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People with mental illness have greater amounts of damaged RNA than those without a mental health condition, which might explain the link between mental illness and age-related diseases such as cancer
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Tag: mental health
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Mental illness may accelerate ageing by damaging RNA
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Mental health conditions may accelerate ageing by damaging RNA
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People with mental health conditions have greater amounts of damaged RNA than those without one, which might explain the link between the conditions and age-related diseases such as cancer
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Anxiety therapy prior to COVID-19 pandemic shields against increased stress
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The start of the COVID-19 pandemic led to unprecedented exposure to stressors driven by fears of a novel and deadly disease, intense uncertainty, and resulting isolation measures, which in turn resulted in increases in anxiety for many. According to new research however, individuals who were in therapy for anxiety prior to the start of the pandemic did not experience upticks in their symptoms throughout this exceptionally challenging time.
The new research suggests that cognitive-behavioral therapy (CBT) and dialectical behavior therapy (DBT) provided tools to help individuals with anxiety to manage their symptoms in the face of these intense stressors, according to the study’s authors. The study, led by psychologists at McLean Hospital, a member of Mass General Brigham, and Touro University, published March 13th in PLOS One.
Our research suggests that CBT and DBT can offer major benefits to protect individuals’ mental health amidst a major world catastrophe and period of upheaval. People who have been treated for anxiety know that fighting it is not helpful, and that there are tools to help accept the current realities of their situations,” he added. “In some ways, having a previous anxiety disorder before a crisis occurs can be a blessing.”
David H. Rosmarin, PhD, ABPP, lead study author, clinical psychologist at McLean Hospital, and associate professor of psychology at Harvard Medical School
For the study, researchers compared the treatment trajectories of 764 individuals who participated in outpatient therapy and divided them into four groups based on when they initiated treatment: pre-pandemic (start date on or prior to 12/31/2019), pandemic-onset (from 01/01/2020 to 03/31/2020), during-pandemic (from 04/01/2020 through 12/31/2020), and post-pandemic once vaccines became available (on or after 01/01/2021).
Anxiety was measured at intake and at each subsequent session using the GAD-7 questionnaire, which assesses for anxiety symptoms. Then, the researchers analyzed the trajectories of anxiety and compared the four groups. Therapy consisted of CBT and DBT.
Their findings revealed that overall, patients presented with moderate anxiety when they began treatment, which rapidly decreased within 25 days of starting therapy, and gradually declined to mild anxiety over the remainder of their sessions. When comparing the four groups of patients, the researchers found no substantive differences between groups, suggesting that treatment effects were robust to environmental stressors related to the pandemic. Moreover, among patients who were in treatment at the start of the pandemic, the researchers did not detect an increase in anxiety during the initial acute phase of COVID-19 (March 20, 2020 through July 1, 2020).
We were surprised. We thought that during the height of the pandemic and before vaccines were available, patients would show increased anxiety and that therapy would be less effective but that was not the case.”
Steven Pirutinsky, PhD, study co-author, assistant professor at Graduate School of Social Work at Touro University
Studies have shown that the COVID-19 pandemic adversely impacted mental health, with measurable increases in anxiety from the pandemic’s onset in early 2020 through the fist availability of vaccinations in early 2021. One report from the World Health Organization found global prevalence of anxiety and depression increased by 25 percent in the first year of the pandemic.
“There is a widespread misperception that anxiety is a risk factor for people crumbling and not being able to function,” says Rosmarin. “However, when people receive evidence-based psychotherapy and learn skills to cope, they can become more resilient than those who have never had anxiety at all.”
Limitations of the study include that the participant pool, while demographically and clinically diverse, consisted primarily of highly educated individuals geographically specific to the northeastern United States. The pandemic-onset group was also smaller than the others, which may be attributed to limited availability of in-person therapy around that time. The study also did not look at other mental health measures, including depression and substance use. More research is needed to gain insights into how these findings may be impacted in other regions of the country, and conditions aside from anxiety disorders.
Source:
Journal reference:
Rosmarin, D. H., et al. (2024) Response to anxiety treatment before, during, and after the COVID-19 pandemic. PLOS ONE. doi.org/10.1371/journal.pone.0296949.
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Wristwatch-like devices detect early signs of Alzheimer’s
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Monitoring daily activity patterns using a wrist-worn device may detect early warning signs of Alzheimer’s disease, according to a new study led by researchers at the Johns Hopkins Bloomberg School of Public Health.
The researchers analyzed movement data from wristwatch-like devices called actigraphs worn by 82 cognitively healthy older adults who were participants in a long-running study of aging. Some of the participants had detectable brain amyloid buildup as measured by PET scan. Buildup of the protein amyloid beta in the brain is a key feature of Alzheimer’s disease.
Using a sensitive statistical technique, the researchers found significant differences between this “amyloid-positive” group and “amyloid-negative” participants in mean activity in certain afternoon periods and differences in variability of activity across days in a broader range of time windows.
The new study was published online February 21 in the journal SLEEP.
We need to replicate these findings in larger studies, but it is interesting that we’ve now seen a similar difference between amyloid-positive and amyloid-negative older adults in two independent studies.”
Adam Spira, PhD, Professor, Department of Mental Health at the Bloomberg School
The new study’s results partly confirm findings from an earlier study in a smaller sample, also led by Spira, and suggest that actigraphs someday could be a tool to help detect incipient Alzheimer’s disease before significant cognitive impairment sets in. Data from the prior study came from participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies.
For their new study, Spira and colleagues investigated the potential of actigraph-based monitoring in 82 community-dwelling individuals whose average age was about 76. Each participant had a PET scan to measure brain amyloid and wore an actigraph 24 hours per day for one week. Using a sensitive statistical technique called FOSR (function-on-scalar regression), the researchers found that the 25 amyloid-positive participants, compared to the 57 amyloid-negative participants, had higher mean activity during the early afternoon, 1:00 to 3:30 p.m., and less day-to-day variability in activity from 1:30 to 4:00 p.m. and 7:30 to 10:30 p.m.
In more conservative analyses, some of these time windows with differences were no longer statistically significant. Nonetheless, the higher afternoon activity and lower afternoon variability echoed the investigators’ prior findings.
Alzheimer’s disease, the leading cause of dementia, is estimated to affect more than 6 million older adults in the U.S. The Alzheimer’s disease process is still not fully understood but is characterized by amyloid plaques and tangles in the brain, which typically begin to accumulate a decade or two before Alzheimer’s is diagnosed.
The only approved treatments that may slow the disease course are those that target amyloid beta and reduce the plaques. Many researchers believe that such treatments can be much more effective if given earlier in the disease course-;ideally, years before dementia becomes evident.
Abnormal patterns of sleep and waking activity have been studied as potential early indicators of Alzheimer’s. Alzheimer’s patients typically have abnormal sleep-wake rhythms, and prior studies have found evidence that amyloid accumulation may disrupt sleep-wake rhythms relatively early in the disease process. There is also evidence that sleep loss promotes amyloid accumulation, suggesting a “vicious circle.”
Such findings hint at the possibility that older adults might someday, among other measures, wear wristwatch-like devices that would automatically track and analyze their sleep and waking activity. Individuals with anomalous activity patterns could then consult their physicians for more in-depth Alzheimer’s screening.
The individuals in the new study were participants in a long-running study, the Baltimore Longitudinal Study of Aging, which is conducted by the Intramural Research Program of the National Institute on Aging (NIA), part of the National Institutes of Health (NIH). Several members of the NIA team were co-authors of the study.
Standard, non-FOSR statistical methods did not detect any significant differences in activity or sleep patterns, suggesting the methods may be less sensitive to amyloid deposition.
In the earlier actigraphy study, the researchers, using FOSR-based analyses in a different sample of 59 participants, found increases in mean activity in afternoon hours and differences in variability, including lower variability in the afternoon, among amyloid-positive participants.
The scientists don’t know why amyloid buildup would trigger differences in activity patterns during these particular times of day. They note that there is a well-known phenomenon among individuals with Alzheimer’s disease called “sundowning,” in which agitation increases in the afternoon and early evening.
“It’s conceivable that the higher afternoon activity we observed is a signal of ‘preclinical sundowning,’” Spira says. “At the same time, it’s important to note that these findings represent averages among a small sample of older people over a short period of time. We can’t predict whether an individual will develop amyloid plaques based on the timing of their activity. So, it would be premature for older people to be concerned because their fitness trackers say they are particularly active in the afternoon, for example.”
He and his colleagues plan to do larger studies of this kind. They also hope to do longer-term studies to see if daily activity-pattern changes are associated not only with brain amyloid but also with actual cognitive decline.
“Evaluating a Novel 24-Hour Rest/Activity Rhythm Marker of Preclinical β-Amyloid Deposition” was co-authored by Adam Spira, Fangyu Liu, Vadim Zipunnikov, Murat Bilgel, Jill Rabinowitz, Yang An, Junrui Di, Jiawei Bai, Sarah Wanigatunga, Mark Wu, Brendan Lucey, Jennifer Schrack, Amal Wanigatunga, Paul Rosenberg, Eleanor Simonsick, Keenan Walker, Luigi Ferrucci and Susan Resnick.
Support for the research was provided by NIH (R01AG050507, HHSN-260-2004-00012C).
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Trauma screening may help connect children to specific mental-health services
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Each year between 200,000 and 270,000 children and youth enter foster care placements with child welfare services, and many more children receive child welfare services while remaining in their parent’s care, according to the U.S. Department of Health and Human Services. Although many of these children have a documented history of abuse or neglect, children may respond differently to incidents of maltreatment or other potentially traumatic events. Incorporating a trauma screening -; which assesses how trauma and maltreatment affected each child -; into the child welfare evaluation process provides information that could be used to connect children to the specific mental-health services they need, according to new research from the Penn State College of Health and Human Development and the Child Health and Development Institute.
Individuals react differently to traumatic events like stress or abuse. Some children develop signs of traumatic stress while other people in similar situations do not. For children who experience distress, some become hypervigilant, and others may become withdrawn.
Christian Connell, associate professor of human development and family studies and director of the Child Maltreatment Solutions Network, and collaborator, Jason Lang, chief program officer at the Child Health and Development Institute and a faculty member in the Yale School of Medicine and University of Connecticut, led a study on the value of screening for traumatic experiences during child welfare system intake evaluations. Their study demonstrated that asking a small number of questions about trauma during these evaluations led to better identification of trauma symptoms and more appropriate trauma-focused service recommendations for children. Results of the study were recently published in Journal of Traumatic Stress.
In 2014, Connell and Lang created the Child Trauma Screen, a 10-item screening questionnaire that measures trauma exposure and symptoms of post-traumatic stress disorder in children. The screen was designed for use with established child welfare service evaluations and is freely available to any government entity or child-serving service organization that wishes to use it. Since 2015, the state of Connecticut has included the Child Trauma Screen as part of evaluations for children placed in the child welfare system.
In this study, the researchers reviewed Connecticut child welfare records from July 2013 through October 2014, before the screening was implemented, and from October 2015 through March 2016, after the screening was integrated into evaluations across the state. The research team examined 70 records from the pre-screening time period and 100 records from the screening time period for children between the ages of six and 17.
“When a child encounters the child welfare system, he or she may have had a number of difficult life experiences. The Child Trauma Screen helps staff understand how the system might best respond to that child’s needs related to these experiences,” said Connell, who is also one of the principal investigators of the Translational Center for Child Maltreatment Studies, within the Penn State Center for Safe and Healthy Children. “While the child welfare investigation processes usually identifies the types of experiences the child may have had leading to child welfare involvement, staff also need a standard way to assess how the child is processing those experiences to better identify appropriate service referrals. This is why we created the Child Trauma Screen.”
By using the Child Trauma Screen when children entered formal involvement with the child welfare system, case workers were able to gather consistent information on the types of traumatic stress reactions experienced by children. Results from the study showed that using the screening led to better documentation of children’s reactions to traumatic events and increased service recommendations and referrals for specific, trauma-focused services.
One potential concern arises from the fact that -; despite the heightened rates of referral for services prompted by the trauma screening -; the results did not demonstrate a corresponding increase in children receiving trauma-related services. The data in this study do not explain why the recommendations did not lead to more services being documented in the child welfare record, but the researchers agreed that identifying that disconnect is critically important so that they can understand and rectify it. Potential explanations include challenges in accessing services within communities or a failure to document services that were provided.
Ultimately, the goal is to connect children who have experienced trauma to the services and supports they need. Our results show that screening can be an important part of that process, but that further work is required to make the connection. The next step is identifying the barriers to providing trauma-related services and then connecting each child with the specific help they need.”
Christian Connell, associate professor of human development and family studies and director of the Child Maltreatment Solutions Network
The Child Trauma Screen has been translated into several languages and is used by juvenile courts and child welfare systems in multiple states and localities in the U.S. and internationally. Connell and Lang said that there are multiple valid tools that can be used for trauma screening, but the most important thing is that children should be screened for trauma experiences and trauma-related symptoms if there in an opportunity to connect them with necessary services.
“Most children who suffer from traumatic stress do not receive behavioral health services, and some suffer in silence alone without telling anybody what they experienced,” Lang said. “Screening is an effective strategy for identifying children who are suffering and providing support and connection with behavioral health or other services. Unfortunately, trauma screening is not commonly used in many settings where it can be helpful, so we are also creating trainings for adults who work with children.”
The Child Health and Development Institute is developing a web-based training program about trauma screening for social workers, health care providers, educators and other people who work with children. Trauma ScreenTIME is a five-module, web-based training on trauma screening developed with funding from the Substance Abuse and Mental Health Services Administration’s National Child Traumatic Stress Network. So far, over 1,600 people have enrolled and more than 500 have completed the training, according to Connell, who is evaluating the effects of the training among participants.
Modules for people who work in schools and pediatric medical care are available now, and modules for people who work in early childcare, child welfare and juvenile justice are in development. Like the Child Trauma Screen, the Trauma ScreenTime trainings are available for free online.
“Many child-serving professionals are reluctant or don’t feel equipped to talk with children and families about trauma,” Lang said. “Trauma ScreenTIME provides comprehensive courses in trauma-screening best practices. The trainings address common questions and concerns and provide simple strategies that can be used in virtually any child-serving setting.”
Ann Shun Swanson, graduate student at Penn State, and Maegan Genovese, research associate at The Consultation Center in the Yale School of Medicine, also contributed to this research.
The United States Department of Health and Human Services, Administration for Children and Families and the Children’s Bureau funded this project.
Source:
Journal reference:
Connell, C. M., et al. (2024). Effects of child trauma screening on trauma‐informed multidisciplinary evaluation and service planning in the child welfare system. Journal of Traumatic Stress. doi.org/10.1002/jts.23001.
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Ketamine’s unlikely conversion from rave drug to mental health therapy
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Ketamine being administered via an intravenous drip at a clinic in New York
Victor Llorente/The New York Times/Redux/eyevine
LAST year, to much ado in the press, Prince Harry wrote candidly in his memoir Spare about taking ketamine to help him deal with his mother’s death. He isn’t the only one talking about the substance, which has previously been known mainly as a horse tranquilliser and a psychedelic rave drug. It is hard to keep track of the many celebrities speaking openly about taking ketamine in an effort to improve their mental health.
Across the US, hundreds of clinics have opened to provide intravenous infusions of the drug in a therapeutic setting, a trend that has now reached the UK too. Trailblazing firms, worried about their employees’ mental health, are starting to offer this therapy as a benefit. One even floated the idea of installing a ketamine clinic at its corporate headquarters. Meanwhile, pharmaceutical companies are developing over-the-counter ketamine products such as lozenges and topical creams. The drug has become the most commonly available psychedelic therapy.
That might sound like good news given the mounting evidence that ketamine can treat depression, post-traumatic stress disorder and addiction. Yet its use in treating mental health conditions is still novel and many uncertainties remain. Illegal use is rising too, perhaps influenced by its popularity as a therapeutic.
All this means it is time to ask whether ketamine really can soothe mental health problems, how it works and whether there are any risks to its new popularity. Psychiatrist …
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Exclusive: Aid groups have no concrete long-term health plans for Gaza
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Children at a temporary shelter in Rafah, in southern Gaza
Rizek Abdeljawad/Xinhua/Alamy
The situation in Gaza is rapidly devolving into the worst humanitarian crisis in modern memory, and international health organisations have no long-term plans for addressing the territory’s post-war needs.
More than three-quarters of Gaza’s 2.2 million residents, half of whom are children, are internally displaced, trapped in one of the most densely populated areas in the world with minimal access to food, water or healthcare. Since 7 October, when Hamas militants from Gaza invaded Israel and killed more than 1000…
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The war in Gaza is creating a health crisis that will span decades
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Palestinian children wait to receive food cooked by a charity kitchen amid shortages of food supplies in Rafah
Ismael Mohamad/UPI/Shutterstock
The situation in Gaza is rapidly devolving into the worst humanitarian crisis in modern memory, and international health organisations have no long-term plans for addressing the territory’s post-war needs.
More than three-quarters of Gaza’s 2.2 million residents, half of whom are children, are internally displaced, trapped in one of the most densely populated areas in the world with minimal access to food, water or healthcare. Since 7 October, when Hamas militants from Gaza invaded Israel and killed more than 1000 civilians, Israel has intensely bombed the enclave, hindered the flow of humanitarian aid and decimated civilian infrastructure. As a result, more than 30,000 Palestinians have died in Gaza – mostly women and children – according to the United Nations, and more than 72,000 have been injured.
Yet, these figures signal only the beginning of the public health catastrophe. Those who survive the war will face lifelong health effects. Thousands of Palestinians will be living with missing limbs, compromised immunity, mental illness and other chronic conditions. Meeting their health needs will be a decades-long undertaking, one that no global aid organisation has adequately planned for.
The World Health Organization, the World Food Programme, UNICEF, the Palestine Red Crescent Society, CARE International, Mercy Corps and Doctors Without Borders all lack concrete, long-term plans to address health needs in Gaza, according to information each organisation shared with New Scientist. Save the Children and the International Committee of the Red Cross didn’t provide a response to questions about their long-term plans.
An unprecedented humanitarian disaster
The lack of planning for the coming decades of healthcare needs is partly due to the enormity of the current humanitarian crisis. Most people in Gaza are living in crowded conditions without sewage treatment and trash removal. On average, people have less than 1 litre of clean water per day. As a result, infectious disease is rampant.
A survey in a limited number of shelters in December and January found that at least 90 per cent of children under 5 years old have one or more infectious illnesses and 70 per cent have had diarrhoea in the past two weeks. “And that doesn’t account for the hundreds of thousands of people who aren’t in refugee shelters,” says Margaret Harris at the WHO.
Hunger is also widespread. Almost two-thirds of households eat one meal a day, and a quarter of the population faces imminent starvation and extreme malnutrition. Conditions are most dire in northern Gaza where 1 in 6 children are malnourished, according to the survey. Gaza’s health ministry reported on 7 March that 20 people, including 15 children, have died from malnutrition and dehydration. Poor surveillance means these numbers are likely much higher.
“The difficult thing about malnutrition in children is that it begets more illness,” says Tanya Haj-Hassan at Doctors Without Borders. Malnourished children are more susceptible to infections, which wears the intestine’s lining, making it difficult to absorb nutrients. “So, they become more malnourished, more immunocompromised, and it just becomes this vicious cycle that’s essentially a snowball down to death,” she says.
Bombing has made much of the territory unsafe. UNICEF found that by December, more than 1000 children had lost one or both of their legs since the conflict began – or more than 10 children a day, on average. And there are few options to obtain care for these injuries: as of 21 February, only 18 of the 40 hospitals in Gaza were still functioning, but with reduced capacity. “They don’t have drugs. They don’t have machines. They don’t have power. They might have a few doctors who are running an emergency room. So, there’s really no functioning health system,” says Selena Victor at Mercy Corps.
The overwhelming humanitarian crisis has left health organisations scrambling. “We’ve not seen such a level of violence, horror, fear and deprivation enacted on any population in modern history,” says Harris. “We are, in a sense, charting unknown territory.”
Gaza’s impending public health crisis
Even if the war ends tomorrow, survivors will face lifelong health consequences. Many will have physical disabilities. Others will have severe mental illness. Some may develop chronic lung conditions, heart disease and cancer from the chemical pollutants in bombs and destroyed buildings, says Harris.
The impact will be most severe for children. Persistent malnutrition early in life stunts growth and impairs brain development, causing deficits in cognition, memory, motor function and intelligence, says Haj-Hassan. It also weakens children’s immune systems, leaving them vulnerable to illness. Research shows that malnutrition during pregnancy increases the risk of babies developing obesity, hypertension, heart disease and type 2 diabetes. A February report from Project Hope, an international aid organisation, found that 1 in 5 pregnant women treated at a Gaza clinic were malnourished, as were 1 in 10 children seen there.
However, the most widespread harm will be the mental health effects, says Harris. “Just imagine what it’s like for the people who are going through this every day relentlessly. They have a terrible sense of uncertainty – no idea where to go, what’s going to happen next, where the next little bit of food is going to come from,” she says. Such traumatic experiences are associated with depression, anxiety, post-traumatic stress disorder (PTSD) and suicidal thoughts. In children, this trauma can disrupt brain and organ development and increase the risk of learning disabilities and mental health conditions. Without early interventions, these problems may continue into adulthood. “We’re going to see an enormous burden of mental illness that is going to be extremely difficult to deal with,” says Harris.
Adults who experience childhood adversity also have 12 times the risk of developing alcohol and drug use disorders and attempting suicide. They are more likely to have physical health conditions, too, such as heart disease or cancer. Young men who survive conflict have almost triple the rates of severe mental disorders, such as psychosis, compared with those who don’t experience war.
Current post-war plans are not enough
Given these consequences, long-term health plans for Gaza must be established. Such plans will have to address rebuilding infrastructure, developing mental and physical rehabilitation programmes and routinely screening for illness.
“It seems absurd to be talking about what the municipal authorities will look like when right now people are dying trying to get a handful of bread for their families. It just doesn’t compute,” says Victor. “But we need to think about it.”
Yet, most organisations have only just begun to do so. The few with protocols in place – including the Palestine Red Crescent Society and CARE International – address the next year or two, but not decades down the line. The WHO is developing plans to address health needs from April 2024 to the end of the year. “We’re working with several different scenarios. The good scenario is a ceasefire that helps us to then genuinely look at [long-term plans],” says Harris. The other plausibility is that the war continues.
This uncertainty, along with the looming question of who will govern Gaza in the aftermath of the conflict, makes future preparations extremely difficult. “Why we are desperate to see not just a ceasefire, but a peaceful resolution, is that until we’ve got that, any plan, anything we even consider, is just castles in the air,” says Harris.
Israel has limited aide organisations’ access to the region, and the few workers who are in Gaza can’t operate safely. “Half the time they can’t do anything. They can’t move around safely. Basic things like communications keep getting shut down,” says Victor. And many of them have died. For instance, a member of the WHO’s limb reconstruction team in Gaza, a 29-year-old named Dima Abdullatif Mohammed Alhaj, was killed by an Israeli airstrike alongside her 6-month-old baby, two brothers and husband, says Harris.
These dangers and hurdles complicate long-term planning. “You can make any plan you like, but if you don’t know what the needs are, you’re not going to make a very useful plan,” says Victor.
It will take an enormous amount of money to address the widespread devastation in Gaza. Margaret Harris at the World Health Organization says that early estimates suggest $204.2 million will be needed to fund its health emergency plan in Gaza for 2024 alone.
Meanwhile, a spokesperson for the Palestine Red Crescent Society says the organisation has a $300 million budget for its campaign in Gaza, which will run until the end of 2025. Roughly $38 million of those funds will be used for the health sector, including restocking medical supplies, deploying additional ambulances and preventing infectious disease.
This won’t begin to address the long-term health needs of Palestinians in Gaza. It is hard to estimate what will be needed now, but Harris says that in the long run “I think it is fair to say we’ll be looking at billions”.
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- public health
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Diabetes drug dulaglutide may reduce symptoms of depression
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A recent Brain and Behavior study investigated the antidepressant effect of dulaglutide and the mechanism that underlies this effect.
Study: Dulaglutide treatment reverses depression-like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress. Image Credit: luchschenF/Shutterstock.com Background
Depression is a chronic mood disorder that is associated with low mood, insomnia, weight loss, a state of unhappiness, aversion to activity, fatigue, and low self-esteem. According to the World Health Organization, depression has become one of the major health burdens across the world.
This mental health condition is commonly treated with an antidepressant that takes around a month to alleviate the symptoms. However, several side effects are associated with the use of antidepressant drugs and could be toxic at high doses.
A combination of psychological, genetic, and neurological factors contributes to the manifestations of depression. Even though the exact etiology of this mental health issue is not fully understood, research has shown chronic stress to be an inducer of depression.
The hippocampus is a region of the brain that is associated with depression and modifies functionally and morphologically in response to stress. Animal model studies have shown that a decrease in neuronal and glial size, reduction in synaptic markers, loss of dendrites, and increase in apoptosis in the hippocampus leads to depression.
Many studies have uncovered the metabolic aspects of depression. For instance, diabetes and obesity are two common metabolic disorders that increase the risk of depression. Considering its high prevalence, novel therapies with high efficacy and fewer side effects are required to combat depression. The chronic mild stress (CMS) model has been recognized as a reliable rodent model to study depression.
Glucagon-like peptide-1 (GLP-1) and its receptor agonists are involved with anti-inflammatory effects and neuroprotective activities and can improve mental disorders, particularly depression and cognition. GLP-1 is a peptide hormone that stimulates the secretion of insulin and restricts the synthesis of glucagon in the pancreas in a glucose-dependent manner. Liraglutide is a GLP-1 analog that exhibited a positive effect in reducing anxiety and depression symptoms.
Dulaglutide is a novel long-acting GLP-1 receptor agonist that improves cognitive dysfunction and neuronal damage in rats with vascular dementia. Although many studies highlighted the efficacy of dulaglutide in preventing depression-like behavior triggered by chronic social defeat stress (CSDS), the underlying mechanism of this effect is not clearly understood.
About the study
The current study used a metabolomics strategy to evaluate the effect of dulaglutide in a CMS model. Furthermore, the underlying mechanism of this effect was also assessed. Adult male ICR mice, which is a strain of albino mice, were selected for this study. All test mice were around seven weeks old.
After one week of acclimatization, 60 mice were randomly assigned in four groups, namely, control (CON), the CMS and Vehicle group (CMS+Veh), the CMS and 0.3 mg/kg dulaglutide group (Low Dula), and the CMS and 0.6 mg/kg dulaglutide group (High Dula). Except for the CON group, all other groups were exposed to stressors.
To establish the CMS model of depression, selected mice were exposed to two or three different stressors for 28 days continuously. For stress induction, mice were deprived of water and food for 12 hours, kept in wet bedding for 24 hours, kept in a tilted cage for 24 hours, pintail for 1 minute, and cold water treatment for five minutes. The body weight of each test mouse was measured weekly, and behavioral tests, such as the tail suspension test (TST), open field test (OFT), and forced swimming test (FST), were performed.
Study findings
The mice subjected to CMS for four weeks exhibited depressive- and anxiety-like symptoms. An LC-MS/MS metabolomics study was performed to understand the potential pathophysiological mechanisms and investigate the efficacy of drugs to alleviate depression-like symptoms.
A distinct difference between the CON group, CMS+Veh group, and High Dula group was observed in accordance with the metabolic disorders induced by chronic stress, which was altered through dulaglutide treatment. Many potential biomarkers were identified that are associated with purine metabolism, arginine and proline metabolism, glycerophospholipid metabolism, glutamate metabolism, sphingolipid metabolism, and bile secretion.
Lipid metabolism pathways could be potential targets through which dulaglutide alleviates depression. Lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), phosphatidylinositol (PI), sphingolipids, and phosphatidylcholine (PC), are involved with the therapeutic effect of dulaglutide in alleviating depression. Consistent with previous studies findings, this study highlighted the association between lipid metabolism and the antidepressant effect of dulaglutide.
The current study indicated the downregulation of N-acetyl-L-aspartic acid (NAA) in the CMS model group. NAA, which is one of the most important metabolites of the vertebrate nervous system, was found in decreased levels in rats with chronic, unpredictable, mild stress. However, the current study indicated that dulaglutide therapy increased the levels of NAA through its upregulation in the hippocampus.
In the CMS model group, an upregulation in L-glutamic acid and L-arginine was observed. Dulaglutide treatment caused a decrease in arginine and proline, thereby indirectly exhibiting a neuroprotective effect.
Conclusions
The current study highlighted the antidepressant effects of dulaglutide using the CMS depression model. Notably, the potential metabolisms that underlie the antidepressant effect of dulaglutide have been elucidated in this study.
Journal reference:
- Jin, M., Zhang, S., Huang, B., Li, L., Liang, H., Ni, A., Han, L., Liang, P., Liu, J., Shi, H. and Lv, P. (2024) Brain and Behavior, 14(3). doi: 10.1002/brb3.3448. https://onlinelibrary.wiley.com/doi/10.1002/brb3.3448?utm_medium=email
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New psychological treatment for epileptic children lowers mental health problems
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A new psychological treatment for children with epilepsy, developed by a UCL-led team of scientists, has been shown to reduce mental health difficulties compared to standard care, a new study finds.
Mental health problems such as worries, low mood and behaviour problems are more common in children and young people with brain conditions such as epilepsy, than in the general population – with up to 60% of those with epilepsy having associated mental health disorders and many having more than one mental health condition.
These conditions can have a big impact on patients’ quality of life and overall health.
Currently, mental health problems in children and young people with epilepsy are often not identified because centres that treat epilepsy are usually separated from those that treat mental health difficulties. When mental health difficulties are identified, standard treatment for children who also have epilepsy is usually carried out by specialists, such as child and adolescent mental health services (CAMHS) or hospital-based paediatric psychology services. The treatment given usually involves treating each mental health condition (ie. anxiety, depression, behavioural issues) individually.
The new treatment, named the Mental Health Intervention for Children with Epilepsy (MICE), is based on the treatments that the National Institute for Health and Care Excellence (NICE) recommends for the treatment of common mental health difficulties, like cognitive behavioural therapy for anxiety and depression. However, it uses a modular approach, that enables multiple mental health conditions to be treated at once, instead of having different treatments for different mental health difficulties.
It was also modified specifically for children and young people with epilepsy, for example including sessions that explain about the relationship between epilepsy and mental health.
Additionally, the treatment can be delivered over the phone or via video call so that people did not have to travel to the hospital and miss time from school or work. And rather than being outsourced to services such as CAMHS, it was integrated into epilepsy services – meaning that it could be delivered by non-mental health specialists.
Lead author Dr Sophie Bennett, who carried out the research while working at UCL Great Ormond Street Institute of Child Health, said: “This treatment breakthrough means that we have a new way to help children and young people with epilepsy who also have mental health difficulties.
“The treatment can be delivered from within epilepsy services to join up care. It doesn’t need to be delivered by specialist mental health clinicians like psychologists.
“Integrating the care can help children with epilepsy and their families more effectively and efficiently. We were particularly pleased that benefits were sustained when treatment ended.”
The new treatment, outlined in The Lancet, was created together with young people and their families and the professionals who care for them, including doctors, nurses and psychologists.
Patients were given an initial assessment followed by weekly calls with the clinician – although face-to-face therapy was available if preferred. The sessions were delivered to either the young person directly, or via their caregiver, based on their individual circumstances.
Researchers trialled the treatment with 334 children and young people aged three to 18. Of these, 166 received the new MICE treatment and 168 received the usual treatment for mental health problems in children with epilepsy.
They assessed adolescents’ mental health and overall well-being from a parent-reported Strengths and Difficulties Questionnaire (SDQ) – covering areas such as emotional problems, conduct, hyperactivity and peer problems.
The results showed that the children who had the MICE treatment had fewer mental difficulties than those who had the usual treatment, and the change is equivalent to a decrease of 40% in the likelihood of having a psychiatric disorder.
These groundbreaking findings not only promise brighter futures for children with epilepsy but also pave the way for a revolutionary shift in mental healthcare practices.
The collaborative efforts of scientists, patients, and healthcare professionals have brought forth a new era of treatment of mental health challenges associated with epilepsy, offering a beacon of hope for families in the face of mental health challenges associated with epilepsy.”
Professor Roz Shafran, Co-Chief Investigator, UCL Great Ormond Street Institute of Child Health and GOSH
Co-Chief Investigator, Professor Helen Cross (UCL Great Ormond Street Institute of Child Health and GOSH), said: “This study shows real progress for clinicians considering the high rate of mental health problems in children with epilepsy, as we demonstrate the benefit of a therapy that can be implemented within existing epilepsy services.”
Co-author, Professor Isobel Heyman (UCL Great Ormond Street Institute of Child Health and Clinical Co-Lead for mental health at Cambridge Children’s Hospital), said: “These promising results show that staff working in paediatric settings can be trained to deliver effective mental health treatment to children with a physical health condition (epilepsy).
“It clearly demonstrates that children’s healthcare needs can be met in a holistic way to treat the ‘whole child’, in the same place at the same time.”
The work was conducted in collaboration with experts at Great Ormond Street Children’s Hospital (GOSH), King’s College London and UCLA, and with funding from the National Institute for Health and Care Research (NIHR).
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