neurosciencestuff:

Brain inflammation dramatically disrupts memory retrieval networks

Brain inflammation can rapidly disrupt our ability to retrieve complex memories of similar but distinct experiences, according to UC Irvine neuroscientists Jennifer Czerniawski and John Guzowski.

Their study – which appears today in The Journal of Neuroscience – specifically identifies how immune system signaling molecules, called cytokines, impair communication among neurons in the hippocampus, an area of the brain critical for discrimination memory. The findings offer insight into why cognitive deficits occurs in people undergoing chemotherapy and those with autoimmune or neurodegenerative diseases.

Moreover, since cytokines are elevated in the brain in each of these conditions, the work suggests potential therapeutic targets to alleviate memory problems in these patients.

“Our research provides the first link among immune system activation, altered neural circuit function and impaired discrimination memory,” said Guzowski, the James L. McGaugh Chair in the Neurobiology of Learning & Memory. “The implications may be beneficial for those who have chronic diseases, such as multiple sclerosis, in which memory loss occurs and even for cancer patients.”

What he found interesting is that increased cytokine levels in the hippocampus only affected complex discrimination memory, the type that lets us differentiate among generally similar experiences – what we did at work or ate at dinner, for example. A simpler form of memory processed by the hippocampus – which would be akin to remembering where you work – was not altered by brain inflammation.

In the study, Czerniawski, a UCI postdoctoral scholar, exposed rats to two similar but discernable environments over several days. They received a mild foot shock daily in one, making them apprehensive about entering that specific site. Once the rodents showed that they had learned the difference between the two environments, some were given a low dose of a bacterial agent to induce a neuroinflammatory response, leading to cytokine release in the brain. Those animals were then no longer able to distinguish between the two environments.

Afterward, the researchers explored the activity patterns of neurons – the primary cell type for information processing – in the rats’ hippocampi using a gene-based cellular imaging method developed in the Guzowski lab. In the rodents that received the bacterial agent (and exhibited memory deterioration), the networks of neurons activated in the two environments were very similar, unlike those in the animals not given the agent (whose memories remained strong). This finding suggests that cytokines impaired recall by disrupting the function of these specific neuron circuits in the hippocampus.

“The cytokines caused the neural network to react as if no learning had taken place,” said Guzowski, associate professor of neurobiology & behavior. “The neural circuit activity was back to the pattern seen before learning.”

The work may also shed light on a chemotherapy-related mental phenomenon known as “chemo brain,” in which cancer patients find it difficult to efficiently process information. UCI neuro-oncologists have found that chemotherapeutic agents destroy stem cells in the brain that would have become neurons for creating and storing memories.

Dr. Daniela Bota, who co-authored that study, is currently collaborating with Guzowski’s research group to see if brain inflammation may be another of the underlying causes of “chemo brain” symptoms.

She said they’re looking for a simple intervention, such as an anti-inflammatory or steroid drug, that could lessen post-chemo inflammation. Bota will test this approach on patients, pending the outcome of animal studies.

“It will be interesting to see if limiting neuroinflammation will give cancer patients fewer or no problems,” she said. “It’s a wonderful idea, and it presents a new method to limit brain cell damage, improving quality of life. This is a great example of basic science and clinical ideas coming together to benefit patients.”

Perhaps I should take anti-inflammatories on a regular basis. My memory is shot. 

Schizophrenia not a single disease but multiple genetically distinct disorders

neurosciencestuff:

New research shows that schizophrenia isn’t a single disease but a group of eight genetically distinct disorders, each with its own set of symptoms. The finding could be a first step toward improved diagnosis and treatment for the debilitating psychiatric illness.

image

The research at Washington University School of Medicine in St. Louis is reported online Sept. 15 in The American Journal of Psychiatry.

About 80 percent of the risk for schizophrenia is known to be inherited, but scientists have struggled to identify specific genes for the condition. Now, in a novel approach analyzing genetic influences on more than 4,000 people with schizophrenia, the research team has identified distinct gene clusters that contribute to eight different classes of schizophrenia.

“Genes don’t operate by themselves,” said C. Robert Cloninger, MD, PhD, one of the study’s senior investigators. “They function in concert much like an orchestra, and to understand how they’re working, you have to know not just who the members of the orchestra are but how they interact.”

Cloninger, the Wallace Renard Professor of Psychiatry and Genetics, and his colleagues matched precise DNA variations in people with and without schizophrenia to symptoms in individual patients. In all, the researchers analyzed nearly 700,000 sites within the genome where a single unit of DNA is changed, often referred to as a single nucleotide polymorphism (SNP). They looked at SNPs in 4,200 people with schizophrenia and 3,800 healthy controls, learning how individual genetic variations interacted with each other to produce the illness.

In some patients with hallucinations or delusions, for example, the researchers matched distinct genetic features to patients’ symptoms, demonstrating that specific genetic variations interacted to create a 95 percent certainty of schizophrenia. In another group, they found that disorganized speech and behavior were specifically associated with a set of DNA variations that carried a 100 percent risk of schizophrenia.

“What we’ve done here, after a decade of frustration in the field of psychiatric genetics, is identify the way genes interact with each other, how the ‘orchestra’ is either harmonious and leads to health, or disorganized in ways that lead to distinct classes of schizophrenia,” Cloninger said. 

Although individual genes have only weak and inconsistent associations with schizophrenia, groups of interacting gene clusters create an extremely high and consistent risk of illness, on the order of 70 to 100 percent. That makes it almost impossible for people with those genetic variations to avoid the condition. In all, the researchers identified 42 clusters of genetic variations that dramatically increased the risk of schizophrenia.

“In the past, scientists had been looking for associations between individual genes and schizophrenia,” explained Dragan Svrakic, PhD, MD, a co-investigator and a professor of psychiatry at Washington University. “When one study would identify an association, no one else could replicate it. What was missing was the idea that these genes don’t act independently. They work in concert to disrupt the brain’s structure and function, and that results in the illness.”

Svrakic said it was only when the research team was able to organize the genetic variations and the patients’ symptoms into groups that they could see that particular clusters of DNA variations acted together to cause specific types of symptoms.

Then they divided patients according to the type and severity of their symptoms, such as different types of hallucinations or delusions, and other symptoms, such as lack of initiative, problems organizing thoughts or a lack of connection between emotions and thoughts. The results indicated that those symptom profiles describe eight qualitatively distinct disorders based on underlying genetic conditions.

The investigators also replicated their findings in two additional DNA databases of people with schizophrenia, an indicator that identifying the gene variations that are working together is a valid avenue to explore for improving diagnosis and treatment.

By identifying groups of genetic variations and matching them to symptoms in individual patients, it soon may be possible to target treatments to specific pathways that cause problems, according to co-investigator Igor Zwir, PhD, research associate in psychiatry at Washington University and associate professor in the Department of Computer Science and Artificial Intelligence at the University of Granada, Spain.

And Cloninger added it may be possible to use the same approach to better understand how genes work together to cause other common but complex disorders.

“People have been looking at genes to get a better handle on heart disease, hypertension and diabetes, and it’s been a real disappointment,” he said. “Most of the variability in the severity of disease has not been explained, but we were able to find that different sets of genetic variations were leading to distinct clinical syndromes. So I think this really could change the way people approach understanding the causes of complex diseases.”

problemglyphs:

Glyph: [MEDICINE MUSE]
Problem:

Anonymous said:
December 27th 2013, 12:45:00 am
I want to be well enough to create the things that I need to manifest.

problemglyphs:

Glyph: [MEDICINE MUSE]
Problem:

Anonymous said:
December 27th 2013, 12:45:00 am
I want to be well enough to create the things that I need to manifest.

problemglyphs:

Glyph: [MEDICINE MUSE]

Problem:

Anonymous said:

December 27th 2013, 12:45:00 am

I want to be well enough to create the things that I need to manifest.

“I am telling you now because I want you to stop telling girls and women with disabilities that we’re broken, that we need prayers, that we’re burdens, that it’s okay if someone hurts us because “they’re probably just stressed” from having to “deal” with us, or that we’re pretty “for a girl in a wheelchair.””

Stop Telling Me That I’m Pretty for a Girl in a Wheelchair: How Your Words Contribute to Violence Against Women with Disabilities

very powerful. please read the entire essay. tw for abuse and assault against women with disabilities. 

(via disabilityhistory)

(via crypticcripple)

neurosciencestuff:

Stress tied to change in children’s gene expression related to emotion regulation, physical health
Children who have been abused or neglected early in life are at risk for developing both emotional and physical health problems. In a new study, scientists have found that maltreatment affects the way genes are activated, which has implications for children’s long-term development. Previous studies focused on how a particular child’s individual characteristics and genetics interacted with that child’s experiences in an effort to understand how health problems emerge. In the new study, researchers were able to measure the degree to which genes were turned “on” or “off” through a biochemical process called methylation. This new technique reveals the ways that nurture changes nature—that is, how our social experiences can change the underlying biology of our genes.
The study, from researchers at the University of Wisconsin, Madison, appears in the journal Child Development. Nearly 1 million children in the United States are neglected or abused every year.
The researchers found an association between the kind of parenting children had and a particular gene (called the glucocorticoid receptor gene) that’s responsible for crucial aspects of social functioning and health. Not all genes are active at all times. DNA methylation is one of several biochemical mechanisms that cells use to control whether genes are turned on or off. The researchers examined DNA methylation in the blood of 56 children ages 11 to 14. Half of the children had been physically abused.
They found that compared to the children who hadn’t been maltreated, the maltreated children had increased methylation on several sites of the glucocorticoid receptor gene, also known as NR3C1, echoing the findings of earlier studies of rodents. In this study, the effect occurred on the section of the gene that’s critical for nerve growth factor, which is an important part of healthy brain development.
There were no differences in the genes that the children were born with, the study found; instead, the differences were seen in the extent to which the genes had been turned on or off. “This link between early life stress and changes in genes may uncover how early childhood experiences get under the skin and confer lifelong risk,” notes Seth D. Pollak, professor of psychology and pediatrics at the University of Wisconsin, Madison, who directed the study.
Previous studies have shown that children who have experienced physical abuse, sexual abuse, and neglect are more likely to develop mood, anxiety, and aggressive disorders, as well as to have problems regulating their emotions. These problems, in turn, can disrupt relationships and affect school performance. Maltreated children are also at risk for chronic health problems such as cardiac disease and cancer. The current study helps explain why these childhood experiences can affect health years later.
The gene identified by the researchers affects the hypothalamic-pituitary-adrenal (HPA) axis in rodents. Disruptions of this system in the brain would make it difficult for people to regulate their emotional behavior and stress levels. Circulating through the body in the blood, this gene affects the immune system, leaving individuals less able to fight off germs and more vulnerable to illnesses.
"Our finding that children who were physically maltreated display a specific change to the glucocorticoid receptor gene could explain why abused children have more emotional difficulties as they age," according to Pollak. "They may have fewer glucocorticoid receptors in their brains, which would impair the brain’s stress-response system and result in problems regulating stress."
The findings have implications for designing more effective interventions for children, especially since studies of animals indicate that the effects of poor parenting on gene methylation may be reversible if caregiving improves. The study also adds to what we know about how child maltreatment relates to changes in the body and mind, findings that were summarized recently in an SRCD Social Policy Report by Sara R. Jaffee and Cindy W. Christian.

neurosciencestuff:

Stress tied to change in children’s gene expression related to emotion regulation, physical health

Children who have been abused or neglected early in life are at risk for developing both emotional and physical health problems. In a new study, scientists have found that maltreatment affects the way genes are activated, which has implications for children’s long-term development. Previous studies focused on how a particular child’s individual characteristics and genetics interacted with that child’s experiences in an effort to understand how health problems emerge. In the new study, researchers were able to measure the degree to which genes were turned “on” or “off” through a biochemical process called methylation. This new technique reveals the ways that nurture changes nature—that is, how our social experiences can change the underlying biology of our genes.

The study, from researchers at the University of Wisconsin, Madison, appears in the journal Child Development. Nearly 1 million children in the United States are neglected or abused every year.

The researchers found an association between the kind of parenting children had and a particular gene (called the glucocorticoid receptor gene) that’s responsible for crucial aspects of social functioning and health. Not all genes are active at all times. DNA methylation is one of several biochemical mechanisms that cells use to control whether genes are turned on or off. The researchers examined DNA methylation in the blood of 56 children ages 11 to 14. Half of the children had been physically abused.

They found that compared to the children who hadn’t been maltreated, the maltreated children had increased methylation on several sites of the glucocorticoid receptor gene, also known as NR3C1, echoing the findings of earlier studies of rodents. In this study, the effect occurred on the section of the gene that’s critical for nerve growth factor, which is an important part of healthy brain development.

There were no differences in the genes that the children were born with, the study found; instead, the differences were seen in the extent to which the genes had been turned on or off. “This link between early life stress and changes in genes may uncover how early childhood experiences get under the skin and confer lifelong risk,” notes Seth D. Pollak, professor of psychology and pediatrics at the University of Wisconsin, Madison, who directed the study.

Previous studies have shown that children who have experienced physical abuse, sexual abuse, and neglect are more likely to develop mood, anxiety, and aggressive disorders, as well as to have problems regulating their emotions. These problems, in turn, can disrupt relationships and affect school performance. Maltreated children are also at risk for chronic health problems such as cardiac disease and cancer. The current study helps explain why these childhood experiences can affect health years later.

The gene identified by the researchers affects the hypothalamic-pituitary-adrenal (HPA) axis in rodents. Disruptions of this system in the brain would make it difficult for people to regulate their emotional behavior and stress levels. Circulating through the body in the blood, this gene affects the immune system, leaving individuals less able to fight off germs and more vulnerable to illnesses.

"Our finding that children who were physically maltreated display a specific change to the glucocorticoid receptor gene could explain why abused children have more emotional difficulties as they age," according to Pollak. "They may have fewer glucocorticoid receptors in their brains, which would impair the brain’s stress-response system and result in problems regulating stress."

The findings have implications for designing more effective interventions for children, especially since studies of animals indicate that the effects of poor parenting on gene methylation may be reversible if caregiving improves. The study also adds to what we know about how child maltreatment relates to changes in the body and mind, findings that were summarized recently in an SRCD Social Policy Report by Sara R. Jaffee and Cindy W. Christian.

jsi3:

Nobody realizes just how much chronic illness takes over a person’s life. You literally think and worry about it from the second you open your eyes to the second you drift off to sleep at night. Even in remission, every slight pain sends your brain into worry mode.

(via crypticcripple)

chronicallyinvisible:

It’s bizarre that some people seem to have this incredibly misinformed attitude that it must be easy to have a chronic illness because you don’t ‘have’ to work or study and you ‘get’ to stay at home all day, when I think most chronic illness sufferers would give almost anything to be able to have some semblance of a job.

Especially because it’s isolating and lonely. 

(via crypticcripple)

“ABSTRACT:
BACKGROUND AND PURPOSE:
There are only a few studies in the literature regarding the influence of atmospheric pressure on intracranial homeostasis and the mechanism of the relation has not been clarified. The aim of the study was to evaluate the influence of atmospheric pressure and ambient temperature on parameters of intracranial volume-pressure homeostasis including intracranial pressure and cerebral perfusion pressure as well as on blood pressure and body temperature.
MATERIAL AND METHODS:
The authors analyzed the influence of atmospheric pressure on intracranial pressure, blood pressure, cerebral perfusion pressure and body temperature in 14 patients who were monitored because of suspicion of having normal pressure hydrocephalus.
RESULTS:
Atmospheric pressure below 760 mm Hg (1013.3 hPa) significantly affects intracranial pressure, arterial blood pressure, cerebral perfusion pressure and body temperature. Atmospheric pressure above 770 mm Hg (1026.6 hPa) does not affect intracranial pressure, arterial blood pressure, cerebral perfusion pressure or body temperature.
CONCLUSIONS:
Atmospheric pressure range of 768 mm Hg (1023.9 hPa) to 770 mm Hg (1026.6 hPa) is the border range to preserve intracranial homeostasis, below which qualitative changes of cerebral blood flow occur. In the high range of atmospheric pressure its increase initiates biological protective mechanisms to maintain normal cerebral blood flow. The mechanism involved in the influence of atmospheric pressure and environmental factors in general on intracranial pressure and other parameters of pressure-volume homeostasis has not been explained.”

Atmospheric pressure and basic parameters of intracranial volume-pressure homeostasis.

http://www.ncbi.nlm.nih.gov/pubmed/18975238

circuitbird:

3liza:

phobias are a tough thing to glyph about since the only cure for phobias is terrifying exposure therapy, and sometimes anti-anxiety medication.  a meta-acceptance—being okay with being afraid—is the only thing i can think of that can help, short of those two clinical approaches.  animal phobias are particularly difficult for me to address since i don’t have any, and the reason I don’t have any is that when i was a kid, i was drilled on the understanding that animals are just trying to make a living like everyone else.  bats, spiders, moths, scary dogs, roaches, maggots.  they all have jobs and they all need to eat and shelter like everyone else.  probably by the time you’re an adult, this kind of “logical” approach to animal acceptance is just going to bounce off phobias—phobias are by definition illogical, can’t be reasoned with, and someone with a phobia isn’t “stupid” or even “ignorant” for having it, and can’t just be “educated” out of their fear. and that isn’t the fault of the person with the phobia.  it’s ok to be afraid.

Part of the pain of having a phobic disorder (at least in my own experience) is the massive disconnect between your own logical understanding of the phobic object or situation and what seems to be this utterly uncontrollable bodily response (i.e., a panic attack) to exposure. My father has an injection phobia and he knows damn well that the needles are for his own good, but it hasn’t stopped him from avoiding the doctor for years. Similarly, I know that panic attacks will not kill me, but I have nonetheless struggled with varying degrees of agoraphobic avoidance since I was a young teenager.

It’s very dehumanizing, in a way, to feel completely at the whim of a hair trigger fight or flight response when there is objectively “nothing to be afraid of.” It’s your lizard brain completely overriding all aspects of the types of cognitive thought that you have come to associate as a defining feature of your humanity. But part of coming to terms with my illness — and as you mentioned, being OK with being afraid (which, for the record, never fails to be a comforting reminder, wherever I may hear it or read it) — is realizing that despite the inherent irrationality of the phobia itself, there is a totally rational component to the avoidant contortions that emerge in response. When I schedule my work week to involve three 12-hour days, I am making a conscious, organized effort to minimize potentially panic-inducing public transit exposure. When I choose to eat when and only when I know I will have prolonged access to a bathroom, it is because my panic attacks have consistently demonstrated their capacity to make me violently sick — it’s an informed, understandable decision from this vantage point, and hardly one that I should continue to dismissively and self-defeatingly write off as “crazy.”

I am currently in a CBT program that involves graduated exposure, but one of the things my therapist has been stressing during the cognitive exercises is that my avoidance behaviors are completely logical given the nature of my subjective experience. If confronting the phobic object (be it spiders, dogs, or situational experiences like public speaking or leaving the house) produced a suite of physical and psychological reactions that I can only describe as a fate almost equivalent to death, would you not, too, jump through fantastic hoops to prevent even the slightest risk of exposure? Framing it from this perspective has helped me accept my current limitations with equanimity rather than resignation, and has also done wonders for my work toward recovery.

(via 3liza)

stretch-love:

They are a little hard to photograph, but these are my knee stretch marks.  They are caused by a connective tissue disorder called Ehlers Danlos Syndrome.  People often think that they are scars because they aren’t used to seeing stretch marks on knees and a lot of people assume that they are from self-harm.

(via edsaware1)

Nearly everyone with ADHD answers an emphatic yes to the question: “Have you always been more sensitive than others to rejection, teasing, criticism, or your own perception that you have failed or fallen short?” This is the definition of a condition called rejection-sensitive dysphoria. When I ask ADHDers to elaborate on it, they say: “I’m always tense. I can never relax. I can’t just sit there and watch a TV program with the rest of the family. I can’t turn my brain and body off to go to sleep at night. Because I’m sensitive to my perception that other people disapprove of me, I am fearful in personal interactions.” They are describing the inner experience of being hyperactive or hyper-aroused. Remember that most kids after age 14 don’t show much overt hyperactivity, but it’s still present internally, if you ask them about it.

The emotional response to the perception of failure is catastrophic for those with the condition. The term “dysphoria” means “difficult to bear,” and most people with ADHD report that they “can hardly stand it.” They are not wimps; disapproval hurts them much more than it hurts neurotypical people.

If emotional pain is internalized, a person may experience depression and loss of self-esteem in the short term. If emotions are externalized, pain can be expressed as rage at the person or situation that wounded them.

In the long term, there are two personality outcomes. The person with ADHD becomes a people pleaser, always making sure that friends, acquaintances, and family approve of him. After years of constant vigilance, the ADHD person becomes a chameleon who has lost track of what she wants for her own life. Others find that the pain of failure is so bad that they refuse to try anything unless they are assured of a quick, easy, and complete success. Taking a chance is too big an emotional risk. Their lives remain stunted and limited.

For many years, rejection-sensitive dysphoria has been the hallmark of what has been called atypical depression. The reason that it was not called “typical” depression is that it is not depression at all but the ADHD nervous system’s instantaneous response to the trigger of rejection.

"Devastated by Disapproval" - William Dodson, M.D., ADDitude Magazine

I did both of those two personality outcomes. Magic or something, I guess. -J

(via coachmcguirkscowtattoo)

My life just suddenly made so much more sense. Jesus Christ.

(via gadaboutgreen)

(via diesaddiscordia)

“P.S. Just a reminder: Grief is not a one-time thing for people with chronic health problems. Just like people grieving the loss of a loved one find the sadness washes over them at holidays or family events or even unexpected everyday moments, we who are grieving the loss of ourselves, or our former lives, will find the feelings come at random—When someone mentions an activity we used to love, or even something as simple as spilling a glass of milk, or not being able to find our keys. It doesn’t mean you’re a failure. It means you’re human. And it’s okay.”
— Sick and Tired: Empathy, Encouragement, and Practical help for Those Suffering from Chronic Health Problems by Kimberly Rae (via brittieslifeasiknowit)

(via crypticcripple)

“People with Ehlers-Danlos syndrome have a heightened awareness of pain… So, if I injure myself I’m going to be sore. But, if a person with Ehlers-Danlos injures themselves they’re going to be sore to the power of ten.”
— Dr. Brian Mulcahy in the EDS Awareness Ireland conference, 2012 (via moretocome)

(via mandymorbid)

iamtheprofessionalpatient:

“Where we were surprised is the difference in how much brain they used to do the task compared with the healthy group. It was 50 times larger,” Chialvo told Reuters.

This is the first demonstration of brain disturbances in chronic pain patients not directly related to the sensation of pain.   


Read more at http://www.redorbit.com/news/health/1244387/chronic_pain_can_damage_brain/#Bz0DdwpMSceMZdSD.99

(via violenceandscience)