Research published in the current issue of the journal, Clinical Science, appears to have found a link between obstructive sleep apnoea and non-alcoholic steatohepatitis. Dr Anne-Christine Piguet and colleagues from the University of Bern, Switzerland, kept mice for a week in low-oxygen atmospheres and found that it led to increased levels of fat and inflammation in their livers.

Apnoea means “without breath” and occurs when the muscles in the airways behind the tongue relax in sleep, causing the person to snore and briefly, to stop breathing.

Nonalcoholic steatohepatitis (NASH) is a common, often “silent” liver disease occurring in around 40% of the population. It resembles alcoholic liver disease, but occurs in people who drink little or no alcohol. The major feature in NASH is fat in the liver, along with inflammation and damage. NASH can be severe and can lead to cirrhosis, in which the liver is permanently damaged and scarred and no longer able to work properly.

Obesity predisposes patients to both fatty liver diseases and obstructive sleep apnoea.

To mimic the effects of low oxygen levels caused by the repeated obstruction of the upper airways in sleep apnoea, the researchers kept mice in a low oxygen environment for seven days. After this time they were found to have more fat and inflammation in their livers compared to mice that had been kept in atmospheres with normal levels of oxygen. When the mice were exposed to low oxygen levels, the genes that controlled fat synthesis in the liver seemed to be more active while those that controlled fat breakdown demonstrated reduced activity.

In addition, the mice exposed to low levels of oxygen became less sensitive to insulin. This is the mechanism by which the body regulates blood sugar and is a cause of diabetes. Metabolic disorders such as diabetes and obesity can cause complications in patients with NASH.

Commenting on the finding, Dr Piguet said, “Hypoxia (lack of oxygen) may be the link leading to accumulation of fat in the liver and to the progression of non-alcoholic steatohepatitis. Our findings show that it is important both to screen obese patients for obstructive sleep apnoea to prevent it contributing to fatty liver disease and to treat those patients who already have NASH for hypoxia which may be making their condition worse”.

Many alcoholic beverages contain byproducts of the materials used in the fermenting process. These byproducts are called “congeners,” complex organic molecules with toxic effects including acetone, acetaldehyde, fusel oil, tannins, and furfural. Bourbon has 37 times the amount of congeners that vodka has. A new study has found that while drinking a lot of bourbon can cause a worse hangover than drinking a lot of vodka, impairment in people’s next-day task performance is about the same for both beverages.

Results will be published in the March 2010 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

“While the toxic chemicals called congeners could be poisonous in large amounts, they occur in very small amounts in alcoholic beverages,” explained Damaris J. Rohsenow, professor of community health at the Center for Alcohol and Addiction Studies at Brown University. “There are far more of them in the darker distilled beverages and wines than in the lighter colored ones. While the alcohol alone is enough to make many people feel sick the next day, these toxic natural substances can add to the ill effects as our body reacts to them.”

Rohsenow added that few studies have looked at the effects of high- versus low-congener beverages on next-day hangover or performance, and some of those early studies were not careful to wait until breath alcohol levels (BALs) were close to zero before measuring performance, so results may have included some of alcohol’s direct effects.

“We wanted to investigate next-day effects of bourbon versus vodka while ensuring that BALs were zero or almost zero when we studied performance, and we used a variety of performance measures classified by their relevance to safety,” said Rohsenow. “We wanted to use a new hangover questionnaire that included only the symptoms that had been found to be valid in laboratory studies of hangover. We wanted to find out if bourbon’s effects the next day were due to different effects on sleep, so people’s sleep patterns were recorded while they slept. Finally, we wanted to know if performance impairments the morning after drinking were associated with how hung-over the person felt.”

Researchers recruited and paid 95 (58 women, 37 men) healthy, heavy drinkers to participate in one acclimatization night, followed by two drinking nights. The participants drank bourbon or vodka to an average of 0.11 g% BAL on one night, with a matched placebo on the other night, randomized for type and order. Polysomnography recordings were made overnight; self-report and neurocognitive measures were assessed the next morning.

“First, while alcohol in the beverage did increase how hung-over people reported feeling the next morning compared to drinking a placebo, bourbon made people feel even worse than vodka did,” said Rohsenow. “Second, alcohol in the beverage did make people do worse when they needed to pay attention for a continuous period of time while making rapid accurate choices, but they did no worse after bourbon than after vodka on these tasks. Therefore, while people felt worse, they didn’t perform worse after bourbon than after vodka. However, people were not aware that they were performing worse since they thought their driving ability was not impaired in the morning even though they could not react as well.” She added that other studies have found that professional pilots do worse on aspects of flying that require continuous attention across tasks the morning after drinking to intoxication.

“A third finding was that while alcohol in the beverages made people sleep less well because they woke up more during the night, this was no worse after bourbon than it was after vodka,” Rohsenow said. “This means that bourbon’s greater effects on hangover are not due to it having greater effects on sleep. Fourth, people who reported more hangover symptoms also did worse in their ability to pay attention for a continuous period of time while making rapid accurate choices.”

Regarding this last finding, that people with more hangover symptoms – feelings of headache, nausea, general lousiness, thirst and fatigue – also performed worse when required to pay continuous attention and make choices, Rohsenow said that feeling worse was perhaps distracting them, or that it just hurt more to use the extra energy needed to pay close attention. “A second possibility is that as alcohol was metabolized into other substances in the body before leaving, these substances had a direct effect on the nervous system in addition to increasing hangover so that these were two separate but related after-effects of drinking to intoxication,” she said.

The bottom line, said Rohsenow, is that becoming intoxicated to a .11 g% BAL makes it less safe for a person to engage in behaviors required for safety-sensitive performance the next morning. “Many safety-sensitive occupations require that workers be able to pay close attention to a number of tasks over a period of time, and to respond quickly with the right choices, and drinking to excess was found to impair this performance just after alcohol had left people’s bodies.”

Shift work exposures can accelerate metabolic syndrome (MetS) development among the large population of middle-aged males with elevated alanine aminotransferase (ALT). Elevated serum alanine aminotransferase (e-ALT) is a common abnormality of health examinations in middle-aged working populations. It is unavoidable nowadays that a large number of asymptomatic workers with e-ALT may be asked to do rotating shift work on 24 h production lines. In some previous studies, e-ALT and shift work had been independently assessed for their associations with MetS, which is associated with cardiovascular disease, one of the leading causes of death among working populations.

In terms of workplace health management and job arrangements, a five-year follow-up study assessing the association between rotating shift work (RSW) and MetS development was conducted in Taiwan for male workers. In some previous studies, e-ALT and shift work had been independently assessed for their associations with MetS, which is associated with cardiovascular disease, one of the leading causes of death among working populations.

A research article written by Dr. Yu-Cheng Lin et al from Tao-Yuan General Hospital, Taiwan, which has recently been published in World Journal of Gastroenterology, took both risk factors together into consideration, and demonstrated significant findings. In Lin’s study, after a five-year interval, the workers with baseline e-ALT had significantly unfavorable changes in MetS-component abnormalities, and higher rates of MetS development, vs subjects with normal baseline ALT. Particularly, workers who had both baseline e-ALT and long-term RSW exposures had the highest rate of MetS development among four subgroups divided by e-ALT and RSW. Statistically, e-ALT-plus-RSW workers had a significant risk for MetS development.

Lin et al stated that, MetS development among middle-aged males with e-ALT should be carefully monitored. In terms of job arrangements, long-term shift workers with e-ALT deserve special attention for MetS development. They suggested that all workers with e-ALT should be carefully evaluated and managed for MetS. Particularly, MetS risk assessment must be emphasized for male employees with e-ALT facing long-term rotating shift work exposures.

Public health experts agreed that this is an important area of research, given the amount of shift work performed around the globe, particularly when proponents claim that shift working is ‘beneficial’ to the health and safety of those concerned.

A study in the Dec. 15 issue of the Journal of Clinical Sleep Medicine shows that being overweight or obese increases the risk for developing obstructive sleep apnea (OSA) in adolescents but not in younger children.

Results indicate that the risk of OSA among Caucasian adolescents 12 years of age and older increased 3.5 fold with each standard-deviation increase in body mass index (BMI) z-score, while the risk of OSA did not significantly increase with increasing BMI among younger children. According to the authors, the results suggest that the increase in risk among overweight and obese adolescents may result from developmental changes such as reductions in upper airway tone and changes to anatomic structures.

“These results were a little surprising to us initially, as obesity is generally considered to increase the risk of sleep apnea amongst all children,” said principal investigator Mark Kohler, PhD, research fellow at the Children’s Research Centre at the University of Adelaide in Australia. “Previous results have been inconsistent, however, and appear to be confounded by using mixed ethnic populations and different ages of children.”

Sleep and OSA severity were assessed by overnight polysomnography in 234 Caucasian children between the ages of 2 and 18 years. All children had been referred for evaluation of snoring and possible OSA and were reported by a parent to snore at least one night per week.

Participants were classified into six age groups, and having an average of at least one obstructive apnea or hypopnea per hour of sleep was considered to be indicative of OSA. Established growth charts corrected for age and sex were used to determine BMI z-scores and classify children as overweight (BMI ≥ 85th percentile) or obese (BMI ≥ 95th percentile).

Risk of OSA alone was not found to be greater among adolescents compared with younger children. Age groups also were not statistically different for measures of OSA severity or for percentage of individuals classified as having OSA, which was detected in 38 percent of 2- to 3-year-old children; 38 percent of 6- to 7-year-olds; and 34 percent of adolescents between 12 and 18 years of age. When considering only children demonstrating OSA, there was a clear increase in the proportion of individuals who were overweight and obese with increasing age.

The American Academy of Sleep Medicine reports that the prevalence of OSA in otherwise healthy young children is approximately two percent. OSA occurs when soft tissue in the back of the throat collapses and blocks the airway during sleep. Most children with OSA have a history of snoring that tends to be loud and may include obvious pauses in breathing and gasps for breath. Parents often notice that the child seems to be working hard to breathe during sleep.

According to authors, developmental changes in the association between obesity and OSA may follow a different age trajectory among other ethnicities. African-American children appear to be at higher risk for OSA independent of obesity, and their pubertal development may occur earlier compared with Caucasian children.

The authors also noted that tonsil size may interact with obesity to increase the risk of developing OSA. But obesity among snoring adolescents should be considered grounds for physician referral regardless of tonsil size.

A study in the Dec. 15 issue of the Journal of Clinical Sleep Medicine indicates that significant associations exist between parent-reported insomnia symptoms and medical complaints of gastrointestinal regurgitation and headaches in young school-aged children.

Results of multivariate regression analysis show that parent-reported insomnia was 3.3 times more likely in children with gastrointestinal regurgitation and 2.3 times more likely in children with headaches. Nineteen percent of children met the criteria for insomnia, which was defined as often having trouble falling asleep and/or waking up often in the night. Gastrointestinal regurgitation was reported in 7.5 percent of children with insomnia and two percent of children who did not have sleep disturbances. Headaches were reported in 24.4 percent of children with insomnia and 13.2 percent of children without disturbed sleep.

Lead author Ravi Singareddy, MD, assistant professor in the department of psychiatry at Penn State College of Medicine in Hershey, Pa., said that children who have insomnia symptoms should be screened by their physician for underlying medical conditions.

“The first and most important step in children with medical complaints and sleep disturbances would be an evaluation for underlying medical disorders and providing treatment,” said Singareddy. “If the associated sleep disturbances do not improve despite improvement in medical complaints the disturbances should be further assessed and treated.”

Data from 700 children between the ages of five and 12 years (mean 8.8 years) were collected from the Penn State Children’s Cohort for this cross-sectional study. All children underwent a medical and psychiatric history, physical examination, overnight polysomnography and neuropsychological testing. Comprehensive sleep and development questionnaires were completed by a parent. To assess gastrointestinal regurgitation the parent was asked, “Does food or liquid come back up into your child’s mouth or does your child complain of tasting food or liquid back up in his mouth?”

Children with sleep disturbances had significantly more parent-reported complaints of gastrointestinal symptoms (heartburn, pain/colic and regurgitation), headaches and bedwetting. After controlling for demographic variables; apnea-hypopnea index; learning, psychiatric and behavioral disorders; and socioeconomic and minority status, only gastrointestinal regurgitation and headaches remained significantly associated with insomnia symptoms.

According to the authors, the cross-sectional nature of the study did not allow for the assessment of a cause-and-effect relationship, which could be bidirectional in nature. The insomnia symptoms may have resulted in medical complaints since it is known that the respiratory, cardiovascular and gastrointestinal systems undergo significant physiological changes during sleep. Activation of the stress response system in association with hyperarousal also could have been responsible for both the sleep disturbances and the comorbid medical complaints in these children.

The authors suggest that future studies should explore the possible underlying pathophysiological causes of such comorbidity between insomnia symptoms and medical complaints in children. These studies should explore whether treatment of sleep complaints improves the associated medical complaints and vice versa.

The AASM published “Practice parameters for behavioral treatment of bedtime problems and night wakings in infants and young children” in the journal SLEEP in 2006. About 94 percent of the studies that were reviewed reported that behavioral interventions as a whole produced clinically significant improvements in bedtime resistance and night waking.

In 2003 an AASM task force of sleep experts examined the use of medications to treat insomnia in children. A consensus meeting summary was published in 2005 in the Journal of Clinical Sleep Medicine. The task force emphasized that behavioral treatment approaches to bedtime struggles and night waking in children have a well-documented empirical basis and are the mainstay of treatment, and that pharmacologic approaches should be largely considered adjuncts in the treatment of pediatric insomnia.

The advice of a pediatrician to place infants on their backs to sleep appears to be the single most important motivator in getting parents to follow these recommendations and a key reason that the rate of sudden death syndrome (SIDS) has plummeted since the “Back to Sleep” campaign was launched in 1994, says a UT Southwestern researcher.

Multiple studies have shown that placing infants on their backs to sleep limits the risk of SIDS, the leading cause of death among children in the U.S. under the age of 1.

In a study available online and in the December issue of Archives of Pediatric and Adolescent Medicine, researchers, including Dr. George Lister, chairman of pediatrics at UT Southwestern and an author of the study, identify three reasons a caregiver might or might not follow the recommendation: concerns for an infant’s comfort; fear that the infant might choke while sleeping on his or her back; and whether a physician advised the caregiver to always place an infant on his or her back to sleep.

“We know that placing infants on their backs to sleep is by far the single most effective way to reduce the risk of SIDS, but the number of deaths has leveled off in recent years,” Dr. Lister said. “We wanted to know why in order to develop practical advice that caregivers will follow.

“Our findings suggest that a physician’s counsel makes a substantial difference when a caregiver is determining whether to place an infant to sleep on its tummy, side or back.”

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHHD) first launched the “Back to Sleep” campaign in 1994. Since then, the number of babies who are placed on their backs to sleep has jumped from 25 percent to 70 percent, while the rate of SIDS has plummeted by more than 50 percent. Despite the overall decrease, however, the rate of SIDS among African-American infants continues to be more than twice as high as among white and Hispanic infants.

For the current study, researchers analyzed data obtained from the National Infant Sleep Position Study from 1993 to 2007 to learn which factors influence a caregiver’s decision whether to follow the recommendation. The national phone study, which is conducted annually, involves interviewing caregivers of infants born within the past seven months. More than 1,000 interviews were conducted each year.

The researchers found that while the number of babies placed to sleep on their backs increased substantially between 1993 and 2001, this number has since stabilized. In addition, the study showed that between 2003 and 2007 only about 54 percent of study participants reported that a physician advised them to only put their infants to sleep on their backs.

Dr. Lister said families who adhered to the “Back to Sleep” recommendation were unlikely to express concerns about their baby choking or being uncomfortable sleeping in that position. These families were more likely, though, to report that a physician recommended the practice as the only option.

The study also found that African-American infants are less likely to be placed to sleep on their backs than either Hispanics or whites. “We estimate that there would have been at least 700 fewer deaths of African-American infants over a five-year period if they were placed on their backs to sleep at the same rate as white infants,” Dr. Lister said.

Dr. Lister said the findings indicate that a possible solution to further reducing the rate of SIDS depends on physicians promoting the “Back to Sleep” recommendation as the only option, while also addressing any potential concerns about choking and comfort.

“Physicians need to be proactive by consistently telling parents and caregivers that infants must always be placed on their backs and on a firm mattress to sleep, even for naps,” Dr. Lister said. “They must also continue to remind caregivers to remove extra blankets, pillows and stuffed animals from the crib during sleep time.”

The next step is for researchers to conduct face-to-face interviews with mothers both before and after delivery to gauge their intentions regarding sleep positions and whether those plans are modified after delivery.

Researchers at the University of Chicago have discovered a technique that is able to determine whether a child has obstructive sleep apnea (OSA) or habitual snoring by screening their urine.

“These findings open up the possibility of developing a relatively simple urine test that could detect OSA in snoring children. This would alleviate the need for costly and inconvenient sleep studies in children who snore, only about 20 to 30 percent of whom actually have OSA,” said lead author David Gozal, M.D., professor and chairman of the pediatrics department at the University of Chicago.

The study results are published in the December 15 issue of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

Dr. Gozal and researchers from University of Chicago and the University of Louisville studied 90 children who were referred to the sleep clinic to be evaluated for suspected sleep disordered breathing. They also recruited 30 healthy, non-snoring children from the community to serve as controls. The children all underwent standard overnight polysomnography and were categorized either as having OSA, habitual snoring or no sleep disordered breathing.

The children’s first sample of urine was collected the morning after the sleep study. The researchers used a sophisticated electrophoresis technique to screen hundreds of proteins simultaneously and found that a number of the proteins were differently expressed in children with OSA compared to children with habitual snoring or healthy, non-snoring children.

“It was rather unexpected that the urine would provide us with the ability to identify OSA,” said Dr. Gozal. “However, the field of biomarkers is one that is under marked expansion and this certainly opens the way for possible simple diagnostic screening methods in the future.”

While it is estimated that one to three percent of all children up to the age of nine may suffer from OSA, many more (up to 12 percent) experience habitual snoring. Because OSA can lead to cognitive, behavioral, cardiovascular and metabolic consequences in children, differentiating it from habitual snoring is essential. The initial approach is surgical by removing the enlarged tonsils and adenoids, and some children may end up needing CPAP after their surgery.

“We wish to validate these findings in urine samples from many children from laboratories around the country and to develop a simple color-based test that can be done in the physician office or by the parents,” said Dr. Gozal.

A study in the Dec.1 issue of the journal Sleep shows that short, unpleasant, dreamlike mental activity occurs during sleepwalking and sleep terrors episodes, suggesting that people with these sleep disorders may be acting out dreamlike thoughts.

Results show that 71 percent of participants reported at least one incident of dreamlike mental content associated with an episode of sleepwalking or sleep terrors, and the action in the dreamlike thoughts corresponded with the observed behavior. A total of 106 reports of dreamlike mental activity were collected; the mental content was brief, with 95 percent of the reports involving a single visual scene. These dreamlike thoughts were frequently unpleasant, with 84 percent involving apprehension, fear or terror; 54 percent involving misfortune, in which injury, mishap or adversity occurred through chance or environmental circumstances; and 24 percent involving aggression, with the dreamer always being the victim. Compared with healthy controls, patients with sleepwalking and sleep terrors reported more severe daytime sleepiness and had four times as many arousals from slow-wave sleep.

Principal investigator Isabelle Arnulf, MD, PhD, neurologist and head of the sleep disorders unit at Unité des Pathologies du Sommeil at Hôpital Pitié-Salpêtrière in Paris, France, said that it has been widely believed that dreams do not occur during sleepwalking and sleep terrors events. However, previous studies focused mostly on children rather than adults.

“The results are surprising, as it is commonly reported that sleepwalkers and patients with sleep terrors do not remember dreaming,” said Arnulf. “Adults involved in the study who experienced sleepwalking and sleep terrors were less confused during the episode than children, making it easier to express their dream mentations.”

According to the AASM, sleepwalking and sleep terrors typically occur during arousals from slow-wave sleep and are classified as “parasomnias,” which are undesirable events or experiences that occur during entry into sleep, within sleep or during arousals from sleep. Sleepwalking occurs when a person gets out of bed and walks around with an altered state of consciousness and impaired judgment. An episode of sleep terrors occurs when a person sits up in bed with a look of intense fear, often making a cry or piercing scream.

Forty-three patients with severe, frequent, dangerous or disturbing episodes of sleepwalking or sleep terrors participated in the study and were matched with 25 healthy control subjects. The mean age of patients was 26 years with a range from 11 to 72 years, and 46 percent were male. Five patients suffered exclusively from sleep terrors, eight subjects suffered from sleepwalking only and 30 experienced both sleepwalking and sleep terrors.

Data were gathered retrospectively by interview, so that the dreamlike thoughts that were collected covered a lifetime span for each patient. Thirty-eight patients (88 percent) were able to reliably answer questions about their mental content during the sleepwalking and sleep terrors episodes. Sleep also was monitored during one night in a laboratory.

For a long time rapid eye movement (REM) sleep has been considered to be the neurobiological basis of dreaming, the authors noted. Although complex mental activity has been reported in non-REM sleep during slow-wave sleep, the extent to which the reported dreamlike thoughts may be described as “dreaming” is still debated.

The authors suggested that the brief, dreamlike activity occurring during sleepwalking and sleep terrors could be either the terminal part of a longer dream that is forgotten at the time of arousal, or a short mental creation elicited before or just at the time of arousal.

A study in the Dec.1 issue of the journal Sleep suggests that changes in children’s sleep patterns that typically occur between the ages of 11 and 12 years are evident before the physical changes associated with the onset of puberty.

Results show that over the two-year course of the study, sleep onset was significantly delayed by an average of 50 minutes, and sleep time was significantly reduced by an average of 37 minutes. Girls had higher sleep efficiency and reported fewer night wakings than boys. Initial levels of sleep predicted an increase in pubertal development over time, whereas there was no similar prediction in the opposite direction. According to the authors, this suggests that the neurobehavioral changes associated with puberty may be seen earlier in measures of sleep organization than in bodily changes.

Lead author Avi Sadeh, D.Sc, professor of psychology at Tel Aviv University in Israel, said that biological factors have a significant influence on sleep during puberty; however, psychosocial issues such as school demands, social activities and technological distractions can lead to the development of bad sleep habits. Therefore, parents and educators can play an important role in helping children understand how to prioritize sleep as they grow and mature.

“It is very important for parents to be aware of the importance of sleep to their developing teenager and to maintain their supervision throughout the adolescent years,” said Sadeh. “School health education should also provide children with compelling information on how insufficient sleep compromises their well-being, psychological functioning and school achievements.”

According to the authors, sleep-wake organization undergoes significant reorganization during the transition to adolescence. The main changes include a delayed sleep phase, which involves a tendency for later bedtimes and rise times; shorter sleep, which is associated with increased levels of daytime sleepiness; and irregular sleep patterns, which involve sleeping very little on weekdays and sleeping longer during weekends to partially compensate for this sleep loss. During maturation adolescents also develop greater tolerance to sleep deprivation or extended wakefulness.

Data from 94 children (41 boys and 53 girls) were collected from a larger study on sleep and neurobehavioral functioning during the transition to puberty. Children were recruited from regular classes of five different elementary schools in the Tel Aviv area. At first assessment the age range was about 10 years to 11 years. Each child completed a number of questionnaires, including the Sexual Maturation Scale (SMS) and the Puberty Development Scale (PDS) for pubertal development assessment. All children were healthy with no chronic medical or psychological problems.

Sleep-wake patterns were observed subjectively with a sleep diary and objectively using an actigraph, which the children wore on their wrist. The same assessment was repeated, at a similar time of year, for two successive years. Eighty-two children completed the second assessment, and 72 completed the third assessment.

The authors noted that Israel has a six-day school week, with Friday being the only day that is not followed by school. As expected, significant differences were found between sleep on Friday nights and sleep on school nights. On Fridays, sleep onset was delayed, sleep time was extended and sleep quality was poorer in comparison with school nights. These differences were not associated with puberty status or gender, suggesting that the tendency for weekend compensatory sleep is relatively steady over the period of early adolescence.

According to the authors, a deeper understanding of the interrelationships between sleep and pubertal maturation may provide new insights into the emergence of vulnerabilities for behavioral and emotional health problems in early adolescence, which could improve prevention and early intervention efforts.

It seems obvious that naturally waking up from sleep and being startled by something in the environment are two very different emotional states. However, the neuroscience that underlies these different forms of arousal has, for the most part, remained a mystery. Now, new research published by Cell Press in the November 25 issue of the journal Neuron demonstrates that there are at least two completely separate and independent forms of arousal in fruit flies. The study answers critical questions about how the nervous system processes arousal and may even shed some light on the neurobiology of human affective disorders, such as attention-deficit hyperactivity disorder (ADHD).

A state of arousal can be defined as in increase in activity or sensitivity and is central to many behaviors in all sorts of organisms. It has not been fully established whether arousal is a generalized state that can be heightened by specific stimuli or is more multidimensional. Further, although many studies have implicated key neurochemicals in arousal, the specific roles of these neuromodulators are unclear. “Previous studies with the fruit fly, Drosophila, have provided evidence that dopamine plays a role in arousal from sleep, known as endogenous arousal. However, evidence for a role for dopamine in exogenously generated arousal, that which is stimulated by a factor in the environment, is less consistent,” explains senior study author Dr. David J. Anderson from the California Institute of Technology.

Dr. Anderson and colleagues developed a novel behavioral paradigm for startle-induced arousal in fruit flies and screened for genetic mutations that potentiated this emotion-like behavior. The researchers identified one loss-of-function mutation in a dopamine receptor, DopR, which potentiated the startle response but decreased endogenous arousal. Essentially, the flies slept more but were hypersensitive to being startled. Additional studies supported the finding that these independent and opposite influences of DopR are exerted in different neural circuits. “Taken together, our data suggest that environmentally stimulated arousal and sleep-wake transitions reflect distinct forms of arousal that are genetically, anatomically, and behaviorally separate,” says Dr. Anderson.

Intriguingly, the hyper-reactivity to environmental stimuli seen in the flies with the DopR mutation is similar to some of the symptoms seen in humans with ADHD, which has also been linked to dopamine. The genetic basis of emotional behavior is significant because it is believed that abnormalities in such behaviors may underlie psychiatric disorders. Further, it is important to note that Drosophila shares most of its genes in common with humans and also has many of the same brain chemicals that have been implicated in psychiatric disorders, including dopamine.

“If humans, like flies, have distinct brain circuits mediating environmentally stimulated and endogenous arousal, then it is possible that ADHD may specifically involve dopaminergic dysfunction in circuits mediating the former rather than the latter type of arousal,” suggests Dr. Anderson. “This view of ADHD as a disorder of arousal circuits suggests that further elucidation of such circuits may deepen our understanding of this disorder and potentially lead to more targeted therapies.”