Stress increases Alzheimer’s risk in female mice but not males

Stress causes the levels of Alzheimer's proteins to rise in females' brains but not males' brains, according to a new study in mice by researchers at Washington University School of Medicine in St. Louis. This difference may contribute to women's greater risk of developing Alzheimer's disease.
Photo Credit: Karolina Grabowska

Women are about twice as likely as men to be diagnosed with Alzheimer’s disease. Some of that is age; in the U.S., women outlive men by five to six years, and advanced age is the strongest risk factor for Alzheimer’s. But there’s more to it than that, so Alzheimer’s researchers continue to look for other reasons why women have an elevated risk of the deadly neurodegenerative disease.

Stress may be one such reason. A study by researchers at Washington University School of Medicine in St. Louis shows that the effect stress has on the brain differs by sex, at least in mice. In stressful situations, levels of the Alzheimer’s protein amyloid beta rises sharply in the brains of females but not males. In addition, the researchers identified a molecular pathway that is active in brain cells from female mice but not male mice, and showed that it accounts for the divergent responses to stress.

The findings, published May 2 in Brain, add to a growing collection of evidence that sex matters in health and disease. From cancer to heart disease to arthritis, scientists have found differences between males and females that could potentially affect how men and women respond to efforts to prevent or treat chronic diseases.

Cannabis exposures in suspected suicide attempts are on the rise

Photo Credit: Jose Luis Sanchez Pereyra

Suspected suicidal cannabis exposures have increased 17% annually, over a period of 12 years, according to a Washington State University-led analysis of U.S. poison center data.

The vast majority of the attempts, more than 92%, involved other substances in addition to cannabis, and the data cannot show a direct causal link between cannabis and suicide attempts. Still, the findings are cause for concern, the researchers said, especially since the increase was more pronounced among children and women during and after the pandemic. They reported their findings in the journal JAMA Network Open.

“This study adds to already ample evidence that cannabis use, particularly by younger people, has significant implications for mental health,” said study co-author Tracy Klein, a WSU associate professor of nursing. “We don’t have evidence that cannabis alone was the primary driver of a suicide attempt, but we do know that cannabis can worsen certain mental health conditions and increase impulsivity.”

The brain’s support cells may play a key role in OCD

An astrocye from the striatum
Image Credit: Joselyn Soto

A type of cell usually characterized as the brain’s support system appears to play an important role in obsessive-compulsive disorder-related behaviors, according to new UCLA Health research published April 12 in Nature.

The new clue about the brain mechanisms behind OCD, a disorder that is incompletely understood, came as a surprise to researchers. They originally sought to study how neurons interact with star-shaped “helper” cells known as astrocytes, which are known to provide support and protection to neurons.

However, scientists are still trying to understand the apparent role these complex cells play in psychiatric and neurodegenerative diseases.

By studying the proteins expressed by neurons and astrocytes in mice, UCLA researchers found a protein associated with OCD and repetitive behaviors in neurons was also found in astrocytes. The discovery suggests therapeutic strategies targeting astrocytes and neurons may be useful for OCD and potentially other brain disorders.

The brain’s cannabinoid system protects against addiction

Test participants’ emotional reactions are measured using electrodes that record tension in the small facial muscles. From left: Madeleine Jones and Irene Perini. 
Photo Credit: Thor Balkhed

High levels of the body’s own cannabinoid substances protect against developing addiction in individuals previously exposed to childhood maltreatment, according to a new study. Those who had not developed an addiction following childhood maltreatment seem to process emotion-related social signals better.

 Childhood maltreatment has long been suspected to increase the risk of developing a drug or alcohol addiction later in life. Researchers at Linköping University have previously shown that this risk is three times higher if you have been exposed to childhood maltreatment compared with if you have not, even when accounting for confounds from genetics and other familial factors.

“There’s been a lot of focus on addiction as a disease driven by a search for pleasure effects and euphoria, but for many it has more to do with the drugs’ ability to suppress negative feelings, stress sensitivity, anxiety and low mood. Based on this, we and other researchers have had a theory that if affected in childhood, the function of the brain’s distress systems is altered, and that this may contribute to addiction risk in adulthood,” says Markus Heilig, professor and director of the Center for Social and Affective Neuroscience, CSAN, at Linköping University and consultant at the Psychiatric Clinic of the University Hospital in Linköping.

Machine learning models rank predictive risks for Alzheimer’s disease

Xiaoyi Raymond Gao, PhD Associate Professor
Photo Credit: Courtesy of Ohio State University

Once adults reach age 65, the threshold age for the onset of Alzheimer’s disease, the extent of their genetic risk may outweigh age as a predictor of whether they will develop the fatal brain disorder, a new study suggests. 

The study, published recently in the journal Scientific Reports, is the first to construct machine learning models with genetic risk scores, non-genetic information and electronic health record data from nearly half a million individuals to rank risk factors in order of how strong their association is with eventual development of Alzheimer’s disease.

Researchers used the models to rank predictive risk factors for two populations from the UK Biobank: White individuals aged 40 and older, and a subset of those adults who were 65 or older. 

Results showed that age – which constitutes one-third of total risk by age 85, according to the Alzheimer’s Association – was the biggest risk factor for Alzheimer’s in the entire population, but for the older adults, genetic risk as determined by a polygenic risk score was more predictive. 

“We all know Alzheimer’s disease is a later-onset disease, so we know age is an important risk factor. But when we consider risk only for people age 65 or older, then genetic information captured by a polygenic risk score ranks higher than age,” said lead study author Xiaoyi Raymond Gao, associate professor of ophthalmology and visual sciences and of biomedical informatics in The Ohio State University College of Medicine. “That means it’s really important to consider genetic information when we work on Alzheimer’s disease.” 

Drug overdose fatalities among US older adults has quadrupled over 20 years

Photo Credit: Christina Victoria Craft

Overdose mortality among people age 65 and older quadrupled over 20 years, suggesting the need for greater mental health and substance use disorder policies addressed at curbing the trend, a new research paper finds.

The deaths stemmed from both suicides and accidental overdoses, with nearly three-fourths of the unintended fatalities involving illicit drugs such as synthetic opioids like fentanyl, heroin, cocaine, and methamphetamines.  Prescription opioids, antidepressants, benzodiazepines, antiepileptics and sedatives were used in 67% of intentional overdoses.

“The dramatic rise in overdose fatalities among adults over 65 years of age in the past two decades underscores how important it is for clinicians and policymakers to think of overdose as a problem across the lifespan,” said co-author Chelsea Shover, assistant professor of medicine in the division of general internal medicine and health services research at the David Geffen School of Medicine at UCLA. “Updating Medicare to cover evidence-based treatment for substance use disorders is crucial, as is providing harm reduction supplies such as naloxone to older adults.”

Use of melatonin linked to decreased self-harm in young people

There is currently a youth mental health crisis, and the risk of self-harm and suicide  is high.
Photo Credit: Vladislav Muslakov

Medical sleep treatment may reduce self-harm in young people with anxiety and depression, an observational study from Karolinska Institutet suggests. The risk of self-harm increased in the months preceding melatonin prescription and decreased thereafter, especially in girls. The study is published in The Journal of Child Psychology and Psychiatry.

Melatonin is a hormone that controls the sleep-wake cycle and is the most commonly prescribed drug for sleep disturbances in children and adolescents in Sweden. Melatonin use has dramatically increased in recent years, and it is available over the counter in Sweden since 2020.

“Given the established link between sleep problems, depression, and self-harm, we wanted to explore whether medical sleep treatment is associated with a lower rate of intentional self-harm in young people,” says Dr Sarah Bergen, docent at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, who led the study.

Clues to the cause of chronic gut pain

Professor Stuart Brierley
Photo Credit: Courtesy of Flinders University

New insights into chronic gut pain offer hope for improved treatments for irritable bowel syndrome and anxiety treatment.

A research team led by Flinders University Professor Stuart Brierley, based at the SA Health and Medical Research Institute, with Nobel Laureate Professor David Julius, Professor Holly Ingraham and Dr James Bayrer at the University of California San Francisco, has shown evidence of a specific pathway of cells and nerves linking the gut to the brain that may be responsible for the chronic gut pain.

Chronic gut pain is commonly experienced by 11% of the global population currently living with irritable bowel syndrome (IBS) and associated psychological conditions, including anxiety and depression.

Described in a new article in Nature, the team used genetic and pharmacologic tools in pre-clinical models to manipulate signals between gut epithelial cells and associated nerve fibers to determine how this pathway stimulates chronic gut pain and anxiety.

Epilepsy could become easier to pinpoint with blood test

Researchers from Lund University in Sweden have discovered higher levels of immune proteins in the blood before and after an epileptic seizure. The possible biomarkers can be identified using a simple blood test. Diagnosing epilepsy is currently resource intensive, and distinguishing it from other conditions can be challenging. Better diagnostic methods as soon as the patient seeks medical care after a suspected seizure is therefore an urgent necessity.

Epilepsy is the collective name for abnormal activity in the brain that causes temporary loss of control of behavior and movement. The condition can be congenital, be caused by a tumor, stroke or infection in the brain and cause very different symptoms depending on which part of the brain the episode begins in or spreads to. Inflammation processes that start as an immune response in the body can also provoke a seizure. That is why researchers started to look for possible biomarkers for epilepsy within the immune system. Previous studies exist, but the results have so far been mixed and difficult to interpret:

“In our study, we have a carefully selected group of participants and we have a lot of background information on each person. We have also taken into account a number of confounding factors that may affect the immune system such as other neurological and immunological illnesses, infections and various psychiatric conditions,” says Christine Ekdahl Clementson.

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.