Placebos reduce stress, anxiety, depression -- even when people know they are placebos

A study out of Michigan State University found that nondeceptive placebos, or placebos given with people fully knowing they are placebos, effectively manage stress -- even when the placebos are administered remotely.

Researchers recruited participants experiencing prolonged stress from the COVID-19 pandemic for a two-week randomized controlled trial.

Half of the participants were randomly assigned to a nondeceptive placebo group and the other half to the control group that took no pills.

The participants interacted with a researcher online through four virtual sessions on Zoom.

Those in the nondeceptive placebo group received information on the placebo effect and were sent placebo pills in the mail along with and instructions on taking the pills.

The study, published in Applied Psychology: Health and Well-Being, found that the nondeceptive group showed a significant decrease in stress, anxiety and depression in just two weeks compared to the no-treatment control group.

Participants also reported that the nondeceptive placebos were easy to use, not burdensome and appropriate for the situation.

"Exposure to long-term stress can impair a person's ability to manage emotions and cause significant mental health problems long-term, so we're excited to see that an intervention that takes minimal effort can still lead to significant benefits," said Jason Moser, co-author of the study and professor in MSU's Department of Psychology.

"This minimal burden makes nondeceptive placebos an attractive intervention for those with significant stress, anxiety and depression."

The researchers are particularly hopeful in the ability to remotely administer the nondeceptive placebos by health care providers.

Read more at Science Daily

Turn up your favorite song to improve medication efficacy

While listening to a favorite song is a known mood booster, researchers at Michigan State University have discovered that music-listening interventions also can make medicines more effective.

"Music-listening interventions are like over-the-counter medications," said Jason Kiernan, an assistant professor in the College of Nursing. "You don't need a doctor to prescribe them."

While previous research studies have used music-listening interventions as a tool to treat pain and anxiety, Kiernan took a novel approach by studying the effects of music-listening interventions on chemotherapy-induced nausea.

"Pain and anxiety are both neurological phenomena and are interpreted in the brain as a state," Kiernan said. "Chemotherapy-induced nausea is not a stomach condition; it is a neurological one."

The small pilot study included 12 patients undergoing chemotherapy treatment who agreed to listen to their favorite music for 30 minutes each time they needed to take their as-needed anti-nausea medication. They repeated the music intervention anytime nausea occurred over the five days beyond their chemotherapy treatment. The patients in the study provided a total of 64 events.

"When we listen to music, our brains fire all kinds of neurons," Kiernan said.

While Kiernan did see a reduction in the ratings of patients' nausea severity and their distress (how much it bothered them to be nauseous), he cautions that it is difficult to isolate whether it was the gradual release of the medication doing its job or the increased benefit of the music. For future studies, Kiernan is drawing inspiration from another previously published study that measured the amount of serotonin, a neurotransmitter, that was released by platelets in the blood after listening to unpleasant and pleasant music.

"Serotonin is the major neurotransmitter that causes chemotherapy-induced nausea," Kiernan said. "Cancer patients take medications to block serotonin's effects."

During that previous study, researchers found that patients who listened to pleasant music experienced the lowest levels of serotonin release, indicating that the serotonin stayed in the blood platelets and was not released to circulate throughout the body. Results also showed that after listening to music they found unpleasant, patients experienced greater stress and increased levels of serotonin release.

"This was intriguing because it provides a neurochemical explanation and a possible way to measure serotonin and the blood platelet release of serotonin in my study," Kiernan said. "In 10 to 20 years, wouldn't it be neat if you could use a nonpharmacological intervention like listening to 10 minutes of your favorite music to complement a medicine?"

Read more at Science Daily

Corporal punishment affects brain activity, anxiety, and depression

Don't spank your kids. That's the conventional wisdom that has emerged from decades of research linking corporal punishment to a decline in adolescent health and negative effects on behavior, including an increased risk for anxiety and depression. Now, a new study explores how corporal punishment might impact neural systems to produce those adverse effects.

Corporal punishment can be simply defined as the "intentional infliction of physical pain by any means for the purpose of punishment, correction, discipline, instruction, or any other reason." This violence, particularly when inflicted by a parent, evokes a complex emotional experience. The researchers, led by Kreshnik Burani, MS, and working with Greg Hajcak, PhD, at Florida State University, wanted to understand the neural underpinnings of that experience and its downstream consequences.

The study appears in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier.

The researchers conducted a longitudinal study on 149 boys and girls ages 11 to 14 from the Tallahassee, FL, area. Participants performed a video game-like task and a monetary guessing game while undergoing continuously recorded electroencephalography, or EEG -- a noninvasive technique to measure brain-wave activity from the scalp. From the EEG data, the researchers determined two scores for each participant -- one reflecting their neural response to error and the other reflecting their neural response to reward.

Two years later, participants and their parents completed a series of questionnaires to screen for anxiety and depression and to assess parenting style. As expected, kids who had experienced corporal punishment were more likely to develop anxiety and depression.

"Our paper first replicates the well-known negative effect that corporal punishment has on a child's wellbeing: we found that corporal punishment is associated with increased anxiety and depressive symptoms in adolescence. However, our study goes further to demonstrate that corporal punishment might impact brain activity and neurodevelopment," said Burani.

That was reflected by larger neural response to error and a blunted response to reward in the adolescents who received physical punishments.

"Specifically," Burani added, "our paper links corporal punishment to increased neural sensitivity to making errors and decreased neural sensitivity to receiving rewards in adolescence. In previous and ongoing work with Dr. Hajcak, we see that increased neural response to errors is associated with anxiety and risk for anxiety, whereas decreased neural response to rewards is related to depression and risk for depression. Corporal punishment, therefore, might alter specific neurodevelopmental pathways that increase risk for anxiety and depression by making children hypersensitive to their own mistakes and less reactive to rewards and other positive events in their environment."

Read more at Science Daily

Neuronal plasticity in chronic pain-induced anxiety revealed

Hokkaido University researchers have shown how chronic pain leads to maladaptive anxiety in mice, with implications for treatment of chronic pain-related psychiatric disorders in humans.

Chronic pain is persistent and inescapable, and can lead to maladaptive emotional states. It is often comorbid with psychiatric disorders, such as depression and anxiety disorders. It is thought that chronic pain causes changes in neural circuits, and gives rise to depression and anxiety.

Researchers at Hokkaido University have identified the neuronal circuit involved in chronic pain-induced anxiety in mice. Their research, which was recently published in Science Advances, could lead to the development of new treatments for chronic pain and psychiatric disorders such as anxiety disorders and major depressive disorder.

"Clinicians have known for a long time that chronic pain often leads to anxiety and depression, however the brain mechanism for this was unclear," said Professor Masabumi Minami of the Faculty of Pharmaceutical Sciences at Hokkaido University, the corresponding author of the paper.

The researchers looked at how neuronal circuits were affected by chronic pain in mice. They used an electrophysiological technique to measure the activities of neurons after four weeks of chronic pain. They found that chronic pain caused the neuroplastic change which suppressed the neuronal pathway projecting from the brain region called bed nucleus of the stria terminalis (BNST) to the region called lateral hypothalamus (LH).

Using chemogenetics, an advanced technique to manipulate neuronal activity, they showed that restoration of the suppressed activity of this neuronal pathway attenuated the chronic pain-induced anxiety. These findings indicate that chronic pain-induced functional changes in the neuronal circuits within the BNST leads to maladaptive anxiety.

Read more at Science Daily

Anxiety cues found in the brain despite safe environment

Imagine you are in a meadow picking flowers. You know that some flowers are safe, while others have a bee inside that will sting you. How would you react to this environment and, more importantly, how would your brain react? This is the scene in a virtual-reality environment used by researchers to understand the impact anxiety has on the brain and how brain regions interact with one another to shape behavior.

"These findings tell us that anxiety disorders might be more than a lack of awareness of the environment or ignorance of safety, but rather that individuals suffering from an anxiety disorder cannot control their feelings and behavior even if they wanted to," said Benjamin Suarez-Jimenez, Ph.D., assistant professor in the Del Monte Institute for Neuroscience at the University of Rochester and first author of the study published in Communications Biology. "The patients with an anxiety disorder could rationally say -- I'm in a safe space -- but we found their brain was behaving as if it was not."

Watching anxiety in the brain

Using fMRI, the researchers observed the brain activity of volunteers with general and social anxiety as they navigated a virtual reality game of picking flowers. Half of the meadow had flowers without bees, the other half had flowers with bees that would sting them -- as simulated by a mild electrical stimulation to the hand. Researchers found all study participants could distinguish between the safe and dangerous areas, however, brain scans revealed volunteers with anxiety had increased insula and dorsomedial prefrontal cortex activation -- indicating their brain was associating a known safe area to danger or threat.

"This is the first time we've looked at discrimination learning in this way. We know what brain areas to look at, but this is the first time we show this concert of activity in such a complex 'real-world-like' environment," said Suarez-Jimenez. "These findings point towards the need for treatments that focus on helping patients take back control of their body."

The brain differences were the only differences seen in these patients. For example, sweat responses, a proxy for anxiety, which was also measured, failed to reveal any clear differences.

Suarez-Jimenez's research

Understanding the neural mechanisms by which the brain learns about the environment is the focus of Suarez-Jimenez's research, particularly how the brain predicts what is threatening and what is safe. He uses virtual reality environments to investigate neural signatures of anxiety disorders and post-traumatic stress disorder (PTSD). His goal is to understand how people build maps in the brain that are based on experience, and the role of those maps in psychopathologies of stress and anxiety.

Read more at Science Daily

Anxiety effectively treated with exercise

Both moderate and strenuous exercise alleviate symptoms of anxiety, even when the disorder is chronic, a study led by researchers at the University of Gothenburg shows.

The study, now published in the Journal of Affective Disorders, is based on 286 patients with anxiety syndrome, recruited from primary care services in Gothenburg and the northern part of Halland County. Half of the patients had lived with anxiety for at least ten years. Their average age was 39 years, and 70 percent were women.

Through drawing of lots, participants were assigned to group exercise sessions, either moderate or strenuous, for 12 weeks. The results show that their anxiety symptoms were significantly alleviated even when the anxiety was a chronic condition, compared with a control group who received advice on physical activity according to public health recommendations.

Most individuals in the treatment groups went from a baseline level of moderate to high anxiety to a low anxiety level after the 12-week program. For those who exercised at relatively low intensity, the chance of improvement in terms of anxiety symptoms rose by a factor of 3.62. The corresponding factor for those who exercised at higher intensity was 4.88. Participants had no knowledge of the physical training or counseling people outside their own group were receiving.

"There was a significant intensity trend for improvement -- that is, the more intensely they exercised, the more their anxiety symptoms improved," states Malin Henriksson, doctoral student at Sahlgrenska Academy at the University of Gothenburg, specialist in general medicine in the Halland Region, and the study's first author.

Importance of strenuous exercise

Previous studies of physical exercise in depression have shown clear symptom improvements. However, a clear picture of how people with anxiety are affected by exercise has been lacking up to now. The present study is described as one of the largest to date.

Both treatment groups had 60-minute training sessions three times a week, under a physical therapist's guidance. The sessions included both cardio (aerobic) and strength training. A warmup was followed by circle training around 12 stations for 45 minutes, and sessions ended with cooldown and stretching.

Members of the group that exercised at a moderate level were intended to reach some 60 percent of their maximum heart rate -- a degree of exertion rated as light or moderate. In the group that trained more intensively, the aim was to attain 75 percent of maximum heart rate, and this degree of exertion was perceived as high.

The levels were regularly validated using the Borg scale, an established rating scale for perceived physical exertion, and confirmed with heart rate monitors.

New, simple treatments needed

Today's standard treatments for anxiety are cognitive behavioral therapy (CBT) and psychotropic drugs. However, these drugs commonly have side effects, and patients with anxiety disorders frequently do not respond to medical treatment. Long waiting times for CBT can also worsen the prognosis.

The present study was led by Maria Åberg, associate professor at the University of Gothenburg's Sahlgrenska Academy, specialist in general medicine in Region Västra Götaland's primary healthcare organization, and corresponding author.

Read more at Science Daily

How micro-circuits in the brain regulate fear

Fear is an important reaction that warns and protects us from danger. But when fear responses are out of control, this can lead to persistent fears and anxiety disorders. In Europe, about 15 percent of the population is affected by anxiety disorders. Existing therapies remain largely unspecific or are not generally effective, because the detailed neurobiological understanding of these disorders is lacking.

What was known so far is that distinct nerve cells interact together to regulate fear responses by promoting or suppressing them. Different circuits of nerve cells are involved in this process. A kind of "tug-of-war" takes place, with one brain circuit "winning" and overriding the other, depending on the context. If this system is disturbed, for example if fear reactions are no longer suppressed, this can lead to anxiety disorders.

Recent studies have shown that certain groups of neurons in the amygdala are crucial for the regulation of fear responses. The amygdala is a small almond-shaped brain structure in the center of the brain that receives information about fearful stimuli and transmits it to other brain regions to generate fear responses. This causes the body to release stress hormones, change heart rate or trigger fight, flight or freezing responses.

Now, a group led by Professors Stephane Ciocchi of the University of Bern and Andreas Luthi of the Friedrich Miescher Institute in Basel has discovered that the amygdala plays a much more active role in these processes than previously thought: Not only is the central amygdala a "hub" to generate fear responses, but it contains neuronal microcircuits that regulate the suppression of fear responses. In animal models, it has been shown that inhibition of these microcircuits leads to long-lasting fear behaviour. However, when they are activated, behaviour returns to normal despite previous fear responses. This shows that neurons in the central amygdala are highly adaptive and essential for suppressing fear. These results were published in the journal Nature Communications.

"Disturbed" suppression leads to long-lasting fear

The researchers led by Stephane Ciocchi and Andreas Luthi studied the activity of neurons of the central amygdala in mice during the suppression of fear responses. They were able to identify different cell types that influence the animals' behaviour. For their study, the researchers used several methods, including a technique called optogenetics with which they could precisely shut down -- with pulses of light -- the activity of an identified neuronal population within the central amygdala that produces a specific enzyme. This impaired the suppression of fear responses, whereupon animals became excessively fearful. "We were surprised how strongly our targeted intervention in specific cell types of the central amygdala affected fear responses," says Ciocchi, Assistant Professor at the Institute of Physiology, University of Bern. "The optogenetic silencing of these specific neurons completely abolished the suppression of fear and provoked a state of pathological fear."

Important for developing more effective therapies

In humans, dysfunction of this system, including deficient plasticity in the nerve cells of the central amygdala described here, could contribute to the impaired suppression of fear memories reported in patients with anxiety and trauma-related disorders. A better understanding of these processes will help develop more specific therapies for these disorders. "However, further studies are necessary to investigate whether discoveries obtained in simple animal models can be extrapolated to human anxiety disorders," Ciocchi adds.

This study was carried out in partnership with the University of Bern, the Friedrich Miescher Institute and international collaborators. It was funded by the University of Bern, the Swiss National Science Foundation and the European Research Council (ERC).

Read more at Science Daily

Introducing play to higher education reduces stress and forms deeper connection material

A new study found higher education students are more engaged and motivated when they are taught using playful pedagogy rather than the traditional lecture-based method. The study was conducted by University of Colorado Denver counseling researcher Lisa Forbes and was published in the Journal of Teaching and Learning.

While many educators in higher education believe play is a method that is solely used for elementary education, Forbes argues that play is important in post-secondary education to enhance student learning outcomes.

Throughout the spring 2020 semester, Forbes observed students who were enrolled in three of her courses between the ages of 23-43. To introduce playful pedagogy, Forbes included games and play, not always tied to the content of that day's lesson, at the start of each class. She then provided many opportunities for role-play to practice counseling skills, and designed competitions within class activities.

During the study, students mentioned they saw more opportunities for growth while learning in a highly interactive environment. Students also described that the hands-on nature of learning through play established a means for skill acquisition, and they were able to retain the content more effectively.

"As we grow older, we're conditioned to believe that play is trivial, childish, and a waste of time," said Forbes. "This social script about play leads to it being excluded from higher education. A more interactive learning approach leads to a deeper and more rigorous connection to the material."

To maintain what Forbes described as "rigor" within higher education, the most common approach tends to be lecture-based learning. However, according to Forbes, this mode of education is counter to the very outcomes educators set out to achieve.

The results of the study suggest there is a unique and powerful classroom experience when play is valued and used in the learning process. According to Forbes, students who participated in this study also indicated that play increased positive emotions and connections with other students and the professor in the course.

"I also saw that when I introduced play, it helped students let their guard down and allowed them to reduce their stress, fear, or anxiety," said Forbes. "Play even motivated students to be vulnerably engaged, take risks, and feel more connected to the content."

Read more at Science Daily

Explanation of how religious beliefs may be formed

Feeling anxious can direct our attention and memory toward supernatural beings such as gods, a University of Otago study has found.

Lead author Dr Thomas Swan, of the Department of Psychology, says the research may help explain how religious beliefs are formed.

For the study, published in the International Journal for the Psychology of Religion, 972 participants completed an online recall test to determine if a bias to recall supernatural agents was stronger in anxious people, rather than non-anxious people.

Those who felt anxious were more likely to remember beings with supernatural abilities than beings without.

"Anxiety is an emotion that evolved to make us pay greater attention to potential threats, so when we feel anxious, a god that can read our thoughts and punish us for them, or flood the Earth, is going to be memorable," he says.

Previous research has shown anxiety can lead to greater levels of religious belief, with the explanation being that belief provides comfort. However, this so-called 'comfort theory' has problems: why are there punishing gods and hellish afterlives when these are far from comforting?

Dr Swan believes the theory also fails to address what comes between feeling anxious and becoming a believer. This research suggests the first step involves the cognitive effects of anxiety, which cause people to attend to and recall threats.

"In our previous research, we found that supernatural beings are perceived as potentially threatening because they have abilities that defy our expectations about the world. The present research confirms that the cognitive effects of anxiety also extend to the threat that is afforded by supernatural beings.

"Ironically then, our research suggests comfort theory has it somewhat backwards: anxious people are attracted, at least initially, to the scary traits of gods, which may explain why so many gods have scary features. Comfort, we suspect, comes later when some people transform their view of the god into something more palatable that they are happier believing," he says.

The research also suggests other supernatural concepts -- such as ghosts, psychics, and astrology -- will be digested in the same way because of how they alarmingly defy our expectations about what is possible.

Dr Swan hopes the research prompts people to develop a greater understanding of how their emotional states affect the information they look at and remember, particularly religious information.

"We should all be mindful of how we came to believe the things we do, especially those with anxiety disorders who feel anxious much of the time -- they should be mindful of what they are attracted to and why. If they find themselves reading fantasy novels, that may be harmless. If they find themselves joining a cult, then it's time for some reflection. The same goes for people without disorders who are just in anxious situations, such as sitting in a hospital bed or suffering financial troubles."

On the flipside, he hopes religious groups pay more attention to people's mental states.

Read more at Science Daily

Brain's 'updating mechanisms' may create false memories

Senior author Professor Bryce Vissel, from the UTS Centre for Neuroscience & Regenerative Medicine, said his team used novel behavioural, molecular and computational techniques to investigate memories that have not been well-formed, and how the brain deals with them.

He explained, "For memories to be useful, they have to have been well-formed during an event -- that is, they have to accurately reflect what actually happened.

"However, in the real world many memories are likely to be inaccurate -- especially in situations where the experience was brief, sudden or highly emotional, as can often occur during trauma. Inaccurate memories can also occur when the memory is poorly encoded, potentially as a result of subtle differences in how each person processes memory or because of disease like Alzheimer's or dementia."

Lead author Dr Raphael Zinn said, "Our findings are exciting because they show that memory updating mechanisms that become activated after recall can refine and improve memories.

"Surprisingly, we found that the same process can, in some circumstances, lead to incorrect updating of the memory. We also identify one molecular mechanism, called reconsolidation, which could be mediating this process.

"This suggests we might be able to target such updating mechanisms therapeutically to treat memory and anxiety disorders where memory formation is poor."

The 6-year study shows that the same mechanism that updates poor memories can also severely distort them if it occurs in the wrong situation.

Professor Vissel said these findings could be useful for understanding memory fallibility in everyday life; fear and memory disorders, post-traumatic stress disorder (PTSD); and situations where accurate recall is critical, like witness testimony in courtrooms.

"While these findings come from studies in mice, this research is likely to apply across many animals with developed brains, including other mammals and humans. They might also tie in with dementias, where the main memory-related problem is an apparent inability to form accurate new memories.

"Why is memory fallible? Our study suggests that when an individual forms a poor memory, the brain reactivates the memory in a similar situation and then updates it. Sometimes a poorly formed memory can be wrongly reactivated in a similar, but irrelevant, situation. The brain may then update the memory from that irrelevant situation, causing the memory to become incorrect -- rather than creating a new and entirely different memory of the new situation."

Read more at Science Daily

Anxiety disorders linked to disturbances in the cells' powerhouses

The powerhouse of the cell, the mitochondria, provides energy for cellular functions. But those activities can become disturbed when chronic stress leads to anxiety symptoms in mice and humans. Iiris Hovatta of the University of Helsinki and colleagues report these findings in a new study published 26th September in PLOS Genetics.

Chronic stress due to stressful life events, such as divorce, unemployment, loss of a loved one and war, are a major risk factor for developing panic attacks and anxiety disorders. Not all people who experience stressful life events go on to develop a disorder, however, and scientists are trying to identify the pathways that lead some people to be resilient to stress, while others become vulnerable to anxiety. In the current study, researchers studied mice that developed symptoms of anxiety and depression, such as avoiding social interactions, after being exposed to high levels of stress. Using a multi-pronged approach, they tracked changes in gene activity and protein production in a key region of the brain for stress-response and anxiety. The analysis pointed to a number of changes in the mitochondria in the brain cells of mice exposed to frequent stress, compared to the non-stressed mice. Furthermore, testing of blood samples collected from patients with panic disorder after a panic attack also showed differences in mitochondrial pathways, suggesting that changes to cellular energy metabolism may be a common way that animals respond to stress.

The discovery that high levels of stress may substantially impact the functioning of the powerhouses of the cell opens up new avenues of research into stress-related diseases. "Very little is known about how chronic stress may affect cellular energy metabolism and thereby influence anxiety symptoms," said author Iiris Hovatta. "The underlying mechanisms may offer a key to new targets for therapeutic interventions of stress-related diseases."

Further studies of what causes these changes to the mitochondria may provide much needed insight into the molecular basis of panic disorder and other anxiety disorders. This is a critical step in developing better therapies to treat anxiety.

From Science Daily