Florida State University College of Medicine researchers have linked aspartame, an artificial sweetener found in nearly 5000 diet foods and drinks, to anxiety-like behaviour in mice.
Along with producing anxiety in the mice who consumed aspartame, the effects extended up to two generations from the males exposed to the sweetener. The study is published in the Proceedings of the National Academy of Sciences.
“What this study is showing is we need to look back at the environmental factors, because what we see today is not only what’s happening today, but what happened two generations ago and maybe even longer,” said co-author Pradeep Bhide, the Jim and Betty Ann Rodgers Eminent Scholar Chair of Developmental Neuroscience in the Department of Biomedical Sciences.
The study came about, in part, because of previous research from the Bhide Lab on the transgenerational effects of nicotine on mice. The research showed temporary, or epigenetic, changes in mice sperm cells. Unlike genetic changes (mutations), epigenetic changes are reversible and don’t change the DNA sequence; however, they can change how the body reads a DNA sequence.
“We were working on the effects of nicotine on the same type of model,” Bhide said. “The father smokes. What happened to the children?”
Aspartame received FDA approval as a sweetener in 1981. Today, nearly 5000 tonnes are produced each year. When consumed, aspartame becomes aspartic acid, phenylalanine and methanol, all of which can have potent effects on the central nervous system.
Led by doctoral candidate Sara Jones, the study involved providing mice with drinking water containing aspartame at approximately 15% of the FDA-approved maximum daily human intake. The dosage, equivalent to six to eight cans of diet fizzy drink a day for humans, continued for 12 weeks in a study spanning four years.
Pronounced anxiety-like behaviour was observed in the mice through a variety of maze tests across multiple generations descending from the aspartame-exposed males.
“It was such a robust anxiety-like trait that I don’t think any of us were anticipating we would see,” Jones said. “It was completely unexpected. Usually you see subtle changes.”
When given diazepam, a drug used to treat anxiety disorder in humans, mice in all generations ceased to show anxiety-like behaviour.
Researchers are planning an additional publication from this study focused on how aspartame affected memory. Future research will identify the molecular mechanisms that influence the transmission of aspartame’s effect across generations.
A quarter of employees in South Africa have been diagnosed with depression, with the country’s economic contributors aged 25 to 44 being most affected and taking more than 18 days off work as a result, according to a recent study conducted by the South African Depression and Anxiety Group (SADAG). “While treatment or talking to someone is advised when dealing with mental health issues, the importance of exercise and healthy living is taking centre stage across pop culture channels,” says Sarah Rice, Chief People Officer at Skynamo.
This was illustrated in the recently released documentary produced by Jonah Hill on Netflix called ‘Stutz’. While highlighting the power of talk therapy, Hill’s therapist, Phil Stutz, outlines various tools that he has developed to help people manage depression, including his ‘life force’ model.
“This is a three levelled pyramid focussing on aspects that drive us forward,” shares Rice, who refers to the film where Stutz says that your life force is the only thing that’s capable of guiding you when you’re lost. “The bottom level of the pyramid is your relationship with your physical body, the second is your relationship with other people and the top level is your relationship with yourself.”
“While we are the only ones who are responsible for our relationship with ourselves, considering the fact that we spend a large amount of time in the office, companies should think about offering activities to improve employees’ wellbeing such as forming a running club or introducing yoga classes. These activities should be built into the company calendar so that it gives people permission to do them and not feel like they’re taking away from work time,” explains Rice.
Not only does this assist with the exercise aspect but also gives colleagues the opportunity to form a real connection and bond with each other, she says. “Additionally, it shows that the business is really keen on providing employees with a work-life balance – something which is trumping salary as a priority for most professionals.”
She notes that, luckily, international companies like Google, Accenture, Microsoft and Nike are recognising that physical health is part of mental health. “A number of South African companies such as Absa, Discovery, Alexander Forbes, Unilever and South African Breweries are tapping into this as well.”
Victoria Henry, Head of Group Marketing at Alphawave, a specialised technology investment group with 16 companies in its portfolio, of which Skynamo is a part, echoes this by saying, “Mental health has definitely moved up the agenda in the workplace. It’s good to see more and more companies taking this seriously. Happy and healthy employees are better employees. Supporting employee mental health can increase engagement and performance, so it’s important that companies are investing in this.”
To encourage corporates – as well as individuals – to get active and connected to each other, Skynamo, in partnership with Alphawave, will be sponsoring the third annual Skynamo CROSS CHALLENGE – South Africa’s biggest off-road triathlon. A crucial component of the event is the Skynamo Corporate Challenge where teams will get to cycle, run and swim for the chance to win prizes, bragging rights and a trophy to showcase in the office – not to mention a team building experience full of exhilarating adventure and healthy competition.
Jacques de Villiers, co-founder of event organising company Scuttle adds that being outdoors and exercising greatly enhances mental health, especially since this reduces employee screen time. “Funnily enough, 70% of employees say that they would exercise more if they spent less time at their computers.”
The Skynamo CROSS CHALLENGE will be taking place on Saturday, 25 February 2023 in Grabouw with races for all ages and fitness levels. The full race comprises a 1000m swim, 22km mountain bike ride and 7,2km trail run, while the sprint race is approximately half the distance. There are also race options available for kids.
In the lead up to the Skynamo CROSS CHALLENGE, teams can test their fitness levels and group dynamics at the Lomond and Franschhoek Cross Triathlons taking place in December 2022 and January 2023 respectively.
Rice concludes by saying, “To help employees’ mental health in 2023, businesses should be raising awareness around and encouraging healthy living. Employers need to see employees as whole people, not just as ‘work people’, and must support them in living their best lives.”
Women with prolonged mental health problems up to three years after childbirth may be suffering from irregular immune system responses, suggests new research published in the American Journal of Reproductive Immunology.
“We found that women who had clinically elevated symptoms of depression, anxiety, and/or post-traumatic stress disorder (PTSD) two to three years after delivery had genetic evidence of a higher prevalence of immune system defence mechanism activation,” said Eynav Accortt, PhD, principal investigator of the study and director of the Reproductive Psychology Program at Cedars-Sinai.
“These women also appeared to have a reduction in the activity of genes related to antiviral immune responses that can offer the body protection from pathogens,” said Accortt, a clinical psychologist.
Roughly 1 in 8 women experience significant symptoms of perinatal mood and anxiety disorders that can interfere with health and quality of life. Much of the research into maternal mental health to date has focused on the perinatal period and the first year after childbirth.
Cedars-Sinai investigators surveyed 33 women about their mental health over a longer period, two to three years after giving birth. Study participants also provided a blood sample, and scientists performed bioinformatic analyses of differential gene expression.
“Delayed or persistent postpartum anxiety, depression and PTSD is an area that is woefully understudied,” said study co-author Sarah Kilpatrick, MD, PhD, chair of the Department of Obstetrics and Gynecology at Cedars-Sinai.
“In this preliminary research, we have identified genetic differences related to inflammation when comparing women experiencing prolonged symptoms of mood and anxiety disorders to those who did not report poor mental health. Additional studies will be needed for a deeper dive into the role inflammation may play in postpartum mental illness,” said Kilpatrick.
One of the research aims is to design a blood test to identify those at high risk for serious and prolonged postpartum mood disorders, according to Accortt.
“A blood test could help us develop early interventions that provide medical and mental health treatments and support. We want to figure out why some women are at greater risk for depression, anxiety and PTSD. No one should have to suffer for years after childbirth,” said Accortt.
Ketamine, an established anaesthetic and increasingly popular antidepressant, dramatically reorganises activity in the brain, as if a switch had been flipped on its active circuits, according to a new study published in a Nature Neuroscience paper.
Researchers observed greatly altered patterns of neuronal activity in the cerebral cortex of animal models after ketamine administration – normally active neurons were silenced while another set that were normally quiet suddenly sprang to action.
This ketamine-induced activity switch in key brain regions tied to depression may impact our understanding of ketamine’s treatment effects and future research in the field of neuropsychiatry.
“Our surprising results reveal two distinct populations of cortical neurons, one engaged in normal awake brain function, the other linked to the ketamine-induced brain state,” said the co-lead and co-senior author Joseph Cichon, MD, PhD, an assistant professor at the University of Pennsylvania. “It’s possible that this new network induced by ketamine enables dreams, hypnosis, or some type of unconscious state. And if that is determined to be true, this could also signal that it is the place where ketamine’s therapeutic effects take place.”
Anaesthesiologists routinely deliver anesthetic drugs before surgeries to reversibly alter activity in the brain so that it enters its unconscious state. Since its synthesis in the 1960s, ketamine has been a mainstay in anaesthesia practice because of its reliable physiological effects and safety profile. One of ketamine’s signature characteristics is that it maintains some activity states across the surface of the brain (the cortex). This contrasts with most anaesthetics, which work by totally suppressing brain activity. It is these preserved neuronal activities that are thought to be important for ketamine’s antidepressant effects in key brain areas related to depression. But, to date, how ketamine exerts these clinical effects remains mysterious.
In their new study, the researchers analysed mouse behaviours before and after they were administered ketamine, comparing them to control mice who received placebo saline. One key observation was that those given ketamine, within minutes of injection, exhibited behavioural changes consistent with what is seen in humans on the drug, including reduced mobility, impaired responses to sensory stimuli, which are collectively termed “dissociation.”
“We were hoping to pinpoint exactly what parts of the brain circuit ketamine affects when it’s administered so that we might open the door to better study of it and, down the road, more beneficial therapeutic use of it,” said co-lead and co-senior author Alex Proekt, MD, PhD, an associate professor at Penn.
Two-photon microscopy was used to image cortical brain tissue before and after ketamine treatment. By following individual neurons and their activity, they found that ketamine turned on silent cells and turned off previously active neurons.
The neuronal activity observed was traced to ketamine’s ability to block the activity of synaptic receptors called NMDA receptors and ion channels called HCN channels. The researchers found that they could recreate ketamine’s effects without the medications by simply inhibiting these specific receptors and channels in the cortex. The scientists showed that ketamine weakens several sets of inhibitory cortical neurons that normally suppress other neurons. This allowed the normally quiet neurons, the ones usually being suppressed when ketamine wasn’t present, to become active.
The study showed that this dropout in inhibition was necessary for the activity switch in excitatory neurons – the neurons forming communication highways, and the main target of commonly prescribed antidepressant medications. More work will need to be undertaken to determine whether the ketamine-driven effects in excitatory and inhibitory neurons are the ones behind ketamine’s rapid antidepressant effects.
“While our study directly pertains to basic neuroscience, it does point at the greater potential of ketamine as a quick-acting antidepressant, among other applications,” said co-author Max Kelz, MD, PhD. “Further research is needed to fully explore this, but the neuronal switch we found also underlies dissociated, hallucinatory states caused by some psychiatric illnesses.”
A study published in the journal Psychological Review describes a possible mechanism by which breathing influences the brain and how breathing exercises influence mood. The researchers synthesised results from more than a dozen studies with rodent, monkey, and human brain imaging, and used it to propose a new computational model that explains how our breathing influences the brain’s expectations.
“What we found is that, across many different types of tasks and animals, brain rhythms are closely tied to the rhythm of our breath. We are more sensitive to the outside world when we are breathing in, whereas the brain tunes out more when we breathe out. This also aligns with how some extreme sports use breathing, for example professional marksmen are trained to pull the trigger at the end of exhalation,” explains Professor Micah Allen from the Department of Clinical Medicine at Aarhus University.
The study suggest that breathing is more than just something we do to stay alive, explains Prof Allen.
“It suggests that the brain and breathing are closely intertwined in a way that goes far beyond survival, to actually impact our emotions, our attention, and how we process the outside world. Our model suggests there is a common mechanism in the brain which links the rhythm of breathing to these events.”
Breathing can affect our mental health
Understanding how breathing shapes our brain, and by extension, our mood, thoughts, and behaviours, is an important goal in order to better prevent and treat mental illness.
“Difficulty breathing is associated with a very large increase in the risk for mood disorders such as anxiety and depression. We know that respiration, respiratory illness, and psychiatric disorders are closely linked. Our study raises the possibility that the next treatments for these disorders might be found in the development of new ways to realign the rhythms of the brain and body, rather than treating either in isolation,” explains Micah Allen.
The new study sheds light on how the brain its possible to stabilise the mind through breathing exercises. It suggests that there are three pathways in the brain that control this interaction between breathing and brain activity. It also suggests that our pattern of breathing makes the brain more “excitable,” meaning neurons are more likely to fire during certain times of breathing.
Prof Allen says that research is underway into investigating how different kinds of emotional and visual perception are influenced by breathing in the brain, as well as the impact of long COVID.
For patients with anxiety disorders, a guided mindfulness-based stress reduction program was as effective as use of the gold-standard drug escitalopram, according to results of a first-of-its-kind, randomised clinical trial published in JAMA Psychiatry.
“Our study provides evidence for clinicians, insurers, and healthcare systems to recommend, include and provide reimbursement for mindfulness-based stress reduction as an effective treatment for anxiety disorders because mindfulness meditation currently is reimbursed by very few providers,” says Elizabeth Hoge, MD, director of the Anxiety Disorders Research Program and associate professor of psychiatry at Georgetown and first author. “A big advantage of mindfulness meditation is that it doesn’t require a clinical degree to train someone to become a mindfulness facilitator. Additionally, sessions can be done outside of a medical setting, such as at a school or community centre.”
Anxiety disorders can be highly distressing; they include generalised anxiety, social anxiety, panic disorder and fear of certain places or situations, including crowds and public transportation, all of which can lead to an increased risk for suicide, disability and distress and therefore are commonly treated in psychiatric clinics. Drugs that are currently prescribed for the disorders can be very effective, but many patients either have difficulty getting them, do not respond to them, or find the side effects (e.g., nausea, sexual dysfunction and drowsiness) as a barrier to consistent treatment. Standardized mindfulness-based interventions, such as mindfulness-based stress reduction (MBSR), can decrease anxiety, but prior to this study, the interventions had not been studied in comparison to effective anti-anxiety drugs. Of note, approximately 15% of the U.S. population tried some form of meditation in 2017.
The clinicians recruited 276 patients between June 2018 and February 2020 from three hospitals in Boston, New York City and Washington, D.C., and randomly assigned people to either MBSR or escitalopram. MBSR was offered weekly for eight weeks via two and a half-hour in-person classes, a day-long retreat weekend class during the 5th or 6th week, and 45-minute daily home practice exercises. Patients’ anxiety symptoms were assessed upon enrolment and again at completion of the intervention at 8 weeks, along with post-treatment assessments at 12 and 24 weeks after enrolment. The assessments were conducted in a blinded manner — the trained clinical evaluators did not know whether the patients they were assessing received the drug or MBSR.
At the end of the trial, 102 patients had completed MBSR and 106 had completed their medication course. The patients were relatively young, with a mean age of 33 and included 156 women, which comprised 75% of the enrolees, mirroring the disease prevalence in the U.S.
The researchers used a validated assessment measure to rate the severity of symptoms of anxiety across all of the disorders using a scale of 1 to 7 (with 7 being severe anxiety). Both groups saw a reduction in their anxiety symptoms (a 1.35 point mean reduction for MBSR and 1.43 point mean reduction for the drug, which was a statistically equivalent outcome), dropping from a mean of about 4.5 for both, which translates to a significant 30% or so drop in the severity of peoples’ anxiety.
Olga Cannistraro, 52, says she uses her MBSR techniques as needed, but more than a decade ago, the practice transformed her life. She was selected for an MBSR study after responding to advertisement asking, “Do you worry?”
“I didn’t think of myself as anxious – I just thought my life was stressful because I had taken on too much,” she recalls. “But I thought ‘yeah, I do worry.’ There was something excessive about the way I responded to my environment.”
After participating in an earlier study led by Hoge, she learned two key MBSR techniques. “It gave me the tools to spy on myself. Once you have awareness of an anxious reaction, then you can make a choice for how to deal with it. It’s not like a magic cure, but it was a life-long kind of training. Instead of my anxiety progressing, it went in the other direction and I’m very grateful for that.”
“It is important to note that although mindfulness meditation works, not everyone is willing to invest the time and effort to successfully complete all of the necessary sessions and do regular home practice which enhances the effect,” Hoge said. “Also, virtual delivery via videoconference is likely to be effective, so long as the ‘live’ components are retained, such as question-and-answer periods and group discussion.”
Hoge points out that there are many phone apps that offer guided meditation, however researchers don’t know how apps compare with the full in-person, weekly group class experience.
Trial enrollment was wrapping up as the COVID pandemic started in early 2020 but most enrollees completed their eight-week course of treatment before the pandemic started. Additionally, the researchers conducted a second phase of the study during the pandemic that involved moving the treatments to an online, videoconference, and that will be the focus of future analyses. The researchers also hope to explore the effects of MBSR on sleep and depression.
According to a study published in JAMA Pediatrics, cases of young people seeking care for eating disorders greatly increased in the months of the pandemic.
Eating disorders (EDs), such as anorexia nervosa and bulimia nervosa, impact a wide range of individuals. In the developmental stages of adolescent and young adulthood, EDs – especially restrictive ones – can have particularly negative impacts. Furthermore, EDs commonly co-occur with other mental health conditions which can influence the trajectory of illness. Individuals with EDs have greater mortality rates, partly due to increased suicidality.
EDs requires intensive specialist care, which is not often available in many settings. A rise in rates of anxiety and depression have been attributed to the COVID pandemic, as well as a worsening of ED. Possible reasons for this include uncertainty about the future, disruptions in daily routines, inconsistent access to food, more time spent in triggering environments, influence from the media, and changes in access to treatment.
Reports from hospitals indicated increasing numbers of diagnoses and hospital admissions for ED, but there was little geographically widespread data.
Therefore, the researchers set out to investigate trends in patient volume for inpatient medical hospitalisation as well as volume of patients seeking outpatient subspecialty care, both before and after the pandemic.
The researchers used an an observational case series design to compare changes in volume in inpatient and outpatient ED-related care at 15 sites between January 2018 and December 2021.
Before the COVID pandemic, the relative number of pooled inpatient ED admissions were increasing over time by 0.7% per month. After onset of the pandemic, there was a significant increase in admissions over time of 7.2% per month through April 2021, then a decrease of 3.6% per month through December 2021. Before the pandemic, relative outpatient ED assessment volume was stable over time, with an immediate 39.7% decline in April 2020. Thereafter, new assessments increased by 8.1% per month through April 2021, then decreased by 1.5% per month through December 2021. The nonhospital-based ED program did not demonstrate a significant increase in the absolute number of admissions after onset of the pandemic but did see a significant increase of 8.2 additional inquiries for care per month in the first year after onset of the pandemic.
“Given inadequate ED care availability prior to the pandemic, the increased postpandemic demand will likely outstrip available resources. Results highlight the need to address ED workforce and program capacity issues as well as improve ED prevention strategies.”
The largest and most rigorous clinical trial to date of psilocybin (a psychoactive ingredient in magic mushrooms), suggests the possibility that COMP360 psilocybin with psychological support could be a beneficial therapeutic strategy for people with treatment-resistant depression (TRD). The trial results were published in the New England Journal of Medicine.
Prompted by promising preliminary findings, this funded multi-centre, randomised, double-blind, phase 2b clinical trial was launched in 2018 to determine the safety and potential antidepressant effects of a single dose of COMP360 psilocybin (25mg or 10mg), compared to 1mg, with psychological support in people with TRD.
The trial, which included 233 people with TRD across 10 countries who received a single dose of 25mg COMP360 psilocybin experienced a highly statistically and clinically significant rapid reduction in symptoms of depression compared to 1mg at three weeks. This offers hope that COMP360 psilocybin with psychological support could be an effective antidepressant treatment paradigm for some people with TRD, if proven effective and safe in larger studies. COMPASS Pathways, the company that developed the psilocybin formulation., will be running a larger phase 3 programme of COMP360 psilocybin therapy in TRD, which is on schedule to begin in 2022.
KEY RESEARCH FINDINGS
25mg COMP360 psilocybin with psychological support led to a statistically and clinically significantly reduction in symptoms of depression in people with TRD compared to 1mg at week 3.
37% of people with TRD in the 25mg group met criteria for response at week 3 (≥ 50% decrease in depressive symptoms).
Approximately 30% of people with TRD in the 25mg group met criteria for remission at week 3 (29.1%).
20% of people with TRD in the 25mg group met criteria for sustained response at week 12.
COMP360 psilocybin was generally well-tolerated.
Dr John R. Kelly, Psychiatrist and Clinical Senior Lecturer, Trinity College said: “This is the largest and most rigorous clinical trial of psilocybin to date. It shows a promising antidepressant signal for 25mg COMP360 psilocybin with psychological support and has paved the way for phase 3 clinical trials, which will determine whether it translates into a much-needed complementary treatment strategy in the psychiatry clinic.”
After being treated with a course of blue light exposure in the morning, people with post-traumatic stress disorder (PTSD) experienced better sleep, a reduction in the severity of PTSD symptoms and had more effective treatments overall, according to a new study recently published in Frontiers in Behavioral Neuroscience.
Sleep is crucial for maintaining physical and mental health, and inadequate sleep over time can impact all aspects of life with serious implications for long-term health, relationships, cognitive abilities such as learning, and healing.
The influence of sleep disruption on PTSD symptom severity is well established. Those who seek treatment to allay their PTSD symptoms often face a vicious cycle where poor sleep interferes with the effectiveness of treatments, negating any lessening of symptoms, which in turn contributes to sleep disruptions. To reduce and eliminate the emotional impact of traumatic memories, the patient needs quality sleep to integrate healing mechanisms achieved through cognitive or exposure therapy treatments.
“This research is exciting and unique because it points to an easy-to-use method for helping those with PTSD to retain the benefits of therapy long after the treatment ends,” said psychiatry professor William “Scott” Killgore, PhD, senior author on the paper, “Morning blue light treatment improves sleep complaints, symptom severity, and retention of fear extinction memory in post-traumatic stress disorder.”
Dr Killgore and the SCAN Lab team conducted a comprehensive assessment of daily morning blue-wavelength light exposure on individuals with clinically significant levels of PTSD. The goal was to ascertain if blue light therapy would help improve sleep and PTSD symptoms and sustain learned fear extinction memories, an analogue of therapeutic treatment for trauma.
Study participants committed to 30 minutes of morning light exposure daily for six weeks, with half of the participants using blue-wavelength light and half using amber light. Researchers examined the neurobiological, autonomic and behavioural outcome changes during the study.
The 43 participants who received blue light therapy not only demonstrated significant improvements in the severity of their PTSD symptoms, but also reported improvements in sleep and showed an increased retention of fear extinction memories. The control 39 controls receiving amber light did not show the same retention of the extinction memories, but rather showed a return of the original fear memories.
“While the limitations of the research include its modest sample size and difficulties monitoring compliance, the possibilities of utilising a treatment that is relatively simple, drug-free and inexpensive can offer hope for the large population of people living with the intense challenges of post-traumatic stress disorder,” Dr Killgore said.
Autistic young men and women are more affected by psychiatric conditions and have an increased risk of hospitalisation as a result of their mental illness. Autistic women are particularly vulnerable, as shown in a study published in JAMA Psychiatry.
Autistic people have an increased risk of suffering from mental illness. Current data indicates that autistic women are more vulnerable than autistic men, but few studies have been able to establish that there are sex differences.
The researchers, from Karolinska Institutet, conducted a register-based cohort study with more than 1.3 million people in Sweden who were followed from the age of 16 to 24 between 2001 and 2013. Just over 20 000 of these were diagnosed with autism.
“We saw an increased risk of eleven different psychiatric conditions, including depression, anxiety disorders, self-harm and difficulty sleeping,” says Miriam Martini, a doctoral student in psychiatric epidemiology at Karolinska Institutet and first author of the study.
High hospitalisation rates
Something that Miriam Martini finds particularly worrying is that 32 out of 100 autistic women had been hospitalised as a result of their mental illness, compared with 19 out of 100 autistic men. For non-autistic people, the corresponding figure was less than five out of 100.
The study focuses on young adults who are at a crucial time in their life when many mental health problems increase, while the transition to adulthood often means poorer access to care, says Miriam Martini.
“Healthcare for young adults needs to be expanded, especially for autistic women, so that mental illness can be detected in time to avoid worsening of symptoms resulting in hospitalization,” says Miriam Martini.
The reason why autistic women are more affected by mental illness than autistic men is not clear, but in the study, the researchers point to several possible factors. Previous research has shown that autistic women to a greater extent use compensatory behaviours to camouflage their autism, which may be due to the fact that women generally tend to adapt to the expectations of those around them. This delays diagnosis and the provision of assistance, which can negatively affect their mental health.
Overlooked by the healthcare system
Another possible explanation may be that it could be difficult to detect autism in women using diagnostic criteria.
“It may be that autism manifests differently in women than in men, which means that women are not detected using today’s diagnostic criteria. This is something we need to do more research on,” says Miriam Martini.
