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Showing posts with label Stressors. Show all posts
Showing posts with label Stressors. Show all posts

Wednesday, 11 February 2015

Mouse study finds that serotonin deficiency does increase depression risk

A new study from researchers at Duke University in Durham, NC, finds that mice deficient in serotonin are more vulnerable to social stressors than a group of healthy control mice.
mice
Although the normal mice saw reduced depression symptoms following treatment with Prozac, the low-serotonin mice did not.
Low serotonin levels have traditionally been suspected as playing a role in depression, but there has been little solid evidence to support this hypothesis. Consequently, scientists have been increasingly moving away from the low-serotonin theory and looking instead at other possible causes of depression, such as the relationship between stress and inflammation and other environmental factors.
Last September, Medical News Today reported on a study published in ACS Chemical Neuroscience that found no difference in behaviors between mice that lacked serotonin and a normal group of control mice.
From this finding, the researchers behind that study - from Dingell VA Medical Center and Wayne State University School of Medicine, both in Detroit, MI - concluded that serotonin may not be a dominant factor in depression. Instead, they suggested that risk for the condition may instead be comprised of a range of different factors.
However, the Duke paper - which is published in the Proceedings of the National Academy of Sciences - reports opposite findings to that study.
Senior author Marc Caron, the James B. Duke professor of cell biology at the Duke University School of Medicine and a member of the Duke Institute for Brain Sciences, explains:
"Our results are very exciting because they establish in a genetically defined animal model of serotonin deficiency, that low serotonin could be a contributing factor to the development of depression in response to psychosocial stress - and can lead to the failure of [selective serotonin reuptake inhibitors] to alleviate symptoms of depression."
In their study, the Duke researchers used a transgenic mouse strain - Tph2KI - bred to have only 20-40% of normal serotonin levels.
The team exposed the mice to stress by briefly housing them with an aggressive stranger mouse every day for 7-10 days. To test for depression-like behaviors, the researchers then examined whether the test mice would avoid interacting with the stranger mouse.
The control mice did not exhibit these depression symptoms after a week of social stress, but the serotonin-deficient mice did. Both groups eventually displayed depression-like symptoms following longer periods of stress exposure.
The mice with depression-like symptoms were then treated with Prozac for 3 weeks. Although the normal mice saw reduced depression symptoms following treatment, the Tph2KI mice did not.
Because Prozac is a selective serotonin reuptake inhibitor (SSRI) and works by blocking cells' ability to "recapture" serotonin, Prof. Caron says it makes sense that the antidepressant would be less effective in animals that have low levels of serotonin.
The researchers think this might explain why some depressed people are unresponsive to treatment with SSRIs.

The lateral habenula as drug target for treatment-resistant depression

A brain region called the lateral habenula has been investigated by some studies as a potential drug target for treatment-resistant depression. The lateral habenula is also known as the "punishment" region of the brain, and scientists think that an overactive lateral habenula may trigger depression.
To investigate this, Prof. Caron's team targeted the lateral habenulae of the mice with "designer receptors exclusively activated by designer drugs." (DREADDs) - designer drugs that control the activity of specific neurons.
The scientists found that by inhibiting neurons in the lateral habenulae of the Tph2KI mice using the DREADDs, they were able to reverse the social avoidance behavior of these mice.
Although this is a promising first step in identifying targets for treatment-resistant depression, the researchers say that DREADDs are not appropriate for use in humans.
"The next step is to figure out how we can turn off this brain region in a relatively non-invasive way that would have better therapeutic potential," says lead author Benjamin Sachs, a postdoctoral researcher in Prof. Caron's group.
An additional finding from the research was that the serotonin-deficient mice produced a signaling molecule - β-catenin - in different areas of the brain to the normal mice when they were exposed to social stress.
According to Sachs, this suggests that serotonin deficiency may block a protective pathway that includes β-catenin: "If we can identify what's both upstream and downstream of β-catenin, we might be able to come up with attractive drug targets to activate this pathway and promote resilience."
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Source:  http://www.medicalnewstoday.com/articles/289230.php

Monday, 9 February 2015

Brain marker hints at depression, anxiety years later

A car accident, the loss of a loved one and financial trouble are just a few of the myriad stressors we may encounter in our lifetimes. Some of us take it in stride, while others go on to develop anxiety or depression. How well will we deal with the inevitable lows of life?
A clue to this answer, according to a new Duke University study, is found in an almond-shaped structure deep within our brains: the amygdala. By measuring activity of this area, which is crucial for detecting and responding to danger, researchers say they can tell who will become depressed or anxious in response to stressful life events, as far as four years down the road.
Published Feb. 4, 2015, in Neuron, the results may eventually lead to new strategies to treat depression and anxiety and prevent them from occurring in the first place.
"Often, individuals only access treatment when depression and anxiety has become so chronic and difficult to live with that it forces them to go to a clinic," said the study's first author Johnna Swartz, a Duke postdoctoral researcher in the lab of senior author Ahmad Hariri. "With a brain marker, we could potentially guide people to seek treatment earlier on, before the disorders become so life altering and disruptive that the person can't go on."
Small studies of people at risk for post-traumatic stress disorder (PTSD), such as soldiers deployed to combat zones, have hinted at the link between individual differences in brain activity and the ability to handle stressors.
Those studies also focused on the amygdala -- for its established link to psychiatric disorders including PTSD, anxiety and depression -- but included participants who had endured highly traumatic events such as active combat. In contrast, most people in the general population experience less severe forms of stress, such as unemployment, divorce, or a death in the family.
In the new study, Hariri's team scanned the brains of healthy college students as they looked at angry or fearful faces, which signal danger in our environment. These threatening pictures normally trigger the amygdala, and the scientists measured the intensity of this activation using functional magnetic resonance imaging, a noninvasive, indirect measure of brain activity.
Every three months after the scan, participants completed an online survey documenting stressful life events and their impact, as well as a questionnaire that assessed symptoms of depression and anxiety.
From the initial 753 participants who were scanned, nearly 200 completed the online surveys an average of two years, and as long as four years, after the scan. In these individuals, the more reactive the amygdala was at the study's start, the more severe their symptoms of anxiety or depression in response to stressful events they encountered after scanning.
Importantly, the participants who had an overzealous amygdala but who had not experienced recent stress did not show these elevations in symptoms.
"To find that a single measure of the brain can tell us something important about a person's psychological vulnerability to stress up to four years later is really remarkable and novel," said Hariri, a professor of psychology and neuroscience and a member of the Duke Institute for Brain Sciences.
The ability for the brain marker to predict symptoms was surprising, Hariri said, given that the population was healthy and, for the most part, dealing with normal and relatively mild stressors for young adults, like an argument with a parent, or problems at work or school.
The new research is part of the Duke Neurogenetics Study, a long-term collection of data on genes, brain activity, environmental factors and symptoms related to psychiatric disorders. The ultimate goal is to understand why some people are more vulnerable to developing depression, anxiety and other mental health problems.
Hariri and his team are continuing to follow their study participants. "We want to know just how far in the future knowing something about an individual's brain helps us understand their risk," he said.
The group is also exploring other measures, such as a person's genes, to predict the differences in amygdala activity, and in turn, the relative risk for anxiety and depression.
Isolating a person's DNA from a saliva sample and looking for specific differences in its letter code is easier and less expensive than having them undergo a brain scan. Thus, a genetic screen that tells us about a person's amygdala reactivity is more likely to be available and useful for doctors working to prevent mental illness in their patients, Hariri said.
Source:  http://www.sciencedaily.com/releases/2015/02/150204125756.htm

Wednesday, 29 January 2014

10 things we learned about surviving anxiety

Generalized anxiety disorder is the single most common mental health diagnosis, and yet it's still taboo to talk about it. I recently went public with a very personal essay about my battle with it, and in doing so, realized an awful lot of people have been aching for a chance to talk about their struggles.
After comments poured in through CNN.com, e-mails, Facebook, Twitter and other channels, CNN Living hosted a live Google Hangout to address some of the issues. Scott Stossel, author of "My Age of Anxiety: Fear, Hope, Dread, and the Search for Peace of Mind"; Daniel Smith, author of "Monkey Mind: A Memoir of Anxiety"; and psychiatrists Dawn M. Porter and Scott Krakower joined me for a robust, hourlong video chat about treatment, taboos, triggers and the breaking of bad habits.
Here are 10 things we learned from that conversation:
Military families may be especially susceptible to anxiety
Porter is a military spouse and treats people in the community. She says that anxiety -- and stressors -- are present and constant.
"There are a lot of issues that our families go through with every transition," she said. "You're moving every two to four years, depending on what your service member's responsibilities are. The service member has to settle into a new position and figure his or her way out; the spouse or partner also has to navigate a new environment and connect with a new community. If there are children involved, they have to get settled into a new school."
The general public isn't aware of such adjustments, Porter said, making it difficult for military families to assimilate into life outside a base. "They don't get that our children are struggling, and their children don't pick up on it. They have their stability and structure and don't bring the military families in -- which makes it even more difficult."
She said she believes her own experiences help make her a more effective therapist for military families.
Physical symptoms are par for the course, but they'll pass
A viewer wrote in, describing "feeling like I am going to faint, my heart will race and I get hot. I went to the doctor and they ran blood tests. Now they are sending me to a cardiologist. After looking up my symptoms it kind of sounds like anxiety but I am not sure. Since I ... went to the doctor I keep feeling this tight pressure in my chest and I keep crying for no reason. Does this sound familiar?"
Members of the panel all shook their heads emphatically. "That's the remarkable thing about anxiety: It's so embodied, such a physical experience," said Smith, who has undergone botox injections to counter excess sweating.
Stossel, whose memoir vividly detailed gastric symptoms he's suffers, said, "My physiology has commandeered my sympathetic nervous system."
I also fight a rapidly beating pulse, twitching muscles and deeply painful acid reflux. These symptoms are no picnic -- and sufferers and ER doctors often mistake them for a heart attack -- but they're not fatal.
Anxiety begets more anxiety
My son Has a mental illness
Coping with PTSD during the holidays
Krakower noted even seeing a specialist to deal with treatment can cause more stress. "We can't rule out a medical problem, but that, in turn, can feed the anxiety."
That response is "definitive of anxiety," Smith said. "You're anxious about something, which leads you to focus more attention on the feeling -- which leads you to be more anxious. Before you can snap your fingers, you're on that merry-go-round, which once it starts, can be inordinately difficult to jump off of."
Stossel agreed the cycle is hard to break. "I know a lot about the neuromechanics and the physiology of panic," he said. "I feel myself having anxious thoughts and I'll tell myself, 'You've been through this a million times, and this is probably a panic attack.' More often than not I can tell myself that it's just a panic attack ... but every once in a while, I'll think, 'But this feels slightly different than the previous 782 times. Maybe I am having a heart attack!' "
Medications aren't one size fits all
People may not be able to benefit from talk therapy if they're in a state of panic. "If the level of anxiety is very high, it may be necessary to bring that down so they can use some relaxing techniques," Porter said.
Stossel started his journey with medication at age 11 or 12, using Thorazine in the 1980s. He's studied all sides of the argument, from those who feel a "rapacious" pharmaceutical industry makes issues worse and prefer a med-free treatment, to physicians who believe that drug therapy should be the first recourse. His view falls somewhere in the middle.
"Medication can be part of a psychotropic arsenal," he said, discussing one therapist who urged him to stop taking Xanax so he could address his anxiety directly and not mask the physical symptoms.
But a psychopharmacologist felt his physical symptoms were so extreme that unless he tamped those down, he couldn't benefit from other coping techniques, according to Stossel.
"Some drugs have worked some of the time," Stossel said. "I couldn't have gotten through my book tour without benzodiazepines, but there are reasons to be wary of dependence, abuse and masking the symptoms but not treating the underlying source of the anxiety."
Younger people may feel less stigma about mental health than their parents
"There's more publicity about anxiety," Krakower said, "and it's becoming more acceptable in the community."
But there are certain things to consider when dealing with children and adolescents, these experts said.
"You first have to work at trying to engage them. If they're not on board, it's not going to work," he said.
Krakower, a child and adolescent psychiatrist, uses a two-pronged approach of cognitive behavioral therapy and gradual medication if needed. He said he pays close attention to which treatment is working best and tries to make younger patients feel comfortable with the process.
He also said some youths self-medicate by smoking pot, but the temporary relief often results in a loss of motivation at school.
Porter agreed that it's important to relate to children and teens. "They're very perceptive about if you're really interested in helping them." She said she also tends to steer clear of certain groups of medications with that age group, so these drugs don't become a crutch in the midst of change, or trigger suicidal impulses.
She also cautioned parents against overloading children with too many activities, expectations and pressures. "They have no downtime to be themselves. How do we balance their lives?"
Cultural taboos can get in the way of people seeking help
"Especially in the African-American community, there are a lot of issues that we face," Porter said. "There's always the stigma, there's always the feeling that you have to be twice as good to get half as much. Because of this, there's always a fear that anything someone finds out about you will be used against you. We're also a strong community, based in our religion. With that, there's a feeling that if you have an issue, you need to take it to God."
As a Christian, she said, she leans into her faith -- but she also believes it's God who brings people to a psychiatrist and provides the medication that helps people to do better or feel better. Porter said pastors, community groups and even celebrities are normalizing the notion of seeking help and encouraging people to share their own stories.
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Anxiety can be the enemy of romance
In Smith's research for "Monkey Mind," he saw a pattern emerge when it came to love. "When you're anxious, you tend to scan around for what may be causing it. And often you alight upon that person who is right next to you."
In addition to assuming a relationship is the root of a problem, he noted some people often experience shame that their partners will see them as weak.
In his own life, Smith pushed away a partner, and then in midst of the resulting sadness, felt he needed her and pulled her back. "That speaks to the whole stigma," he said, "the whole worry that if someone knows you are suffering from anxiety, they will consider you to be somehow less."
Gender expectations take a toll
Writer Stossel was struck by the extra burden many men face when it comes to anxiety. "There's a stigma around vulnerability," he said.
"Women have higher rates of diagnosis of anxiety disorder than men do," Stossel said. "That could be for temperamental reasons or for social reasons -- because of glass ceilings or extra pressures. It could also be because it's more acceptable for women to seek out treatment and accept a diagnosis. Whereas men have higher rates of alcoholism, and it may be that we're all just trying to sublimate and are afraid to seek help."
Krakower said he believes it's important, when working with young, male patients, to understand they may feel more stigmatized by school and friends than their female peers. "It's important to make them feel accepted in the individual therapy sessions and then teach them more ways to control their anxiety." These may include learning relaxation techniques, or how to be more assertive and not feel so nervous.
Anxiety doesn't have to define you, so make peace with it
Smith was diagnosed in college -- by his mother, a therapist who specializes in anxiety -- and he called the diagnosis a doubled-edged sword. "It's helpful to name something, but at the same time makes you feel trapped in that particular diagnosis," he said.
"It's important not just to think of it as a disorder or a mental construct, but as an emotion -- a universally held and rather important emotion. We need anxiety, and if we didn't have it, we'd be hit by cars far more frequently," Smith said. "You don't necessarily want to banish your anxiety; you want it to be there to some extent but not rule your life."
Stossel, now 44, spent the first 43 years of his life trying to hide his condition -- before penning a wildly popular and public memoir about it. "There are times when the level of suffering (is) so high, not to treat it as an illness ... is unfair and almost handicapping the therapist's ability to treat it. Even then, I've had to come to terms with thinking of this as woven into my personality and part of my temperament, but not what completely defines who I am."
It might not feel like it in the thick of things, but it's possible to fight back
Porter starts by asking her patients to make a list of what relaxes them and what activities they enjoy. These might include exercising, taking a walk around the block, deep breathing, talking to family members or listening to music. When in the throes of a panic attack, they will have some solutions at the ready and can pick out which are the most effective in the moment.
Smith has found cognitive behavioral therapy effective in changing some of his patterns and also seeks peace through Buddhist meditation, and in particular Zen. Both methods focus on mindfulness and paying attention to thoughts that trigger anxiety.
"The one thing you're not doing when you're anxious is existing in the present moment," Smith said.
Stossel recalled that when an excerpt of "My Age of Anxiety" ran in The Atlantic, strangers inundated him with advice to cut out gluten, sugar and caffeine, eat more fish oil and magnesium, try massages or yoga and smoke pot. But the things that sound the most banal are the most effective, he said.
"They're the things that your internist and your mother and your grandmother told you," he said. "Get enough sleep. It's good for you physically; it reduces depression and anxiety." He also swears by exercise, breathing techniques and cognitive behavioral therapy.
"So many of us with generalized anxiety disorder are gifted catastrophizers and worry that any decision we make or anything we enter into is going to be absolutely catastrophic and existentially damaging," Stossel said.
"But if you actually think it through and imagine the worst thing that could happen, well, did anybody die? Is it really that bad? Then use that to try to calm yourself."