A new clinical trial has found that adding repeated intravenous ketamine infusions to standard care for hospitalized patients with serious depression did not provide a significant additional benefit. The study, which compared ketamine to a psychoactive placebo, suggests that previous estimates of the drug’s effectiveness might have been influenced by patient and clinician expectations. These findings were published in the journal JAMA Psychiatry.

Ketamine, originally developed as an anesthetic, has gained attention over the past two decades for its ability to produce rapid antidepressant effects in individuals who have not responded to conventional treatments. Unlike standard antidepressants that can take weeks to work, a single infusion of ketamine can sometimes lift mood within hours. A significant drawback, however, is that these benefits are often short-lived, typically fading within a week.

This has led to the widespread practice of administering a series of infusions to sustain the positive effects. A central challenge in studying ketamine is its distinct psychological effects, such as feelings of dissociation or detachment from reality. When compared to an inactive placebo like a saline solution, it is very easy for participants and researchers to know who received the active drug, potentially creating strong expectancy effects that can inflate the perceived benefits.

To address this, the researchers designed their study to use an “active” placebo, a drug called midazolam, which is a sedative that produces noticeable effects of its own, making it a more rigorous comparison.

“Ketamine has attracted a lot of interest as a rapidly-acting antidepressant but it has short-lived effects. Therefore, its usefulness is quite limited. Despite this major limitation, ketamine is increasingly being adopted as an off-label treatment for depression, especially in the USA,” said study author Declan McLoughlin, a professor at Trinity College Dublin.

“We hypothesized that repeated ketamine infusions may have more sustained benefit. So far this has been evaluated in only a small number of trials. Another problem is that few ketamine trials have used an adequate control condition to mask the obvious dissociative effects of ketamine, e.g. altered consciousness and perceptions of oneself and one’s environment.”

“To try address some of these issues, we conducted an independent investigator-led randomized trial (KARMA-Dep 2) to evaluate antidepressant efficacy, safety, cost-effectiveness, and quality of life during and after serial ketamine infusions when compared to a psychoactive comparison drug midazolam. Trial participants were randomized to receive up to eight infusions of either ketamine or midazolam, given over four weeks, in addition to all other aspects of usual inpatient care.”

The trial, conducted at an academic hospital in Dublin, Ireland, aimed to see if adding twice-weekly ketamine infusions to the usual comprehensive care provided to inpatients could improve depression outcomes. Researchers enrolled adults who had been voluntarily admitted to the hospital for moderate to severe depression. These participants were already receiving a range of treatments, including medication, various forms of therapy, and psychoeducation programs.

In this randomized, double-blind study, 65 participants were assigned to one of two groups. One group received intravenous ketamine infusions twice a week for up to four weeks, while the other group received intravenous midazolam on the same schedule. The doses were calculated based on body weight. The double-blind design meant that neither the patients, the clinicians rating their symptoms, nor the main investigators knew who was receiving which substance. Only the anesthesiologist administering the infusion knew the assignment, ensuring patient safety without influencing the results.

The primary measure of success was the change in participants’ depression scores, assessed using a standard clinical tool called the Montgomery-Åsberg Depression Rating Scale. This assessment was conducted at the beginning of the study and again 24 hours after the final infusion. The researchers also tracked other outcomes, such as self-reported symptoms, rates of response and remission, cognitive function, side effects, and overall quality of life.

After analyzing the data from 62 participants who completed the treatment phase, the study found no statistically significant difference in the main outcome between the two groups. Although patients in both groups showed improvement in their depressive symptoms during their hospital stay, the group receiving ketamine did not fare significantly better than the group receiving midazolam. The average reduction in depression scores was only slightly larger in the ketamine group, a difference that was small and could have been due to chance.

Similarly, there were no significant advantages for ketamine on secondary measures, including self-reported depression symptoms, cognitive performance, or long-term quality of life. While the rate of remission from depression was slightly higher in the ketamine group (about 44 percent) compared to the midazolam group (30 percent), this difference was not statistically robust. The treatments were found to be generally safe, though ketamine produced more dissociative experiences during the infusion, while midazolam produced more sedation.

“We found no significant difference between the two groups on our primary outcome measure (i.e. depression severity assessed with the commonly used Montgomery-Åsberg Depression Rating Scale (MADRS)),” McLoughlin told PsyPost. “Nor did we find any difference between the two groups on any other secondary outcome or cost-effectiveness measure. Under rigorous clinical trial conditions, adjunctive ketamine provided no additional benefit to routine inpatient care during the initial treatment phase or the six-month follow-up period.”

A key finding emerged when the researchers checked how well the “blinding” had worked. They discovered that it was not very successful. From the very first infusion, the clinicians rating patient symptoms were able to guess with high accuracy who was receiving ketamine.

Patients in the ketamine group also became quite accurate at guessing their treatment over time. This functional unblinding complicates the interpretation of the results, as the small, nonsignificant trend favoring ketamine could be explained by the psychological effect of knowing one is receiving a treatment with a powerful reputation.

“Our initial hypothesis was that repeated ketamine infusions for people hospitalised with depression would improve mood outcomes,” McLoughlin said. “However, contrary to our hypothesis, we found this not to be the case. We suspect that functional unblinding (due to its obvious dissociative effects) has amplified the placebo effects of ketamine in previous trials. This is a major, often unacknowledged, problem with many recent trials in psychiatry evaluating ketamine, psychedelic, and brain stimulation therapies. Our trial highlights the importance of reporting the success, or lack thereof, of blinding in clinical trials.”

The study’s authors acknowledged some limitations. The research was unable to recruit its planned number of participants, partly due to logistical challenges created by the COVID-19 pandemic. This smaller sample size reduced the study’s statistical power, making it harder to detect a real, but modest, difference between the treatments if one existed. The primary limitation, however, remains the challenge of blinding.

The results from this trial suggest that when tested under more rigorous conditions, the antidepressant benefit of repeated ketamine infusions may be smaller than suggested by earlier studies that used inactive placebos. The researchers propose that expectations for both patients and clinicians may play a substantial role in ketamine’s perceived effects. This highlights the need to recalibrate expectations for ketamine in clinical practice and for more robustly designed trials in psychiatry.

Looking forward, the researchers emphasize the importance of reporting negative or null trial results to provide a balanced view of a treatment’s capabilities. They also expressed concern about a separate in the field: the promotion of ketamine as an equally effective alternative to electroconvulsive therapy, or ECT.

“Scrutiny of the scientific literature shows that this includes methodologically flawed trials and invalid meta-analyses,” McLoughlin said. “We discuss this in some detail in a Comment piece just published in Lancet Psychiatry. Unfortunately, such errors have been accepted as scientific evidence and are already creeping into international clinical guidelines. There is a thus a real risk of patients and clinicians being steered towards a less effective treatment, particularly for patients with severe, sometimes life-threatening, depression.”

The study, “Serial Ketamine Infusions as Adjunctive Therapy to Inpatient Care for Depression: The KARMA-Dep 2 Randomized Clinical Trial,” was authored by Ana Jelovac, Cathal McCaffrey, Masashi Terao, Enda Shanahan, Emma Whooley, Kelly McDonagh, Sarah McDonogh, Orlaith Loughran, Ellie Shackleton, Anna Igoe, Sarah Thompson, Enas Mohamed, Duyen Nguyen, Ciaran O’Neill, Cathal Walsh, and Declan M. McLoughlin.

A new long-term follow-up study has found that a significant majority of individuals treated for major depressive disorder with psilocybin-assisted therapy were still in remission from their depression five years later. The research, which tracked participants from an earlier clinical trial, suggests that the combination of the psychedelic substance with psychotherapy can lead to lasting improvements in mental health and overall well-being. The findings were published in the Journal of Psychedelic Studies.

Psilocybin is the primary psychoactive compound found in certain species of mushrooms, often referred to as “magic mushrooms.” When ingested, it can produce profound alterations in perception, mood, and thought. In recent years, researchers have been investigating its potential as a therapeutic tool when administered in a controlled clinical setting alongside psychological support.

The rationale for this line of research stems from the limitations of existing treatments for major depressive disorder. While many people benefit from conventional antidepressants and psychotherapy, a substantial portion do not achieve lasting remission, and medications often come with undesirable side effects and require daily, long-term use.

Psychedelic-assisted therapy represents a different treatment model, one where a small number of high-intensity experiences might catalyze durable psychological changes. This new study was conducted to understand the longevity of the effects observed in an earlier, promising trial.

The research team, led by Alan Davis, an associate professor and director of the Center for Psychedelic Drug Research and Education at The Ohio State University, sought to determine if the initial antidepressant effects would hold up over a much longer period. Davis co-led the original 2021 trial at Johns Hopkins University, and this follow-up represents a collaborative effort between researchers at both institutions.

“We conducted this study to answer a critical question about the enduring effects of psilocybin therapy – namely, what happens after clinical trials end, and do participants experience enduring benefits from this treatment,” Davis told PsyPost.

The investigation was designed as a long-term extension of a clinical trial first published in 2021. That initial study involved 24 adults with a diagnosis of major depressive disorder. The participants were divided into two groups: one that received the treatment immediately and another that was placed on a wait-list before receiving the same treatment.

The therapeutic protocol was intensive, involving approximately 13 hours of psychotherapy in addition to two separate sessions where participants received a dose of psilocybin. The original findings were significant, showing a large and rapid reduction in depression symptoms for the participants, with about half reporting a complete remission from their depression that lasted for up to one year.

For the new follow-up, conducted an average of five years after the original treatment, the researchers contacted all 24 of the initial participants. Of those, 18 enrolled and completed the follow-up assessments. This process involved a series of online questionnaires designed to measure symptoms of depression and anxiety, as well as any functional impairment in their daily lives.

Participants also underwent a depression rating assessment administered by a clinician and took part in in-depth interviews. These interviews were intended to capture a more nuanced understanding of their experiences and life changes since the trial concluded, going beyond what numerical scores alone could convey.

The researchers found that 67% of the original participants were in remission from their depression. This percentage was slightly higher than the 58% who were in remission at the one-year follow-up point.

“We found that most people reported enduring benefits in their life since participating in psilocybin therapy,” Davis said. “Overall, many reported that even if depression came back, that it was more manageable, less tied to their identity, and that they found it was less interfering in their life.”

To ensure their analysis was robust, the scientists took a conservative approach when handling the data for the six individuals who did not participate in the long-term follow-up. They made the assumption that these participants had experienced a complete relapse and that their depression symptoms had returned to their pre-treatment levels.

“Even controlling for those baseline estimates from the people who didn’t participate in the long-term follow-up, we still see a very large and significant reduction in depression symptoms,” said Davis, who also holds faculty positions in internal medicine and psychology at Ohio State. “That was really exciting for us because this showed that the number of participants still in complete remission from their depression had gone up slightly.”

The study also revealed that these lasting improvements were not solely the product of the psilocybin therapy sessions from five years earlier. The reality of the participants’ lives was more complex. Through the interviews, the researchers learned that only three of the 18 follow-up participants had not received any other form of depression-related treatment in the intervening years. The others had engaged in various forms of support, including taking antidepressant medications, undergoing traditional psychotherapy, or trying other treatments like ketamine or psychedelics on their own.

However, the qualitative data provided important context for these decisions. Many participants described a fundamental shift in their relationship with depression after the trial. Before undergoing psilocybin-assisted therapy, they often felt their depression was a debilitating and all-encompassing condition that prevented them from engaging with life. After the treatment, even if symptoms sometimes returned, they perceived their depression as more situational and manageable.

Participants reported a greater capacity for positive emotions and enthusiasm. Davis explained that these shifts appeared to lead to important changes in how they related to their depressive experiences. This newfound perspective may have made other forms of therapy more effective or made navigating difficult periods less impairing.

“Five years later, most people continued to view this treatment as safe, meaningful, important, and something that catalyzed an ongoing betterment of their life,” said Davis, who co-led the 2021 trial at Johns Hopkins University. “It’s important for us to understand the details of what comes after treatment. I think this is a sign that regardless of what the outcomes are, their lives were improved because they participated in something like this.”

Some participants who had tried using psychedelics on their own reported that the experiences were not as helpful without the supportive framework provided by the clinical trial, reinforcing the idea that the therapeutic context is a vital component of the treatment’s success.

Regarding safety, 11 of the participants reported no negative effects since the trial. A few recalled feeling unprepared for the heightened emotional sensitivity they experienced after the treatment, while others noted that the process of weaning off their previous medications before the trial was difficult.

The researchers acknowledge several limitations of their work. The small sample size of the original trial means that the findings need to be interpreted with caution and require replication in larger studies. Because the study was a long-term follow-up without a continuing control group, it is not possible to definitively attribute all the observed benefits to the psilocybin-assisted therapy, especially since most participants sought other forms of treatment during the five-year period. It is also difficult to know how natural fluctuations in mood and life circumstances may have influenced the outcomes.

“I’d like for people to know that this treatment is not a magic bullet, and these findings support that notion,” Davis noted. “Not everyone was in remission, and some had depression that was ongoing and a major negative impact in their lives. Thankfully, this was not the case for the majority of folks in the study, but readers should know that this treatment does not work for everyone even under the most rigorous and clinically supported conditions.”

Future research should aim to include larger and more diverse groups of participants, including individuals with a high risk for suicide, who were excluded from this trial. Despite these limitations, this study provides a first look at the potential for psilocybin-assisted therapy to produce durable, long-term positive effects for people with major depressive disorder. The findings suggest the treatment may not be a simple cure but rather a catalyst that helps people re-engage with their lives and other therapeutic processes, ultimately leading to sustained improvements in functioning and well-being.

“Next steps are to continue evaluating the efficacy of psilocybin therapy among larger samples and in special populations,” Davis said. “Our work at OSU involves exploring this treatment for Veterans with PTSD, lung cancer patients with depression, gender and sexual minorities with PTSD, and adolescents with depression.”

The study, “Five-year outcomes of psilocybin-assisted therapy for Major Depressive Disorder,” was authored by Alan K. Davis, Nathan D. Sepeda, Adam W. Levin, Mary Cosimano, Hillary Shaub, Taylor Washington, Peter M. Gooch, Shoval Gilead, Skylar J. Gaughan, Stacey B. Armstrong, and Frederick S. Barrett.

An analysis of data from the China Health and Retirement Longitudinal Study combined with weather and air pollution information showed that exposure to heatwaves, air pollution, and lack of access to blue spaces are all associated with an increased risk of depression. The increase in depression risk was even higher in individuals simultaneously exposed to these factors. The paper was published in the Journal of Environmental Psychology.

Climate change refers to long-term alterations in global temperatures, weather patterns, and ecosystems. It is understood that currently observed climate changes are mainly driven by human activities such as burning fossil fuels, industrial emissions, and deforestation. These processes release large amounts of greenhouse gases like carbon dioxide and methane, trapping heat in the atmosphere and disrupting natural climate systems. As a result, the planet experiences more frequent heat waves, droughts, floods, and wildfires.

Air pollution, which often comes from the same sources that cause climate change, adds another layer of harm by degrading air quality and contributing to respiratory and cardiovascular diseases. Fine particulate matter and toxic pollutants can adversely affect brain health as well. Extreme weather events linked to climate change can create massive devastation, triggering physical and psychological trauma, post-traumatic stress disorder, and long-lasting psychological distress for those affected.

Chronic exposure to uncertainty about the environment fuels eco-anxiety, a growing concern especially among young people. Communities facing displacement or loss of livelihoods due to environmental degradation may suffer from grief and helplessness. The psychological burden is particularly heavy on farmers, children, and low-income populations with limited access to healthcare.

The study’s authors, Weiqi Wang and his colleagues, wanted to investigate the individual and joint impacts of heatwaves, air pollutants, and access to blue and green spaces on depressive symptoms in middle-aged and older Chinese populations.

They analyzed data from the China Health and Retirement Longitudinal Study (CHARLS). CHARLS is a national survey in China focused on the issue of population aging, encompassing data from individuals aged 45 and older. It was started with a survey in 2011 and included four additional surveys conducted up to 2020. In each of these follow-up surveys, the study recruited a small number of additional participants.

The data analyzed in this study came from 12,316 participants across 124 cities in 28 of 31 provinces of China. The number of participants per city ranged between 51 and 211. Participants’ average age was approximately 58 years. About 53% were men, and 58% lived in rural areas.

This study used data on depressive symptoms from the CHARLS dataset (assessed using the Center for Epidemiologic Studies Depression Scale), and air pollution data (concentrations of ground-level pollutants CO, SO₂, PM_2.5, and PM₁₀ derived from the China High Air Pollutants (CHAP) dataset), data on heatwave exposure (based on maximum daily temperature data during the warm season from monitoring stations across China, provided by the United States Air Force Weather Agency), and exposure to green and blue spaces (based on the degree of vegetation cover and the proportion of open water bodies in a city).

Green spaces are areas of land covered with vegetation such as parks, gardens, forests, and grasslands that provide natural environments within urban or rural settings. Blue spaces are natural or artificial water environments like rivers, lakes, seas, and fountains.

Results indicated that exposure to heatwaves was associated with a 4-14% increase in the odds of depression. Likewise, exposure to air pollution was also associated with depression risk. The authors reported that for every 10 μg/m³ increase in ambient concentrations of PM_2.5 particles, the odds of depression increased by 25%. The increase was 13% per the same unit increase in PM₁₀ particle concentrations, 1% for CO, while the odds increased 55% for every 10 μg/m³ increase in SO₂ concentrations.

The risk of depression was also heightened in areas where access to blue spaces was lower. The study found a synergistic effect: individuals simultaneously exposed to both heatwaves and high air pollution, or to heatwaves combined with a lack of green and blue spaces, had a significantly higher increase in depression risk than would be expected from adding the individual risks together.

“The findings indicate that heatwaves, air pollution, and lack of blue spaces each independently have a detrimental impact on depressive symptoms. Furthermore, the interactive effects of air contaminants, insufficient blue and green spaces, and heatwaves exposure significantly affect depressive symptoms, both on multiplicative and additive scales. Our results emphasize the necessity of developing public health strategies to curb air pollution, and preserve blue and green spaces, especially during periods of heatwaves,” study authors concluded.

The study contributes to the scientific understanding of the links between climate and mental health. However, it should be noted that the design of this study does not allow any definitive causal inferences to be derived from the results.

The paper, “Individual and combined effects of heatwaves, air pollution, green spaces, and blue spaces on depressive symptoms incidence,” was authored by Weiqi Wang, Yuqing Hao, Meiyu Peng, Jin Yan, Longzhu Xu, Haiyang Yu, Zhugen Yang, and Fanyu Meng.

A new study suggests that a person’s genetic predisposition for chronic inflammation helps define a specific subtype of depression linked to metabolic issues. The research also found this genetic liability is connected to antidepressant treatment outcomes in a complex, nonlinear pattern. The findings were published in the journal Genomic Psychiatry.

Major depressive disorder is a condition with wide-ranging symptoms and variable responses to treatment. Many patients do not find relief from initial therapies, a reality that has pushed scientists to search for biological markers that could help explain this diversity and guide more personalized medical care. One area of growing interest is the connection between depression and the body’s immune system, specifically chronic low-grade inflammation. A key blood marker for inflammation is C-reactive protein, which is often found at elevated levels in people with depression.

However, measuring C-reactive protein directly from blood samples can be problematic for research because levels can fluctuate based on diet, infection, or stress. An international team of researchers, led by Alessandro Serretti of Kore University of Enna, Italy, sought a more stable way to investigate the link between inflammation and depression. They turned to genetics, using a tool known as a polygenic score. This score summarizes a person’s inherited, lifelong tendency to have higher or lower levels of C-reactive protein. While previous studies have connected this genetic score to specific depressive symptoms or to treatment outcomes separately, this new research aimed to examine both within the same large group of patients to build a more complete picture.

The investigation involved 1,059 individuals of Caucasian descent who were part of the European Group for the Study of Resistant Depression. All participants had a diagnosis of major depressive disorder and had been receiving antidepressant medication for at least four weeks. Researchers collected detailed clinical information, including the severity of depressive symptoms, which was assessed using the Montgomery–Åsberg Depression Rating Scale. Based on their response to medication, patients were categorized as responders, nonresponders, or as having treatment-resistant depression if they had not responded to two or more different antidepressants.

For each participant, the science team calculated a polygenic score for C-reactive protein. This was accomplished by analyzing each person’s genetic data and applying a statistical model developed from a massive genetic database, the UK Biobank. The resulting score provided a single, stable measure of each individual’s genetic likelihood of having high inflammation. The researchers then used statistical analyses to look for connections between these genetic scores and the patients’ symptoms, clinical characteristics, and their ultimate response to antidepressant treatment.

The results showed a clear link between a higher genetic score for C-reactive protein and a specific profile of symptoms and characteristics. Individuals with a greater genetic tendency for inflammation were more likely to have a higher body mass index and a lower employment status. They also reported less weight loss and appetite reduction during their depressive episodes, which are symptoms associated with metabolic function. The genetic score was not associated with the overall severity of depression or with core emotional symptoms like sadness or pessimism. This suggests that the genetic influence of inflammation is tied to a particular cluster of physical and metabolic symptoms, sometimes referred to as an immunometabolic subtype of depression.

When the researchers examined the connection to treatment outcomes, they discovered a more complicated relationship. The link was not a simple straight line where more inflammation meant a worse outcome. Instead, they observed what is described as a nonlinear or U-shaped pattern. Patients who did not respond to treatment tended to have the lowest genetic scores for C-reactive protein. In contrast, both patients who responded well to their medication and those with treatment-resistant depression had higher genetic scores. The very highest scores were observed in the group with treatment-resistant depression.

This complex finding remained significant even after the researchers statistically accounted for a range of other factors known to influence treatment success, such as the patient’s age, the duration of their illness, and the number of previous antidepressant trials. The genetic score for C-reactive protein independently explained an additional 1.9 percent of the variation in treatment outcomes. While a modest figure, it indicates that genetic information about inflammation provides a unique piece of the puzzle that is not captured by standard clinical measures. This U-shaped relationship echoes previous findings that used direct blood measurements of C-reactive protein, suggesting that both very high and very low levels of inflammation may be associated with different treatment pathways.

The researchers note some limitations of their work. The study’s design was cross-sectional, meaning it captures a single point in time and cannot prove that the genetic predisposition for inflammation causes certain symptoms or treatment outcomes. The participants were treated naturalistically with a variety of medications, which reflects real-world clinical practice but lacks the control of a randomized trial. Additionally, the sample consisted exclusively of individuals with European ancestry, so the findings may not be applicable to people from other backgrounds. The team also suggests that replication in other large studies is needed.

For future research, the authors propose integrating genetic scores with direct measurements of inflammatory biomarkers from blood tests. This combined approach could provide a more powerful tool for understanding both a person’s lifelong tendency and their current inflammatory state. Ultimately, this line of research could help refine psychiatric diagnosis and treatment. By identifying an immunometabolic subtype of depression, it may be possible to develop more targeted therapies. The findings contribute to a growing body of evidence supporting a move away from a “one-size-fits-all” approach to depression, opening the door for inflammation-guided strategies in personalized psychiatry.

The study, “Polygenic liability to C-reactive protein defines immunometabolic depression phenotypes and influences antidepressant therapeutic outcomes,” was authored by Alessandro Serretti, Daniel Souery, Siegfried Kasper, Lucie Bartova, Joseph Zohar, Stuart Montgomery, Panagiotis Ferentinos, Dan Rujescu, Raffaele Ferri, Giuseppe Fanelli, Raffaella Zanardi, Francesco Benedetti, Bernhard T. Baune, and Julien Mendlewicz.

A study has found that engaging with frightening entertainment, such as horror films, is associated with temporary changes in brain network activity common in depression. The research also found that individuals with moderate depressive symptoms may require a more intense scare to experience peak enjoyment, hinting at an intriguing interplay between fear, pleasure, and emotion regulation. These findings were published in the journal Psychology Research and Behavior Management.

The investigation was conducted by researchers Yuting Zhan of Ningxia University and Xu Ding of Shandong First Medical University. Their work was motivated by a long-standing psychological puzzle known as the fear-pleasure paradox: why people voluntarily seek out and enjoy frightening experiences. While this phenomenon is common, little was known about how it functions in individuals with depression, a condition characterized by persistent low mood, difficulty experiencing pleasure, and altered emotional processing.

The researchers were particularly interested in specific brain network dysfunctions observed in depression. In many individuals with depression, the default mode network, a brain system active during self-referential thought and mind-wandering, is overly connected to the salience network, which detects important external and internal events. This hyperconnectivity is thought to contribute to rumination, where a person gets stuck in a cycle of negative thoughts about themselves. Zhan and Ding proposed that an intense, controlled fear experience might temporarily disrupt these patterns by demanding a person’s full attention, pulling their focus away from internal thoughts and onto the external environment.

To explore this, the researchers designed a two-part study. The first study aimed to understand the psychological and physiological reactions to recreational fear across a spectrum of depressive symptoms. It involved 216 adult participants who were grouped based on the severity of their depressive symptoms, ranging from minimal to severe. These participants were exposed to a professionally designed haunted attraction. Throughout the experience, their heart rate was monitored, and saliva samples were collected to measure cortisol, a hormone related to stress. After each scary scenario, participants rated their level of fear and enjoyment.

The results of this first study confirmed a pattern seen in previous research: the relationship between fear and enjoyment looked like an inverted “U”. This means that as fear intensity increased, enjoyment also increased, but only up to a certain point. After that “sweet spot” of optimal fear, more intense fear led to less enjoyment. The study revealed that the severity of a person’s depression significantly affected this relationship.

Individuals with moderate depression experienced their peak enjoyment at higher levels of fear compared to those with minimal depression. Their physiological data showed a similar pattern, with the moderate depression group showing the most pronounced cortisol stress response. In contrast, participants with the most severe depressive symptoms showed a much flatter response curve, indicating they experienced less differentiation in enjoyment across various fear levels.

The second study used neuroimaging to examine the brain mechanisms behind these responses. For this part, 84 participants with mild-to-moderate depression were recruited. While inside a functional magnetic resonance imaging scanner, which measures brain activity by detecting changes in blood flow, participants watched a series of short clips from horror films. They had resting-state scans taken before and after the film clips to compare their baseline brain activity with their activity after the fear exposure.

The neuroimaging data provided a window into the brain’s reaction. During the scary clips, participants showed increased activity in the ventromedial prefrontal cortex, a brain region critical for emotion regulation and processing safety signals. The analysis also revealed that after watching the horror clips, the previously observed hyperconnectivity between the default mode network and the salience network was temporarily reduced. For a short period after the fear exposure, the connectivity in the brains of these participants with depression more closely resembled patterns seen in individuals without depression. This change was temporary, beginning to revert to baseline by the end of the post-exposure scan.

Furthermore, the researchers found a direct link between these brain changes and the participants’ reported feelings. A greater reduction in the connectivity between the default mode network and salience network was correlated with higher ratings of enjoyment. Similarly, stronger activation in the ventromedial prefrontal cortex during the fear experience was associated with greater positive feelings after the experiment. These findings suggest that the controlled fear experience may have been engaging the brain’s emotion-regulation systems, momentarily shifting brain function away from patterns associated with rumination.

The authors acknowledge several limitations to their study. The research primarily included individuals with mild-to-moderate depression, so the findings may not apply to those with severe depression. The study was also unable to control for individual differences like prior exposure to horror media or co-occurring anxiety disorders, which could influence reactions. Another consideration is that a laboratory or controlled haunted house setting does not perfectly replicate how people experience recreational fear in the real world.

Additionally, the observed changes in brain connectivity were temporary, and the correlational design of the study means it cannot prove that the fear experience caused a change in mood, only that they are associated. The researchers also did not include a high-arousal, non-fearful control condition, such as watching thrilling action movie clips, making it difficult to say if the effects are specific to fear or to general emotional arousal.

Future research is needed to explore these findings further. Such studies could investigate a wider range of participants and fear stimuli, track individuals over a longer period to see if the neural changes have any lasting effects, and conduct randomized controlled trials to establish a causal link. Developing comprehensive safety protocols would be essential before any potential therapeutic application could be considered, as intense fear could be distressing for some vulnerable individuals.

The study, “Fear-Pleasure Paradox in Recreational Fear: Neural Correlates and Therapeutic Potential in Depression,” was published June 27, 2025.