Month: November 2019

Health and Wellbeing

New way to think about brain’s link to postpartum depression

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Science News

Research in animals shows brain’s immune system is activated by stress during pregnancy

October 21, 2019

Source: Ohio State University

Chronic stress during pregnancy triggers an immune response in the brain that has potential to alter brain functions in ways that could contribute to postpartum depression, new research in animals suggests.

The study is the first to show evidence of this gestational stress response in the brain, which is unexpected because the immune system in both the body and the brain is suppressed during a normal pregnancy.

The Ohio State University researchers who made the discovery have been studying the brain biology behind postpartum depression for several years, creating depressive symptoms in pregnant rats by exposing them to chronic stress. Chronic stress during pregnancy is a common predictor of postpartum depression, which is characterized by extreme sadness, anxiety and exhaustion that can interfere with a mother’s ability to care for herself or her baby.

Stress is known to lead to inflammation, which prompts an immune response to protect against inflammation’s harmful effects. Based on what they already know about compromised brain signaling in rats stressed during pregnancy, the scientists suspect the immune cells in the brain responding to stress may be involved. If that’s the case, the immune changes may create circumstances in the brain that increase susceptibility to depression.

In unstressed pregnant rats, the normal suppression of the immune system in the body and the brain remained intact throughout pregnancy. In contrast, stressed rats showed evidence of neuroinflammation. The study also showed that the stressed rats’ immune response in the rest of their bodies was not active.

“That suggests there’s this disconnect between what’s happening in the body and what’s happening in the brain,” said Benedetta Leuner, associate professor of psychology at Ohio State and lead author of the study. She speculated that the signaling changes her lab has seen before in the brain and this immune response are happening in parallel, and may be directly related.

Leuner presented the findings Saturday (Oct. 19, 2019) at the Society for Neuroscience meeting in Chicago.

In this work, rats are exposed to unpredictable and varied stressful events throughout their pregnancies, a practice that adds a component of psychological stress but does not harm the health of the mother or her offspring.

In the stressed animals, the researchers found numerous pro-inflammatory compounds that indicated there was an increase in the number and activity levels of the primary immune cells in the brain called microglia. Their findings also suggested the microglia were affecting brain cells in the process.

Leuner’s lab previously determined in rats that chronic stress during pregnancy prevented motherhood-related increases in dendritic spines, which are hair-like growths on brain cells that are used to exchange information with other neurons. These same rats behaved in ways similar to what is seen in human moms with postpartum depression: They had less physical interaction with their babies and showed depressive-like symptoms.

Leuner and colleagues now plan to see whether the brain immune cells activated during gestational stress are responsible for the dendritic spine elimination. They suspect that microglia might be clearing away synaptic material on dendrites.

Leuner has partnered on this research with Kathryn Lenz, assistant professor of psychology at Ohio State, whose work explores the role of the immune system in brain development.

Though pregnancy was known to suppress the body’s immune system, Lenz and Leuner showed in a previous study that the same suppression of the immune system happens in the brain during pregnancy — the number of microglia in the brain decreases.

“By layering gestational stress onto a normal pregnancy, we’re finding this normal immunosuppression that should happen during pregnancy doesn’t occur, and in fact there’s evidence of inflammatory signaling in the brain that could be bad for dendritic spines and synapses,” Lenz said. “But we’ve also found changes in the microglia’s appetite. Every characteristic we’ve looked at in these cells has changed as a result of this stress.”

The researchers are now trying to visualize microglia while they’re performing their cleanup to see if they are eating synaptic material. They are also manipulating inflammatory changes in the brain to see if that reverses postpartum depression-like behavior in rats.

“We’ve seen the depressive-like symptoms and neural changes in terms of dendritic spines and synapses, and now we have neuroimmune changes suggesting that those microglia could be contributing to the neural changes — which we think ultimately underlie the behaviors,” Leuner said.

The research was supported by the National Institutes of Health.

Ohio State current and former students Caitlin Goodpaster, Nicholas Deems and Rachel Gilfarb also worked on the study.

Story Source:

Materials provided by Ohio State University. Original written by Emily Caldwell. Note: Content may be edited for style and length.

Cite This Page:

Ohio State University. “New way to think about brain’s link to postpartum depression: Research in animals shows brain’s immune system is activated by stress during pregnancy.” ScienceDaily. ScienceDaily, 21 October 2019. <www.sciencedaily.com/releases/2019/10/191021151538.htm>.

 

Health and Wellbeing

How should the FDA evaluate new medications for pain?

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Dear U.S. Pain volunteer advocates,  

We wanted to make you aware of an opportunity to submit public comments to the Food and Drug Administration (FDA). Specifically, the FDA would like the public’s views on two main issues: 1. What criteria the FDA should use to evaluate new opioids to treat pain2. What new incentives are needed to better support and encourage the development of new treatments for pain
On Sept. 17 the FDA held a public hearing called “Standards for Future Opioid Analgesic Approvals and Incentives for New Therapeutics to Treat Pain and Addiction.” While the public hearing has passed, the FDA is accepting written comments until Nov. 18.  
How to submit
Written comments are to be submitted to the Division of Docket’s Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Electronic comments can be submitted by using the button below.All comments must be identified with the docket number FDA-2019-N-2514. Please keep in mind that all comments submitted to the docket are public.
Why advocates should engageWe think it is important for people with pain to let FDA know your thoughts on these issues. A number of people and organizations at the hearing said that they thought no new opioids should be allowed on the market. What’s your opinion about this?
People with pain need new options
There has long been a lack of new non-opioid medications approved for pain. We encourage you to tell FDA what impact pain has had on your life and how speeding up the development of new drugs in the pipeline could make a difference to your life and the lives of so many others debilitated by chronic pain. People with pain need to make our voices heard. We encourage you to write into the docket.Sincerely,
Cindy SteinbergNational Director of Policy & AdvocacyU.S. Pain FoundationSubmit comments here!
U.S. Pain Foundation 
contact@uspainfoundation.org | uspainfoundation.org 
670 Newfield Street 
Suite B 
Middletown, CT 06457 
Fun

#SoCS Prompt “dream”

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StreamOfConsciousnessQuaintRevival2019

Your Friday prompt for Stream of Consciousness Saturday is “dream.” Use it any way you’d like. Have fun!

Dream or dreaming would seem like an easy topic to write about but dreaming comes in many forms. Dreams I have for the world, for my friends, dreams I have for family and not least dreams I have for myself. I believe one should dream, set a bar higher from where you are and visualize it with all your heart. The problem with dreaming is some people never get past dreaming about something instead of doing something to make the dream come true.

In my early 20’s, I wasn’t meeting the type of men I wanted to have a long term relationship with. I dreamed of a nice man to share a respectful relationship with but it was not happening. I had to make a change, get way out of my box and go to where I thought nice men would be. I enrolled in college courses, mostly art, attended wine tastings even though I knew nothing about wine and I went to art galleries to see what my classes were talking about when it came to masterpieces.

I’m not a rocket scientist, it didn’t take long, I met professional men, some I dated, others became good friends and most of all I learned a lot about myself. You have to do something to make a dream come true or it just remains a dream.

Melinda

 

 

Here are the rules:

  1. Your post must be Stream of Consciousness writing, meaning no editing (typos can be fixed), and minimal planning on what you’re going to write.
  2. Your post can be as long or as short as you want it to be. One sentence – one thousand words. Fact, fiction, poetry – it doesn’t matter. Just let the words carry you along until you’re ready to stop.
  3. I will post the prompt here on my blog every Friday, along with a reminder for you to join in. The prompt will be one random thing, but it will not be a subject. For instance, I will not say “Write about dogs”; the prompt will be more like, “Make your first sentence a question,” “Begin with the word ‘The,’” or will simply be a single word to get you started.
  4. Ping back! It’s important, so that I and other people can come and read your post! For example, in your post you can write “This post is part of SoCS:” and then copy and paste the URL found in your address bar at the top of this post into yours.  Your link will show up in my comments for everyone to see. The most recent pingbacks will be found at the top. NOTE: Pingbacks only work from WordPress sites. If you’re self-hosted or are participating from another host, such as Blogger, please leave a link to your post in the comments below. https://lindaghill.com
  5. Read at least one other person’s blog who has linked back their post. Even better, read all of them! If you’re the first person to link back, you can check back later or go to the previous week by following my category, “Stream of Consciousness Saturday,” which you’ll find below the “Like” button on my post.
  6. Copy and paste the rules (if you’d like to) in your post. The more people who join in, the more new bloggers you’ll meet and the bigger your community will get!
  7. As a suggestion, tag your post “SoCS” and/or “#SoCS” for more exposure and more views.
  8. Have fun!
Health and Wellbeing · Men & Womens Health

Ketamine and Future Depression Treatments

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October 16, 2019

Psychiatry Advisor Contributing Writer

doctor holding nasal spray
Most antidepressants take time to alleviate symptoms, but ketamine reduces symptoms quickly in most patients with major depressive disorder.

Researchers are hailing ketamine as the most significant new development in psychiatry given its high efficacy for treating major depression. Recent evidence has shown that in addition to depression, ketamine may also be a promising treatment for obsessive-compulsive disorder, post-traumatic stress disorder, and a number of other treatment-refractory neuropsychiatric disorders. In a recent paper published in Drug Discovery Today, researchers explore ketamine’s role in revolutionizing new mental health treatments and discuss how this drug’s mechanism of action has led to an influx of new research and studies on depression treatment.

Ketamine was approved by the US Food and Drug Administration (FDA) in 1970 as an anesthetic and safe alternative to phencyclidine. The therapeutic benefits of ketamine as an antidepressant were explored years later because of a stigma on from its widespread recreational use during the late 1960s and 1970s, and this agent was initially only administered intravenously.

In 2000, researchers found that ketamine had strong, fast-acting, and long-term effects in depression. In a randomized, placebo-controlled, crossover design study, patients with depression received 0.5 mg/kg of ketamine or saline on the first day of testing. Treatments were switched 1 week later. Researchers found that the antidepressant effects of ketamine began within 4 hours, peaked at 72 hours, and lasted for 1 to 2 weeks thereafter.1 In a 2006 study, this finding was replicated in an independent group of 18 patients with major depressive disorder who were resistant to other treatments. Compared with participants who received placebo, those who received ketamine showed significant improvement in symptoms within 110 minutes, with 35% maintaining significant response for at least 1 week.2

In subsequent years, results from a number of placebo-controlled studies revealed that ketamine is largely effective and long-acting in treatment of bipolar disorder and treatment-resistant major depressive disorder and produces antisuicidal and anti-anhedonic effects in mood disorders.

Many of today’s depression treatments are monoaminergic-based, including monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors. These treatments have been proven effective for a large number of patients. However, a significant subset of patients with major depressive disorder do not respond to these agents.1 When compared with ketamine, these agents have a delayed onset of action that can take up to several weeks — increasing the risk for organ failure and suicide in this subset.

A single dose of ketamine is shown to produce rapid and robust effects within hours to days of administration. This agent is also shown to rapidly reduce suicidal ideation, fatigue, and anhedonia, and improve circadian rhythm and sleep patterns in major depressive disorder.1 Researchers point out that these symptoms are synonymous across several psychiatric disorders but remain inadequately treated by monoaminergic-based agents.

The notable differences between ketamine and standard antidepressants have spurred researchers to develop new ketamine treatments that are less invasive than those involving intravenous administration. In March 2019, the FDA approved an intranasal version of ketamine called esketamine for adults with treatment-resistant depression.

Researchers say that ketamine’s mechanism of action in the context of clinical antidepressant efficacy is only partially clear. At present, researchers understand that ketamine’s mechanism of action goes beyond modulating the neurotransmission of glutamate and includes direct and indirect high affinity antagonistic binding properties at the N-methyl-D-aspartate receptor, as well as a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid throughput modulation.1 Researchers have also noted that ketamine is a weak agonist at the mu, delta, and kappa opioid receptors.1

Other mechanisms that may contribute to ketamine’s efficacy for depression treatment include agonism at the dopamine receptor, antagonism at the M1–3 muscarinic receptors, and inhibition of the reuptake of serotonin, dopamine, and norepinephrine.1

Researchers are continuing to investigate ketamine’s underlying mechanism of action so they can progress with identifying and developing new agents that work similarly and that offer fewer side effects, as well as prolonged therapeutic effects.

Ketamine has influenced researchers to place more focus on the glutamatergic system when developing new therapies, since it is thought that rapid-acting antidepressants may trigger neurobiological events deeply rooted in the rapid reconfiguration of limbic circuitries.1 In addition to intranasal esketamine, other examples of rapid-acting glutamatergic agents that show promising results are nitrous oxide and sarcosine.

Nitrous oxide has been used as an anesthetic for more than 150 years and offers many of the same mechanisms as ketamine. Results from a 2015 study revealed that patients with treatment-resistant depression who received nitrous oxide experienced significant improvement in symptoms at 2 hours and 24 hours compared with placebo. Symptoms that showed the largest changes in improvement were depressed mood, guilt, suicidal ideation, and psychic anxiety.3 Additional trials are being conducted to determine the safety, efficacy, and optimal dosing of nitrous oxide for depression.

Sarcosine is an amino acid that functions as a glycine transporter-1 inhibitor and has co-agonistic properties at the N-methyl-D-aspartate receptor. Results from clinical trials have shown that sarcosine is a promising treatment for major depressive disorder and produces no adverse events. However, compared with ketamine, sarcosine does not produce the same rapid-acting effects within the same amount of time.1 Studies are currently underway to replicate the effects of both nitrous oxide and sarcosine in depression.

Ketamine has been found to enhance the transmission of gamma-aminobutyric acid (GABA) to reduce depression. Shortly after approving intranasal esketamine, the FDA approved an agent called brexanolone that acts as a positive allosteric modulator of GABA receptors. Brexanolone is currently being used to treat postpartum depression since this therapy produces rapid- and long-acting antidepressant effects similar to that produced by ketamine. The exact mechanism of action of brexanolone remains unclear, though researchers theorize that it binds to synaptic and extrasynaptic GABA receptors to increase functionality. Brexanolone is still being tested in clinical trials, since this agent has been associated with serious adverse events including syncope, altered state of consciousness, suicidal ideation, and intentional overdose.1

Related Articles

Buprenorphine, an opioidergic agent currently used to treat opioid use disorder, is also being studied for treatment of depression. Opioidergic agents were once used to treat melancholia during the 1950s before less addictive therapies became available and are shown to have a wide variety of actions in the brain that reduce depression. Studies evaluating the effects of buprenorphine by itself and combined with other agents on depression have produced promising results, though the FDA has stated it needs additional clinical data before this agent can be used to treat major depressive disorder.

Given what studies have since revealed about the efficacy of ketamine in depression, many researchers are reconsidering the potential benefits of banned or scheduled drugs for psychiatric patients.

Psychoactive drugs being reevaluated include lysergic acid diethylamide (LSD), 3,4-methylenedioxy-methamphetamine, and psilocybin. Researchers are determining whether microdosing these substances could produce therapeutic benefits without harmful side effects or abuse. Results from a 2011 study revealed that psilocybin was successful at significantly reducing symptoms of depression for up to 6 months in patients treated for advanced-stage cancer.1 In a 2015 study that examined the effects of LSD in patients with life-threatening diseases who were experiencing anxiety, LSD was safe, well-tolerated, and effective at reducing psychiatric symptoms.1

Researchers say that the recent FDA approval of intranasal ketamine represents a major breakthrough in psychiatry and that advances in ketamine or ketamine-like treatments may greatly improve the quality of life for patients with depression who do not respond to current treatments. Studies conducted on ketamine have paved the way for research evaluating novel approaches for the prevention and treatment of depression.

Disclosure: One author is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation, among others. Please see original reference for a full list of authors’ disclosures.

References

1. Kraus C, Wasserman D, Henter ID, Acevedo-Diaz E, Kadriu B, Zarate CA Jr. The influence of ketamine on drug discovery in depression [published online August 2, 2019]. Drug Discov Today. doi: 10.1016/j.drudis.2019.07.007

2. Zarate CA Jr, Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63(8):856-64.

3. Nagele P, Duma A, Kopec M, et al. Nitrous oxide for treatment-resistant major depression: a proof-of-concept trial. Biol Psychiatry. 2015;78(1):10-18.

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Health and Wellbeing · Men & Womens Health

Bring Change To Mind November Newsletter

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BC2M 4th Annual SF Student Summit
300 BC2M High School club members gathered in San Francisco on November 2nd to mark our 4th Annual Student Summit. Thanks to our amazing host, Pinterest, these teens spent an afternoon engaging in mental health conversations, participating in exciting activities, and meeting other students from around the Bay Area. We are so grateful for our keynote speaker, Jen Gotch, CCO and founder of ban.do, in sharing her personal story and path to successfully managing her mental illness. She spent hours engaging in Q&A following her time on stage!
After a morning filled with various speakers and an exciting activity fair, our students dispersed into breakout sessions where they chose workshop tracks covering the following topics: Advocacy in High School and Beyond; Mental Health & Interpersonal Relationships; Mental Health in the 21st Century; and Identity and Mental Health. The track system was a hit and our students gave us amazing feedback on this new change we implemented.

The BC2M Summit is one of the biggest highlights of the year for the students and allows them to learn from one another, build a movement of change in their community, deepen their understanding of mental health topics, and make life-long friends. With the inspiration and hope that filled the room, we know that these students will put an end to stigma and create a more empathetic and compassionate world. 
 Special thanks to our sponsors for making the event possible: Pinterest, David & Lucile Packard Foundation, Palo Alto Medical Foundation and Kaiser Permanente. 
An Extraordinary Evening Fighting the Stigma
Sydel Curry and Damion Lee, Ben Stiller and Zak Williams, Dave Grohl and Violet Grohl
For the last seven years, Bring Change to Mind has set aside one night each Fall to celebrate Revels & Revelations. This magical night is meant to bring our stories forward; highlight our student advocates; laugh, cry and sing along to wonderful entertainers; and most importantly, fund our efforts to end stigma. October 17th in San Francisco was quite a night and we wish you all could have been with us. 24 BC2M High School club members represented their peers at Revels and shared the work they are doing on their campuses and why mental health advocacy is so important to them.  Their stories are courageous and inspirational. Each guest was asked to share why they support BC2M – the students later brought these notes and special intentions to the stage in a very emotional processional.  

We were honored to bestow the third Robin Williams Legacy of Laughter Award to Ben Stiller. His heartfelt acceptance speech made for an emotional evening. Performances at Revels included the incredible line up of: Darren Criss, Dave Koz, JB Smoove, Malin Akerman, Margaret Cho, Charles Jones, and the beautiful voice of Violet Grohl, accompanied by her father, Dave Grohl, and Rami Jaffee of the Foo Fighters. Our hearts continue to soar as we think of the generosity of each person in the room that night. 
 
We thank those that attended, have made contributions to support our work or choose to share our work on social media. A special thanks to our Revels partners: American Airlines, VX Capital, St. Regis San Francisco, WindRacer wines, and Ideas Events. Together we will save lives and put an end to stigma.
 
Take a moment to watch a few highlights from the night!
Support Bring Change to Mind Today
Help support the life-changing work our high school students are accomplishing in their communities and our expansion to bring this program to more schools throughout the country. 
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