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  • richardmitnick 12:04 pm on January 22, 2020 Permalink | Reply
    Tags: , Caitlin Clements, Depression, ,   

    From University of Pennsylvania: Women in STEM-“A Spectrum of Possibilities” Caitlin Clements 

    U Penn bloc

    From University of Pennsylvania

    January 16, 2020
    Karen Brooks

    A doctoral candidate in psychology, puts autism-related lore to the test.

    Caitlin Clements, a doctoral candidate in psychology

    U Pennsylvania OMNIA-All things Penn Arts and Sciences

    “Is this my fault?”

    It’s the question Caitlin Clements has heard more than any other since she began studying autism a decade ago. Currently completing a year-long clinical internship at SUNY Upstate Medical University, the Ph.D. candidate in psychology counsels families with children who have developmental or psychological disorders.

    “When I see parents going through the early diagnostic process for autism, so often, they ask me why this happened and what they did wrong,” Clements says. “While we know they are not to blame, there is so much we don’t know. I wish I could give them more concrete answers—that’s what motivates me to keep working.”

    Before beginning her undergraduate degree at Yale, Clements had only known one person with autism: a family friend’s son. The child’s behavior had seemed different for years, and she jumped at the opportunity to learn more about it by working in an autism-focused lab. Her commitment to exploring the condition hasn’t wavered since.

    Supervised by faculty advisor Robert Schultz—scientific director of the Center for Autism Research, a collaboration between Penn and Children’s Hospital of Philadelphia—Clements has studied the relationship between IQ and autism across patients of varying ages and abilities. Recently, she has examined whether common cognitive tests like the Differential Ability Scales-II (DAS-II) test, which were developed based on neurotypical children, accurately assess the intellectual capacities of autistic children.

    “When using the DAS-II with autistic kids, clinicians sometimes place a greater emphasis on nonverbal scores, thinking that maybe their verbal scores are not as meaningful because they often have lower language levels than expected for their age,” Clements says. “This seems like good intuition, but as clinicians, we have made these judgments without having real data to support them.”

    Clements accessed data from the 2,000 neurotypical children used in the development of the DAS-II as well as from a study applying the test to 1,200 children with autism. In comparing their verbal and nonverbal subtest scores, she discovered that the “rule of thumb” that a child with autism has stronger nonverbal than verbal skills is, in fact, a bit of medical lore.

    “It turns out that both verbal and nonverbal subtests work really well in autistic populations and capture the same things as in the normative sample. A higher nonverbal than verbal score barely predicts autism better than chance,” she says.

    The study revealed another unexpected finding: Performance patterns on the test’s spatial components differed significantly between children with and without autism. Those with the condition excelled at pattern construction—an exercise in which they copied a pattern using colored blocks—but struggled with recall of design, an exercise that involved remembering and reproducing abstract designs.

    “We are in the process of analyzing what these results mean and looking at whether there is a bias, and if that bias is an overprediction or underprediction of these kids’ abilities,” she explains.

    Although autism is her primary focus, Clements also maintains an interest in depression—a condition she studied in 2018 as a Fulbright Scholar at the Karolinska Institutet in Sweden. Working under psychiatrist Mikael Landén, she aimed to identify genetic causes for severe depression.

    “Like with autism, there are a lot of individual differences in clinical presentation among people with depression. A general label of ‘depression’ doesn’t capture these important differences, just like a general label of ‘autism’ doesn’t, either,” she says. “People with severe symptoms could have very different underlying biology than those with milder symptoms.”

    To ensure a sample of individuals with truly severe depression, Clements, Landén, and their team selected those who had received electroconvulsive therapy (ECT), a “last-ditch” treatment used only with patients who had not responded to any other therapies. They then performed a genome-wide association, an approach that involves scanning markers across many complete sets of DNA to pinpoint genetic variations associated with a particular disease—and detected a potential culprit on a region of one particular chromosome.

    “The landscape for the genetics of depression is no longer as bleak as it once was,” she notes. “What’s exciting about this paper’s approach is that a giant international consortium is now trying to do what we’ve done in Sweden all over the world, building up much larger samples of individuals who have received ECT to gain more traction in analyzing a more homogeneous subset. Identifying more severely affected subsets is a good direction for researchers studying autism to go, as well.”

    Clements defended her dissertation, “Phenotypic and genotypic heterogeneity of autism spectrum disorders,” last spring and will graduate when she finishes her internship in August. She is applying for postdoc positions in which she can continue to study the biological basis of autism and plans to pursue a career in academic research.

    “I like to see patients because it keeps me in touch with clinical issues,” she says, “but gaining knowledge about why a child has autism is cathartic for families, and my priority is to do research that helps answer these questions.”

    See the full article here .


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    Academic life at Penn is unparalleled, with 100 countries and every U.S. state represented in one of the Ivy League’s most diverse student bodies. Consistently ranked among the top 10 universities in the country, Penn enrolls 10,000 undergraduate students and welcomes an additional 10,000 students to our world-renowned graduate and professional schools.

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  • richardmitnick 10:34 am on June 13, 2017 Permalink | Reply
    Tags: , Depression, , TMS - transcranial magnetic stimulation,   

    From UCLA: “UCLA doctors use magnetic stimulation to ‘rewire’ the brain for people with depression” 

    UCLA bloc


    June 12, 2017

    FDA-approved therapy appears to be effective for some whose condition isn’t improved with medication.

    Dr. Andrew Leuchter talks with a patient who is about to undergo transcranial magnetic stimulation, which treats depression by sending magnetic pulses to a specific area of the brain. UCLA Health

    Americans spend billions of dollars each year on antidepressants, but the National Institutes of Health estimates that those medications work for only 60 percent to 70 percent of people who take them. In addition, the number of people with depression has increased 18 percent since 2005, according to the World Health Organization, which this year launched a global campaign encouraging people to seek treatment.

    The Semel Institute for Neuroscience and Human Behavior at UCLA is one of a handful of hospitals and clinics nationwide that offer a treatment that works in a fundamentally different way than drugs. The technique, transcranial magnetic stimulation, beams targeted magnetic pulses deep inside patients’ brains — an approach that has been likened to rewiring a computer.

    TMS has been approved by the FDA for treating depression that doesn’t respond to medications, and UCLA researchers say it has been underused. But new equipment being rolled out this summer promises to make the treatment available to more people.

    “We are actually changing how the brain circuits are arranged, how they talk to each other,” said Dr. Ian Cook, director of the UCLA Depression Research and Clinic Program. “The brain is an amazingly changeable organ. In fact, every time people learn something new, there are physical changes in the brain structure that can be detected.”

    Nathalie DeGravel, 48, of Los Angeles had tried multiple medications and different types of therapy, not to mention many therapists, for her depression before she heard about magnetic stimulation. She discussed it with her psychiatrist earlier this year, and he readily referred her to UCLA.

    Within a few weeks, she noticed relief from the back pain she had been experiencing; shortly thereafter, her depression began to subside. DeGravel says she can now react more “wisely” to life’s daily struggles, feels more resilient and is able to do much more around the house. She even updated her resume to start looking for a job for the first time in years.

    During TMS therapy, the patient sits in a reclining chair, much like one used in a dentist’s office, and a technician places a magnetic stimulator against the patient’s head in a predetermined location, based on calibrations from brain imaging.

    The stimulator sends a series of magnetic pulses into the brain. People who have undergone the treatment commonly report the sensation is like having someone tapping their head, and because of the clicking sound it makes, patients often wear earphones or earplugs during a session.

    TMS therapy normally takes 30 minutes to an hour, and people typically receive the treatment several days a week for six weeks. But the newest generation of equipment could make treatments less time-consuming.

    “There are new TMS devices recently approved by the FDA that will allow patients to achieve the benefits of the treatment in a much shorter period of time,” said Dr. Andrew Leuchter, director of the Semel Institute’s TMS clinical and research service. “For some patients, we will have the ability to decrease the length of a treatment session from 37.5 minutes down to 3 minutes, and to complete a whole course of TMS in two weeks.”

    Leuchter said some studies have shown that TMS is even better than medication for the treatment of chronic depression. The approach, he says, is underutilized.

    “We are used to thinking of psychiatric treatments mostly in terms of either talk therapies, psychotherapy or medications,” Leuchter said. “TMS is a revolutionary kind of treatment.”

    Bob Holmes of Los Angeles is one of the 16 million Americans who report having a major depressive episode each year, and he has suffered from depression his entire life. He calls the TMS treatment he received at UCLA Health a lifesaver.

    “What this did was sort of reawaken everything, and it provided that kind of jolt to get my brain to start to work again normally,” he said.

    Doctors are also exploring whether the treatment could also be used for a variety of other conditions including schizophrenia, epilepsy, Parkinson’s disease and chronic pain.

    “We’re still just beginning to scratch the surface of what this treatment might be able to do for patients with a variety of illnesses,” Leuchter said. “It’s completely noninvasive and is usually very well tolerated.”

    See the full article here .

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    We doubt the critics, reject the status quo and see opportunity in dissatisfaction. Our campus, faculty and students are driven by optimism. It is not naïve; it is essential. And it has fueled every accomplishment, allowing us to redefine what’s possible, time after time.

    This can-do perspective has brought us 12 Nobel Prizes, 12 Rhodes Scholarships, more NCAA titles than any university and more Olympic medals than most nations. Our faculty and alumni helped create the Internet and pioneered reverse osmosis. And more than 100 companies have been created based on technology developed at UCLA.

  • richardmitnick 12:17 pm on May 31, 2017 Permalink | Reply
    Tags: , Depression, , STRADL (Stratifying Resilience and Depression Longitudinally),   

    From Aberdeen: “Major depression study gathers momentum” 

    U Aberdeen bloc

    University of Aberdeen

    30 May 2017
    The Communications Team
    Office of External Affairs, University of Aberdeen, King’s College, Aberdeen
    +44 (0)1224 272014

    Some of the Children of the 1950s volunteers posing with their own brain scans, taken as part of the STRADL study into depression

    More than 500 Aberdeen volunteers have been recruited to a major £4.7million study to understand depression more clearly than ever before.

    Researchers held a celebration and information event today (May 30) to thank participants and call for more to come forward.

    Clinical depression is the leading cause of non-fatal disability in the world and contributes to massive socioeconomic impact in terms of time off work and reduced productivity.

    Experts say that rather than being one disease, clinical depression is a collection of different disorders with one common symptom – that of low mood.

    However, there has been a lack of high quality research to understand different brain disorders that may cause the condition.

    The STRADL (Stratifying Resilience and Depression Longitudinally) study, led by Professor Andrew McIntosh at the University of Edinburgh and run by researchers at the universities of Aberdeen, Dundee and Edinburgh, is funded by the Wellcome Trust. It uses brain scans, blood tests and cognitive tests to study people with and without a history of depression to identify and arrange different subgroups in a bid to identify common risk factors and new treatments.

    The STRADL study is built on Generation Scotland – a massive resource of biological samples available for medical research. Researchers at the University of Aberdeen have targeted a subset of the Aberdeen Children of the 1950s Cohort and their relatives. In primary school the Aberdeen Children of the 1950s – a group made up of all the children born in the city between 1950 and 1956 – sat tests of reading and mental ability. As such, researchers are able to build up a lifelong profile of participants. At the University of Dundee recruitment has targeted the Walker Cohort, people with prior birth details, and their relatives.

    Each participant in the STRADL study is scanned in an MRI machine because the resulting images show differences in brain structure and function that may be associated with depression. Importantly, this means people who have been exposed to the same risk factors but not developed depression, can be compared to those who have become depressed.

    Participants are also given a test of their cognitive abilities – thinking and memory tests as well as other clinical and emotional tests.

    Professor Alison Murray who is leading the study in Aberdeen said: “Depression remains very complicated to diagnose. There is no simple set of criteria that allow us to identify those who are most at risk and how best to treat them.

    “The STRADL study aims to reclassify depression based on biology. By gathering information such as brain scans, cognitive tests and other clinical measurements, we hope to be able to better categorise people and as such identify more specific areas to develop new treatments.

    “The beauty of working with the Aberdeen Children of the 1950s Cohort, is that we can compare the results of people who have depression and those who don’t, not just today, but also from when they were in primary school. This helps us better understand why even when people who are exposed to the same risk factors in life, some are resilient and don’t get depression, whilst others do. There may be life course events, or genetic differences that predispose some to depression. There are also things we can detect in blood samples or brain scans about how they process information differently.

    “We are delighted to have recruited more than 500 people already in Aberdeen and along with our partners at the University of Dundee, we are more than halfway towards our overall goal. We’re so grateful for all those from Generation Scotland who have already taken part and we would call for any other members who haven’t yet, to contact us for a chance to help us come up with new ways to treat this debilitating condition.”

    Any members of the Children of the 1950s Cohort who would like to get involved in the study should contact 01224 438443 or children1950s@abdn.ac.uk. Or visit http://www.abdn.ac.uk/birth-cohorts/ or http://facebook.com/aberdeenbirthcohorts

    See the full article here .

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    U Aberdeen Campus

    Founded in 1495 by William Elphinstone, Bishop of Aberdeen and Chancellor of Scotland, the University of Aberdeen is Scotland’s third oldest and the UK’s fifth oldest university.

    William Elphinstone established King’s College to train doctors, teachers and clergy for the communities of northern Scotland, and lawyers and administrators to serve the Scottish Crown. Much of the King’s College still remains today, as do the traditions which the Bishop began.

    King’s College opened with 36 staff and students, and embraced all the known branches of learning: arts, theology, canon and civil law. In 1497 it was first in the English-speaking world to create a chair of medicine. Elphinstone’s college looked outward to Europe and beyond, taking the great European universities of Paris and Bologna as its model.
    Uniting the Rivals

    In 1593, a second, Post-Reformation University, was founded in the heart of the New Town of Aberdeen by George Keith, fourth Earl Marischal. King’s College and Marischal College were united to form the modern University of Aberdeen in 1860. At first, arts and divinity were taught at King’s and law and medicine at Marischal. A separate science faculty – also at Marischal – was established in 1892. All faculties were opened to women in 1892, and in 1894 the first 20 matriculated female students began their studies. Four women graduated in arts in 1898, and by the following year, women made up a quarter of the faculty.

    Into our Sixth Century

    Throughout the 20th century Aberdeen has consistently increased student recruitment, which now stands at 14,000. In recent years picturesque and historic Old Aberdeen, home of Bishop Elphinstone’s original foundation, has again become the main campus site.

    The University has also invested heavily in medical research, where time and again University staff have demonstrated their skills as world leaders in their field. The Institute of Medical Sciences, completed in 2002, was designed to provide state-of-the-art facilities for medical researchers and their students. This was followed in 2007 by the Health Sciences Building. The Foresterhill campus is now one of Europe’s major biomedical research centres. The Suttie Centre for Teaching and Learning in Healthcare, a £20m healthcare training facility, opened in 2009.

  • richardmitnick 1:01 pm on January 6, 2017 Permalink | Reply
    Tags: , Depression, EVO Project, ,   

    From U Washington: “Game your brain to treat depression, studies suggest” 

    U Washington

    University of Washington

    Bobbi Nodell

    Project: EVO targets an individual’s core neurological ability to process multiple streams of information and helps to treat the cause of depression, researchers found. Scott Areman

    Researchers have found promising results for treating depression with a video game interface that targets underlying cognitive issues associated with depression rather than just managing the symptoms.

    “We found that moderately depressed people do better with apps like this because they address or treat correlates of depression,” said Patricia Areán, a UW Medicine researcher in psychiatry and behavioral sciences.

    The first study enrolled older adults diagnosed with late-life depression into a treatment trial where they were randomized to receive either a mobile, tablet-based treatment technology developed by Akili Interactive Labs called Project: EVO or an in-person therapy technique known as problem-solving therapy (PST).

    Project: EVO runs on phones and tablets and is designed to improve focus and attention at a basic neurological level. The results, published Jan. 3 in the journal Depression and Anxiety, showed that the group using Project: EVO demonstrated specific cognitive benefits (such as attention) compared to the behavioral therapy, and saw similar improvements in mood and self-reported function. Joaquin A. Anguera, a University of California, San Francisco (UCSF), researcher in neurology and psychiatry, is the lead author, and Areán is the senior author. The researchers have no commercial interests in the intervention manufactured by Akili Interactive Labs in Boston. The studies were funded by the National Institute of Mental Health.

    “While EVO was not directly designed to treat depressive symptoms; we hypothesized that there may indeed be beneficial effects on these symptoms by improving cognitive issues with targeted treatment, and so far, the results are promising,” said Anguera.

    People with late-life depression (60+) are known to have trouble focusing their attention on personal goals and report trouble concentrating because they are so distracted by their worries. Akili’s technology was designed to help people better focus their attention and to prevent people from being easily distracted.

    Arean said most of the participants had never used a tablet, let alone played a video game, but compliance was more than 100 percent. The participants were required to play the game five times a week for 20 minutes, but many played it more. Participants in this arm of the study also attended weekly meetings with a clinician. The meetings served as a control for the fact that participants in the problem-solving therapy arm were seen in person on a weekly basis, and social contact of this nature can have a positive effect on mood.

    Second study

    A second study, which was another joint effort by UW and UCSF, randomized more than 600 people across the United States assessed as moderately or mildly depressed to one of three interventions: Akili’s Project: EVO; iPST, an app deployment of problem-solving therapy; or a placebo control (an app called Health Tips, which offered healthy suggestions).

    Areán, the lead researcher on the study published Dec. 20 in the Journal of Medical Internet Research (JIMR), found that people who were mildly depressed were able to see improvements in all three groups, including the placebo. However, those individuals who were more than mildly depressed showed a greater improvement of their symptoms following their use of Project EVO or iPST versus the placebo.

    Areán said much of her research is aimed at providing effective treatment to people who need it, and these results provide great potential for helping people who don’t have the resources to access effective problem solving therapy. But, she stressed, the apps should be used under clinical supervision because without a human interface, people were not as motivated to use it. In the JIMR study, 58 percent of participants did not download the app.

    Akili’s technologies are based on a proprietary neuroscience approach developed to target specific neurological systems through sensory and digital mechanics. The company’s technology platform used in this trial is based on cognitive science exclusively licensed from the lab of Dr. Adam Gazzaley at UCSF, and adaptive algorithms developed at Akili, which are built into action video game interfaces. The technology targets an individual’s core neurological ability to process multiple streams of information.

    Project: EVO is undergoing multiple clinical trials for use in cognitive disorders — including Alzheimer’s disease, traumatic brain injury and pediatric attention deficit hyperactivity disorder (ADHD), and the company is on path for potential FDA clearance to treat pediatric ADHD.

    Areán is recruiting for a study at UW and Cornell of older adults (60+) willing to have their brains scanned before and after interacting with Akili’s technology. A separate UW Medicine study is seeking participants 45+ with depression. For details, email brighten@uw.edu.

    See the full article here .

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  • richardmitnick 4:00 pm on May 30, 2016 Permalink | Reply
    Tags: , Big Data Sleuths Uncover Clues to the Roots of Depression, Depression,   

    From SA: “Big Data Sleuths Uncover Clues to the Roots of Depression” 

    Scientific American

    Scientific American

    May 30, 2016
    Gary Stix

    The daunting complexity of neurological disorders has begun to yield to methods that allow intensive scrutiny of genes and neural circuits.

    Model of a gene network used to study depression. Credit: Rosemary Bagot

    Scientists will never find a single gene for depression—nor two, nor 20. But among the 20,000 human genes and the hundreds of thousands of proteins and molecules that switch on those genes or regulate their activity in some way, there are clues that point to the roots of depression. Tools to identify biological pathways that are instrumental in either inducing depression or protecting against it have recently debuted—and hold the promise of providing leads for new drug therapies for psychiatric and neurological diseases.

    A recent paper* in the journal Neuron illustrates both the dazzling complexity of this approach and the ability of these techniques to pinpoint key genes that may play a role in governing depression. Scientific American talked with the senior author on the paper—neuroscientist Eric Nestler from the Icahn School of Medicine at Mt. Sinai in New York. Nestler spoke about the potential of this research to break the logjam in pharmaceutical research that has impeded development of drugs to treat brain disorders.

    Scientific American: The first years in the war on cancer met with a tremendous amount of frustration. Things look like they’re improving somewhat now for cancer. Do you anticipate a similar trajectory may occur in neuroscience for psychiatric disorders?

    Eric Nestler: I do. I just think it will take longer. I was in medical school 35 years ago when the idea that identifying a person’s specific pathophysiology was put forward as a means of directing treatment of cancer. We’re now three decades later finally seeing the day when that’s happening. I definitely think the same will occur for major brain disorders. The brain is just more complicated and the disorders are more complicated so it will take longer.

    SA: Do you have any estimates of how long it might take?

    EN: I don’t think it will be 30 years because we’ve learned a lot from cancer and other fields like immunology. That will guide us and teach us as we make progress for the brain so I would say between five or 10 years. There are already insights—specific genes and biochemical pathways—that have been identified now for brain disorders that are being followed up on. If we get lucky and some of those prove to be useful, we can start to see some clinical advances within about five years.

    SA: There have been a lot of genetic studies that have looked for links between genes and psychiatric disorders but they turn up hundreds of genes of interest. How do you actually proceed to use that information to do something useful to both understand disease and to treat it?

    EN: This is a major question of our time. One approach is to determine how differences in hundreds of genes would affect key biochemical pathways inside the brain. Although there are hundreds of genes, the expectation is that there’s just a handful of altered biochemical pathways. Now if we could find those pathways and how they’re altered and figure out ways to reverse those changes, we might be able to come up with new therapeutics. That is our working hypothesis now.

    SA: Can you take information from one of these large genetic studies of recent years and use a technique to find either a key gene or pathway?

    EN: Doing that is complicated because we’re dealing with literally tens of thousands of gene products—proteins or RNAs (the latter are molecules that, along with DNA, encode the making of proteins). And so we must sift through how a few hundred out of tens of thousands of these gene products are altered. How they influence biochemical pathways is a complicated process in and of itself. But this process is tractable and it is work that can be done now.

    SA: Aren’t you using multiple techniques to try to deal with this complexity?

    EN: We use several approaches. First we identify the tens of thousands of RNAs present in different brain areas and put that information together with direct measures of how different brain areas function abnormally in an animal model of depression. It’s an effort to help us determine which of many thousands of these gene products would be the most important to study. The real challenge right now is one of bandwidth. If you find hundreds or thousands of genes, how do you know which ones are the best to study first?

    SA: How do you?

    EN: It is overwhelming at first, but we use several statistical approaches and overlay different data sets on one another. Genes that come up repeatedly in multiple models in multiple ways from multiple angles are more likely to be important than others.

    SA: What are one or two examples of the techniques that you have now that you didn’t say 10 or 20 years ago that would have made this research impossible back then?

    EN: Right now it’s possible to identify all of the gene products expressed in a given brain area or even within a single type of cell within a given brain area. That couldn’t have been done years ago. Then we can use various tools to identify the genes that are most dramatically regulated in those cells in mice exposed to chronic social stress. And then we identify several specific genes that come up as being important in overlapping approaches and study them directly.

    We can have a single gene make more protein than normal or turn that gene off within a targeted cell type within the brain. We can thereby see whether turning that gene expression up or down mimics or reverses depression-like behavior in an animal model. Then we can understand how that gene product alters the functioning of the cell. Does it excite the cell, make it more active or make it less active? Next, we can use optogenetics tools that can directly manipulate the activity of that given cell type in an awake, behaving animal. So for the first time it’s possible for the field to start out with genetic methods and bring them all the way forward to see how nerve cells are functioning within the brain in a live animal to influence depression-related behaviors.

    SA: What tools would you still really like to have if you could?

    EN: I think the main advances that are still needed now are to find ways to make it easier to manipulate individual cell types. The ability exists, we just need to expand the tools available. The second thing is the ability to manipulate several genes at once. Right now the tools that we and others use enable manipulating only a single gene at a time. It would be very nice to go into an experimental animal and manipulate multiple genes at one time. New gene-editing techniques make it possible theoretically to do that, but it’s still not straightforward, particularly in brain.

    SA: What did you do in the experiment reported in the Neuron paper?

    EN: Rosemary Bagot, the study’s first author, and our colleagues used these methods to identify the most important genes in a mouse depression model and then developed tools to either overexpress a given gene of interest or to knock it out. We then studied the consequences of those manipulations on behavior. One of the most interesting genes that we found by looking with statistical tools through 20,000 genes was Dkkl1. The gene is known to be involved in signaling in a basic biochemical pathway called Wnt inside of cells. We identified the brain area where this gene seemed to be playing the most important role and that was the hippocampus (an area important for learning, memory and emotional behavior). We thus overexpressed Dkkl1 (encoded more of its protein than normal) in the hippocampus and studied the effects on behavior and gene expression.

    Our molecular data suggested that Dkkl1 is a very important hub gene that regulates other key genes and we showed that overexpressing Dkkl1 in the hippocampus was enough to make mice susceptible to stress and to induce depression-like behavior. Dkkl1 overexpression also selectively regulated genes that it was predicted to regulate in our data sets. This illustrates the ability go from using very basic statistical methods for gene discovery all the way to finding a new gene never studied before in models of depression-like phenomena.

    SA: Would you say that this approach could be used in studying other psychiatric diseases as well?

    EN: Yes, most definitely. And, in fact, efforts are under way by us and others to do this kind of work in several other syndromes such as autism, schizophrenia, bipolar disorder, drug abuse and so on.

    SA: What will be the potential payoff both in understanding depression and in developing drugs to treat it?

    EN: Right now we still have very limited understanding of the molecular underpinnings of depression. So studies like this can identify a more complete list of genes and biochemical pathways involved in depression. The work now provides a template that can guide drug discovery efforts. If Dkkl1 is in a depression-related pathway, we can ask how we might affect this pathway in a way that would be predicted to produce an antidepressant response?

    SA: How would a drug produced in this way potentially be better than the antidepressants we have now?

    EN: All of the antidepressants we have now are based on serendipitous discoveries from six decades ago. Antidepressants act on monoamines (molecules also known as neurotransmitters). There is no approved antidepressant that’s non-monoamine acting.

    We think that focusing on these gene networks would provide novel treatments for depression. Since all of today’s treatments for depression focus on monoamine pathways, they’re very limited. Even though we have hundreds of molecules, they’re all basically the same.

    SA: And today’s antidepressants don’t help all people?

    EN: Large clinical trials show that only about half, maybe fewer than half of all people with depression, are fully treated—meaning they get fully well with available treatments. It’s no surprise that the same range of patients that respond to one drug respond to the others because all of the drugs basically act in the same way. There’s been this desperate need in the field to develop antidepressants with novel mechanisms for those who aren’t helped by available drugs and we think this is one approach to doing that.

    SA: Is it also possible that you might be able to take a wholly new approach of making those at risk for depression more resilient so that they don’t become depressed?

    EN: Yes, absolutely. Another approach is to look at the resilient mice in this study and ask: Can we identify genes that control resilience and then can we design still additional medications to boost resilience as a novel approach to antidepressant therapy. We think that that’s definitely possible. We have another study that’s in the works now where we’ve looked at groups of genes that we’ve found through this type of analysis to be important for resilience and have demonstrated already the ability to manipulate these genes and make a mouse more resilient.

    SA: These are only mouse models.

    EN: This is a mouse study and one of the first things we need to do is to now validate these genes that have been found in depressed mice in post-mortem human brain tissue from depressed humans and that’s work that we and others are also doing. We have another study that’s under way employing very similar statistical approaches on human brain tissue, which we think is essential. The validity of this approach has been demonstrated by an ongoing clinical trial for depression at Mount Sinai: our clinical colleagues are testing in humans a molecule that was first shown to boost resilience in mouse models based on our gene expression data. Preliminary data are encouraging although far more work is needed to validate this finding.

    SA: How would you describe your approach as being different from early-stage development for neurological drugs?

    EN: First of all, very few companies are still in the psychiatry space. There is a desperate need because psychiatric disorders are among the most impactful on humanity and it’s a tragedy that drug companies are not doing this. As far as drug development, almost all drug discovery efforts thus far have focused on candidate genes one at a time—in other words, they are not looking at all 20,000 genes at once and seeing which are the most important, but just basically guessing based on limited information about whether gene “A,” “B” or “C” might be interesting and then trying to develop something using that gene or its pathway. We think that we and others have articulated a fundamentally broader approach to drug discovery to really look at all genes in total and see which ones are the most important and then target those. I think that drug companies will start to do that pretty soon and that that will represent a major advance for the field, but we’re still in very early stages.

    (Other researchers on the Neuron paper (not all from Mt. Sinai) were: Rosemary C. Bagot, Hannah M. Cates, Immanuel Purushothaman, Zachary S. Lorsch, Deena M. Walker, Junshi Wang, Xiaojie Huang, Oliver M. Schlüter, Ian Maze, Catherine J. Peña, Elizabeth A. Heller, Orna Issler, Minghui Wang, Won-min Song, Jason. L. Stein, Xiaochuan Liu, Marie A. Doyle, Kimberly N. Scobie, Hao Sheng Sun, Rachael L. Neve, Daniel Geschwind, Yan Dong, Li Shen and Bin Zhang.)

    *Science paper:
    Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility

    See the full article here .

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  • richardmitnick 12:49 pm on May 17, 2016 Permalink | Reply
    Tags: , Depression, Magic-mushroom drug lifts depression in first human trial,   

    From Nature: “Magic-mushroom drug lifts depression in first human trial” 

    Nature Mag

    17 May 2016
    Zoe Cormier

    Researchers’ long fight to test psilocybin’s safety finally yields fruit.

    Magic mushrooms are taken for their psychedelic effects, but end up improving depression treatment. Diverse Images/UIG/Getty Images

    A hallucinogenic drug derived from magic mushrooms could be useful in treating depression, the first safety study of this approach has concluded.

    Researchers from Imperial College London gave 12 people psilocybin, the active component in magic mushrooms. All had been clinically depressed for a significant amount of time — on average 17.8 years. None of the patients had responded to standard medications, such as selective serotonin re-uptake inhibitors (SSRIs), or had electroconvulsive therapy.

    Brain scans reveal how LSD affects consciousness

    One week after receiving an oral dose of psilocybin, all patients experienced a marked improvement in their symptoms. Three months on, five patients were in complete remission.

    “That is pretty remarkable in the context of currently available treatments,” says Robin Carhart-Harris, a neuropsychopharmacologist at Imperial College London and first author of the latest study, which is published* in The Lancet Psychiatry.

    The equivalent remission rate for SSRIs is around 20%.

    The study’s authors are not suggesting that psilocybin should be a treatment of last resort for depressed patients. “Our conclusion is more sober than that — we are simply saying that this is doable,” says Carhart-Harris. “We can give psilocybin to depressed patients, they can tolerate it, and it is safe. This gives us an initial impression of the effectiveness of the treatment.”

    Drug problems

    Demonstrating the safety of psilocybin is no small task. Magic mushrooms are categorized as a Class A illegal drug in the United Kingdom — the most serious category, which also includes heroin and cocaine.

    The ethics committee that granted approval for the trial was so concerned that trial volunteers could experience delayed onset psychotic symptoms that it requested a three-month follow-up on the subjects.

    “This was unprecedented,” says neuropsychopharmacologist David Nutt at Imperial, who is senior author of the study.

    It took 32 months between having the grant awarded and dosing the first patient, says Nutt. By comparison, it took six months “to get through the machinations” for his team’s previous studies using the equally illegal drugs LSD and MDMA, he says.

    “Every interaction — applying for licenses, waiting for licenses, receiving the licenses, applying for contracts for drug manufacture, on and on — involved a delay of up to two months. It was enormously frustrating, and most of it was unnecessary,” says Nutt. “The study result isn’t the remarkable part — it’s the fact that we did it at all.”

    Scientists at the Heffter Research Institute in Santa Fe, New Mexico, have been investigating how psilocybin could be used to alleviate depression and anxiety in people with terminal cancer, but this is the first study to look specifically at how psilocybin could be used to treat depression alone.

    The World Health Organisation calls depression “the leading cause of disability worldwide”. But effective therapies are hard to find. Searching for new treatments, researchers have looked to potent and quirky alternatives such as ketamine and ayahuasca, both of which have shown promise in clinical trials.

    “It’s worth noting that we have not developed any new treatments which are widely used since the 1970s for depression, despite the fact that this is the major public-health problem in the Western world and middle-income countries,” says Glyn Lewis, who studies psychiatric disorders at University College London.

    Particularly interesting, he says, is the fact that psilocybin seems to take effect with a single dose, unlike some current medications for depression that must be taken daily.

    “This study is simply asking: is this interesting enough to pursue further as a treatment for depression?” says Lewis. “My own judgement is that yes, it is.”

    *Science paper:
    Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

    See the full article here .

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  • richardmitnick 11:03 am on September 17, 2014 Permalink | Reply
    Tags: , Depression,   

    From Huff Post: “A Blood Test For Depression Shows The Illness Is Not A Matter Of Will” 

    Huffington Post
    The Huffington Post

    Anna Almendrala

    Screening for depression might soon be as easy as a blood test.


    A new test that identifies particular molecules in the blood could help doctors diagnose patients with clinical depression, according to a new study published in the journal Translational Psychiatry. The blood test can also predict which therapies would be most successful for patients, and lays the groundwork for one day identifying people who are especially vulnerable to depression — even before they’ve gone through a depressive episode.

    But perhaps just as important, said lead investigator Eva Redei, Ph.D., is the potential the test has for taking some of the stigma out of a depression diagnosis. When depression can be confirmed with a blood test like any other physical ailment, she said, there’s less stigma about having the disease and getting treatment.

    “I really believe that having an objective diagnosis will decrease stigma,” Redei, a neuroscientist and professor at the Northwestern University Feinberg School of Medicine, told The Huffington Post. “Once you have numbers in your hand, you can identify that [depression] is an illness — not a matter of will.”

    The most effective way to treat depression is to treat it early, but past studies show that it takes an average of two to 40 months to diagnose depression — if it gets diagnosed at all. Redei’s depression blood test could lead to faster and more accurate diagnoses, thereby transforming the way depression is treated.

    If Redei’s findings are independently replicated and confirmed, then approved by the Food and Drug Administration, laboratories across the U.S. could incorporate the test into their battery of routine exams. This is in contrast to MDDScore, a depression blood test owned by Ridge Diagnostics that was announced in 2012. Because the test is proprietary to Ridge Diagnostics, doctors have to submit samples to the company’s lab in North Carolina, where the company analyzes the blood and sends back results. Redei’s test, however, “can be done by any clinical laboratory anywhere, just like a cholesterol test,” Redei explained. “That is, assuming that we can go through the FDA approval [process] fast.”

    Redei’s study compared the blood samples of 32 patients who had been diagnosed with depression in the traditional way (a clinical interview) with samples taken from 32 people without depression. She found nine RNA blood markers — the molecules that carry out DNA’s instructions — that differed significantly between the two groups, which she then used as the basis for the depression diagnosis.

    Then, the depressed patients went through 18 weeks of cognitive behavioral therapy, a common treatment for depression. Re-testing their blood, Redei was able to tell which patients had benefitted the most from therapy, just by examining the changes in their RNA markers. In other words, the test was also a biological way to tell if treatment had been effective.

    Finally, Redei also noticed that there were three RNA markers that didn’t change in depressed patients, no matter if they had benefitted from cognitive behavioral therapy or not. She suspects they may be markers that show if a person is predisposed to depression.

    “Being aware of people who are more susceptible to recurring depression allows us to monitor them more closely,” said David Mohr, Ph.D., co-lead author of the study in a press release. “They can consider a maintenance dose of antidepressants or continued psychotherapy to diminish the severity of a future episode or prolong the intervals between episodes.”

    Zachary Kaminsky, Ph.D., of the Mood Disorders Center at Johns Hopkins Medicine, wasn’t involved with the study but is excited about its potential implications for depression treatment. Kaminsky is a pioneer in blood tests to predict suicide risk, and although he and Redei measure very different things in their tests, he sees that both researchers have similar goals when it comes to creating biological tests for mental illnesses.

    “It’s an exciting time — there is potential to find factors that are going to distinguish between various mental illnesses as well as responses to direct clinical treatment,” said Kaminsky to HuffPost. “Any finding that gets us closer to that is very interesting and worth following up.”

    But Kaminsky also pointed out that Redei and Mohr’s research still needs to be independently validated by other patient populations to confirm that it works. For instance, Kaminsky pointed out, the study would have been more scientifically rigorous if it had used a different patient group to confirm the blood test, as opposed to using the same participants to both create and then test the predictions.

    “I think this is very early stage and this model needs to be investigated in an independent sample,” Kaminsky said. “It will be important to test the predictability of these expression measures in independent cohorts.”

    Redei acknowledged that the next step in research would be to run the tests on larger samples in order to validate the models and then submit them for FDA approval.

    “The major question here is always funding,” said Redei. “We are really trying to gather as much funding from as many sources as possible so it can move ahead.”

    Major depressive disorder affects an estimated 6.7 percent of the U.S. population and is the leading cause of disability for Americans ages 15 to 44, according to the Anxiety and Depression Association of America. Despite the research hurdles she still needs to overcome, Redei is confident that her test can make a positive impact on the millions who struggle with depression — not only by making treatment more precise, but by bringing psychiatry “into the 21st century,” Redei said. “We’ll get to the point where there won’t be any discrimination between physical illness and mental illness.”

    See the full article here.

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