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Researchers get to the roots of chronic stress and depression

A study in mice provides clues about the common molecular origins of chronic stress and depression. The discovery could inform new treatments for mood disorders.

Millions of years ago, our ancestors evolved the physiological responses needed to survive in the face of sudden threats from rivals and predators.

The release of hormones, including epinephrine (adrenaline), noradrenaline (norepinephrine), and the steroid hormone cortisol, trigger these “fight-or-flight” stress responses.

However, sustained or chronic stress that does not resolve when the immediate threat passes is a major risk factor for the development of mood disorders such as anxiety and depression.

Traumatic experiences, for example, in military combat, can also damage the body’s ability to regulate its stress responses, causing post-traumatic stress disorder.

People with these mood disorders have abnormally high and sustained stress hormone levels, which puts them at an increased risk of developing cardiovascular disease.

Researchers at the Karolinska Institutet in Stockholm, Sweden, suspected that a protein called p11 plays a pivotal role in damping down stress responses in healthy brains after an acute threat has passed.

Their previous research found that p11 enhances the effect of the hormone serotonin, which regulates mood and has a calming effect.

Unusually low levels of p11 have been found in the brains of people with depression and in individuals who died by suicide.

Mice with reduced p11 levels also show depression and anxiety-like behaviors. In addition, three different classes of antidepressants that are effective in humans increase levels of this protein in the animals’ brains.

Now the Karolinska researchers have discovered that reduced p11 levels in the brains of mice make the animals more sensitive to stressful experiences.

The scientists also demonstrated that the protein controls activity in two distinct stress signaling pathways in the brain. It reduces not only the release of cortisol via one pathway but also adrenaline and noradrenaline via the other.

“We know that an abnormal stress response can precipitate or worsen depression and cause anxiety disorder and cardiovascular disease,” says first author Vasco Sousa. “Therefore, it is important to find out whether the link between p11 deficiency and stress response that we see in mice can also be seen in patients.”

The study, which appears in the journal Molecular Psychiatry, was a collaboration between the Karolinska Institutet and researchers at VU University in Amsterdam, The Netherlands.

To investigate the role of p11 in stress responses, the scientists bred “knockout” mice that lack the gene that makes this protein.

They compared their behavior with normal mice using a variety of standard tests. These suggested that those without p11 experienced heightened stress and anxiety.

For example, in one test, mice pups were separated from their mothers for 3 hours a day. The researchers found that pups lacking p11 produced more high-pitched distress calls, known as ultrasonic vocalizations, compared with normal pups.

In another test of anxiety-like behavior, the team gave the adult mice a choice of spending time in a brightly lit area or a dark space. Mice that were deficient

New Research Finds Link Between Stress And Depression

Researchers at Karolinska Institutet in Sweden have identified a protein in the brain that is important both for the function of the mood-regulating substance serotonin and for the release of stress hormones. The findings, which are published in the journal Molecular Psychiatry, show that after experiencing trauma or severe stress, some people develop chronic stress. This increases the risk of developing other diseases such as depression and anxiety, but it remains unknown what mechanisms are behind it or how the stress response is regulated.

The research group at Karolinska Institutet has previously shown that a protein called p11 plays an important role in the function of serotonin, a neurotransmitter in the brain that regulates mood. Depressed patients and suicide victims have lower levels of the p11 protein in their brain, and laboratory mice with reduced p11 levels show depression- and anxiety-like behavior. The p11 levels in mice can also be raised by some antidepressants.

The new study shows that p11 affects the initial release of the stress hormone cortisol by modulating the activity of specific neurons in the brain area hypothalamus. Through a completely different signalling pathway originating in the brainstem, p11 also affects the release of two other stress hormones, adrenaline and noradrenaline. In addition, the tests showed that mice with p11 deficiency react more strongly to stress, with a higher heart rate and more signs of anxiety, compared to mice with normal p11 levels.

“We know that an abnormal stress response can precipitate or worsen a depression and cause anxiety disorder and cardiovascular disease,” says first author Vasco Sousa, researcher at the Department of Clinical Neuroscience, Karolinska Institutet. “Therefore, it is important to find out whether the link between p11 deficiency and stress response that we see in mice can also be seen in patients.”

The researchers believe that the findings may have implications for the development of new, more effective drugs. There is a great need for new treatments because current antidepressants are not effective enough in many patients.

“One promising approach involves administration of agents that enhance localised p11 expression, and several experiments are already being conducted in animal models of depression,” says Per Svenningsson, professor at the Department of Clinical Neuroscience, Karolinska Institutet, who led the study. “Another interesting approach which needs further investigation involves developing drugs that block the initiation of the stress hormone response in the brain.”


Vasco C. Sousa, Ioannis Mantas, Nikolas Stroth, Torben Hager, Marcela Pereira, Haitang Jiang, Sandra Jabre, Wojciech Paslawski, Oliver Stiedl, Per Svenningsson. (2020). P11 deficiency increases stress reactivity along with HPA axis and autonomic hyperresponsiveness. Molecular Psychiatry, DOI: 10.1038/s41380-020-00887-0

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Breast cancer awareness: Battling depression post-treatment

It took about a month of biopsies, more mammograms, MRIs, ultrasounds and genetic testing in my suburban Chicago hospital before I was diagnosed with stage I breast cancer. I then had a unilateral mastectomy, followed months later by reconstructive surgery.

I was lucky that my type of cancer responds well to hormone therapy, with no chemotherapy or radiation. Despite my excellent prognosis and low chance of recurrence, my breast cancer almost killed me.

That’s because although my medical team did an excellent job getting rid of the cancer, I was left to my own devices with the surprise bout of depression that took its place.

As frightened as I was during the initial call with my doctor, where she informed me that I had cancer, I had little time to think during the month-long flurry of tests and appointments.

My local hospital’s nurse navigator took my many phone calls, answered my questions and helped me make appointments for everything. She held my hand during a painful biopsy. I had a mastectomy and five months later, a breast reconstruction procedure.

The symptoms I wasn’t expecting started shortly after my breast reconstruction. Before my reconstruction procedure, I was told to plan on two weeks of recovery time. But six weeks later, I was still suffering from pain, swelling in my chest and face, and limited mobility in my shoulder.

The onset of depression

My medication was putting me in menopause, triggering hot flashes, weight gain and sleep disturbances. Insomnia-fueled Googling convinced me that I still had cancer. I cried all the time. I slowly began to realize that I was depressed.

This was not my first bout of depression. I suffered from depression in my 20s and again after the traumatic birth of my first child. The difference was that I had prepared for postpartum depression. Every gynecological and pediatrician’s visit included a depression screener.

No one warned me that having breast cancer and a mastectomy could lead to depression — not my cancer doctors nor the nurse navigator who helped me through the maze of treatment. My depression made me feel guilty and isolated. I assumed that I had failed because I wasn’t sufficiently grateful for my “lucky” stage I diagnosis.

CDC study sheds new light on mental health crisis linked to coronavirus pandemic

I learned later that post-breast cancer treatment depression is common.

The lasting effects of a mastectomy, the post-surgical maintenance drugs and fear of recurrence can all lead to depression, according to Tasha Chasson, an oncology support counselor for Wellness House, a cancer support center located in Hinsdale, Illinois.

Many women find themselves in “survival mode” during treatment and only have time to consider their emotions when treatment is over, Chasson said.

Cancer patients can feel worse when they compare themselves to people with different diagnoses and prognoses, according to Kelley Kitley, a Chicago-based psychotherapist and women’s mental health expert.

Support is key

Luckily, I had scheduled an appointment to meet with my general practitioner to discuss my sleep issues. Having known me for 15 years, she was concerned about my

Anxiety, Depression, and Women; Suicide Linked to ADHD

Prior to the COVID-19 pandemic, women were more likely to report symptoms of anxiety and depression versus men. However, Black and Hispanic women were less likely to receive treatment than white women. (ABC News)

But not surprisingly, stress and depressive symptoms have spiked during the pandemic, with one study linking media consumption to this rise. (ScienceDaily)

Dasotraline, a novel dopamine and norepinephrine reuptake inhibitor, was both safe and effective at reducing the number of binge-eating days per week after 12 weeks of treatment. Although the FDA accepted Sunovion’s new drug application for this treatment in July 2019, the company withdrew the application in May 2020 citing a need for more clinical studies. (Journal of Clinical Psychiatry)

A new app aimed at diagnosing autism may soon be a new arrow in pediatricians’ quiver. (Digital Trends)

In similar news, apps aiding in eating disorder recovery have boomed during the COVID-19 pandemic. (Wired)

Janssen is in pursuit of a court order to block Mylan’s generic version of its extended-release injectable schizophrenia treatment paliperidone (Invega Trinza). (Bloomberg Law)

States with a higher rate of firearm ownership had an increased risk of adolescent firearm suicide, as well as a near 7% increased risk in all-cause suicide. (Journal of the American Academy of Child & Adolescent Psychiatry)

Young adults with ADHD were more likely to attempt suicide than those without, a new study found. And this was particularly true among women. (Journal of Clinical Psychiatry)

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    Kristen Monaco is a staff writer, focusing on endocrinology, psychiatry, and dermatology news. Based out of the New York City office, she’s worked at the company for nearly five years.

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