Effectiveness of a Fully Automated Mobile Therapeutic Versus a General Chatbot in Reducing Depression and Anxiety and Improving Well-Being: Feasibility Randomized Controlled Trial

Background: Given the increasing prevalence of depression and anxiety disorders and enduring barriers to care, there is a critical need for alternative treatment options. Generative artificial intelligence (AI) chatbots show promise for increasing access to mental health care, though more direct research is needed to establish their efficacy. Objective: This pilot study aimed to test the efficacy of a generative mental health chatbot rooted in solution-focused therapy compared to the general-purpose ChatGPT and an assessment-only control (AOC) group on depression, anxiety, and well-being. Methods: A total of 185 English-speaking adults were recruited online and randomly assigned to one of three groups: AI therapy, ChatGPT, or AOC. Of these, 147 eligible participants filled out a pretreatment assessment. Over a 3-week period, the AI therapy group (n=44) was instructed to complete 3 structured, fully automated app-based sessions per week (9 total), while the ChatGPT group (n=60) was instructed to engage in 9 unstructured conversations with ChatGPT (GPT-4o–based models). The control group (n=43) received no intervention. In the AI therapy group, 39% (n=17) completed all sessions, as did 62% (n=38) of those in the ChatGPT group. Primary outcome measures, self-assessed online at baseline and postintervention, included the Patient Health Questionnaire-9 (PHQ-9), Overall Depression Severity and Impairment Scale (ODSIS) (depression), 7-item Generalized Anxiety Disorder Scale (anxiety), and World Health Organization Well-Being Index (5-item version) (well-being). Linear mixed effects models were used for data analysis. Results: Compared to AOC, both the AI therapy group (=−0.47; =.01) and the ChatGPT group (=−0.44; =.02) demonstrated significant reductions in depression scores measured by PHQ-9. The AI therapy group showed nonsignificant reductions in anxiety (=−0.37; =.11) and ODSIS depression scores (=−0.25; =.22) and an increase in well-being (=0.12; =.53) compared to AOC. Similarly, a nonsignificant reduction in anxiety (=−0.27; =.22) and ODSIS depression scores (=−0.12; =.53) and an increase in well-being (=0.20; =.29) were observed in the ChatGPT group compared to AOC. The AI therapy group did not significantly outperform the ChatGPT group on any outcomes (PHQ-9: =−0.19; =0.03; =.87; 7-item Generalized Anxiety Disorder Scale: =−0.57; =−0.11; =.62; ODSIS: =−0.59; =−0.13; =.50; and WHO: =−0.38; =−0.07; =.69). Conclusions: Both the structured generative AI chatbot and ChatGPT showed a significant reduction in depression scores compared to the control group. No significant effects were observed across other outcomes, although descriptive trends indicated improvements in anxiety. While the AI therapy group showed descriptively better outcomes for depression and anxiety, differences between groups were not significant. A larger sample and longer intervention may be needed for the emerging trends to yield clinically meaningful effect sizes. Trial Registration: OSF Registries osf.io/r76ef;
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<![CDATA[Two-dose oral R‑MDMA, EMP-01, cuts social anxiety symptoms and real‑world avoidance in phase 2a study, with strong responder rates and good tolerability.]]>

Oral administration of kratom leaf extract alleviates anxiety-like behavior, urinary bladder pain, voiding dysfunction, and bladder hypercontractility via attenuating muscarinic receptor response in male mice exposed to chronic water avoidance stress

Psychological stress causes and deteriorates interstitial cystitis/painful bladder syndrome with urinary frequency, incontinence, bladder pain and urgency. The major alkaloid of kratom (Mitragyna speciosa), mitragynine, shows analgesic, anxiolytic, and smooth muscle relaxant effects. However, the effects of kratom leaf extract on stress-induced anxiety-like behavior, urinary bladder pain and urinary bladder dysfunction remain unknown. Therefore, this study aims to examine the effect of kratom leaf extract administration on anxiety-like behaviors, bladder pain, bladder contractile properties, and mast cell number in mice exposed to water avoidance stress. Male C57BL/6 mice were exposed to water avoidance stress (WAS) protocol for 10 consecutive days and compared with the stress-exposed mice receiving oral administration of kratom leaf extract (2.5 and 5 mg/kg of mitragynine) or solifenacin (10 mg/kg). Anxiety-like behaviors were assessed using open field test. Bladder pain sensitivity was evaluated with von Frey test, while voiding behavior was analyzed using voiding pattern analysis. Bladder contractility was examined using an in vitro organ bath technique, and urinary bladder mast cell infiltration was assessed by toluidine blue staining. Results show that mice receiving WAS had a reduction in the total duration and number of unsupported rearing behaviors, reduced voiding area, and increased bladder pain responses; however, these effects were reversed by treatment with kratom leaf extract (2.5 and 5 mg/kg of mitragynine). Interestingly, the WAS group also exhibited markedly increased tonic contractions in response to carbachol, a muscarinic agonist; these responses were attenuated in mice treated with kratom leaf extract (2.5 and 5 mg/kg) The enhanced tonic contractile response to carbachol was abolished by pre-incubation with ondansetron (a 5-HT₃ antagonist). The WAS group showed an increased total number of mast cells in the urinary bladder, which was reduced by treatment with kratom leaf extract at both 2.5 and 5 mg/kg. Our results indicate that treatment with kratom leaf extract attenuated chronic stress–induced bladder pain responses, voiding abnormalities, and mast cell numbers, and was associated with reduced contractile response to muscarinic stimulation, suggesting a potential modulatory effect on stress-induced bladder dysfunction.

Psychometric properties of Lithuanian translation of the self-report version of the Liebowitz social anxiety scale in young adult sample

BackgroundSocial anxiety disorder starts in adolescence or young adulthood and may have damaging effects on psychosocial development of the individual. Any intervention starts from assessment and the Liebowitz social anxiety scale with later developed self-report version is a valuable tool for practitioners for almost four decades. Even though the original version and adaptations have consistently demonstrated good reliability, there remains considerable debate regarding the factor structure. The aim is to test the factor structure and internal consistency of Lithuanian translation of the self-report version of the Liebowitz social anxiety scale (LSAS-SR) in a non-clinical young adult sample.MethodData of 452 young adults (mean age 21.3, 69.7% female) who volunteered participate in the study was used. Two factor solutions were tested: a single-factor model, with anxiety/fear and avoidance ratings loading on one factor, and a higher-order factor model, including two second-order scales (anxiety/fear scale and avoidance scale) and four first-order subscales (social interaction anxiety, performance anxiety, social interaction avoidance, performance avoidance). Internal consistency assessed using Cronbach’s alpha.ResultsLithuanian version has excellent internal consistency for the total score, scales and subscales, with Cronbach’s alfas ranging.85-.96. Confirmatory factor analysis shows that both tested models have acceptable data fit (RMSEA = .062-.067; CFI = .93-.94), however strong associations between (sub)scales, i.e. correlations exceeding.80, suggests that the use of scale and subscale scores may be less informative, especially in cross-sectional research, but could provide nuanced information in individual assessment.ConclusionFurther research on psychometric properties of Lithuanian versions of LSAS-SR should focus on verifying these results in a representative sample and in a clinical sample as well as testing the convergent and discriminant validity.

The temporal stability of core symptoms of social media addiction and their comorbidity with anxiety and depression in adolescents: a longitudinal network analysis

IntroductionSocial media addiction (SMA) is often comorbid with anxiety and depression. This study examined the temporal stability of core SMA symptoms and the bridging symptoms with anxiety and depression.MethodsA total of 1,240 adolescents (179 males, 1,061 females; mean age = 15.46 ± 0.63 years, age range: 14 – 18) completed the Bergen Social Media Addiction Scale (BSMAS), the Patient Health Questionnaire–9 (PHQ–9), and the Generalized Anxiety Disorder–7 (GAD–7) on two separate occasions in 2023 (T1) and 2024 (T2). The four symptom networks, including the BSMAS networks, two comorbidity networks (the BSMAS–GAD and the BSMAS–PHQ), and the integrated BSMAS–GAD–PHQ network, were estimated using Gaussian graphical models. Core symptom centrality was assessed using Expected Influence (EI), whereas bridge symptoms were identified using Bridge Expected Influence (BEI).Results1) Although SMA, anxiety, and depression levels of respondents rose significantly over the year, all four networks showed strong temporal stability, with the edge weights (r = .892 –.973, p < .001), the EI (r = .806 – .961, p ≤ .002), and the BEI (r = .699 – .804, p ≤ .008) highly correlated between T1 and T2; network comparison tests showed no significant changes in overall structures of all four networks, with most edges showing stable weights. 2) Within the BSMAS network, BSMAS2 (tolerance) and BSMAS6 (conflict) exhibited the highest EI at both time points. 3) In the comorbidity networks, BSMAS3 (mood modification), BSMAS5 (withdrawal), and BSMAS6 (conflict) consistently served as bridge symptoms on the SMA side at both T1 and T2. 4) Across both time points, PHQ1 (anhedonia) and PHQ7 (concentration problems) exhibited the highest BEI on the depression side, whereas GAD1 (nervousness) and GAD5 (restlessness) did so on the anxiety side. 5) These bridge symptoms were also confirmed in the integrated network.DiscussionThese findings illuminate the temporal persistence and development of symptom relationships, offering a more dynamic understanding of SMA–depression–anxiety comorbidity in adolescents.

There is no nature anymore

When people talk about “nature,” they’re generally talking about things that aren’t made by human beings. Rocks. Reefs. Red wolves. But while there is plenty of God’s creation to go around, it is hard to think of anything on Earth that human hands haven’t affected.

Mat Honan

In the Brazilian rainforest, scientists have found microplastics in the bellies of animals ranging from red howler monkeys to manatees. In remotest Yakutia, where much of the earth remains untrodden by human feet, the carbon in the sky above melts the permafrost below. In the Arctic Ocean, artificial light from ship traffic—on the rise as the polar ice cap melts away—now disrupts the nightly journey of zooplankton to the ocean surface, one of the largest animal migrations on the planet. The remote mountain lakes of the Alps are contaminated with all kinds of synthetic chemicals. Polar bears are full of flame retardants. Cesium-137, fallout from nuclear bomb explosions, lightly rimes the entire planet. 

These examples are mostly pollution—nuclear, carbon, chemical, light—but I raise them not to highlight the ways human industry and technology degrade the environment but to note how the things humans build change it. Nobody really knows what the exact effects of all that will be, but my point is that no part of the globe is free of human fingerprints. We have literally changed the world.  

We’ve changed ourselves as well. Humans are especially adept at bending human nature. Everything about us is up for grabs—appearance, health, our very thoughts. Pharmaceuticals, surgeries, vaccines, and hormones give us longer lives, take away our pain, ease our anxiety and depression, make us faster, stronger, more resilient. We’re getting glimpses of technologies that will let us change who our children will become before they’re even born. Electrodes implanted in people’s brains let them control computers and translate thoughts into speech. Prosthetics and exoskeletons straight out of comic books restore and enhance physical abilities, while gene-­editing technologies like CRISPR are rewriting our very DNA. And meanwhile, people have taken the sum total of all the information we have ever written down and poured it into vast calculating machines in an effort—at least by some—to build an intelligence greater than our own. 

So what even is nature, or natural, in this context? Is it “environmentalist,” in the conventional sense, to try to preserve what one could argue no longer exists? Should we employ technology to try to make the world more “natural”?  

Those questions led us to approach this Nature issue with humility. We try to grapple with them all the time—MIT Technology Review is, after all, a review of how people have altered and built upon nature.

And it’s a place to think about how we might repair it. Take solar geoengineering, for example—a subject we have covered with increasing frequency over the past few years. The basic idea of geoengineering is to find a technological fix for a problem technology caused: Burning ­petrochemicals to fuel the Industrial Revolution turned Earth’s atmosphere into a heat sink, fundamentally breaking the climate. Some geoengineers think that releasing particulate matter into the stratosphere would reflect sunlight back into space, thus reducing global temperatures. After years of theoretical discussions, some companies have begun to actively experiment with such technologies. This might seem like a great way to restore the world to a more natural state. It’s also fraught with controversy and peril. It could, for example, benefit some nations while harming others. It may give us license to continue burning fossil fuels and releasing greenhouse gases. The list goes on. 

Nature isn’t easy. 

In our May/June issue, we have attempted to take a hard look at nature in our unnatural world. We have stories about birds that can’t sing, wolves that aren’t wolves, and grass that isn’t grass. We look for the meaning of life under Arctic ice and within ourselves—and in the far future, on a distant world, courtesy of new fiction by the renowned author Jeff VanderMeer. I don’t know if any of that will answer the questions I’ve been asking here—but we can’t help but try. It’s in our nature. 

A Mindfulness-Based Stress Reduction Training Program Model

Conditions: Depression; Anxiety; Stress; Well-Being, Psychological

Interventions: Behavioral: The mindfulness group-“Mindfulness-Based Stress Reduction Program”; Behavioral: The life skills workshop group-“Lifestyle Management and Well-being Workshop”

Sponsors: Istanbul Medeniyet University

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