Two studies were published this week that made the connection between genetic variations and anxiety disorders in both humans and animals.
One study, published in the journal Science, found that mice and humans with the same mutation in an anxiety-related gene behave similarly. The study, titled "A Genetic Variant BDNF Polymorphism Alters Extinction Learning in Both Mouse and Human," sounds almost deliberately obtuse, but the results are interesting. Lab rats (or in this case, lab mice) are often used in research for any number of reasons, which include the fact that they are small and relatively easy to handle, they reproduce quickly, and over a century of intense breeding and research has enabled researchers to know an animal's exact genetic profile. Many studies in behavioral neuroscience use mice and rats for these reasons, and also because it's generally difficult to get humans to participate in many of these experiments (which are often ended by autopsy so the brain can be examined). From a genetic standpoint, there aren't a whole lot of differences between a human and a mouse. Many of the tasks we both have to complete--digesting food, eliminating waste, maintaining homeostasis--are pretty darn similar, so researchers have hypothesized that the neural circuits controlling behavior in mice and people are actually similar.
This most recent study looked at a variation in the gene that makes Brain Derived Neurotropic Factor (BDNF), a protein responsible for brain growth and development. The interesting result was that the mice and humans who had this variation had similar behaviors. From a Science Daily press release:
To make their comparison, the researchers paired a harmless stimulus with an aversive one, which elicits an anxious-like response, known as conditioned fear. Following fear learning, exposure to numerous presentations of the harmless stimulus alone, in the absence of the aversive stimulus, normally leads to subjects extinguishing this fear response. That is, a subject should eventually stop having an anxious response towards the harmless stimulus.
"But both the mice and humans found to have the alternation in the BDNF gene took significantly longer to 'get over' the innocuous stimuli and stop having a conditioned fear response," explains Dr. Fatima Soliman...
...[Researchers] found that a circuit in the brain involving the frontal cortex and amygdala -- responsible for learning about cues that signal safety and danger -- was altered in people with the abnormality, when compared with control participants who did not have the abnormality.
"Testing for this gene may one day help doctors make more informed decisions for treatment of anxiety disorders," explains Dr. Francis S. Lee.
Specifically, it may help therapists tailor approaches to treating anxiety such as exposure therapy, which is an empirically supported treatment for a variety of anxiety disorders, such as phobias and PTSD.
"Exposure therapy may still work for patients with this gene abnormality, but a positive test for the BDNF genetic variant may let doctors know that exposure therapy may take longer, and that the use of newer drugs may be necessary to accelerate extinction learning," explains Dr. Soliman.
BDNF has also been associated with both anorexia nervosa and bulimia nervosa.
In a completely separate study, researchers have identified a genetic mutation that results in compulsive behaviors in a wide variety of animals. From a New York Times article on the study:
Researchers studied Doberman pinschers that curled up into balls, sucking their flanks for hours at a time, and found that the afflicted dogs shared a gene...the findings [have] broad implications for compulsive disorders in people and animals.
Dr. Dodman and his collaborators searched for a genetic source for this behavior by scanning and comparing the genomes of 94 Doberman pinschers that sucked their flanks, sucked on blankets or engaged in both behaviors with those of 73 Dobermans that did neither. They also studied the pedigrees of all the dogs for complex patterns of inheritance. The researchers identified a spot on canine chromosome 7 that contains the gene CDH2 (Cadherin 2), which showed variation in the genetic code when the sucking and nonsucking dogs were compared.
The statistical association led to further investigation to determine for which protein the gene contained instructions. It did for one of the proteins called cadherins, which are found throughout the animal kingdom and are apparently involved in cell alignment, adhesion and signaling.
Cadherins have also been recently associated with autism spectrum disorder, which includes repetitive and compulsive behaviors...
...“Stress and anxiety, as well as physical trauma and illness, can trigger repetitive behavior that then takes on a life of its own,” Dr. Ginns said.
But he believes that in many cases there is an underlying genetic predisposition that responds to environmental stimuli in such a way that once-normal behavior turns into something pathological. Those genetic dispositions may differ markedly between different behaviors.
Considering the links recently postulated between anorexia and autism as well as anorexia and OCD, these results may one day have an effect on our understanding of eating disorders.
Showing posts with label anxiety disorders. Show all posts
Showing posts with label anxiety disorders. Show all posts
Wednesday, January 20, 2010
Tuesday, March 24, 2009
Which came first...
...the over-protective mother or the anxious child?
According to a new study from the Journal of Clinical Child & Adolescent Psychology, over-protective mothering appears to be a "natural response" to anxious children.
The researchers, led by Jennifer Hudson of Macquarie University, knew from previous researchers that the mothers of anxious children tended to be over-protective and over-involved. What they didn't know, said Hudson, was "whether it is the child's anxiety that brings out over protective behavior."
For this study, titled "Child and Maternal Influence on Parenting Behavior in Clinically Anxious Children," the researchers compared clinically anxious children to their non-anxious counterparts as they interacted with mothers not their own. Hudson's group found that "when mothers interacted with an anxious child, they provided significantly more help to the child than mothers interacting with a child who did not have an anxiety disorder. "
"These results suggest that over-protection is a normal response to an anxious child and not the fault of the mother," Hudson said. "These findings may help reduce parental feelings of guilt and blame and may help parents understand their own and their child's behavior."
Many mothers of eating disordered children are accused of being over-protective, and many eating disordered children also show pre-morbid anxiety traits or disorders. This indicates that mothers of ED'd children may perhaps be more over-protective but that this is not necessarily indicative of any pathology on the mother's behalf. It's just a natural response to an anxious child.
According to a new study from the Journal of Clinical Child & Adolescent Psychology, over-protective mothering appears to be a "natural response" to anxious children.
The researchers, led by Jennifer Hudson of Macquarie University, knew from previous researchers that the mothers of anxious children tended to be over-protective and over-involved. What they didn't know, said Hudson, was "whether it is the child's anxiety that brings out over protective behavior."
For this study, titled "Child and Maternal Influence on Parenting Behavior in Clinically Anxious Children," the researchers compared clinically anxious children to their non-anxious counterparts as they interacted with mothers not their own. Hudson's group found that "when mothers interacted with an anxious child, they provided significantly more help to the child than mothers interacting with a child who did not have an anxiety disorder. "
"These results suggest that over-protection is a normal response to an anxious child and not the fault of the mother," Hudson said. "These findings may help reduce parental feelings of guilt and blame and may help parents understand their own and their child's behavior."
Many mothers of eating disordered children are accused of being over-protective, and many eating disordered children also show pre-morbid anxiety traits or disorders. This indicates that mothers of ED'd children may perhaps be more over-protective but that this is not necessarily indicative of any pathology on the mother's behalf. It's just a natural response to an anxious child.
Thursday, March 19, 2009
Cortisol and eating disorders
I was excited to see that my recent survey about sleep/wake habits here on the blog supported my hypothesis: that those with restrictive patterns tend to rise earlier, and those with more binge/purge patterns rise later. Of course, in order to really look at the data, I'd need to compare the early bird and night owl percentages of each category with those of a non-ED sample.
Although many things affect circadian rhythm--most of which are under genetic control--one of the key hormones is cortisol. Released from the adrenal cortex, cortisol levels generally peak upon waking and reach a low point shortly after you go to sleep. What's more, cortisol is released during times of stress or anxiety, increasing both blood pressure and blood sugar. A PubMed search of eating disorders and circadian rhythm produced mainly results on night eating syndrome. However, one study found a negative correlation between awakening cortisol response and "high anxiety, disinhibition and hunger scores, as well as poor body esteem and a high weight preoccupation" in women, but not men. That means that women with a low awakening cortisol response have high levels of anxiety, poor body esteem, etc. Of course, we don't know if this is cause or effect- just that it exists.
A study in men found a significant relationship between cortisol and perfectionism, which makes sense. Perfectionism is stressful (and don't I know that!), and higher stress means higher cortisol. As well, abnormalities in cortisol have been found in other psychiatric disorders, such as depression.
In otherwise healthy women who did not have regular menstrual periods, cortisol levels were increased compared to normal women, indicating stress on the body (the authors hypothesized that the reason for this amenorrhea was insufficient fat intake, despite sufficient calories and without excessive physical activity).
And indeed, women with anorexia were found not only to have higher cortisol levels but a significant proportion lacked a circadian cortisol rhythm. These abnormal cortisol levels are directly related to the starvation state- after weight restoration, cortisol levels return to normal. I'm not sure how the lack of cortisol rhythm is important. In general, starvation disturbs the sleep cycle, and refeeding is typically associated with improvements in sleep. The general school of thought is that the body is urging the starving person to go get food, and this may be true. But the high levels of cortisol brought out by the stress of malnutrition and starvation may also play a role. High cortisol levels in people with AN have been positively associated with both osteoporosis andhyperactivity.
Although one study found that overall daily cortisol rhythms in normal weight bulimic women were pretty much the same as in healthy women, another found evidence of greatly increased cortisol levels. It appears that, in bulimia, cortisol levels might be much higher than usual, although they still have a daily rhythm, unlike in anorexia. Even recovered bulimic patients continued to show a hyperreactivity to corticotropin-releasing hormone, which stimulates the release of cortisol, indicating an underlying neuroendocrine dysfunction.
Yet when cortisol levels were examined in relation to impulsivity, researchers found an inverse relationship between cortisol levels and impulsivity:
Patients with bulimic symptoms had significantly higher rates of cortisol suppression than controls and than restrictive anorectic patients. Percent cortisol suppression showed a strong and significant correlation with the patient's score on the Barratt Impulsiveness Scale. A hypersensitive cortisol response to dexamethasone, which might reflect hypothalamic-pituitary-adrenal axis dysfunctions might be specifically associated with impulsive subtypes of eating disorders.
Clearly, cortisol is just one player on a much larger field. Nor is it clear whether abnormalities in cortisol levels are cause or effect, and perhaps it's a little bit of either. Certainly the eating disorder exaggerates any underlying abnormalities. Whether the ED behaviors themselves cause the specific differences observed in cortisol levels in anorexia and bulimia, or whether these differences are part of the underlying risk factors for these illnesses also remains unclear.
(originally posted at ED Bites)
Although many things affect circadian rhythm--most of which are under genetic control--one of the key hormones is cortisol. Released from the adrenal cortex, cortisol levels generally peak upon waking and reach a low point shortly after you go to sleep. What's more, cortisol is released during times of stress or anxiety, increasing both blood pressure and blood sugar. A PubMed search of eating disorders and circadian rhythm produced mainly results on night eating syndrome. However, one study found a negative correlation between awakening cortisol response and "high anxiety, disinhibition and hunger scores, as well as poor body esteem and a high weight preoccupation" in women, but not men. That means that women with a low awakening cortisol response have high levels of anxiety, poor body esteem, etc. Of course, we don't know if this is cause or effect- just that it exists.
A study in men found a significant relationship between cortisol and perfectionism, which makes sense. Perfectionism is stressful (and don't I know that!), and higher stress means higher cortisol. As well, abnormalities in cortisol have been found in other psychiatric disorders, such as depression.
In otherwise healthy women who did not have regular menstrual periods, cortisol levels were increased compared to normal women, indicating stress on the body (the authors hypothesized that the reason for this amenorrhea was insufficient fat intake, despite sufficient calories and without excessive physical activity).
And indeed, women with anorexia were found not only to have higher cortisol levels but a significant proportion lacked a circadian cortisol rhythm. These abnormal cortisol levels are directly related to the starvation state- after weight restoration, cortisol levels return to normal. I'm not sure how the lack of cortisol rhythm is important. In general, starvation disturbs the sleep cycle, and refeeding is typically associated with improvements in sleep. The general school of thought is that the body is urging the starving person to go get food, and this may be true. But the high levels of cortisol brought out by the stress of malnutrition and starvation may also play a role. High cortisol levels in people with AN have been positively associated with both osteoporosis andhyperactivity.
Although one study found that overall daily cortisol rhythms in normal weight bulimic women were pretty much the same as in healthy women, another found evidence of greatly increased cortisol levels. It appears that, in bulimia, cortisol levels might be much higher than usual, although they still have a daily rhythm, unlike in anorexia. Even recovered bulimic patients continued to show a hyperreactivity to corticotropin-releasing hormone, which stimulates the release of cortisol, indicating an underlying neuroendocrine dysfunction.
Yet when cortisol levels were examined in relation to impulsivity, researchers found an inverse relationship between cortisol levels and impulsivity:
Patients with bulimic symptoms had significantly higher rates of cortisol suppression than controls and than restrictive anorectic patients. Percent cortisol suppression showed a strong and significant correlation with the patient's score on the Barratt Impulsiveness Scale. A hypersensitive cortisol response to dexamethasone, which might reflect hypothalamic-pituitary-adrenal axis dysfunctions might be specifically associated with impulsive subtypes of eating disorders.
Clearly, cortisol is just one player on a much larger field. Nor is it clear whether abnormalities in cortisol levels are cause or effect, and perhaps it's a little bit of either. Certainly the eating disorder exaggerates any underlying abnormalities. Whether the ED behaviors themselves cause the specific differences observed in cortisol levels in anorexia and bulimia, or whether these differences are part of the underlying risk factors for these illnesses also remains unclear.
(originally posted at ED Bites)
Wednesday, September 17, 2008
Predicting Anxiety Disorders
Anxiety disorders are some of the most common brain diseases amongst adults and teens. Walter Kaye found that an anxiety disorder is the strongest risk factor for an eating disorder. That researchers have found a better way to predict anxiety in teens is important in and of itself, but it might also be able to identify people at a much higher risk for eating disorders.
Says a summary of the research on Science Daily:
Craske and her colleagues are finding that neuroticism — the tendency to experience negative emotions such as fear, anxiety, guilt, shame, sadness or anger — is a powerful predictor of both anxiety and depression. Newly published research from the long-term study highlights a potential mechanism by which neuroticism confers risk. The researchers report that teenagers who are high in neuroticism appear to become unnecessarily anxious in ways that are out of proportion with actual circumstances.
Neuroticism is also a common trait of people with eating disorders, especially those with anorexia nervosa.
Furthermore:
"This is interpreted as neuroticism leading to enhanced anxiety under conditions associated with aversive events but in which negative events themselves are very unlikely," Craske said. "It may represent a failure to distinguish conditions that are safe from conditions in which threatening events are very likely to occur. By translation, these findings suggest that persons with high neuroticism would respond with appropriate fear to actual threatening events, but with additional unnecessary anxiety to surrounding conditions. This type of responding may explain why neuroticism contributes to the development of pervasive anxiety."
Craske and her colleagues report their findings this month in the journal Biological Psychiatry. She hopes the study will reveal the risk factors that predict anxiety, versus depression, and which risk factors are common to both anxiety and depression.
"Anxiety and depression often go hand in hand; we're trying to learn what factors place adolescents at risk for the development of anxiety and depression, what is common between anxiety and depression, and what is unique to each," Craske said.
It would be interesting to see whether this leads to any better predictions of what traits in what people predispose them to eating disorders.
Because many eating disorder prevention efforts are targeted more generally at improving self-esteem and media literacy, and important population at higher risk may be overlooked. Perhaps these teens would benefit from lessons in decreasing perfectionism and increasing resilience. No doubt it would help with anxiety. Might it also help with eating disorders?
Says a summary of the research on Science Daily:
Craske and her colleagues are finding that neuroticism — the tendency to experience negative emotions such as fear, anxiety, guilt, shame, sadness or anger — is a powerful predictor of both anxiety and depression. Newly published research from the long-term study highlights a potential mechanism by which neuroticism confers risk. The researchers report that teenagers who are high in neuroticism appear to become unnecessarily anxious in ways that are out of proportion with actual circumstances.
Neuroticism is also a common trait of people with eating disorders, especially those with anorexia nervosa.
Furthermore:
"This is interpreted as neuroticism leading to enhanced anxiety under conditions associated with aversive events but in which negative events themselves are very unlikely," Craske said. "It may represent a failure to distinguish conditions that are safe from conditions in which threatening events are very likely to occur. By translation, these findings suggest that persons with high neuroticism would respond with appropriate fear to actual threatening events, but with additional unnecessary anxiety to surrounding conditions. This type of responding may explain why neuroticism contributes to the development of pervasive anxiety."
Craske and her colleagues report their findings this month in the journal Biological Psychiatry. She hopes the study will reveal the risk factors that predict anxiety, versus depression, and which risk factors are common to both anxiety and depression.
"Anxiety and depression often go hand in hand; we're trying to learn what factors place adolescents at risk for the development of anxiety and depression, what is common between anxiety and depression, and what is unique to each," Craske said.
It would be interesting to see whether this leads to any better predictions of what traits in what people predispose them to eating disorders.
Because many eating disorder prevention efforts are targeted more generally at improving self-esteem and media literacy, and important population at higher risk may be overlooked. Perhaps these teens would benefit from lessons in decreasing perfectionism and increasing resilience. No doubt it would help with anxiety. Might it also help with eating disorders?
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