Researchers Uncover Mechanisms of Brexanolone and the Role of Inflammation in Post-partum Depression

Post-partum depression (PPD) develops after childbirth
Photo Credit: Iuliia Bondarenko

A research collaboration between clinical and preclinical investigators in the Department of Psychiatry at the UNC School of Medicine, has found that a drug for post-partum depression works by inhibiting systemic inflammatory pathways.

Post-partum depression (PPD) develops after childbirth and affects both the mother’s and the infant’s health by preventing healthy bonding. Women with PPD experience intense anxiety, feelings of depression, sleeplessness, inability to care for their child, and risk for suicide.

Brexanolone, an IV infusion comprised of a derivative of progesterone, was approved by the U.S. Food and Drug Administration for the treatment of PPD in 2019. The fast-acting medication significantly reduces depression symptoms and provides effects for up to 90 days. However, exactly how the drug provides these therapeutic effects has remained a mystery – until now.

A research team led by A. Leslie Morrow, PhD, the John Andrews Distinguished Professor of Psychiatry and Pharmacology in the UNC School of Medicine, has found that brexanolone works within the body by inhibiting the key systemic inflammatory pathways that are associated with depression. The new finding is monumental in that it suggests that PPD is likely caused, at least in part, by inflammation.

Stress levels sky high for families of neurodiverse kids

Almost 80 per cent of caregivers experienced poor wellbeing, high levels of stress and poor mental health
Photo Credit: Jordan Whitt

New Curtin University-led research has found caregivers of neurodivergent children are more likely to experience clinically significant levels of stress, poor mental health, financial hardship, and negative relationships.

The research, published in the Journal of Autism and Developmental Disorders, explored the health and wellbeing of caregivers of children living with neurological conditions such as autism spectrum disorder, attention deficit/ hyperactive disorder (ADHD), cerebral palsy, and learning disabilities, and whether current support services were sufficient to meet their needs.

Lead researcher Dr Ben Milbourn, from the Curtin School of Allied Health, said children diagnosed with neurodevelopmental conditions often require significant levels of support from their caregivers and meeting their emotional, physical, social and learning needs can be challenging.

Serious eating disorder ARFID is highly heritable, according to new twin study

Cynthia Bulik, PhD, founding director of the UNC Center of Excellence for Eating Disorders, is senior author of the article published in JAMA Psychiatry.
Photo Credit: Courtesy of University of North Carolina School of Medicine

ARFID is a serious eating disorder that leads to malnutrition and nutritional deficiencies. Researchers estimate that between one to five percent of the population is affected by the eating disorder.

Unlike anorexia, ARFID is not about the patient’s experience of their own body and fear of gaining weight. Instead, the disease is characterized by the avoidance of certain types of food due to a sensory discomfort because of the characteristics or appearance of food, or for example, the fear of choking, a food poisoning phobia or lack of appetite.

17,000 pairs of twins involved in the study

Researchers at Karolinska Institutet and the University of North Carolina School of Medicine have now investigated the importance of genetic factors for developing ARFID. A cohort of almost 17,000 pairs of twins in Sweden born between 1992 and 2010 participated in the study. A total of 682 children with ARFID between the ages of six and twelve years could be identified.

Common heart medicine is linked to a reduced risk of committing violent crimes

Yasmina Molero.
Photo Credit: Niklas Faye-Wevle Samuelson

Beta blockers, commonly used to treat heart disease and high blood pressure, can be linked to a reduced risk of committing violent crimes. It shows a new registry study from Karolinska Institutet and the University of Oxford published in the journal PLOS Medicine.

Beta blockers lower blood pressure by blocking the effect of hormones like adrenaline. The medicine is used to treat a variety of conditions including high blood pressure, cardiovascular events, heart failure and anxiety. It has also been suggested to work for clinical depression and aggression, but some studies have found a link to increased suicidal tendencies and the results are contradictory.

In the current study, the researchers investigated the relationship between beta blockers and hospitalization for mental illness, suicidal tendencies, suicide and reports of violent crime. They studied 1.4 million individuals in Sweden and compared periods with and without beta blockers in the same individual over an eight-year period (2006-2013). In this way, the researchers were able to control factors that can affect relationships, such as genetics or disease history.

Periods of medication were associated with a 13 percent lower risk of being charged with violent crime. Since it is an observational study, conclusions about causation should be interpreted with caution.

One way to deal with aggression

- If the results are confirmed in other studies, including randomized controlled trials, beta blocks may be considered as a way to manage aggression in individuals with psychiatric diagnoses, say Yasmina Molero, researchers at Department of Clinical Neuroscience and Department of Medical Epidemiology and Biostatistics at Karolinska Institutet.

Use of beta-blockers was also linked to eight percent lower risk of hospitalization due to mental illness and eight percent increased risk of being treated for suicidal tendencies or dying in suicide. However, these relationships were inconsistent.

- The risk of hospitalization and suicidal tendencies varied depending on psychiatric diagnosis and previous mental health problems, but also on the severity and type of heart problems that the beta blockers were used to treat. This indicates that there are no links between beta blockers and these outcomes, says Yasmina Molero.

Heart problems are associated with depression

Previous research has linked serious heart events to an increased risk of depression and suicide. This may indicate that the mental disorders and other disabilities associated with serious heart problems, rather than the treatment with beta blockers, increase the risk of serious mental illness, according to the researchers.

Funding: The study was funded by the Wellcome Trust, Forte, the American Foundation for Suicide Prevention and the Karolinska Institutet's funds. Co-author Henrik Larsson has received grants from Shire Pharmaceuticals, Medice Speaker Fees, Shire / Takeda Pharmaceuticals and Evolan Pharma as well as sponsorship for a conference on adhd from Shire / Takeda Pharmaceuticals, all outside the current study.

Published in journal: PLOS Medicine

Source/Credit: Karolinska Institutet

Reference Number: ns013123_02

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An action plan to prevent Alzheimer’s disease

As the population ages, the number of people with Alzheimer’s disease in Europe will double by 2050.
Image Credit: Gerd Altmann

A task force led by UNIGE and HUG is laying the foundations for a preventive protocol.

Memory loss, behavioral changes, cognitive deficits: Alzheimer’s disease leads to a dramatic loss of autonomy for those affected and has a heavy impact on health costs. Its prevention has become a real social challenge. An international task force, led by the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG), is setting out guidelines for innovative services to prevent Alzheimer’s disease. These will soon be an integral part of second-generation memory clinics. These guidelines are detailed in an article published in the Lancet Regional Health - Europe.

With 10 million people affected in Europe, Alzheimer’s disease is the most common neurodegenerative disease. It is characterized by progressive disabling memory loss and cognitive deficits caused by an accumulation of toxic proteins in the brain. Its social and economic impact is considerable. On a global scale, it is estimated to be worth around USD 1,500 billion per year* and in Switzerland CHF 11.8 billion per year**.

Not just mood swings but premenstrual depression

The scientists took images of the womens’ brain with positron emission tomography (PET) at different cycle times. 
Image Credit: © MPI CBS

Researchers find serotonin transporter in the brain increased

Scientists led by Julia Sacher from Max Planck Institute for Human Cognitive and Brain Sciences and Osama Sabri from the Leipzig University Hospital have discovered in an elaborate patient study that the transport of the neurotransmitter serotonin in the brain increases in women with premenstrual dysphoric disorder (PMDD) shortly before menstruation. Their findings provide the basis for a more targeted therapy of this specific mood disorder, in which patients only have to take antidepressants for a few days.

PMS, or premenstrual syndrome, is now a familiar term to many - about 50 per cent of all women experience these symptoms a few days before onset of their menstruation. The more severe form, called premenstrual dysphoric disorder (PMDD), affects eight percent of women of childbearing age and is associated with physical symptoms such as sleep disturbances or breast pain as well as psycho-emotional symptoms, including depression, loss of control, irritability, aggressiveness and concentration problems. As a result, many women with PMDD experience disruptions in their personal and professional lives.

Genes Common to Different Species Found to Be Connected to the Development of Depression

Affective disorders, also known as mood disorders, are a group of mental illnesses that involve changes in emotional states.
Photo Credit:: Christopher Lemercier

Russian scientists performed a cross-species analysis of brain gene expression in danio fish, rats and humans to identify new common molecular targets for the therapy of affective disorders of the central nervous system induced by chronic stress. The study was able to identify several key brain proteins that may play important roles in the pathogenesis of affective disorders.

The article was published in the journal Scientific Reports. Affective disorders, also known as mood disorders, are a group of mental illnesses that involve changes in emotional states. They include various forms of depression and mania, psychosis, and increased anxiety. They are widespread because they occur not only as independent mental pathologies, but also as complications of neurological and other somatic diseases.

This fact determines the difficulty of diagnosis: people classify low mood, anxiety and irritability as temporary, situational manifestations. According to statistics, emotional disorders of varying severity occur in 20% of people, but only a quarter of them receive qualified help.

Scientists explain emotional ‘blunting’ caused by common antidepressants

Depression
Photo Credit: Ethan Sykes

According to the NHS, more than 8.3 million patients in England received an antidepressant drug in 2021/22. A widely-used class of antidepressants, particularly for persistent or severe cases, is selective serotonin reuptake inhibitors (SSRIs). These drugs target serotonin, a chemical that carries messages between nerve cells in the brain and has been dubbed the ‘pleasure chemical’.

One of the widely-reported side effects of SSRIs is ‘blunting’, where patients report feeling emotionally dull and no longer finding things as pleasurable as they used to. Between 40-60% of patients taking SSRIs are believed to experience this side effect.

To date, most studies of SSRIs have only examined their short-term use, but, for clinical use in depression these drugs are taken chronically, over a longer period of time. A team led by researchers at the University of Cambridge, in collaboration with the University of Copenhagen, sought to address this by recruiting healthy volunteers and administering escitalopram, an SSRI known to be one of the best-tolerated, over several weeks and assessing the impact the drug had on their performance on a suite of cognitive tests.

In total, 66 volunteers took part in the experiment, 32 of whom were given escitalopram while the other 34 were given a placebo. Volunteers took the drug or placebo for at least 21 days and completed a comprehensive set of self-report questionnaires and were given a series of tests to assess cognitive functions including learning, inhibition, executive function, reinforcement behavior, and decision-making.

Mouse pups cry for help most urgently while active

Mouse pups produce ultrasonic vocalizations, called isolation USVs, when they are separated from the nest. It’s a survival mechanism – baby mice need their parents to regulate their temperature and feed them – that diminishes with age.

But before the USV reflex peters out around 20 days after birth, the rate at which mouse pups cry varies a lot, even within the same individual at the same age, according to Katherine Tschida, the Mary Armstrong Meduski ’80 Assistant Professor of psychology in the College of Arts and Sciences. Exploring this variation, researchers in the Tschida Lab found a link between mouse pup USV rates and their activity levels; the greater amount of body movement, the higher the rate of vocalizations. The connection is important for understanding mouse neural circuitry and development and provides a richer understanding of behavioral differences in mouse models of communication disorders, including autism spectrum disorder (ASD.)

“Rates of Ultrasonic Vocalizations are More Strongly Related Than Acoustic Features to Non-vocal Behaviors in Mouse Pups” was published Dec. 19 in Frontiers in Behavioral Neuroscience. Tschida and doctoral student Nicole Pranic are first authors. Contributions were made by Thomas Cleland, professor of psychology; Chen Yang, programmer and analyst in the Cleland Lab; and by Caroline Kornbrek ’23.

UCLA-developed soft brain probe could be a boon for depression research

 Illustration of the soft probe with aptamer biosensors implanted in the brain.
Illustration Credit: Zhao, et al., 2022

Anyone familiar with antidepressants like Prozac or Wellbutrin knows that these drugs boost levels of neurotransmitters in the brain like serotonin and dopamine, which are known to play an important role in mood and behavior.

It might come as a surprise, then, that scientists still have very little data about the specific relationship between neurotransmitters — chemicals that relay messages from one brain cell to others — and our psychological states. Simply put, monitoring fluctuations of these neurochemicals in living brains has proved a persistent challenge.

Now, for the first time, UCLA scientists have attached nanoscale biochemical sensors, which are tuned to identify specific neurotransmitters, to a soft, implantable brain probe in order to continuously monitor these chemicals in real time. The new brain probe, described in a paper published in ACS Sensors, would allow scientists to track neurotransmitters in laboratory animals — and, ultimately, humans — during their day-to-day activities.

Internet treatment for anger works

Two emotion regulation strategies, mindful emotion awareness and cognitive reappraisal, can help people with problems in managing anger.
Photo Credit: Obie Fernandez

Problems with managing anger can have severe consequences for the afflicted individual and their loved ones. A new study from the Centre for Psychiatry Research at Karolinska Institutet shows that four weeks of therapy delivered over the internet can help people with anger and aggression. The results have been published in the Journal of Consulting and Clinical Psychology.

The study, which the researchers have chosen to call the “anger study”, is the first to compare different internet-mediated emotion regulation strategies against anger. The results are expected to be important for understanding emotion regulation and for the dissemination of evidence-based methods.

You can learn to be fearless

Katharina Spoida (left) and Sandra Süß have examined how the lack of a specific receptor affects the ability to unlearn fear.
Photo Credit: RUB, Marquard

The lack of a specific serotonin receptor helps to unlearn fear faster.

The messenger serotonin plays an important role in the development, but also in the learning of fear and fear. A research team in general zoology and neurobiology around Dr. Katharina Spoida and Dr. Sandra Süß examined in the collaborative research center "Extinction Learning" at the Ruhr University Bochum. The researchers were able to show that mice that lack a certain serotonin receptor unlearn fear much faster than the wild type. The results of the study provide a possible explanation of how drugs for post-traumatic stress disorders (PTSDs) change our brain activity. Those affected often have the ability to unlearn fear, making therapies difficult. The study was carried out on 19. November 2022 published in the journal Translational Psychiatry.

Everyday sensations cause fear

After a traumatic experience, those affected sometimes suffer fear long later, which is caused by certain sensory impressions from our everyday environment and is then overpowering. Post-traumatic stress disorder, or PTSD for short, is what experts call it. In this disorder, it is not or only with difficulty that those affected can unlearn the connection once they have learned between a neutral environmental stimulus and fear, which affects the success of therapies.

NIH researchers unlock pattern of gene activity for ADHD

A new study uses postmortem brain tissues to understand genomic differences in individuals with attention deficit hyperactivity disorder.
Image Credit: Gerd Altmann

Researchers at the National Institutes of Health have successfully identified differences in gene activity in the brains of people with attention deficit hyperactivity disorder (ADHD). The study, led by scientists at the National Human Genome Research Institute (NHGRI), part of NIH, found that individuals diagnosed with ADHD had differences in genes that code for known chemicals that brain cells use to communicate. The results of the findings, published in Molecular Psychiatry, show how genomic differences might contribute to symptoms.

To date, this is the first study to use postmortem human brain tissue to investigate ADHD. Other approaches to studying mental health conditions include non-invasively scanning the brain, which allows researchers to examine the structure and activation of brain areas. However, these studies lack information at the level of genes and how they might influence cell function and give rise to symptoms.

The researchers used a genomic technique called RNA sequencing to probe how specific genes are turned on or off, also known as gene expression. They studied two connected brain regions associated with ADHD: the caudate and the frontal cortex. These regions are known to be critical in controlling a person’s attention. Previous research found differences in the structure and activity of these brain regions in individuals with ADHD.

In utero exposure to flame retardants increases anxiety symptoms in adolescents

Dr. Strawn.
Photo Credit: Colleen Kelley/UC Marketing + Brand.

New research led by the University of Cincinnati and Cincinnati Children’s Hospital Medical Center sheds light on the connection between exposure to environmental toxins in utero and the later development of anxiety during adolescence.

Lead author Jeffrey Strawn, MD, and his colleagues recently published the study in the journal Depression & Anxiety.

Strawn said researchers are increasingly interested in learning more about risk factors for anxiety and depression in children, particularly since there has been a surge of these symptoms during the pandemic. Even prior to the pandemic, anxiety disorders were among the most prevalent and earliest presenting mental health conditions for children, he said.

“We know a lot about early risk factors, including psychological risk factors, temperament, behaviors and family relationships,” said Strawn, professor in the Department of Psychiatry and Behavioral Neuroscience in UC’s College of Medicine and a UC Health child and adolescent psychiatrist. “But we know incredibly little about the effects of environmental factors like air pollution and other environmental toxicants on anxiety.”

The study focused on a class of chemicals called polybrominated diphenyl ethers (PBDEs) that were used as flame retardants for products like furniture foam padding, insulation, rugs, upholstery, computers and appliances. Exposure to PBDEs during early brain development has been associated with cognitive deficits, reduced language skills and attention-deficit/hyperactivity disorder, and the chemicals were banned in the United States in 2004.

Substance use disorders linked to poor health outcomes in wide range of physical health conditions

Photo Credit: Concord90

In a study published today in The Lancet Psychiatry, researchers looked at the risk of mortality and loss of life-years among people who developed 28 different physical health conditions, comparing those who had previously been hospitalized with substance use disorder against those who had not.

They found that patients with the most health conditions were more likely than their counterparts to die during the study period if they had been hospitalized with substance use disorder prior to the development of these conditions. For most subsequent health conditions, people with substance use disorders also had shorter life-expectancies than did individuals without substance use disorders.

One in twenty people worldwide aged 15 years or older lives with alcohol use disorder, while around one in 100 people have psychoactive drug use disorders. Although substance use disorders have considerable direct effects on health, they are also linked to a number of physical and mental health conditions. Consequently, the presence of these contributes to higher risk of mortality and shorter lifespan in people with substance use disorders.

To explore this link further, researchers analyzed patient records from Czech nationwide registers of all-cause hospitalizations and deaths during the period from 1994-2017. They used a novel design, estimating the risk of death and life-years lost after the onset of multiple specific physical health conditions in individuals with a history of hospitalization for substance use disorders, when compared with matched counterparts without substance use disorder but with the same physical health condition.

Daytime Naps Reinforce Memories of Emotional Trauma and Anxiety

According to Yuri Pavlov, the positive effect of sleep on memory can be observed years later.
Photo Credit: Nadezhda Pavlova

Scientists from Ural Federal University and the University of Tübingen (Germany) studied the effect of sleep on the formation and translation of primary memories of something scary into long-term memory. Neurobiologists discovered that sleeping during the day strengthens memory of disturbing and frightening events, but a similar effect of memory strengthening is also observed after a period of calm wakefulness. The findings will be useful for developing rehabilitation strategies for people who have been emotionally traumatized by disasters, warfare, and violence. The study was published in the journal Cognitive, Affective, & Behavioral Neuroscience.

Memory consolidation - the transition of memories from short-term memory to long-term memory - occurs primarily during sleep. Studies show that sleep after learning can have positive effects that are superior to passive wakefulness. This occurs by reactivating important memories, which may also be reflected in dreams. The positive effects of dreaming can be observed even years later. However, there are currently no studies that analyze whether sleep enhances the effect of remembering emotionally difficult events. Therefore, scientists decided to find out how sleep affects the memory of a person's experience of fear.

‘A silent killer’ - COVID-19 shown to trigger inflammation in the brain

A COVID-19 infected mouse brain showing 'angry' microglia in green and SARS-CoV-2 in red.
Source/Credit: University of Queensland

Research led by The University of Queensland has found COVID-19 activates the same inflammatory response in the brain as Parkinson’s disease.

The discovery identified a potential future risk for neurodegenerative conditions in people who’ve had COVID-19, but also a possible treatment.

The UQ team was led by Professor Trent Woodruff and Dr Eduardo Albornoz Balmaceda from UQ’s School of Biomedical Sciences, and virologists from the School of Chemistry and Molecular Biosciences.

“We studied the effect of the virus on the brain’s immune cells, ‘microglia’ which are the key cells involved in the progression of brain diseases like Parkinson’s and Alzheimer’s,” Professor Woodruff said.

“Our team grew human microglia in the laboratory and infected the cells with SARS-CoV-2, the virus that causes COVID-19.

“We found the cells effectively became ‘angry’, activating the same pathway that Parkinson’s and Alzheimer’s proteins can activate in disease, the inflammasomes.”

Autistic women have increased risk of mental illness

Photo credit: Alexander Grey

Young men and women with autism are more affected by psychiatric conditions and are at increased risk of being threatened as a result of their mental illness, compared to people without autism. Practically vulnerable are autistic women. This is shown by researchers from the Karolinska Institutet in a study published in JAMA Psychiatry.

People with autism have an increased risk of suffering from mental illness. Current data indicates that women with autism are more vulnerable than autistic but are, but few studies have been able to establish that there are gender differences.

Researchers from Karolinska Institutet have now done a register-based cohort study with just over 1.3 million people in Sweden, which was followed from 16 to 24 years between 2001 and 2013. More than 20,000 of these were diagnosed with autism.

The researchers could see that by the age of 25, 77 out of 100 women with autism, compared to 62 out of 100 but with autism, had received at least one psychiatric diagnosis.

We saw an increased risk of eleven different psychiatric conditions, including depression, anxiety syndrome, self-harm behavior and insomnia, says Miriam Martini, PhD student in psychiatric epidemiology at Department of Medical Epidemiology and Biostatics at Karolinska Institutet and first author of the study.

Electroshock Therapy More Successful for Depression than Ketamine

Electroconvulsive therapy, often viewed with skepticism by members of the public, outperforms the drug ketamine in treating depression, according to a new report.
Credit: Tiago Bandeira

An analysis of six studies found that electroconvulsive therapy (ECT) is better at quickly relieving major depression than ketamine, a team of researchers report in JAMA Psychiatry on October 19.

Depression is a common illness affecting about 5% of adults worldwide, according to the World Health Organization (WHO). Feeling sad, irritable, losing pleasure in activities that used to be enjoyable, and sometimes experiencing unexplained pain or fatigue for weeks at a time are all symptoms of depression. Most people diagnosed with depression are offered an oral antidepressant (in combination with psychotherapy) as a first-line treatment option. But if oral antidepressants don’t help, or if the person is at imminent risk of hurting themselves, there are other, more rapid treatment options: ECT, and more recently ketamine or esketamine.

Esketamine, a nasal spray approved by the Food and Drug Administration to treat depression, is more commonly used in the US than ketamine. But there are no studies comparing esketamine’s effectiveness with ECT. There are studies done with ketamine, a sister drug to esketamine. Ketamine is commonly used in medicine as an injected anesthetic but has recently been tested as a fast-acting intervention to help people with major depression.

Covid-19 is linked to increased degradation of connections between nerve cells in a new brain model

Postdoctoral fellow Samudyata and doctoral student Susmita Malwade.
Source: Karolinska Institutet

Researchers at Karolinska Institutet have used cellular reprogramming in a new study to create human three-dimensional brain models and infected them with SARS-CoV-2. In infected models, the brain's immune cells showed an excessive elimination of connections between the nerve cells. The gene expression of these cells also mimicked changes observed in neurodegenerative diseases. The results hope to identify new treatments for cognitive symptoms after Covid-19 infection.

Several studies have reported persistent cognitive symptoms following a covid-19 infection, but the underlying mechanisms for this are still unknown. The researchers behind the study, published in the journal Molecular Psychiatry, have created from human induced pluripotent stem cells (iPS) three-dimensional models of the brain in test tubes, so-called brain organoids. The model differs from previous organoid models in that they also contain microglia - the brain's immune cells. In the infected models, microglia regulated genes involved in phagocytosis, "cell-eating," the researchers could also see how microglia contained an increased amount of proteins from brain cell connections, so-called synapses. The developed model and results of the study can help guide future efforts to address cognitive symptoms in the aftermath of COVID-19 and other neuroinvasive viral infections.