A brain rhythm working in tandem with the body’s natural sleep-wake cycle may explain why bipolar patients alternate between mania and depression, according to new research.
The McGill University-led study published in Science Advances marks a breakthrough in understanding what drives shifts between the two states, something that, according to lead author Kai-Florian Storch, is considered the “holy grail” of bipolar-disorder research.
“Our model offers the first universal mechanism for mood switching or cycling, which operates analogously to the sun and the moon driving spring tides at specific, recurring times,” said Storch, an Associate Professor in McGill’s Department of Psychiatry and a researcher at the Douglas Research Centre.
The findings suggest that regularly occurring mood switches in bipolar disorder patients are controlled by two “clocks”: the biological 24-hour clock, and a second clock that is driven by dopamine-producing neurons that typically influence alertness. A manic or depressed state may arise depending on how these two clocks, which run at different speeds, align at a given time.
Notably, the authors say this second dopamine-based clock probably stays dormant in healthy people.
To carry out their study, the scientists activated the second clock in mice to create behavioral rhythms similar to the mood swinging in bipolar disorder. When they disrupted dopamine-producing neurons in the brain’s reward centre, these rhythms ceased, highlighting dopamine as a key factor in the mood swings of bipolar disorder.
Hope for new treatments: Silencing the clock
Current treatments for bipolar disorder focus on stabilizing moods but often don’t address the root causes of mood swings, the researchers said.
“Our discovery of a dopamine-based arousal rhythm generator provides a novel and distinct target for treatment, which should aim at correcting or silencing this clock to reduce the frequency and intensity of mood episodes,” said Storch.
What remains unknown is the exact molecular workings of the dopamine clock, as well as the genetic and environmental factors that may activate it in humans. The research team’s next step will be to focus on these molecular “gears” and investigate these potential triggers.
Some people living with chronic stress have a higher risk of stroke, according to a study published on online in Neurology®, the medical journal of the American Academy of Neurology. The study looked at younger adults and found a correlation between stress and stroke, with no known cause, in female participants, but not male participants.
“Younger people often experience stress due to the demands and pressures associated with work, including long hours and job insecurity, as well as financial burdens,” said Nicolas Martinez-Majander, MD, PhD, of the Helsinki University Hospital in Finland.
“Previous research has shown that chronic stress can negatively affect physical and mental health. Our study found it may increase the risk of stroke in younger women.”
For the study, researchers looked at 426 people aged 18 to 49 who had an ischaemic stroke with no known cause. They were matched for age and sex with 426 people who did not have stroke. Participants completed a questionnaire about stress levels over a one-month period. Those with stroke were asked after their stroke to record stress levels in the month prior to their stroke.
Participants were asked 10 questions, such as “In the last month, how often have you felt that you were unable to control the important things in your life?” Scores for each question ranged from zero to four, with four meaning “very often.” A total score of 0 to 13 represented low stress; 14 to 26, moderate stress; and 27 to 40, high stress.
Those with stroke had an average score of 13 compared to those without stroke who had an average score of 10. People with stroke were more likely to have at least moderate stress levels. Of those with stroke, 46% had moderate or high stress levels compared to 33% of those who did not have stroke. After adjusting for factors that could affect risk of stroke such as education level, alcohol use and blood pressure, researchers found for female participants, moderate stress was associated with a 78% increased risk of stroke and high stress was associated with a 6% increased risk.
Researchers did not find a link between stress and stroke in male participants. “More research is needed to understand why women who feel stressed, but not men, may have a higher risk of stroke,” said Martinez-Majander.
“In addition, we need to further explore why the risk of stroke in women was higher for moderate stress than high stress. Knowing more about how stress plays a role could help us to create better ways to prevent these strokes.”
A limitation of the study was that people experiencing higher levels of stress may have been less likely to enrol in the study, which could have affected the results.
Paediatric critical care (PCC) staff are known to experience high levels of moral distress, symptoms of post-traumatic stress disorder (PTSD) and burnout, but often feel little is offered to help them with their mental health. The SWell team at Aston University, led by Professor Rachel Shaw from the Institute of Health and Neurodevelopment, realised following a literature review that there are no existing, evidence-based interventions specifically designed to improve PCC staff wellbeing. Initial work by SWell identified the ‘active ingredients’ likely to create successful intervention designs.
Together with a team from NHS England, the Aston University researchers set up the SWell Collaborative Project: Interventions for Staff Wellbeing in Paediatric Critical Care, in PCC units across England and Scotland. The aim of the project was to determine the feasibility and acceptability of implementing wellbeing interventions for staff working in PCC in UK hospitals. In total, 14 of the 28 UK PCC units were involved. One hundred and four intervention sessions were run, attended by 573 individuals.
Professor Shaw said: “The significance of healthcare staff wellbeing was brought to the surface during the COVID-19 pandemic, but it’s a problem that has existed far longer than that. As far as we could see researchers had focused on measuring the extent of the problem rather than coming up with possible solutions. The SWell project was initiated to understand the challenges to wellbeing when working in paediatric critical care, to determine what staff in that high-pressure environment need, and what could actually work day-to-day to make a difference. Seeing PCC staff across half the paediatric critical care units in the UK show such enthusiasm and commitment to make the SWell interventions a success has been one of the proudest experiences in my academic career to date.”
The two wellbeing sessions tested are low-resource and low-intensity, and can be delivered by staff for staff without any specialist qualifications.
In the session ‘Wellbeing Images’, a small group of staff is shown images representing wellbeing, with a facilitated discussion using appreciative inquiry – a way of structuring discussions to create positive change in a system or situation by focusing on what works well, rather than what is wrong.
In the ‘Mad-Sad-Glad’ session, another small group reflective session, participants explore what makes them feel mad, sad and glad, and identify positive actions to resolve any issues raised.
The key ingredients in both sessions are social support – providing a psychologically safe space where staff can share their sensitive experiences and emotions without judgement, providing support for each other; self-belief – boosting staff’s self-confidence and ability to identify and express their emotions in response to work; and feedback and monitoring – encouraging staff to monitor what increases their stress, when they experience challenging emotions, and what might help boost their wellbeing in those scenarios.
Feedback from staff both running and participating in the SWell interventions was very positive, with high satisfaction and feasibility ratings. Participants like that the session facilitated open and honest discussions, provided opportunities to connect with colleagues and offered opportunities for generating solutions and support.
One hospital staff member responsible for delivering the sessions said:
“Our staff engaged really well, and it created a buzz around the unit with members of the team asking if they could be ‘swelled’ on shift. A really positive experience and we are keeping it as part of our staff wellbeing package.”
The team concluded that even on busy PCC units, it is feasible to deliver SWell sessions. In addition, following the sessions, staff wellbeing and depression scores improved, indicating their likely positive impact on staff. Further evaluations are needed to determine whether positive changes can be sustained over time following the SWell sessions.
Donna Austin, an advanced critical care practitioner at University Hospital Southampton paediatric intensive care unit, said: “We were relatively new to implementing wellbeing initiatives, but we recognised the need for measures to be put in place for an improvement in staff wellbeing, as staff had described burnout, stress and poor mood. SWell has enabled our unit to become more acutely aware of the needs of the workforce and adapt what we deliver to suit the needs of the staff where possible. Staff morale and retention has been the greatest outcomes from us participating in the SWell study and ongoing SWell related interventions.”
Calorie labels on restaurant menus are negatively impacting people with eating disorders, according to a new study published in the BMJ Public Health.
The review, which is the first of its kind, is led by researchers at King’s College London. It found that individuals who have been diagnosed with an eating disorder changed their behaviours if presented with a menu featuring calorie labels.
This included avoiding restaurants, triggering eating disorder thoughts and paying more attention to calorie labels as identified by eye tracking research.
The research found that some people with eating disorders reported that seeing menu labels reinforced their eating disorder beliefs.
The study evaluated existing research to help build a picture of how nutritional labels on menus impact people with a lived experience of eating disorders or disordered eating. It reviewed 16 studies from the UK, US, Canada and Saudi Arabia which included 8,074 participants in total.
The study highlights that people with eating disorders can feel that eating disorders are perceived as less important in the light of obesity prevention policies.
However, physical health cannot be measured by a single indicator such as weight. Some argue that calorie labels can be seen as a blunt instrument to fix a complicated problem and that people with eating disorders could be losing out.
Food labelling came into force in England in 2022. Restaurants, take-aways and cafes with 250 employees or more must display the calories of the food and drink they sell on menus, online menus and take-away platforms. The measure was an attempt to curb rising obesity levels. The United States and Canada have also made calorie displays mandatory, however, few policies targeting obesity have considered the potential impact on eating disorders.
The eating disorder charity Beat estimates that at least 1.25 million people in the UK have an eating disorder. The number of people admitted to hospital with an eating disorder has risen approximately 7% each year since 2005 – 2006.
Senior author Dr Tom Jewell, Lecturer in Mental Health Nursing at King’s College London, said: “Our study highlights that people with lived experience of eating disorders are frustrated at being left out of the conversation around calorie labels.”
Striking a balance between the positive and harmful impacts of calorie labels on menus is vital in any public health policies.Dr Tom Jewell, Senior author and Lecturer in Mental Health Nursing at King’s College London
“Policymakers should consider the impact on both obesity and eating disorders when making decisions about nutrition labelling. A recent review found that calorie labelling has a modest effect on people’s behaviour but this needs to be counterbalanced with the potential harm it does for people with eating disorders.”
Co-author Dr Nora Trompeter, Research Fellow University College London, said: “Our study provides an important addition to the evidence base around calorie labels.”
Typically, there is a lot of focus on whether policies are effective in reducing obesity, but it is also critical to investigate whether these policies inadvertently harm people with eating disorders.
“Our review also shows that more research is needed to fully understand the impact of calorie labels on individuals with eating disorders. For example, none of the studies included young people.”
Coronal brain slice showing projections from different visual areas in the cerebral cortex to the ventrolateral geniculate nucleus (vLGN). These pathways are part of the circuit identified as mediating the suppression of instinctive fear responses.
Researchers at the Sainsbury Wellcome Centre (SWC) at UCL have unveiled the precise brain mechanisms that enable animals to overcome instinctive fears. Published today in Science, the study in mice could have implications for developing therapeutics for fear-related disorders such as phobias, anxiety and post-traumatic stress disorder (PTSD).
The research team, led by Dr Sara Mederos and Professor Sonja Hofer, mapped out how the brain learns to suppress responses to perceived threats that prove harmless over time.
“Humans are born with instinctive fear reactions, such as responses to loud noises or fast-approaching objects,” explains Dr Mederos, Research Fellow in the Hofer Lab at SWC. “However, we can override these instinctive responses through experience – like children learning to enjoy fireworks rather than fear their loud bangs. We wanted to understand the brain mechanisms that underlie such forms of learning”.
Using an innovative experimental approach, the team studied mice presented with an overhead expanding shadow that mimicked an approaching aerial predator. Initially, the mice sought shelter when encountering this visual threat. However, with repeated exposure and no actual danger, the mice learned to remain calm instead of escaping, providing researchers with a model to study the suppression of fear responses.
Based on the lab’s previous work, the team knew that the ventrolateral geniculate nucleus (vLGN) could suppress fear reactions when active and was able to track knowledge of previous experience of threat. The vLGN also receives strong input from visual areas in the cerebral cortex, and so the researchers explored whether this neural pathway had a role in learning not to fear a visual threat.
The study revealed two key components in this learning process: (1) specific regions of the visual cortex proved essential for the learning process, and (2) a brain structure called the ventrolateral geniculate nucleus (vLGN) stores these learning-induced memories.
“We found that animals failed to learn to suppress their fear responses when specific cortical visual areas were inactivated. However, once the animals had already learned to stop escaping, the cerebral cortex was no longer necessary,” explained Dr Mederos.
“Our results challenge traditional views about learning and memory,” notes Professor Hofer, senior author of the study. “While the cerebral cortex has long been considered the brain’s primary centre for learning, memory and behavioural flexibility, we found the subcortical vLGN and not the visual cortex actually stores these crucial memories. This neural pathway can provide a link between cognitive neocortical processes and ‘hard-wired’ brainstem-mediated behaviours, enabling animals to adapt instinctive behaviours.”
The researchers also uncovered the cellular and molecular mechanisms behind this process. Learning occurs through increased neural activity in specific vLGN neurons, triggered by the release of endocannabinoids – known to regulate mood and memory. This release decreases inhibitory input to vLGN neurons, resulting in heightened activity in this brain area when the visual threat stimulus is encountered, which suppresses fear responses.
The implications of this discovery extend beyond the laboratory. “Our findings could also help advance our understanding of what is going wrong in the brain when fear response regulation is impaired in conditions such as phobias, anxiety and PTSD. While instinctive fear reactions to predators may be less relevant for modern humans, the brain pathway we discovered exists in humans too,” explains Professor Hofer. “This could open new avenues for treating fear disorders by targeting vLGN circuits or localised endocannabinoid systems.”
The research team is now planning to collaborate with clinical researchers to study these brain circuits in humans, with the hope of someday developing new, targeted treatments for maladaptive fear responses and anxiety disorders.
New postpartum depression research from the School of Medicine and Weill Cornell Medicine could lead to a blood test to identify women at risk and possibly even to a preventive treatment.
The research, published in Neuroposychopharmacology, suggests that pregnant women may have characteristic levels of certain molecules in their blood that can warn that they are at risk of developing postpartum depression (PPD). These molecules, called neuroactive steroids, are derived from progesterone.
Measuring those molecules via a simple blood test could let doctors get women treatment for PPD sooner – possibly even before symptoms appear, the researchers say. “Studying postpartum depression gives us a way to identify biological changes that occur before someone becomes depressed because the timing of postpartum depression is predictable,” said researcher Jennifer Payne, MD, an expert in reproductive psychiatry at UVA Health and the University of Virginia School of Medicine.
Understanding Postpartum Depression
Postpartum depression affects 10% to 15% of new moms.
“Postpartum is the only time in people’s lifespans when we know there is a biological trigger which guarantees that a certain percentage of people will become ill,” said Weill Cornell’s Lauren Osborne, MD, who co-led the study with Payne. “If we can untangle this biology and find predictors for it, not only will we be helping women, but it may give us a step up in trying to find predictors for other psychiatric illnesses also.”
It’s unclear why some women develop postpartum depression, but the new findings suggest that an imbalance in the body’s metabolism of progesterone may be a factor.
About the Study
To better understand the role of progesterone, the researchers focused on the hormone and on its “metabolic pathway” in the body. The scientists measured levels of neuroactive steroids derived from progesterone in the blood of 136 women during their second and third trimesters. Of these, 33 went on to develop postpartum depression after giving birth.
Two neuroactive steroids seem to affect the risk of developing PPD – pregnanolone and isoallopregnanolone. Pregnanolone acts on a particular cellular receptor to reduce stress. Isoallopregnanolone, on the other hand, acts on the same receptor to increase stress.
In the third trimester, women who went on to develop PPD had a lower pregnanolone/progesterone ratio and a higher isoallopregnanolone/pregnanolone ratio compared with those who did not, the researchers found. Elevated progesterone levels in late pregnancy were also associated with a higher risk of PPD.
Next Steps
The researchers plan to attempt to replicate their results in a larger, more diverse group of women in hopes of developing a clinical test to predict the risk of PPD. Further, they say their work could lead to a preventive treatment – possibly one of two prescription drugs, brexanolone and zuranolone, already available to treat PPD.
“We don’t know if these drugs would work as a preventive measure for people who are at risk of developing postpartum depression, but based on our findings, they have the potential to prevent [its] development,” Osborne said.
Breast cancer is the world’s most prevalent cancer. Although earlier detection and targeted treatment have resulted in high survival rates, many breast cancer survivors experience fear of cancer recurrence. For some survivors this fear is occasional, for others it is persistent and often debilitating.
A new study of breast cancer survivors has found this psychosocial challenge impacts almost every important domain of their lives – the emotional, behavioural, cognitive, relational and professional. A larger number of domains was affected, and they were affected more frequently in those with greater fear of recurrence.
“Study participants were reportedly disease free and trying to rebuild their lives during their post-treatment survivorship,” said senior author Shelley Johns, PsyD, a researcher-clinician with the Regenstrief Institute, the Indiana University School of Medicine and the IU Melvin and Bren Simon Comprehensive Cancer Center. “Our findings provide clarity about how breast cancer survivors are impacted by fear of recurrence and insight into how they cope with this understandable fear.”
The impact of fear of recurrence ranged from mildly to severely disruptive. Women experiencing mild fear reported sporadic occurrences. Those with significant fear described it as persistent and/or easily triggered across multiple life domains.
Disturbed sleep prior to mammograms was reported by survivors with mild fear, while frequent need to absent themselves from social activities, get into bed and pull the blanket over their eyes to avoid thinking about cancer was an example of severe, also known as clinical, fear of recurrence. Approximately 74 percent of study participants were experiencing clinical fear of recurrence.
347 women completed the study’s open-ended survey:
Many reported feelings of stress, irritability and sadness.
Some said fear of recurrence frequently interrupted their train of thought, for example interfering with their job when their disease popped into their mind.
Survivors who thought that they were more worried than they should be compared to other breast cancer survivors reported feelings of embarrassment.
Some indicated it was too hard to be around their family because they were constantly wondering how many more Christmases and birthdays they were going to have with their children.
The paper’s title includes the phrase, “out of a dark place,” a direct quote from a breast cancer survivor who said that she joined the study to support “getting out of a dark place.”
Other survivors noted the specific impact of fear of cancer recurrence on daily life:
“It motivates me to maintain healthy habits. Such as eating five servings of fruits and vegetables, working out and drinking less alcohol. It also motivates me to maintain mental health and physical health.”
“Whenever I feel any kind of pain or discomfort in the area where I had cancer it concerns me and I feel anxious and irritable.”
“Cancer is all around us. Everything is a trigger. Anniversaries, other family/friends’ diagnosis, commercials about drugs, social media, etc. …it’s a daily thought or a daily emotion.”
“Sit for hours doing nothing, do not turn on TV, sleepless, find hours pass by and I am in the same place just thinking, do not participate in activities, get lost driving because I’m deep in thought, compulsive online shopping, collecting things.”
Survivors offered specifics on their coping mechanisms:
“Just trying to be positive, eat healthy, take my meds, get enough sleep, exercise three times a week, and hope for the best.”
“I try to avoid things that make me think about recurrence. For example, unfollowing social media accounts, fast forwarding or leaving the room when commercials about cancer medications are on.”
“I try not to focus on it. I also speak with family members who have lived with cancer longer than myself.”
“Prayer, meditation, staying in the moment, and focusing on making the best of each day.”
While many survivors cited avoidance of thoughts and feelings as their primary coping behaviour, Dr Johns, a health services researcher and clinical health psychologist, observes that research is needed to probe the function of various coping behaviours’ to determine if they are helpful.
In a question seldom posed to participants in a clinical trial, when asked what they hoped to gain by participating in the study, the majority indicated that they sought senses of purpose, belonging, control and connection with others.
The paper concludes, “Fear of cancer recurrence is one of the most common psychological challenges for cancer survivors. Understanding affected life domains, coping strategies employed prior to intervention, and reasons for seeking guidance can inform the development and implementation of evidence-based interventions to effectively address fear of cancer recurrence among persons living with breast cancer.”
Glucagon-like peptide 1 receptor agonists (GLP1RA) – medications for type 2 diabetes and obesity that have recently been making headlines due to a rise in popularity as weight loss agents – have been linked with behavioural side effects. A large population-based analysis in Diabetes, Obesity and Metabolismassessed whether certain genetic variants might help explain these effects.
GLP1RA mimic the GLP-1 hormone in the body that helps control insulin and blood glucose levels and promotes feelings of satiety. GLP-1 binds to GLP1R on cells in the brain and pancreas.
Observational and epidemiological studies have shown that there may be neutral or protective effects of GLP1RAs on mental health symptoms. However, a study based on individuals taking GLP1RA suggests there is increased prescription of anti-depressants when used for treatment of diabetes. Early evidence in animal models suggest GLP1RA may decrease depressive and anxious symptoms, potentially presenting new treatment pathways; however, comparing these studies to human clinical evidence will not be possible for some time.
For the analysis, investigators examined common genetic variants in the GLP1R gene in 408 774 white British, 50 314 white European, 7 667 South Asian, 10 437 multiple ancestry, and 7641 African-Caribbean individuals.
Variants in the GLP1R gene had consistent associations with cardiometabolic traits (body mass index, blood pressure, and type 2 diabetes) across ancestries. GLP1R variants were also linked with risk-taking behavior, mood instability, chronic pain, and anxiety in most ancestries, but the results were less consistent. The genetic variants influencing cardiometabolic traits were separate from those influencing behavioral changes and separate from those influencing expression levels of the GLP1R gene.
The findings suggest that any observed behavioral changes with GLP1RA are likely not acting directly through GLP1R.
“Whilst it is not possible to directly compare genetic findings to the effects of a drug, our results suggest that behavioural changes are unlikely to be a direct result of the GLPRAs. Exactly how these indirect effects are occurring is currently unclear,” said corresponding author Rona J. Strawbridge, PhD, of the University of Glasgow, in the UK.
A study conducted at Turku PET Centre in Finland and published in showed that changes in the functioning of opioid neurotransmitters in the brain may underlie anorexia.
Anorexia nervosa is a serious psychiatric disorder characterised by restricted eating, fear of gaining weight, and body image disturbances, which may lead to severe malnutrition, depression and anxiety. This new study from Turku PET Centre, published in Molecular Psychiatry, shows how changes in neurotransmitter function in the brain may underlie anorexia.
“Opioid neurotransmission regulates appetite and pleasure in the brain. In patients with anorexia nervosa, the brain’s opioidergic tone was elevated in comparison with healthy control subjects. Previously we have shown that in obese patients the activity of the tone of this system is lowered. It is likely that the actions of these molecules regulate both the loss and increase in appetite,” says Professor Pirjo Nuutila from the University of Turku.
Number of opioid receptors in the brain (top row) and sugar intake (bottom row) in patients with anorexia nervosa. Credit: University of Turku
In addition, the researchers measured the brain’s glucose uptake. The brain accounts for about 20% of the body’s total energy consumption, so the researchers were interested in how a reduction in the energy intake affects the brain’s energy balance in anorexia.
“The brains of patients with anorexia nervosa used a similar amount of glucose as the brains of the healthy control subjects. Although being underweight burdens physiology in many ways, the brain tries to protect itself and maintain its ability to function for as long as possible,” says Professor Lauri Nummenmaa from Turku PET Centre and continues:
“The brain regulates appetite and feeding, and changes in brain function are associated with both obesity and low body weight. Since changes in opioid activity in the brain are also connected to anxiety and depression, our findings may explain the emotional symptoms and mood changes associated with anorexia nervosa.”
A study based on interviews with primary care physicians has found that treating patients who were adopted is challenging due to limited access to their family medical history. The study, published in Annals of Family Medicine, also found that there was a desire by physicians to fill the information using genetic testing.
Adopted individuals often only have limited information about their biological family, or even none at all, complicating their treatment. The growing availability and popularity of direct-to-consumer genetic testing kits amplifies the need for physicians to be prepared to address genetic testing for adoptees with limited family medical history. To address this, the present study explored the approaches of primary care physicians when caring for adult adopted patients with limited family medical history.
In-depth interviews were conducted by the researchers, including hypothetical clinical scenarios, with 23 primary care physicians from Rhode Island and Minnesota to understand their experiences, practices, knowledge, and training gaps when addressing limited family medical history and adoption-related issues.
The researchers found that primary care physicians report knowledge gaps and receive little training or resources on adult adoptees with limited family medical history. As a result, they seek guidance around appropriate preventative screening and genetic testing. Limited interaction with adoptees compared to non-adopted patients also influenced perceptions. There was also an over-reliance on stereotypes and the danger of inaccurate media representation affecting how physicians interacted with adoptee patients. Likewise, those physicians who had experience with adoption might be at risk of over-generalising those experiences, especially given how heterogeneous adoptees are as a population.
Furthermore, the researchers found that mental illness and trauma are under-recognised and under-addressed. Care for adoptees includes trauma-informed care which can address factors such as loss, grief, identity development, and to helping adoptees in searching for biological family, reunion, or with complex family dynamics.
To make matters worse, primary care physicians often obtain family medical history imprecisely, risking miscommunication, microaggressions, and damage to the patient-physician relationship.
The findings of this study highlight the significant gaps in knowledge and training for primary care physicians caring for adult adopted patients with limited family medical history. Addressing these gaps may improve the quality of care and strengthen physician-patient relationships.
