Researchers have reported finding a link between allergic diseases and mental health conditions, but one which was likely not causal.
The analysis of data from the UK Biobank was published in Clinical and Experimental Allergy. The researchers used a genetic instrument derived from associated variants for a broad allergic disease phenotype to test for causal relationships with various mental health outcomes. They also investigated whether these relationships were specific to atopic dermatitis (AD), asthma or hayfever.
The researchers found that people with asthma, atopic dermatitis, and hay fever also had a higher likelihood of having depression, anxiety, bipolar disorder, or neuroticism. However neither category appeared to play a role in causing the other. Nevertheless, future studies should investigate whether interventions that aim to improve allergic diseases might also have an effect on mental health (and vice versa).
“Our research does not rule out a potential causal effect upon the progression of disease, which is yet to be investigated and could help uncover novel treatment strategies for allergic disease or mental health traits,” said lead author Ashley Budu-Aggrey, PhD, of the University of Bristol.
Senior author Hannah Sallis, MSc, PhD, added that the research used a combination of approaches and data from several studies. “This helps to strengthen our confidence in the findings,” she said. “Establishing whether allergic disease causes mental health problems, or vice versa, is important to ensure that resources and treatment strategies are targeted appropriately.”
A proof-of-principle trial has shown that an electrical implant wired into the brain can detect and treat depression, thanks to positive results for the first patient to be fitted with the device.
The patient, Sarah (36), says the matchbox-sized implant in her skull has turned her life around since it was fitted a year ago. Her depression persisted despite anti-depressants and electroconvulsive therapy.
Sarah said that “any kind of relief” was better than her suffering. “My daily life had become so restricted. I felt tortured each day. I barely moved or did anything.”
The device, including its battery, was inserted into her skull beneath the scalp and holes were drilled for wires into her brain.
Recalling how the implant changed her life, she said: “When the implant was first turned on, my life took an immediate upward turn. My life was pleasant again.
“Within a few weeks, the suicidal thoughts disappeared. When I was in the depths of depression all I saw is what was ugly.”
“In the early few months, the lessening of the depression was so abrupt, and I wasn’t sure if it would last,” she said. “But it has lasted. And I’ve come to realise that the device really augments the therapy and self-care I’ve learned while being a patient here at UCSF.”
The treatment however has to be personalised to the individual and their unique brain circuitry. Researcher Dr Katherine Scangos, a psychiatrist at University of California, San Francisco, said locating the ‘depression circuits’ in Sarah’s brain was what made the innovation possible. “We found one location, which is an area called the ventral striatum, where stimulation consistently eliminated her feelings of depression.
“And we also found a brain activity area in the amygdala that could predict when her symptoms were most severe.”
Dr Scangos, who has enrolled two other patients in the trial and hopes to recruit nine more, said they need to repeat the work, looking for any changes in biomarkers or brain circuits. She said, “We didn’t know if we were going to be able to treat her depression at all because it was so severe. So in that sense we are really excited about this. It’s so needed in the field right now.”
However, the researchers stress that much more research is needed to see if this novel treatment is effective in other patients, and if it can be applied to other disorders.
New research with low doses of the anaesthetic ketamine, recently approved by the FDA for use as an antidepressant, shows the drug could provide longer-lasting relief.
Depression is often treated with selective serotonin reuptake inhibitors, or SSRIs, but they can take six weeks before symptom relief begins, and in up to 30% of people they are ineffective.
For the past two decades, however, psychiatrists have been using low doses of ketamine, normally a veterinary anaesthetic, to treat patients whose depression has not responded to other treatments. It also has hallucinogenic effects and is sometimes abused as a street drug. Its use in psychiatry was long considered “off label,” but in 2019 the U.S. Food and Drug Administration approved a nasal spray version for use as an antidepressant, followed in 2020 by expanding the approval to include patients with depression who are having suicidal thoughts or have recently tried to take their own lives or otherwise harm themselves.
The approval opened up new possibilities as well as new lines of research that may change the way psychiatrists think about depression. Dr Benjamin Brody, an assistant professor of clinical psychiatry at Cornell University is heading a programme exploring ketamine to treat the condition. “What’s so exciting about ketamine is not only that it works for people whose symptoms are not responding to traditional treatments, but it also works much more rapidly — in days or even hours,” says Dr. Brody, who developed the protocol before the spray was approved, and still prefers infusions because they allow him to tailor each dose to a patient’s weight (while the spray only comes in two pre-set doses). “For some people, ketamine really does provide almost immediate relief. That’s wonderful and very gratifying to see.”
One problem with ketamine, however, is that its positive effects wear off within weeks or months. “Another major issue,” says Dr. Brody, “is that we have so little information on the long-term effects, or what type of treatment patients will need to remain well.”
Dr Conor Liston, associate professor of neuroscience in the Feil Family Brain and Mind Research Institute, is exploring the question of how ketamine works in the long term to create more synapses in a region of the brain called the medial prefrontal cortex. The new connections seem temporary, but if they could be augmented with another treatment, a person might be permanently cured of depression.
For a study published last year in Science, Dr. Liston and his team worked with mice that exhibited depression-like behavior, as determined by their reaction to a stressful situation. A mouse that freezes more than it attempts to wriggle free, known as “motivated escape behaviour”, displays an important feature of depression. “Mice are not people, and many symptoms that we think of as core to depression — sadness, hopelessness — are hard or probably even impossible to imagine modelling in a mouse,” said Dr Liston. “But there are some things we can measure.”
Dr Liston examined the mice’s brains before administering ketamine. As predicted, lacking motivated escape behaviour was correlated with lost synapses in the medial prefrontal cortex. Just hours after one dose, the mice no longer exhibited that ‘depressed’ behaviour and their brains showed that synapses had regrown. But just like humans, depressive symptoms returned days later and the new synapses had disappeared.
Interestingly, the reduction in depressive behaviour occurred before the new synapses appeared, meaning they could not have caused the immediate relief. However, the new synapses were apparently necessary for maintaining the antidepressant effects long after the ketamine dose. If those synapses were eliminated, the mice quickly became depressed again. “We think that some kind of intervention aimed at boosting the restoration of those synapses or enhancing their survival over time could be useful for augmenting ketamine’s antidepressant effects,” said Dr. Liston, adding that it could be another drug or an intervention as simple as exercise or improved sleep, two known factors in synapse survival.
Dr Liston noted that his team’s work is just a first step and more basic science needs to be done before work involving human subjects.
Individuals with a history of using cannabis have a much greater risk of developing mental health problems including anxiety and depression, as well as more severe mental illnesses, according to new research.
The findings indicate the need to emphasise the importance of general practitioners to continue enquiring about recreational drug use.
While there is extensive research linking cannabis use to severe mental illnesses such as schizophrenia and psychosis, associations are less clear between cannabis use as described in patient’s GP records and mental health problems such as anxiety.
In a new study, published in Psychological Medicine, researchers reported a strong link between general practice recorded cannabis use and mental ill health in one of the largest cohorts ever studied.
Senior author Dr Clara Humpston said: “Cannabis is often considered to be one of the ‘safer’ drugs and has also shown promise in medical therapies, leading to calls for it be legalised globally. Although we are unable to establish a direct causal relationship, our findings suggest we should continue to exercise caution since the notion of cannabis being a safe drug may well be mistaken.”
Dr Joht Singh Chandan said: “The research reaffirms the need to ensure a public health approach to recreational drug use continues to be adopted across the UK. We must continue to progress measures to improve the prevention and detection of drug use as well as implement the appropriate supportive measures in an equitable manner to prevent the secondary negative health consequences.”
Drawing on primary care data from the IQVIA Medical Research Database (IMRD-UK), analysis showed that following the first recorded use of cannabis, patients were three times more likely to develop common mental health problems such as depression and anxiety. In addition, they were almost 7 times more likely to develop severe mental illnesses such as psychosis or schizophrenia.
The dataset included records from 787 GP practices gathered between 1995 and 2018. The researchers were able to include data from 28 218 patients with a recorded exposure to cannabis. These were matched to 56 208 patients who had not been using cannabis and controlled for factors such as sex and age.
The cannabis users also had much higher rates of having a recorded history of using other drugs such as heroin, cocaine and amphetamines. The next steps will be to investigate levels of cannabis use or the potency of ingredients.
Fruit and vegetable consumption and exercise can directly increase levels of self-reported happiness, according to findings from a new study.
Public health campaigns encourage healthier diets and exercise by virtue of the well-studied link between lifestyle and wellbeing, and will benefit from new findings published by the Journal of Happiness Studies showing that there is also a positive causation from lifestyle to life satisfaction.
This research is the first to identify the causation of happiness, the consumption of fruit and vegetables and exercising are related, rather than generalising a correlation. The researchers, Dr Adelina Gschwandtner (Kent’s School of Economics), Dr Sarah Jewell and Professor Uma Kambhampati (both from the University of Reading’s School of Economics), used an instrumental variable approach to filter out any effect from happiness to lifestyle. This approach revealed that it is the effect of fruit and vegetables and exercising that makes people happy and not the other way round.
The findings show individuals’ ability to delay gratification and apply self-control plays a major role in influencing lifestyle decisions, which in turn has a positive impact on wellbeing. The research also shows that men appear to exercise more, and women eat more fruit and vegetables.
Dr Gschwandtner said: ‘Behavioural nudges that help the planning self to reinforce long-term objectives are likely to be especially helpful in maintaining a healthy lifestyle. If a better lifestyle not only makes us healthier but also happier, then it is a clear win-win situation.’
Professor Kambhampati said: ‘There has been a bigger shift in recent years for healthier lifestyle choices. To establish that eating more fruit and vegetables and exercising can increase happiness as well as offer health benefits is a major development. This may also prove useful for policy campaigns around environment and sustainability.’
A Polish study found that, after a week-long recovery from sleep deprivation, only reaction speed is restored to baseline levels while other functions are still lacking.
The negative impacts of sleep deficiency are well known, and include deficits in attention and memory, increased risk of car accidents, heart problems, and other medical issues. However, while some research has addressed recovery after chronic sleep deprivation, it has been unclear how much time is needed to fully recover from prolonged periods of deficient sleep.
To shed more light on this topic, Jeremi Ochab of the Jagiellonian University in Kraków and colleagues conducted a small study, published in PLOS ONE, with several healthy adults who underwent 10 days of purposeful sleep restriction followed by seven recovery days with unrestricted sleep. Participants completed the study in their normal day-to-day environments, wearing wrist sensors to track sleep and activity. Daily electroencephalography (EEG) monitored their brain activity, and they answered daily questions (Stroop tasks) to measure reaction times and accuracy.
After 7 days of recovery, the participants had not yet returned to their baseline performance on most measures of functioning. These included several EEG measures of brain activity, rest-versus-activity patterns captured by wrist sensors, and accuracy on Stroop tasks. Only their reaction times had recovered to baseline levels.
While the researchers note that it is difficult to compare these results with other studies that employed different methods, the findings contribute new insights into recovery from chronic sleep loss. Future research could include more participants, investigate longer recovery periods, and determine in what order different functions return to normal.
The authors added: “The investigation of the recovery process following an extended period of sleep restriction reveal that the differences in behavioural, motor, and neurophysiological responses to both sleep loss and recovery.”
Histamine from inflammation dampens serotonin levels and antidepressants’ ability to boost them, according to experiments in mice models.
The findings, published in The Journal of Neuroscience add to mounting evidence that inflammation, and the accompanying release of the molecule histamine, affects serotonin, a key molecule responsible for mood in the brain.
Inflammation triggers the release of histamine in the body, increasing blood flow to affected areas to flood them with immune cells. While these effects help the body fight infections, both long-term and acute inflammation is increasingly linked to depression. There is already strong evidence that patients with both depression and severe inflammation are the ones most likely not to respond to antidepressants.
Dr Parastoo Hashemi, Lead Author, Imperial’s Department of Bioengineering, said: “Our work shines a spotlight on histamine as a potential key player in depression. This, and its interactions with the ‘feel-good molecule’ serotonin, may thus be a crucial new avenue in improving serotonin-based treatments for depression.”
Chemical messengers Serotonin is a key target for depression-tackling drugs, and selective serotonin reuptake inhibitors (SSRIs) inhibit the re-absorption of serotonin in the brain, allowing it to circulate for longer and improve mood.
However, although SSRIs bring relief to many who take them, an increasing number of people are resistant to it. This could be due to the specific interactions between chemical messengers, or neurotransmitters, including serotonin and histamine.
With this in mind, researchers set out to investigate the relationship between histamine, serotonin, and SSRIs. They created tiny serotonin-measuring microelectrodes and put them into the hippocampus of the brains of live mice, an area known to regulate mood. The technique, known as fast scan cyclic voltammetry (FSCV), allowed them to measure brain serotonin levels in real time..
After placing the microelectrodes, they injected half the mice with lipopolysaccharide (LPS), an inflammation-causing toxin found in some bacteria, and half the mice with a saline solution as a control.
Within minutes of LPS injection, brain serotonin levels dropped, whereas they remained the same in control mice, demonstrating the rapid action of inflammatory responses on the brain and serotonin. Since LPS cannot cross the blood-brain barrier, it could not cause the drop in serotonin. The inflammatory response triggered histamine in the brain which directly inhibited the release of serotonin by attaching to inhibitory receptors.
To counter this, the researchers administered SSRIs to the mice, but they were much less able to boost serotonin levels than in control mice. They posited that this is because the SSRIs directly increased the amount of histamine in the brain, cancelling out its serotonin boosting action.
The researchers then administered histamine reducing drugs alongside the SSRIs to counter histamine’s inhibitory effects, and saw serotonin levels rise back to control levels. This appears to confirm the theory that histamine directly dampens serotonin release in the mouse brain. These histamine reducing drugs cause a whole-body reduction in histamine and are distinct from antihistamines taken for allergies, which block histamine’s effects on neurons.
A new molecule of interest More work is needed before progressing to human studies. However, it is not currently feasible to use microelectrodes to make similar measurements in human brains, so the researchers are now looking at other ways to get a snapshot of the brain by looking at other organs which use serotonin and histamine, like the gut.
A new study has helped researchers understand the experiences of people who withdraw from clinical cancer trials.
Cancer clinical trials (CCTs) provide patients with an opportunity to receive experimental drugs, tests, and/or procedures that may lead to remissions. Such opportunities can be a great benefit for those who took part, but there is little known of the experiences of participants who withdraw from CCTs.
To address this, a first-of-its-kind study from the University of Pennsylvania School of Nursing (Penn Nursing) was conducted to better understand the post-trial needs of these patients and define responsible transitions when patients exit CCTs.
“Understanding the post-trial needs of patients with cancer and their families represents a measure of ethical respect of the many contributions that patients with cancer make to advancing our scientific knowledge and finding treatments that save lives,” said the study’s lead researcher, Connie M Ulrich, the Lillian S Brunner Chair in Medical and Surgical Nursing, professor of nursing, professor of medical ethics and health policy.
The study revealed three important areas:
Patients exiting CCTs feel intense symptoms, emotions, and awareness that their life spans are short and options seem limited.
The limited discussions with patients who are exiting on their immediate post-trial care needs can result in many feeling that there is no clear path forward.
Good communication that deliberately includes attention to post-trial needs throughout the CCT is needed to help scared and disappointed patients navigate their next steps.
The study is set for publication on the JAMA Network.
Medical students who experienced mistreatment during medical school were more likely to become exhausted or disengaged, have less empathy, and have career regret, a new study has revealed.
Among a large national sample of trainees, the 22.9% of respondents who reported mistreatment on the Association of American Medical Colleges’ Medical School Year 2 Questionnaire (Y2Q) had higher exhaustion and disengagement scores on the Graduation Questionnaire (GQ) 2 years later, reported Liselotte Dyrbye, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues writing in JAMA Network Open.
Furthermore, of those who had experienced mistreatment, 18.8% reported career regret on the GQ.
Conversely, medical students who experienced a better environment more likely to:
Have lower exhaustion scores: for each 1-point increase on the Y2Q, there was a 0.05 reduction in exhaustion score Report lower disengagement scores on the GQ: for each 1-point increase on the Y2Q, there was a 0.04 reduction in disengagement score Further, reports of having positive interactions with faculty on the Y2Q were associated with higher empathy scores on the GQ. For each 1-point increase, there was a rise of 0.02 in empathy score. Positive student-to-student interactions were linked to having lower odds of career regret during the last year of medical school.
“The potential protective effect of positive experiences within the learning environment may provide insight into strengths that organizations can amplify to mitigate burnout, decline in empathy, and career choice regret among their students,” wrote Dyrbye and colleagues.
The team noted the opportunity for potential interventions. “Although the most effective approaches to addressing mistreatment of learners remain elusive, the frequency of mistreatment varies between educational programs, suggesting there are likely to be levers within the control of the organisation that adequate commitment, leadership, infrastructure, resources, and accountability can lead to a meaningful reduction in mistreatment.”
Average age of the respondents was 28 years, 52% were women, 72.8% were single, and 91% reported having no dependents. The study also found that older medical students reported higher disengagement scores, and that women reported lower exhaustion (by 0.27 points) and disengagement (by 0.47 points) scores on the GQ.
However, women and older medical students had higher empathy scores compared with their male peers (0.74 points and 0.05 points, respectively).
The researchers observed that conflicting findings on burnout among women in medicine have been reported. For example, a longitudinal cohort study of resident physicians across specialties in the US found that female residents were “more likely to develop burnout and have worsening in the severity of their emotional exhaustion between the second and third year of training compared with male residents, even after controlling for various forms of mistreatment.”
Limitations of their own study, the researchers noted, included unestablished differences between the exhaustion, disengagement, and empathy scale measures that were used in the questionnaires; and the varying response rates between questionnaires: 55.5% for the Y2Q and 81.5% for the GQ.
A US study showed that adults with atopic dermatitis (AD) had a higher burden of disease than those with other chronic diseases. Even mild dermatitis can negatively affect quality of life (QoL), increasing risk of anxiety, depression, and suicide.
Persistent itching and skin pain can disrupt sleep, leading to poor work or study performance. In moderate to severe disease, oozing, crusting lesions can lead to stigmatisation social isolation. More adults are affected than previously thought, with some 16.5 million adults in the US estimated to have AD.
In a study of 1278 patients using the US web-based Growth from Knowledge (GfK) panel, 60.1% had mild disease, 28.9% had moderate AD, and 11% had severe AD. Patients with more severe disease had higher scores on the dermatology life quality index and on the hospital anxiety and depression scale (HADS) when compared with controls.
This indicates “a worse impact on quality of life and an increased likelihood of anxiety or depression,” the researchers wrote in the Journal of Investigative Dermatology. “Our study confirms the high prevalence and disease burden of atopic dermatitis in this population.”
Quality of life threatened A pair of studies in patients from the GfK panel reinforce these findings. The first, with 602 patients, showed that AD carried a “profound” disease burden, based on a comparison of patient-oriented AD measures between patients with and without AD. Those with moderate and severe AD had lower mean mental health scores compared with those who had mild disease, and lower QoL compared with patients with other chronic disorders.
“We recommend that clinicians incorporate QoL assessments in clinical practice to determine disease burden, identify patients requiring step-up treatment of their skin disease, and potentially screen for patients with mental health disturbance,” wrote Jonathan I Silverberg, MD, PhD, MPH, of George Washington University, and colleagues in the Annals of Allergy, Asthma and Immunology.
A subsequent study in 2137 patients from the GfK Knowledge Panel found that 40% of patients with AD had a higher prevalence of anxiety or depression in the previous 12 months compared with 17.5% of adults without AD. The researchers concluded that anxiety and depression were driven primarily by disease severity, and were heavily underdiagnosed.
Breaking the ‘vicious cycle’ AD can be life-threatening in some patients, warned the authors of a systematic review and meta-analysis of AD studies. The combination of pruritus, visible skin lesions, social isolation, depression, and anxiety likely sets up a “vicious cycle,” according to the authors.
The investigators found a positive and significant association between AD in adulthood and depression, anxiety, and suicidal ideation, regardless of where the patients lived. And while only a few studies examined the risk of completed suicide, the majority showed a positive association, the authors said. A positive association between AD and depression in children was also identified.
They advised that “depression, anxiety, and suicidal ideation should be considered by doctors when treating patients with AD,” adding: “Because AD disease improvement appears to reduce these risks, this should be a priority.”
Better systemic and topical AD therapies are improving the QoL of patients. “It is important to recognise that improvement of AD often results in improvements in symptoms of depression and anxiety, as these mental health symptoms are caused or worsened by the AD,” Dr Silverberg told MedPage Today. “We already have data for dupilumab and the JAK inhibitors that show improvements of HADS scores and other patient-reported outcome measures of mental health.”
Robert Sidbury, MD, MPH, of the University of Washington School of Medicine in Seattle said, “relatively recent literature suggests screening for depression is particularly important for kids with AD, especially those with severe disease.”
AD affects children of all ages, including the very young, and more than 50% of children with AD are diagnosed by age 1 year, he noted.”Dupilumab has been the most effective new available therapy to date by far,” Dr Sidbury told MedPage Today. “Pipeline drugs, particularly the JAK inhibitors like upadacitinib show tremendous promise.”
