitive and behavioral function seen in this population as they mature.

Depression: Patients Body Clocks are Altered at Cell Level

The researchers used gene expression patterns to try to predict the time of death for each person in the study (inner circles), and then compared it with the actual time of death (outer circles). 

The two matched closely in healthy people, as shown by the short lines between the two points in the left diagram. 

But in depressed people, the two were out of sync, as seen with the longer lines at right. 

Credit: Image courtesy of University of Michigan Health System

Every cell in our bodies runs on a 24-hour clock, tuned to the night-day, light-dark cycles that have ruled us since the dawn of humanity.

The brain acts as timekeeper, keeping the cellular clock in sync with the outside world so that it can govern our appetites, sleep, moods and much more.

But new research shows that the clock may be broken in the brains of people with depression -- even at the level of the gene activity inside their brain cells.

It's the first direct evidence of altered circadian rhythms in the brain of people with depression, and shows that they operate out of sync with the usual ingrained daily cycle.

The findings, in the Proceedings of the National Academy of Sciences, come from scientists from the University of Michigan Medical School and other institutions.

The discovery was made by sifting through massive amounts of data gleaned from donated brains of depressed and non-depressed people.

With further research, the findings could lead to more precise diagnosis and treatment for a condition that affects more than 350 million people worldwide.

What's more, the research also reveals a previously unknown daily rhythm to the activity of many genes across many areas of the brain -- expanding the sense of how crucial our master clock is.

In a normal brain, the pattern of gene activity at a given time of the day is so distinctive that the authors could use it to accurately estimate the hour of death of the brain donor, suggesting that studying this "stopped clock" could conceivably be useful in forensics.

By contrast, in severely depressed patients, the circadian clock was so disrupted that a patient's "day" pattern of gene activity could look like a "night" pattern -- and vice versa.

Read more of this article here

Journal Reference:

1. Jun Z. Li, Blynn G. Bunney, Fan Meng, Megan H. Hagenauer, David M. Walsh, Marquis P. Vawter, Simon J. Evans, Prabhakara V. Choudary, Preston Cartagena, Jack D. Barchas, Alan F. Schatzberg, Edward G. Jones, Richard M. Myers, Stanley J. Watson, Jr., Huda Akil, and William E. Bunney. Circadian patterns of gene expression in the human brain and disruption in major depressive disorder. PNAS, 2013 DOI: 10.1073/pnas.1305814110