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(https://www.psypost.org/testosterone-and-estradiol-levels-linked-to-depression-symptoms-and-ssri-side-effects-in-men/) Testosterone and estradiol levels linked to depression symptoms and SSRI side effects in men
Nov 6th 2024, 08:00

A study conducted in Denmark examined the relationship between sex hormone levels and major depressive disorder (MDD) in unmedicated men. Researchers found that higher levels of testosterone were associated with more severe depressive symptoms, particularly vegetative symptoms like weight loss, gastrointestinal issues, and insomnia. Men with lower sex hormone levels before beginning treatment were more likely to experience sexual side effects from antidepressant medication and tended to report lower sexual desire (libido). The research was published in (https://www.sciencedirect.com/science/article/pii/S2772408524001157) Neuroscience Applied.
Major depressive disorder, commonly referred to as depression, is a mental health condition characterized by persistent feelings of sadness, hopelessness, and a loss of interest or pleasure in activities that were once enjoyed. Depression affects thoughts, emotions, and behaviors, often causing significant impairment in daily functioning, including work, relationships, and self-care. Common symptoms include fatigue, difficulty concentrating, changes in appetite or sleep patterns, and, in severe cases, thoughts of self-harm or suicide.
Depression occurs at different rates between sexes, with men diagnosed with MDD about half as often as women. Researchers believe this difference may be related to sex hormones. Studies indicate that women after menopause and men tend to respond less effectively to selective serotonin reuptake inhibitors (SSRIs)—a common class of antidepressant drugs—compared to women in their reproductive years. In older men, lower testosterone levels have been linked with depression, and testosterone replacement therapy has been shown to reduce depressive symptoms. These findings suggest that sex hormones may play an important role in depression.
Study author Kristian H. Reveles Jensen and colleagues aimed to explore whether testosterone and estradiol levels in unmedicated men with MDD are linked to their depressive symptoms, response to SSRI treatment, and sexual side effects of these drugs.
Testosterone is a steroid hormone primarily produced in the testes, with smaller amounts generated in the adrenal glands and ovaries. It plays a key role in male sexual development, muscle mass, and libido. Estradiol is a form of estrogen (the primary female sex hormone) primarily produced in the ovaries. In men, estradiol is mainly produced by converting testosterone through the enzyme aromatase, with smaller amounts coming from the testes and adrenal glands.
SSRIs are a class of antidepressants that work by increasing levels of the neurotransmitter serotonin in the brain by blocking its reabsorption into nerve cells. This helps to improve mood and reduce symptoms of depression and anxiety.
The study involved 26 men with moderate to severe depression, who participated in a study on biomarkers for predicting antidepressant treatment response. Researchers measured their testosterone and estradiol levels before they started taking antidepressant medication.
Participants were treated with 10-20 milligrams of escitalopram (an SSRI) daily. If this treatment did not produce results after four weeks, it was replaced with 60-90 milligrams of duloxetine, a serotonin-norepinephrine reuptake inhibitor (SNRI).
Depression severity was assessed using the Hamilton Depression Rating Scale (HAMD-17) before starting treatment and then again after eight weeks. Sexual side effects were assessed at five time points up to the 12th week of treatment using the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale, where a clinician rated the reported side effects and categorized how likely they were induced by the medications taken.
The results showed that men with higher testosterone levels tended to have more severe depressive symptoms, driven primarily by vegetative symptoms like weight loss, gastrointestinal problems, and insomnia. However, the effectiveness of antidepressant medication did not appear to be linked to sex hormone levels.
Men with lower levels of testosterone and estradiol before treatment were more likely to experience sexual side effects from escitalopram, including erectile and ejaculatory dysfunction and reduced libido. Additionally, individuals with higher estradiol levels before treatment were less likely to develop these sexual side effects, particularly erectile and ejaculatory issues.
“We find a positive association between testosterone and overall depression severity, driven by vegetative symptoms, i.e., weight loss, gastrointestinal symptoms, and insomnia. Pretreatment sex hormone levels were not associated with antidepressant treatment outcomes but were associated with sexual side-effects of SSRI [selective serotonin reuptake inhibitor] treatment. Our results highlight the possibility that plasma estrogen and testosterone can serve as potential prognostic biomarkers of SSRI-induced sexual dysfunction in men, which should be evaluated in larger patient groups,” the study authors concluded.
This study provides insights into the role of sex hormones in depression. However, it is important to note that the sample size was small and limited to men, so these findings may not apply to women or to larger, more diverse groups. Additionally, the study’s design does not allow for cause-and-effect conclusions.
The paper, “(https://doi.org/10.1016/j.nsa.2024.104050) Psychoneuroendocrine profiles of unmedicated men with major depressive disorder and associations to treatment effects and sexual side-effects”, was authored by Kristian H.Reveles Jensen, Malene Ravn Aarestrup, Søren Vinther Larsen, Kristin Kohler-Forsberg, Gitte Moos Knudsen, Martin Balslev Jørgensen, and Vibe G. Frokjaer.

(https://www.psypost.org/researchers-discover-surprising-gender-gap-in-online-reviews-on-a-gigantic-scale/) Researchers discover surprising gender gap in online reviews on “a gigantic scale”
Nov 6th 2024, 06:00

In a recent study published in (https://www.nature.com/articles/s41562-024-02003-6) Nature Human Behaviour, researchers uncovered a “gender rating gap” in online reviews, revealing that women generally give higher ratings than men across several online review platforms. The study, which analyzed over a billion reviews from major sites like Amazon, Google, and Yelp, found that women tend to rate products and services more favorably than men do. Follow-up lab studies suggest that this discrepancy is largely due to women’s reluctance to leave negative reviews.
Online reviews are a primary source of information for consumers, who rely on others’ experiences to make informed decisions. However, online reviews are prone to biases, with previous research suggesting that gender influences various online behaviors and expressions. This study sought to investigate whether men and women show different tendencies when rating products or experiences and to determine what drives any observed disparities.
“User-generated content (UGC) over digital platforms has been shown to have an incredible social and economic influence on our daily lives,” said study author (https://www.linkedin.com/in/yaniv-dover-1615643/) Yaniv Dover, the Vice Dean of Research at the (https://bschool-en.huji.ac.il/yaniv-dover) Jerusalem Business School and a member of the Federmann Center for the Study of Rationality at the Hebrew University of Jerusalem.
“Online reviews are an especially important example of UGC – they are very pervasive and were shown to impact markets, businesses and consumers. Supposedly, the purpose of online reviews is to increase transparency in markets, reduce scamming and help consumers share useful information – empowering consumers and pushing businesses to improve. But it all relies on the fact that reviews are not systematically biased. So, our motivation was to check whether that is true — is there any systematic bias? We tried something fundamental like gender — we were hoping to find that gender doesn’t matter. We were wrong.”
The researchers gathered observational data from five major online platforms—Amazon, Google, IMDb, TripAdvisor, and Yelp—to examine potential gender differences in online review ratings. Their goal was to identify if a consistent gender rating gap existed across various types of platforms, products, and services. They collected a total of 1.2 billion reviews, which allowed them to examine a wide range of user experiences and a massive dataset across different years, locations, and categories of products or services.
Across all platforms, the study consistently found that women provided higher ratings on average than men. This gap persisted even after the researchers accounted for different factors, such as the category of review (e.g., restaurant or e-commerce) and differences in geographic location. Interestingly, the gap was also consistent across different years, suggesting that the observed trend was stable over time.
The team analyzed the rating distributions and found that, in general, men and women tended to use the more positive end of the rating scale, but men were slightly more critical. In other words, a larger percentage of female reviewers tended to give five-star ratings, while male reviewers had a higher tendency to give lower ratings, resulting in a modest but consistent gender gap.
“We have to admit that the fact that women are on average consistently more positive on such a gigantic scale was surprising,” Dover told PsyPost. “When we first started collecting data and were trying to guess what we’ll see, we each did a little not-so-scientific ‘survey’ to try and predict what we’ll find. We asked family, colleagues, students and anecdotally – when they had to guess, women usually got it wrong, i.e., women thought women are generally more negative. We haven’t done extensive surveys, but if our little convenient sample is representative – this may be an interesting misconception – women thinking they are themselves more negative when actually they are more positive.”
To investigate the reasons behind this gender gap, the researchers conducted two lab-based studies, Studies 2 and 3. These studies were intended to test whether differences in attitudes, rating adjustments, or the willingness to post negative reviews might contribute to the observed gap.
Study 2 used a controlled environment to examine how men and women rate products in a situation where they could immediately experience and evaluate them. In this study, the researchers recruited over 1,100 participants from the United States and had them rate AI-generated paintings. The design of Study 2 allowed researchers to compare both participants’ private attitudes (how they felt about the painting) and their willingness to post a public review if they were dissatisfied.
Interestingly, Study 2 confirmed that men and women did not significantly differ in their private attitudes toward the paintings, meaning that both genders had similar reactions when judging the art without any social implications. However, when asked to post a public review, women showed greater hesitation to give lower ratings, especially when dissatisfied. The researchers observed that the gender rating gap emerged largely because women were less likely to post negative reviews, aligning with the idea that women may have greater concerns about appearing overly critical or being judged negatively for their opinions.
Study 3 aimed to replicate the findings of Study 2 in a new context to see if the results held when participants rated a different type of content. Instead of paintings, this study had participants listen to short musical pieces and rate them in the same way. The researchers again recruited over 1,100 participants, ensuring an even balance between male and female respondents.
The design of Study 3 was nearly identical to that of Study 2, but it added a new element: participants were asked about their fear of negative evaluation, a measure of their discomfort with receiving criticism or disapproval. This measure was intended to help determine if fear of negative evaluation might be a driving factor in women’s lower likelihood of posting negative reviews.
As with Study 2, the results of Study 3 showed that men and women did not differ in their private attitudes toward the music. However, women again demonstrated a reluctance to post negative reviews when they felt dissatisfied.
The analysis revealed that women reported a higher level of fear of negative evaluation than men, which was linked to their lower likelihood of posting negative feedback publicly. This provided additional evidence that fear of negative evaluation could be a significant factor behind the observed gender rating gap. The researchers concluded that women’s concerns about social judgment or backlash might discourage them from posting reviews when they are dissatisfied, thereby leading to a more positive overall rating from female reviewers.
“This may sound trivial, but it is not: you can’t take what you read online at face value,” Dover said. “When you read online reviews to help you make decisions you need to realize there is a real person behind the content, in a specific social context and influenced by social norms. It’s not just a person providing their authentic opinion, they are affected by their environment and how people may judge them for their opinions.”
“There is this thinking that because communication on the internet is done through screens and keyboards, that people will freely express themselves and write whatever is on their minds. On the contrary, we find that women more readily censor themselves when they think their opinions are negative, whether it is because they don’t want to appear judgmental or they have more empathy towards the review subject.”
“The internet should be a place where everyone feels free to contribute, especially if their opinion is economically important and useful. What we find hints that a big part of the population does not feel that way, and not only that this is not ‘fair,’ it may be hurting whole markets, reducing representativeness and biasing consumer decisions.”
The researchers highlighted some limitations of the study and proposed areas for future investigation.
“Like all scientific work, one should be very careful when interpreting data analysis,” Dover explained. “The main finding of this work is that there is a consistent gap in favor of women, across relatively very big data sets and different platforms and categories. While we ran a few experimental studies, these are just the first efforts in what should be a whole research agenda to go deeper and find out why this gap exists. We find initial evidence of this self-censoring effect, but to really establish it – future research should look at other contexts, try to replicate what we find in and out of the lab and study larger samples.”
“There is more and more evidence that user-generated content on digital platforms is strongly affecting social dynamics and our lives in good and bad ways,” Dover added. “Think about misinformation and negative influence in social media, increasing polarization, on the one hand but also positive social connections in the digital world, more transparency, improved access to useful information, etc.”
“We want to understand more broadly how to construct digital platforms such that they do more good than harm, how to shape technology such that humanity benefits from it towards a better future, while decreasing risks. This is probably one of the most important roles of social scientists studying human behavior on digital platforms, we believe.”
The study, “(https://doi.org/10.1038/s41562-024-02003-6) Gender rating gap in online reviews,” was authored by (https://www.linkedin.com/in/andreas-bayerl/) Andreas Bayerl, Yaniv Dover, (https://www.hilariemer.com/) Hila Riemer, and (https://www.linkedin.com/in/dr-danny-shapira-558268280/) Daniel Shapira.

(https://www.psypost.org/indirect-exposure-to-gun-violence-linked-to-reduced-quality-of-life-in-four-different-domains/) Indirect exposure to gun violence linked to reduced quality of life in four different domains
Nov 5th 2024, 14:00

A recent study published in the (https://link.springer.com/article/10.1007/s11524-024-00891-7) Journal of Urban Health reveals that even indirect exposure to gun violence—such as witnessing or hearing about shootings—is associated with a diminished quality of life for individuals living near these incidents. The study suggests that exposure to gun violence impacts people’s physical, psychological, social, and environmental well-being, even if they themselves are not directly injured. This sheds light on the far-reaching impacts of gun violence on communities, suggesting that its effects extend well beyond traditional victim counts.
Every year, tens of thousands of Americans are affected by gun-related incidents, which include not only homicides and injuries but also non-lethal threats and witnessing shootings. While those directly injured by gun violence face physical and psychological challenges, many others who are indirectly exposed—such as those witnessing a shooting or knowing a victim—also experience substantial distress.
Researchers from the (https://gunviolenceresearchcenter.rutgers.edu/) New Jersey Gun Violence Research Center at Rutgers University conducted their study to explore these less visible effects of gun violence. They recognized that while there is extensive data on the physical and mental health challenges faced by people directly injured in gun violence incidents, less is known about the broader impacts on community members who live near or hear about these events.
“Studies have previously examined the relationship between gun violence and specific health outcomes (for example, sleep or a PTSD diagnosis). But health is more than these specific outcomes and incorporates broad aspects of well-being and quality of life. Therefore, we wanted to study how exposure to gun violence was associated with five different types of quality of life (overall, physical, psychological, social, and environmental),” said lead author Jennifer Paruk, a research associate at the research center.
To investigate these effects, the researchers recruited participants from nine diverse states in the United States—Mississippi, New Jersey, Colorado, Texas, Minnesota, Washington, Pennsylvania, Ohio, and Florida. The final sample (7,785 participants) included individuals from varied backgrounds to ensure broad representation across racial, economic, and geographic lines.
The data collection took place in June and July 2023 through the Ipsos KnowledgePanel, a national online survey panel, where participants received an invitation to complete a survey. The survey included questions drawn from the World Health Organization’s Quality of Life Scale, a tool designed to capture people’s perceptions of their well-being in different life domains. Participants were asked to reflect on the past two weeks and rate aspects such as their physical health, mental wellness, satisfaction with personal relationships, and feelings about their environment.
The study specifically explored four types of gun violence exposure: (1) being threatened with a firearm, (2) being shot, (3) knowing a friend or family member who was shot, and (4) witnessing or hearing about shootings in the neighborhood. By categorizing these experiences, the researchers aimed to differentiate the impacts of direct, indirect, and cumulative exposure to gun violence.
The results showed a clear connection between gun violence exposure and lower quality of life. Of the forms of exposure, witnessing or hearing about a neighborhood shooting was the most common, reported by 22% of participants. People who reported this form of exposure experienced reduced quality of life in all areas studied, including physical, psychological, social, and environmental well-being.
“This study shows that even indirectly experiencing gun violence is associated with lower quality of life,” Paruk told PsyPost. “Those who witnessed/heard about shootings in their neighborhoods reported lower scores in all types of quality of life. Reducing gun violence can improve numerous aspects of community well-being.”
The researchers found that exposure to multiple forms of gun violence, or cumulative exposure, was linked to even greater reductions in quality of life. For instance, individuals who had experienced three or more types of exposure reported significantly lower scores in physical health, social connections, and environmental satisfaction. This pattern suggests that the more gun violence one encounters, the greater the toll on overall well-being, highlighting what the researchers describe as a “dose-response” relationship.
“Across all types of quality of life, those with the most exposure to gun violence report the lowest quality of life,” Paruk said.
In terms of numbers, witnessing or hearing about shootings was associated with a 2.33% decrease in overall quality of life. Each additional type of exposure further decreased scores across various life domains. For instance, cumulative gun violence exposure led to an 11% reduction in physical quality of life, emphasizing that indirect exposure alone can have significant physical consequences.
This may be due to chronic stress responses—such as heightened vigilance and reduced movement within one’s neighborhood—related to fear and concern over personal safety. The findings point to the likelihood that indirect exposure to violence may impact community members at a cellular level, producing physical stress markers over time that can have long-term effects on health.
Despite its valuable insights, this study is not without limitations. First, the survey data collected is cross-sectional, meaning it only represents a snapshot in time rather than a cause-and-effect relationship. Additionally, the study focused on a limited number of states, so the results might differ if conducted on a national scale or in other regions.
Furthermore, while the researchers took multiple demographic factors into account, there may be other influences on quality of life that were not controlled for, such as personal coping mechanisms or community support systems. Lastly, only a small percentage of participants (2%) reported having been directly injured by gun violence, so it is challenging to assess the specific impacts of direct physical injuries on quality of life from this dataset.
Looking ahead, the researchers suggest that further studies could investigate the long-term impacts of cumulative gun violence exposure and how different forms of exposure impact quality of life over time. They are also interested in understanding how people’s coping strategies and available community resources might mitigate or amplify these effects. This could involve exploring whether support groups, neighborhood interventions, or policy changes can alleviate some of the stress that gun violence places on communities.
“This study is part of a larger goal at the New Jersey Gun Violence Research Center (GVRC) to better understand how gun violence affects mental and physical health,” Paruk said. “We are currently analyzing the results of a nationally representative survey, studying in-depth how the frequency and recency of different types of gun violence exposure are associated with mental and physical health. Stay tuned to the NJ GVRC for findings!”
The study, “(https://doi.org/10.1007/s11524-024-00891-7) Gun Violence Exposure and Quality of Life in Nine US States,” was authored by Jennifer Paruk and Daniel Semenza.

(https://www.psypost.org/machine-learning-algorithm-identifies-three-unique-autism-subtypes-in-males/) Machine learning algorithm identifies three unique autism subtypes in males
Nov 5th 2024, 12:00

In a recent study published in (https://doi.org/10.1002/aur.3183) Autism Research, researchers discovered three distinct subtypes of autism spectrum disorder (ASD) in males, each associated with unique brain structure patterns and behavioral traits. These findings suggest that there is considerable diversity in the neural profiles of individuals with ASD, which may influence their specific needs and how they respond to treatment.
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition primarily characterized by difficulties in social interaction, communication, and repetitive behaviors. People with autism experience these symptoms to varying degrees, which is why it is often referred to as a “spectrum.” In addition to these common traits, individuals with ASD may have unique sensory sensitivities, cognitive abilities, and motor skills, contributing to the diversity of the disorder.
Autism’s complexity poses challenges in understanding its causes and developing effective interventions. Despite increased awareness and research, there remains a substantial need for personalized approaches that account for the wide variability in autism’s presentation.
The rationale behind this study stems from the limitations of current diagnostic methods, which often focus on categorizing autism based on symptom severity alone. While helpful, this approach does not fully capture the underlying biological differences that may give rise to similar behaviors. In other words, two individuals may display the same level of social or communication difficulties but could have fundamentally different brain structures contributing to these challenges. This has led researchers to explore other ways to categorize ASD that go beyond outward symptoms, aiming to develop a more nuanced understanding of the brain structures involved in the disorder.
“The incidence of autism has been showing an increasing trend year by year, placing a heavy burden on families and society,” said study author (https://lixw777.github.io/) Xinwei Li, a professor at Chongqing University of Posts and Telecommunications. “Currently, there is no effective cure for this neurodevelopmental disorder; however, it is certain that the heterogeneity of the brains of patients is a breakthrough point in revealing the mechanisms of this disease. Recent international research directions and our paper’s findings also support this point.”
The researchers used a dataset called the Autism Brain Imaging Data Exchange, which includes magnetic resonance imaging data for individuals with autism and healthy individuals as a control group. For this study, they focused on 225 male participants with autism and 255 males without the condition, with ages ranging from around 10 to 20. They selected only male participants because most autism cases are diagnosed in males, and including females could introduce confounding effects, as the structural characteristics of autism in females can differ significantly from those in males.
Using T1-weighted MRI images, the researchers analyzed brain structures, focusing on gray matter—one of the key components of the brain involved in processing information. They constructed brain networks based on the similarities in gray matter structure between various brain regions, known as the gray matter network. This analysis allowed them to view the brain’s network in individual participants, giving insight into each person’s unique neural architecture. By applying a specialized machine learning method, called Heterogeneity through Discriminative Analysis, they were able to divide the autism participants into subtypes.
The researchers identified three main subtypes of ASD, each distinguished by differences in how certain brain regions were connected. The first subtype exhibited high connectivity in the left anterior and right posterior central gyri, regions associated with sensorimotor functions, indicating that these participants may experience heightened sensitivity or altered sensorimotor processing.
The second subtype showed decreased connectivity in the left anterior central gyrus, a region associated with motor control, but increased connectivity in the left fusiform gyrus and the lingual gyrus, which are associated with visual and language processing. These findings suggest that individuals in this subtype may face challenges in motor and social visual functions.
The third subtype displayed alterations in the left medial superior frontal gyrus and the left middle frontal gyrus, both regions involved in higher-order cognitive processes, implying that these participants may experience difficulties with planning, decision-making, and social cognition.
“Several aspects of our research findings were unexpected,” Li told PsyPost. “For instance, we observed that the differences in comparisons between different subtypes and control groups were mostly concentrated in the same brain regions, indicating that these areas are likely closely related to the patients’ cognition and functioning. Additionally, we found that the numbers of each subtype were quite similar, which is inconsistent with some studies and necessitates a deeper exploration of individual differences. Overall, these surprises highlight the complexity of the issues we are studying and reinforce the importance of continued research in this area.”
In addition to these brain connectivity differences, the study found significant variations in clinical measures across the three subtypes. For instance, participants in the third subtype scored higher in verbal and performance intelligence tests than those in the other subtypes, while those in the first subtype had more challenges in communication and social interaction. These differences provide further insight into how the brain’s structure correlates with autism’s diverse behavioral and cognitive manifestations.
“The average person should be aware that autism is a complex neurodevelopmental disorder with a rising incidence, which highlights the importance of early detection and intervention,” Li said. “At the same time, autism has different subtypes, and targeted interventions should be conducted based on the specific subtype.”
However, the study has some limitations. First, it included only male participants, meaning that these subtypes may not fully capture the variation in females with ASD. “The exclusion of females from the study restricts the broader applicability of the findings,” Li noted. “Future study is necessary to explore whether our results could be generalized to females with ASD.”
Additionally, the cross-sectional nature of the study does not allow for observing changes over time, which would be important to track developmental trajectories within each subtype. Furthermore, the sample size, though large, may not encompass the entire range of ASD presentations, especially among individuals with intellectual disabilities, as most participants had IQs above 70.
In the future, the researchers aim to build on their findings by incorporating data from other types of brain imaging and conducting long-term studies to see how these brain patterns change over time in relation to behavior and cognition. By expanding the data and exploring additional brain network properties, they hope to develop diagnostic tools that can detect autism subtypes more quickly and precisely, ultimately leading to treatments tailored to each individual’s unique brain structure.
“Next, we hope to expand the dataset by incorporating multimodal data to explore the mechanisms of the patients’ conditions,” Li explained. “Additionally, we aim to conduct in-depth follow-ups on the long-term changes in patients and how these changes affect cognitive and behavioral aspects, as well as to enable rapid diagnosis and prediction of the disease.”
The study, “(https://onlinelibrary.wiley.com/doi/10.1002/aur.3183) Three autism subtypes based on single-subject gray matter network revealed by semi-supervised machine learning,” was authored by Guomei Xu, Guohong Geng, Ankang Wang, Zhangyong Li, Zhichao Liu, Yanping Liu, Jun Hu, Wei Wang, and Xinwei Li.

(https://www.psypost.org/single-dose-psilocybin-therapy-shows-promise-for-veterans-with-treatment-resistant-depression/) Single-dose psilocybin therapy shows promise for veterans with treatment-resistant depression
Nov 5th 2024, 10:00

A recent study published in the (https://www.sciencedirect.com/science/article/abs/pii/S0165032724016227) Journal of Affective Disorders suggests that a single dose of psilocybin may offer hope for U.S. military veterans facing severe, treatment-resistant depression. Many veterans who had endured years of depression despite numerous treatments showed significant improvements following psilocybin-assisted therapy. Yet, the results were mixed, with some participants experiencing limited relief. This study marks the first to explore psilocybin’s potential specifically for veterans with treatment-resistant depression.
Treatment-resistant depression refers to a form of major depressive disorder that does not respond to conventional treatments, such as antidepressant medications or psychotherapy. Individuals with treatment-resistant depression often experience prolonged and severe symptoms despite multiple attempts to alleviate their condition. For those affected, it can feel as though no options are left, leading to further feelings of hopelessness and distress. The risk of suicide and other health complications can be high, making it an important area of focus in mental health research.
Psilocybin-assisted therapy is an emerging approach that combines the use of psilocybin, a psychedelic compound found in certain “magic” mushrooms, with therapeutic support. Psilocybin is known for its mind-altering effects and has been studied for its potential to provide rapid and sustained relief from depressive symptoms.
In a therapeutic setting, psilocybin is administered in a controlled environment under the guidance of trained professionals. Participants are often prepared in advance and receive support during and after the experience, helping them process and integrate their insights. Some research suggests that psilocybin may affect brain regions associated with mood and perception, allowing individuals to experience shifts in their perspective on life and emotional struggles, even with just a single dose.
The motivation behind the new study stemmed from the unique challenges faced by U.S. military veterans, who experience high rates of treatment-resistant depression and related conditions like post-traumatic stress disorder. Many veterans struggle with depression as a result of trauma, combat exposure, and other stressors that complicate their mental health. Conventional treatments often fall short in this population, leading researchers to investigate alternative options.
The research team conducted their pilot study at the Veterans Affairs Palo Alto Health Care System and Stanford University. They recruited 15 veterans, ages 18 to 65, who had experienced depression resistant to at least five treatment attempts, or who had been struggling with depression for over two years. Participants underwent a rigorous screening process that included detailed medical and psychiatric assessments. To ensure safety, individuals with a history of psychosis, active substance use disorders, or untreated medical issues were excluded from the study.
After the initial screening, each participant attended three preparatory therapy sessions to build a rapport with the therapists, learn about psilocybin’s effects, and establish goals for their experience. The psilocybin sessions took place in a calm, comfortable setting with low lighting, cushions, and music to help participants feel at ease. During these sessions, veterans received a single 25 mg dose of synthetic psilocybin under the supervision of trained therapists who remained present throughout the session to provide support and ensure safety.
Afterward, participants had a 90-minute integration session to discuss and make sense of their experience. Follow-up assessments were conducted over a 12-week period, with clinical evaluations at specific intervals (Weeks 1, 2, 3, 6, 9, and 12) to monitor changes in depression symptoms, suicidal thoughts, and overall well-being.
The primary measure of improvement was the Montgomery-Åsberg Depression Rating Scale (MADRS), a commonly used scale for assessing the severity of depression. Three weeks after the psilocybin session, participants’ average MADRS scores had dropped significantly, indicating a substantial reduction in depressive symptoms. At this three-week point, 60% of participants met the criteria for “response” (a 50% or greater reduction in MADRS scores), and 53% met the criteria for remission, meaning their depression symptoms had reduced to very low levels.
By the study’s end at 12 weeks, 47% still showed a response, and 40% remained in remission. In other words, about half of the participants no longer met the threshold for a significant response or remission at the study’s conclusion. This outcome highlights the variability in how individuals respond to psilocybin, indicating that while some veterans found meaningful relief, others saw little improvement in their symptoms.
“Due to media attention, there are heightened expectations of miraculous response levels in psychedelic research trials,” the researchers wrote. “Even in this pilot study, about a third of participants did not have an antidepressant response to a single dose of psilocybin at the primary endpoint, and by the study endpoint 50% no longer met response criteria. Future studies must be cautious to mitigate the expectations of participants so that those who do not respond to this treatment are able to navigate feelings of disappointment.”
“Too often, patients are approaching these new tools as a ‘last-ditch effort’ in their attempt to recover from depression, and risks of increased suicidality or other self-harm behaviors could be heightened. It is critical to measure and manage participant expectations prior to dosing, and to prepare participants for an unknown outcome—one that may not meet their expectations.”
Interestingly, the researchers found no significant link between the intensity of participants’ psychedelic experiences and their improvements in depression symptoms, suggesting that psilocybin’s therapeutic effects may not rely solely on the depth of the psychedelic experience itself.
Psilocybin was generally well-tolerated. Some participants reported mild side effects like headaches, nausea, and mild back pain during the dosing day, but these symptoms resolved within a day. No severe adverse events or increases in suicidal ideation were observed during the study. For participants who had tapered off antidepressants before the study, four chose to restart them by the end of the follow-up period.
It is important to note that as an open-label pilot study, this research lacked a control group and involved a small sample size, which limits the ability to generalize the findings. Additionally, both participants and researchers were aware that everyone in the study would receive psilocybin, which may have influenced the outcomes.
The study design also required participants to taper off existing medications, which might have impacted their response to the psilocybin treatment. Larger trials with placebo groups, longer follow-up, and varied dosing methods could help confirm these findings and improve understanding of psilocybin’s effectiveness in the veteran population.
Looking forward, researchers will need to examine whether psilocybin’s effects endure over the long term and whether these benefits extend to other individuals with complex mental health needs. Additional studies are planned to explore how brain function may change after psilocybin treatment and to examine responses to psilocybin in a broader veteran population.
The study, “(https://doi.org/10.1016/j.jad.2024.09.133) Single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression – A first-in-kind open-label pilot study,” was authored by Sara Ellis, Catherine Bostian, Wendy Feng, Eileen Fischer, Garrett Schwartz, Katherine Eisen, Melanie Lean, Elizabeth Conlan, Michael Ostacher, Scott Aaronson, and Trisha Suppes.

Forwarded by:
Michael Reeder LCPC
Baltimore, MD

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