Vulnerability to Sleep Loss Varies by Individual

Vulnerability to Sleep Loss Varies by Individual
Researchers studying the effects of sleep restriction on brain function have found that some individuals are more vulnerable to sleep deprivation than others, and that the ability to recover from chronic sleep restriction also varies.

Through a series of nine studies, David Dinges, PhD, Professor and Chief of the Division of Sleep and Chronobiology in the Department of Psychiatry at the University of Pennsylvania School of Medicine in Philadelphia, and colleagues sought to identify changes in brain function as a result of chronic sleep deprivation, as well as differences in individuals’ sleep need, vulnerability to sleep restrictions, and ease of recovery after sleep deprivation.

The studies involved more than 500 healthy adults, including men, women, whites, and minorities. The average age of participants was 30 (range, 21 to 50). Each study included 40 to 150 participants, who lived in the laboratory 24 hours a day for two to three weeks.

The researchers found that there were large individual differences among healthy persons in response to chronic sleep restriction. Some people were severely affected and showed a dramatic decline in alertness from continued deprivation. Others were not as severely affected, and a subset showed no cognitive deficits from the sleep restriction.

“Our findings indicate that there are likely people who are resistant to the effects of sleep restriction and those who are very vulnerable,” said Dr. Dinges. “Even though they all obtain the same amount of sleep normally in their lives, and even though they are getting the same restriction in the laboratory, they are having markedly different neurobehavioral responses to the reduction of sleep.”

The researchers found that all subjects who slept seven to eight hours a night functioned normally, but with each day of sleep restriction, differences between the groups started to emerge. As sleep was reduced, cognitive functioning was impaired, with the rate of change determined by membership in one of the three groups. Changes began to occur when participants slept fewer than seven hours each night and became much more dramatic when sleep time was reduced to four hours per night.

Through psychomotor vigilance testing, a test of sustained attention that is used to detect sleepiness, the investigators identified the effects of sleep restriction on each participant. Using this test as a marker, they found that attention was profoundly affected by inadequate sleep. For most people, attention destabilizes early in the sleep restriction and was more affected by restriction than any other cognitive area. However, not everyone showed these effects.

“This is not a simple story, because each person’s sleep needs and response to sleep restriction are unique,” Dr. Dinges said. “The bottom line is that it is important not to restrict your sleep, and that if you do it night after night, most people will begin to see the effects in behavior and brain function. Furthermore, it’s important to oversleep when possible in order to recover from any sleep deficit to the extent possible.”

High-Fat Diet During Pregnancy Causes Brain Inflammation in Offspring
A pregnant mother’s high-fat diet can have profound and lasting effects on the brain of her offspring, according to evidence from an animal study. Researchers believe that high-fat diets activate immune cells in the brain, causing inflammation, a process that may lead to neurodegenerative conditions such as multiple sclerosis and Alzheimer’s disease.

“Obesity is generally thought of as a condition that happens to the body but doesn’t impact the brain,” said Staci Bilbo, PhD, Assistant Professor of Psychology and Neuroscience at Duke University in Durham, North Carolina. “But our research found that changes in the brain of offspring are linked to what a mother eats during pregnancy.”

Previous research has shown a link between obesity and inflammation in the body, but little is known about whether obesity might affect inflammation in the brain or if obesity in a pregnant mother can affect brain functions in her offspring. Dr. Bilbo and her team investigated how immune cells in the brain of a pup respond to or are activated by a high-fat content in its mother’s diet during pregnancy.

“When the brain’s immune system is out of balance, it becomes inflamed,” said Dr. Bilbo. “Inflammation is good in the short term, because it can aid in healing and alert us to tissue damage, but in the long run, constant inflammation can be damaging to neurons and brain function.”

The researchers fed female breeding rats one of three diets—a 60% saturated high-fat diet, a 60% trans high-fat diet, or a 10% low-fat control diet for four weeks prior to mating and throughout pregnancy and lactation. After weaning (day 21), all pups were fed the low-fat diet, so they were never on a high-fat diet themselves.

To examine the pups’ response to the mothers’ diets, brain samples and peripheral tissue (fat, blood, and liver) were collected at one day after birth, at weaning (20 days after birth), and in early adulthood (days 60 to 90). The investigators tested immune system functioning in the liver and in the brain, as well as behavioral measures of anxiety and the ability to learn and remember a maze.

Inflammatory response was tested in the pups after weaning (day 20) and in adulthood (days 60 to 90) by comparing immune response four hours after injections of dead bacteria. This procedure activates the immune system without causing an infection that would have a negative impact on an animal’s health.

The researchers observed clear evidence of brain inflammation in the pups born to mothers on high-fat diets. From birth through adulthood, there was evidence of low-level inflammation in brain samples from high-fat groups, including activation of microglia (immune cells) in the hippocampus of the brain. Inflammation also was present outside the brain as evidenced by increased C-reactive protein in the liver.

Most striking was the difference in response to immune challenge. Adult animals whose mothers had been on high-fat diets had a greatly exaggerated inflammatory response in these same areas, compared with low-fat control animals.

“It was absolutely one of the largest responses we have ever seen,” said Dr. Bilbo. In response to anxiety and cognition tests, adult animals whose mothers were given the high-fat diets were considerably more anxious than adult animals from the low-fat group. However, no negative impact was noted on cognition as a consequence of mothers’ high-fat diets.

“Dietary fats are critical to a healthy pregnancy, so we were unsure if the placenta would serve as a protector from the negative effects of the fats, but it seems this is not the case,” said Dr. Bilbo. “The mothers’ diet during pregnancy determines a lifelong neuroinflammatory condition for the fetus that cannot be reversed with low-fat diet alone.”

Dr. Bilbo emphasized that while these findings are noteworthy, this is the first look at the effects of mothers’ obesity on the fetal brain. More research is needed on the composition of the diet before drawing inferences for humans.

The next step in Dr. Bilbo’s research will be to look at the success of reversing the impact of the mothers’ diet of brain inflammation through interventions that target the fetal immune response.

Eating Disorders Linked With Disrupted Rewards Process in the Brain
New findings on eating disorders, including obesity and anorexia nervosa, demonstrate the influence the brain has on appetite and weight control.

Obesity and anorexia, often considered metabolic in nature, appear to also reflect brain functions involving reward and inhibition. Past studies have shown that individual differences may predispose a person to undereat or overeat. These behaviors are influenced by the pleasure derived from eating and drinking, sensory properties of food and a person’s prior experiences, current internal state, expectations, beliefs, and genes.

Multiple studies examined several of these factors and the brain activity associated with them. They revealed a complex, integrated system in which signals from the body interact with brain circuitry to control eating behavior. Desensitization to these signals may lead to pathologic eating. As in other addictions, the dopamine reward system is critically involved. The similarities hold implications for potential treatment and prevention of obesity, according to Nora D. Volkow, MD, Director of the National Institute on Drug Abuse in Bethesda, Maryland.

“The brain is a complicated, integrated system whose responses are linked to changes in the body, as well as predisposing factors associated with a person’s experiences with food,” said Dr. Volkow. “When the brain senses the need for food, the reward system is activated. But the more a person overeats, the more insensitive to food rewards they may become, potentially causing a need to increase stimuli, which in this case is more food intake.”

Examining the brain’s response to certain foods, Dana M. Small, PhD, of the John B. Pierce Laboratory and Yale University in New Haven, Connecticut, found an inverse relationship between a person’s BMI and the brain’s response to a milkshake. Obese persons experienced much less activation of reward centers as they ate the food. The study determined that the response of the caudate to a milkshake was a better predictor of future weight gain than many traditional measures.

Cary R. Savage, PhD, of the University of Kansas Medical Center in Kansas City, conducted a study of food motivation using fMRI. He and his colleagues found that individuals who were obese differed from healthy-weight participants in the way that the brain responded to anticipated food or monetary rewards and punishments. Obese individuals showed greater brain sensitivity to anticipated rewards and less sensitivity to anticipated negative consequences than did healthy-weight individuals.

Other researchers made presentations on the topic as well. To better understand the brain functions of individuals with anorexia nervosa and bulimia nervosa, Walter H. Kaye, MD, and colleagues at the University of California, San Diego, used fMRI to examine the brain’s response to the taste of sucrose and an artificial sweetener and the brain’s response to pictures of palatable foods, compared with color-matched neutral objects. Their findings suggest that individuals who undereat or overeat have an altered sensitivity when consuming sucrose.

Julie L. Fudge, MD, of the University of Rochester Medical Center, followed the “taste pathway” in humans to better understand how information received by various areas of the brain is involved in eating behaviors. Her findings suggest a way that emotional associations with food can converge with taste and instinctive sensations to influence eating behavior.

Disturbances in appetite and weight regulation affect a significant proportion of the US population, and obesity is considered a national epidemic. One in every three adults and one of six children are obese, a condition that arises from chronic imbalances between energy intake and expenditure.

“The studies in this panel represent a growing body of research linking the brain and the wiring in the brain to overeating and obesity,” Dr. Volkow commented. “We really need to do much more work to better understand integration with processes that regulate food intake and reward processing in the brain. This research opens the doors to a much greater understanding of obesity.”

Omega-3 Supplements Show Promise in Alleviating Depression
A new analysis of the effects of omega-3 essential fatty acids offers the hope of enhanced treatment options for patients with depression. Two critical omega-3 essential fatty acids available from certain food or nutritional supplements but not manufactured by the body—eicosapentaenoic acid (EPA) and docosahexaenoic (DHA)—may play a role in optimal brain functioning and have antidepressant benefits that have not been fully recognized.

In a meta-analysis of 15 randomized, double-blind, placebo-controlled studies, researchers from the University of Illinois at Chicago, led by John M. Davis, MD, found that patients taking omega-3 with either EPA or a combination of EPA and DHA experienced clear antidepressant benefits. However, across studies, patients taking the pure DHA form of omega-3 showed no antidepressant effect.

“Our analysis clarifies the precise type of omega-3 fatty acid that is effective for people with depression and explains why previous findings have been contradictory,” said Dr. Davis. “The EPA predominant formulation is necessary for the therapeutic action to occur. The DHA predominant formulation does not have antidepressant efficacy.”

Although the investigators noted that omega-3 produces beneficial effects in patients with depression, EPA does not improve mood in persons who are not depressed. In several studies, people without depression experienced no difference in mood as a result of omega-3 consumption.

In another study, Dr. Davis and his team found that women with inadequate omega-3 intake were more likely to experience depression during and after pregnancy than were women with adequate omega-3 in their diets.

“The findings are unambiguous,” said Dr. Davis. “Omega-3 fatty acids have antidepressant properties, and this effect is ready to be tested in a large study to establish the dose range and to pave the way for FDA approval. In the meantime, omega-3 fatty acids containing EPA could be useful to augment effects of antidepressant medications.”

However, the researchers cautioned that patients should always talk with their physician before taking omega-3 fatty acids to alleviate symptoms of depression.

Dr. Davis and colleagues are now examining the link between soy intake and depression, and they expect those findings to be published next year. He noted that soy products contain omega-6 fatty acids, which compete with omega-3 fatty acids.

Vulnerability to Sleep Loss Varies by Individual
Researchers studying the effects of sleep restriction on brain function have found that some individuals are more vulnerable to sleep deprivation than others, and that the ability to recover from chronic sleep restriction also varies.

Through a series of nine studies, David Dinges, PhD, Professor and Chief of the Division of Sleep and Chronobiology in the Department of Psychiatry at the University of Pennsylvania School of Medicine in Philadelphia, and colleagues sought to identify changes in brain function as a result of chronic sleep deprivation, as well as differences in individuals’ sleep need, vulnerability to sleep restrictions, and ease of recovery after sleep deprivation.

The studies involved more than 500 healthy adults, including men, women, whites, and minorities. The average age of participants was 30 (range, 21 to 50). Each study included 40 to 150 participants, who lived in the laboratory 24 hours a day for two to three weeks.

The researchers found that there were large individual differences among healthy persons in response to chronic sleep restriction. Some people were severely affected and showed a dramatic decline in alertness from continued deprivation. Others were not as severely affected, and a subset showed no cognitive deficits from the sleep restriction.

“Our findings indicate that there are likely people who are resistant to the effects of sleep restriction and those who are very vulnerable,” said Dr. Dinges. “Even though they all obtain the same amount of sleep normally in their lives, and even though they are getting the same restriction in the laboratory, they are having markedly different neurobehavioral responses to the reduction of sleep.”

The researchers found that all subjects who slept seven to eight hours a night functioned normally, but with each day of sleep restriction, differences between the groups started to emerge. As sleep was reduced, cognitive functioning was impaired, with the rate of change determined by membership in one of the three groups. Changes began to occur when participants slept fewer than seven hours each night and became much more dramatic when sleep time was reduced to four hours per night.

Through psychomotor vigilance testing, a test of sustained attention that is used to detect sleepiness, the investigators identified the effects of sleep restriction on each participant. Using this test as a marker, they found that attention was profoundly affected by inadequate sleep. For most people, attention destabilizes early in the sleep restriction and was more affected by restriction than any other cognitive area. However, not everyone showed these effects.

“This is not a simple story, because each person’s sleep needs and response to sleep restriction are unique,” Dr. Dinges said. “The bottom line is that it is important not to restrict your sleep, and that if you do it night after night, most people will begin to see the effects in behavior and brain function. Furthermore, it’s important to oversleep when possible in order to recover from any sleep deficit to the extent possible.”

High-Fat Diet During Pregnancy Causes Brain Inflammation in Offspring
A pregnant mother’s high-fat diet can have profound and lasting effects on the brain of her offspring, according to evidence from an animal study. Researchers believe that high-fat diets activate immune cells in the brain, causing inflammation, a process that may lead to neurodegenerative conditions such as multiple sclerosis and Alzheimer’s disease.

“Obesity is generally thought of as a condition that happens to the body but doesn’t impact the brain,” said Staci Bilbo, PhD, Assistant Professor of Psychology and Neuroscience at Duke University in Durham, North Carolina. “But our research found that changes in the brain of offspring are linked to what a mother eats during pregnancy.”

Previous research has shown a link between obesity and inflammation in the body, but little is known about whether obesity might affect inflammation in the brain or if obesity in a pregnant mother can affect brain functions in her offspring. Dr. Bilbo and her team investigated how immune cells in the brain of a pup respond to or are activated by a high-fat content in its mother’s diet during pregnancy.

“When the brain’s immune system is out of balance, it becomes inflamed,” said Dr. Bilbo. “Inflammation is good in the short term, because it can aid in healing and alert us to tissue damage, but in the long run, constant inflammation can be damaging to neurons and brain function.”

The researchers fed female breeding rats one of three diets—a 60% saturated high-fat diet, a 60% trans high-fat diet, or a 10% low-fat control diet for four weeks prior to mating and throughout pregnancy and lactation. After weaning (day 21), all pups were fed the low-fat diet, so they were never on a high-fat diet themselves.

To examine the pups’ response to the mothers’ diets, brain samples and peripheral tissue (fat, blood, and liver) were collected at one day after birth, at weaning (20 days after birth), and in early adulthood (days 60 to 90). The investigators tested immune system functioning in the liver and in the brain, as well as behavioral measures of anxiety and the ability to learn and remember a maze.

Inflammatory response was tested in the pups after weaning (day 20) and in adulthood (days 60 to 90) by comparing immune response four hours after injections of dead bacteria. This procedure activates the immune system without causing an infection that would have a negative impact on an animal’s health.

The researchers observed clear evidence of brain inflammation in the pups born to mothers on high-fat diets. From birth through adulthood, there was evidence of low-level inflammation in brain samples from high-fat groups, including activation of microglia (immune cells) in the hippocampus of the brain. Inflammation also was present outside the brain as evidenced by increased C-reactive protein in the liver.

Most striking was the difference in response to immune challenge. Adult animals whose mothers had been on high-fat diets had a greatly exaggerated inflammatory response in these same areas, compared with low-fat control animals.

“It was absolutely one of the largest responses we have ever seen,” said Dr. Bilbo. In response to anxiety and cognition tests, adult animals whose mothers were given the high-fat diets were considerably more anxious than adult animals from the low-fat group. However, no negative impact was noted on cognition as a consequence of mothers’ high-fat diets.

“Dietary fats are critical to a healthy pregnancy, so we were unsure if the placenta would serve as a protector from the negative effects of the fats, but it seems this is not the case,” said Dr. Bilbo. “The mothers’ diet during pregnancy determines a lifelong neuroinflammatory condition for the fetus that cannot be reversed with low-fat diet alone.”

Dr. Bilbo emphasized that while these findings are noteworthy, this is the first look at the effects of mothers’ obesity on the fetal brain. More research is needed on the composition of the diet before drawing inferences for humans.

The next step in Dr. Bilbo’s research will be to look at the success of reversing the impact of the mothers’ diet of brain inflammation through interventions that target the fetal immune response.

Eating Disorders Linked With Disrupted Rewards Process in the Brain
New findings on eating disorders, including obesity and anorexia nervosa, demonstrate the influence the brain has on appetite and weight control.

Obesity and anorexia, often considered metabolic in nature, appear to also reflect brain functions involving reward and inhibition. Past studies have shown that individual differences may predispose a person to undereat or overeat. These behaviors are influenced by the pleasure derived from eating and drinking, sensory properties of food and a person’s prior experiences, current internal state, expectations, beliefs, and genes.

Multiple studies examined several of these factors and the brain activity associated with them. They revealed a complex, integrated system in which signals from the body interact with brain circuitry to control eating behavior. Desensitization to these signals may lead to pathologic eating. As in other addictions, the dopamine reward system is critically involved. The similarities hold implications for potential treatment and prevention of obesity, according to Nora D. Volkow, MD, Director of the National Institute on Drug Abuse in Bethesda, Maryland.

“The brain is a complicated, integrated system whose responses are linked to changes in the body, as well as predisposing factors associated with a person’s experiences with food,” said Dr. Volkow. “When the brain senses the need for food, the reward system is activated. But the more a person overeats, the more insensitive to food rewards they may become, potentially causing a need to increase stimuli, which in this case is more food intake.”

Examining the brain’s response to certain foods, Dana M. Small, PhD, of the John B. Pierce Laboratory and Yale University in New Haven, Connecticut, found an inverse relationship between a person’s BMI and the brain’s response to a milkshake. Obese persons experienced much less activation of reward centers as they ate the food. The study determined that the response of the caudate to a milkshake was a better predictor of future weight gain than many traditional measures.

Cary R. Savage, PhD, of the University of Kansas Medical Center in Kansas City, conducted a study of food motivation using fMRI. He and his colleagues found that individuals who were obese differed from healthy-weight participants in the way that the brain responded to anticipated food or monetary rewards and punishments. Obese individuals showed greater brain sensitivity to anticipated rewards and less sensitivity to anticipated negative consequences than did healthy-weight individuals.

Other researchers made presentations on the topic as well. To better understand the brain functions of individuals with anorexia nervosa and bulimia nervosa, Walter H. Kaye, MD, and colleagues at the University of California, San Diego, used fMRI to examine the brain’s response to the taste of sucrose and an artificial sweetener and the brain’s response to pictures of palatable foods, compared with color-matched neutral objects. Their findings suggest that individuals who undereat or overeat have an altered sensitivity when consuming sucrose.

Julie L. Fudge, MD, of the University of Rochester Medical Center, followed the “taste pathway” in humans to better understand how information received by various areas of the brain is involved in eating behaviors. Her findings suggest a way that emotional associations with food can converge with taste and instinctive sensations to influence eating behavior.

Disturbances in appetite and weight regulation affect a significant proportion of the US population, and obesity is considered a national epidemic. One in every three adults and one of six children are obese, a condition that arises from chronic imbalances between energy intake and expenditure.

“The studies in this panel represent a growing body of research linking the brain and the wiring in the brain to overeating and obesity,” Dr. Volkow commented. “We really need to do much more work to better understand integration with processes that regulate food intake and reward processing in the brain. This research opens the doors to a much greater understanding of obesity.”

Omega-3 Supplements Show Promise in Alleviating Depression
A new analysis of the effects of omega-3 essential fatty acids offers the hope of enhanced treatment options for patients with depression. Two critical omega-3 essential fatty acids available from certain food or nutritional supplements but not manufactured by the body—eicosapentaenoic acid (EPA) and docosahexaenoic (DHA)—may play a role in optimal brain functioning and have antidepressant benefits that have not been fully recognized.

In a meta-analysis of 15 randomized, double-blind, placebo-controlled studies, researchers from the University of Illinois at Chicago, led by John M. Davis, MD, found that patients taking omega-3 with either EPA or a combination of EPA and DHA experienced clear antidepressant benefits. However, across studies, patients taking the pure DHA form of omega-3 showed no antidepressant effect.

“Our analysis clarifies the precise type of omega-3 fatty acid that is effective for people with depression and explains why previous findings have been contradictory,” said Dr. Davis. “The EPA predominant formulation is necessary for the therapeutic action to occur. The DHA predominant formulation does not have antidepressant efficacy.”

Although the investigators noted that omega-3 produces beneficial effects in patients with depression, EPA does not improve mood in persons who are not depressed. In several studies, people without depression experienced no difference in mood as a result of omega-3 consumption.

In another study, Dr. Davis and his team found that women with inadequate omega-3 intake were more likely to experience depression during and after pregnancy than were women with adequate omega-3 in their diets.

“The findings are unambiguous,” said Dr. Davis. “Omega-3 fatty acids have antidepressant properties, and this effect is ready to be tested in a large study to establish the dose range and to pave the way for FDA approval. In the meantime, omega-3 fatty acids containing EPA could be useful to augment effects of antidepressant medications.”

However, the researchers cautioned that patients should always talk with their physician before taking omega-3 fatty acids to alleviate symptoms of depression.

Dr. Davis and colleagues are now examining the link between soy intake and depression, and they expect those findings to be published next year. He noted that soy products contain omega-6 fatty acids, which compete with omega-3 fatty acids.

Vulnerability to Sleep Loss Varies by Individual
Researchers studying the effects of sleep restriction on brain function have found that some individuals are more vulnerable to sleep deprivation than others, and that the ability to recover from chronic sleep restriction also varies.

Through a series of nine studies, David Dinges, PhD, Professor and Chief of the Division of Sleep and Chronobiology in the Department of Psychiatry at the University of Pennsylvania School of Medicine in Philadelphia, and colleagues sought to identify changes in brain function as a result of chronic sleep deprivation, as well as differences in individuals’ sleep need, vulnerability to sleep restrictions, and ease of recovery after sleep deprivation.

The studies involved more than 500 healthy adults, including men, women, whites, and minorities. The average age of participants was 30 (range, 21 to 50). Each study included 40 to 150 participants, who lived in the laboratory 24 hours a day for two to three weeks.

The researchers found that there were large individual differences among healthy persons in response to chronic sleep restriction. Some people were severely affected and showed a dramatic decline in alertness from continued deprivation. Others were not as severely affected, and a subset showed no cognitive deficits from the sleep restriction.

“Our findings indicate that there are likely people who are resistant to the effects of sleep restriction and those who are very vulnerable,” said Dr. Dinges. “Even though they all obtain the same amount of sleep normally in their lives, and even though they are getting the same restriction in the laboratory, they are having markedly different neurobehavioral responses to the reduction of sleep.”

The researchers found that all subjects who slept seven to eight hours a night functioned normally, but with each day of sleep restriction, differences between the groups started to emerge. As sleep was reduced, cognitive functioning was impaired, with the rate of change determined by membership in one of the three groups. Changes began to occur when participants slept fewer than seven hours each night and became much more dramatic when sleep time was reduced to four hours per night.

Through psychomotor vigilance testing, a test of sustained attention that is used to detect sleepiness, the investigators identified the effects of sleep restriction on each participant. Using this test as a marker, they found that attention was profoundly affected by inadequate sleep. For most people, attention destabilizes early in the sleep restriction and was more affected by restriction than any other cognitive area. However, not everyone showed these effects.

“This is not a simple story, because each person’s sleep needs and response to sleep restriction are unique,” Dr. Dinges said. “The bottom line is that it is important not to restrict your sleep, and that if you do it night after night, most people will begin to see the effects in behavior and brain function. Furthermore, it’s important to oversleep when possible in order to recover from any sleep deficit to the extent possible.”

High-Fat Diet During Pregnancy Causes Brain Inflammation in Offspring
A pregnant mother’s high-fat diet can have profound and lasting effects on the brain of her offspring, according to evidence from an animal study. Researchers believe that high-fat diets activate immune cells in the brain, causing inflammation, a process that may lead to neurodegenerative conditions such as multiple sclerosis and Alzheimer’s disease.

“Obesity is generally thought of as a condition that happens to the body but doesn’t impact the brain,” said Staci Bilbo, PhD, Assistant Professor of Psychology and Neuroscience at Duke University in Durham, North Carolina. “But our research found that changes in the brain of offspring are linked to what a mother eats during pregnancy.”

Previous research has shown a link between obesity and inflammation in the body, but little is known about whether obesity might affect inflammation in the brain or if obesity in a pregnant mother can affect brain functions in her offspring. Dr. Bilbo and her team investigated how immune cells in the brain of a pup respond to or are activated by a high-fat content in its mother’s diet during pregnancy.

“When the brain’s immune system is out of balance, it becomes inflamed,” said Dr. Bilbo. “Inflammation is good in the short term, because it can aid in healing and alert us to tissue damage, but in the long run, constant inflammation can be damaging to neurons and brain function.”

The researchers fed female breeding rats one of three diets—a 60% saturated high-fat diet, a 60% trans high-fat diet, or a 10% low-fat control diet for four weeks prior to mating and throughout pregnancy and lactation. After weaning (day 21), all pups were fed the low-fat diet, so they were never on a high-fat diet themselves.

To examine the pups’ response to the mothers’ diets, brain samples and peripheral tissue (fat, blood, and liver) were collected at one day after birth, at weaning (20 days after birth), and in early adulthood (days 60 to 90). The investigators tested immune system functioning in the liver and in the brain, as well as behavioral measures of anxiety and the ability to learn and remember a maze.

Inflammatory response was tested in the pups after weaning (day 20) and in adulthood (days 60 to 90) by comparing immune response four hours after injections of dead bacteria. This procedure activates the immune system without causing an infection that would have a negative impact on an animal’s health.

The researchers observed clear evidence of brain inflammation in the pups born to mothers on high-fat diets. From birth through adulthood, there was evidence of low-level inflammation in brain samples from high-fat groups, including activation of microglia (immune cells) in the hippocampus of the brain. Inflammation also was present outside the brain as evidenced by increased C-reactive protein in the liver.

Most striking was the difference in response to immune challenge. Adult animals whose mothers had been on high-fat diets had a greatly exaggerated inflammatory response in these same areas, compared with low-fat control animals.

“It was absolutely one of the largest responses we have ever seen,” said Dr. Bilbo. In response to anxiety and cognition tests, adult animals whose mothers were given the high-fat diets were considerably more anxious than adult animals from the low-fat group. However, no negative impact was noted on cognition as a consequence of mothers’ high-fat diets.

“Dietary fats are critical to a healthy pregnancy, so we were unsure if the placenta would serve as a protector from the negative effects of the fats, but it seems this is not the case,” said Dr. Bilbo. “The mothers’ diet during pregnancy determines a lifelong neuroinflammatory condition for the fetus that cannot be reversed with low-fat diet alone.”

Dr. Bilbo emphasized that while these findings are noteworthy, this is the first look at the effects of mothers’ obesity on the fetal brain. More research is needed on the composition of the diet before drawing inferences for humans.

The next step in Dr. Bilbo’s research will be to look at the success of reversing the impact of the mothers’ diet of brain inflammation through interventions that target the fetal immune response.

Eating Disorders Linked With Disrupted Rewards Process in the Brain
New findings on eating disorders, including obesity and anorexia nervosa, demonstrate the influence the brain has on appetite and weight control.

Obesity and anorexia, often considered metabolic in nature, appear to also reflect brain functions involving reward and inhibition. Past studies have shown that individual differences may predispose a person to undereat or overeat. These behaviors are influenced by the pleasure derived from eating and drinking, sensory properties of food and a person’s prior experiences, current internal state, expectations, beliefs, and genes.

Multiple studies examined several of these factors and the brain activity associated with them. They revealed a complex, integrated system in which signals from the body interact with brain circuitry to control eating behavior. Desensitization to these signals may lead to pathologic eating. As in other addictions, the dopamine reward system is critically involved. The similarities hold implications for potential treatment and prevention of obesity, according to Nora D. Volkow, MD, Director of the National Institute on Drug Abuse in Bethesda, Maryland.

“The brain is a complicated, integrated system whose responses are linked to changes in the body, as well as predisposing factors associated with a person’s experiences with food,” said Dr. Volkow. “When the brain senses the need for food, the reward system is activated. But the more a person overeats, the more insensitive to food rewards they may become, potentially causing a need to increase stimuli, which in this case is more food intake.”

Examining the brain’s response to certain foods, Dana M. Small, PhD, of the John B. Pierce Laboratory and Yale University in New Haven, Connecticut, found an inverse relationship between a person’s BMI and the brain’s response to a milkshake. Obese persons experienced much less activation of reward centers as they ate the food. The study determined that the response of the caudate to a milkshake was a better predictor of future weight gain than many traditional measures.

Cary R. Savage, PhD, of the University of Kansas Medical Center in Kansas City, conducted a study of food motivation using fMRI. He and his colleagues found that individuals who were obese differed from healthy-weight participants in the way that the brain responded to anticipated food or monetary rewards and punishments. Obese individuals showed greater brain sensitivity to anticipated rewards and less sensitivity to anticipated negative consequences than did healthy-weight individuals.

Other researchers made presentations on the topic as well. To better understand the brain functions of individuals with anorexia nervosa and bulimia nervosa, Walter H. Kaye, MD, and colleagues at the University of California, San Diego, used fMRI to examine the brain’s response to the taste of sucrose and an artificial sweetener and the brain’s response to pictures of palatable foods, compared with color-matched neutral objects. Their findings suggest that individuals who undereat or overeat have an altered sensitivity when consuming sucrose.

Julie L. Fudge, MD, of the University of Rochester Medical Center, followed the “taste pathway” in humans to better understand how information received by various areas of the brain is involved in eating behaviors. Her findings suggest a way that emotional associations with food can converge with taste and instinctive sensations to influence eating behavior.

Disturbances in appetite and weight regulation affect a significant proportion of the US population, and obesity is considered a national epidemic. One in every three adults and one of six children are obese, a condition that arises from chronic imbalances between energy intake and expenditure.

“The studies in this panel represent a growing body of research linking the brain and the wiring in the brain to overeating and obesity,” Dr. Volkow commented. “We really need to do much more work to better understand integration with processes that regulate food intake and reward processing in the brain. This research opens the doors to a much greater understanding of obesity.”

Omega-3 Supplements Show Promise in Alleviating Depression
A new analysis of the effects of omega-3 essential fatty acids offers the hope of enhanced treatment options for patients with depression. Two critical omega-3 essential fatty acids available from certain food or nutritional supplements but not manufactured by the body—eicosapentaenoic acid (EPA) and docosahexaenoic (DHA)—may play a role in optimal brain functioning and have antidepressant benefits that have not been fully recognized.

In a meta-analysis of 15 randomized, double-blind, placebo-controlled studies, researchers from the University of Illinois at Chicago, led by John M. Davis, MD, found that patients taking omega-3 with either EPA or a combination of EPA and DHA experienced clear antidepressant benefits. However, across studies, patients taking the pure DHA form of omega-3 showed no antidepressant effect.

“Our analysis clarifies the precise type of omega-3 fatty acid that is effective for people with depression and explains why previous findings have been contradictory,” said Dr. Davis. “The EPA predominant formulation is necessary for the therapeutic action to occur. The DHA predominant formulation does not have antidepressant efficacy.”

Although the investigators noted that omega-3 produces beneficial effects in patients with depression, EPA does not improve mood in persons who are not depressed. In several studies, people without depression experienced no difference in mood as a result of omega-3 consumption.

In another study, Dr. Davis and his team found that women with inadequate omega-3 intake were more likely to experience depression during and after pregnancy than were women with adequate omega-3 in their diets.

“The findings are unambiguous,” said Dr. Davis. “Omega-3 fatty acids have antidepressant properties, and this effect is ready to be tested in a large study to establish the dose range and to pave the way for FDA approval. In the meantime, omega-3 fatty acids containing EPA could be useful to augment effects of antidepressant medications.”

However, the researchers cautioned that patients should always talk with their physician before taking omega-3 fatty acids to alleviate symptoms of depression.

Dr. Davis and colleagues are now examining the link between soy intake and depression, and they expect those findings to be published next year. He noted that soy products contain omega-6 fatty acids, which compete with omega-3 fatty acids.