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.
Chronic stress and cognitive dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome: HPA axis dysregulation and hippocampal plasticity
Cognitive dysfunction is a common and disabling clinical feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), often described by patients as “brain fog.” These symptoms typically manifest as difficulties in attention, memory, and concentration. Chronic stress has been proposed as an important contributing factor in ME/CFS. The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the stress response, and prolonged adverse stress may contribute to HPA axis dysregulation, including altered cortisol rhythmicity and impaired negative feedback regulation. Such dysregulation may be associated with cognitive dysfunction in ME/CFS through mechanisms involving neuroinflammatory responses, oxidative stress, and disturbances in neurotransmitter homeostasis. Studies suggest that these alterations may affect hippocampal structure and function, thereby contributing to impaired learning and memory processes. As a key brain region involved in cognition and stress regulation, the hippocampus may be implicated in the neurobiological mechanisms underlying cognitive dysfunction in ME/CFS. This review integrates current evidence on the potential role of HPA axis dysregulation and related neurobiological alterations in chronic stress-associated cognitive dysfunction in ME/CFS, with the aim of providing a theoretical basis for identifying potential intervention targets and informing strategies centered on HPA axis regulation.
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.
From stigma to support: the mediating role of sympathy between nurses’ perceived stigma and helping behavior tendency for alcohol use disorder
BackgroundThe detrimental effect of stigma on healthcare for individuals with alcohol use disorders (AUDs) is well-established, often resulting in social distance and diminished helping behavior tendencies. However, contemporary neuroscience reconceptualizes addiction as a brain disease, potentially altering emotional responses to stigma. This study examines a seemingly paradoxical possibility: that under specific conditions, perceived stigma is primarily associated with sympathy (rather than anger or fear), which in turn is linked to helping behavior tendencies among nurses.MethodsA cross-sectional survey was administered to 348 clinical nurses from tertiary hospitals in China. Participants completed standardized scales assessing perceived stigma of patients with AUDs, causal attributions, emotional responses (including sympathy, anger, and fear), and helping behavior tendencies. Data were analyzed using Pearson correlation and mediation analysis (PROCESS macro, Model 4) with 5,000 bootstrap samples to test the mediating role of sympathy.ResultsPerceived stigma showed a significant positive correlation with sympathy (r= .160, p<.05), which was in turn positively correlated with helping behavior tendencies (r= .269, p<.05). Critically, mediation analysis revealed that sympathy fully mediated the relationship between perceived stigma and helping behavior tendencies. The standardized indirect effect was significant (β= 0.15, 95% CI [0.08, 0.23]), accounting for the total observed relationship, as the direct effect was non-significant. Additionally, compared to non-psychiatric nurses, psychiatric nurses perceived patients as significantly less dangerous and reported lower levels of fear and anger, along with a stronger intention to help and a lower tendency to avoid patients.ConclusionChallenging conventional perspectives, this study supports a dual-pathway model in which perceived stigma can indirectly associated with professional helping behavior tendencies through the elicitation of sympathy. While other emotions like anger and fear were also measured, the findings highlight the pivotal role of cognitive-affective processes, shaped by neurobiological understandings of addiction, in determining nursing care. Specifically, sympathy, but not anger or fear, was found to mediate the stigma-helping relationship. Enhancing neuroscience-informed education and targeted empathy training, particularly for general nurses, could transform stigmatizing attitudes into supportive care, ultimately improving outcomes for patients with AUDs.
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.
Group CBT targeting hostile attribution bias in adolescents and young adults with ASD traits
BackgroundAdolescence is characterized by heightened self-consciousness and sensitivity to social evaluations. During this period, hostile attribution bias—interpreting ambiguous social cues as hostile—can lower quality of life (QOL) and contribute to future mental health problems. Adolescents with autism spectrum disorder (ASD) show similar difficulties, often more pronounced due to their cognitive style and interpersonal vulnerabilities. Group cognitive behavioral therapy (CBT) aims to correct such biases through structured cognitive and social experiences. This study evaluated the psychological effects of group CBT on hostile attribution bias, social functioning, and QOL in adolescents and young adults with ASD traits.MethodsWe conducted an 8-session group CBT program focusing on hostile attribution bias and suspiciousness in 21 adolescents and young adults with ASD traits attending a hospital psychiatric outpatient department. The 15 participants who completed the program were included in analyzes. Psychological indices included hostile attribution bias (Ambiguous Intentions Hostility Questionnaire), social functioning (Social Responsiveness Scale, Second Edition [SRS-2]), and subjective QOL. Pre–post changes were quantified as change rates ((post − pre)/pre × 100). Group-level changes were tested with paired analyzes; exploratory associations among change rates were examined using Spearman correlations.ResultsGroup CBT significantly improved hostile attribution bias (effect size [ES] = 0.698, p = 0.017), social communication and interaction (SRS-2; ES = 0.780, p = 0.012), and subjective QOL (ES = 0.752, p = 0.011). Exploratory individual-level analyzes showed a discordant pattern: smaller reductions in hostile attribution bias (less negative change rates) were associated with greater increases in subjective QOL (ρ = 0.597, p = 0.019).ConclusionsThis pilot study suggests that group CBT may reduce hostile attribution bias and improve QOL and social functioning in adolescents and young adults with ASD traits. Notably, the positive correlation between hostile attribution bias change rates and QOL change rates suggests that greater QOL gains were not necessarily accompanied by larger reductions in hostile attribution bias, indicating that improvements in cognitive bias and perceived well-being may arise through partly distinct or non-linear pathways rather than a simple one-to-one relationship.Clinical trial registryUniversity Hospital Medical Information Network (UMIN000030140).
Editorial: Treatment and management of stimulant use disorder and co-occurring disorders
Deeper is not always better in plasma proteomics
Nature Biotechnology, Published online: 22 April 2026; doi:10.1038/s41587-026-03106-3
This Comment discusses depth, robustness and bias in plasma proteomics, concluding that increasing the depth of coverage does not necessarily translate to quantitative robustness.
Synthetic biology’s uncertain regulatory future in the wake of Loper Bright Enterprises v. Raimondo
Nature Biotechnology, Published online: 22 April 2026; doi:10.1038/s41587-026-03114-3
The US Supreme Court’s decision in Loper Bright Enterprises v. Raimondo, along with federal spending cuts, may limit the potential of synthetic biology to provide innovative solutions for environmental challenges, medicine and biomanufacturing.
Reference-free discovery with barcoded single-cell sequencing
Nature Biotechnology, Published online: 22 April 2026; doi:10.1038/s41587-026-03084-6
sc-SPLASH extends reference-free analysis to barcoded single-cell and spatial transcriptomics data.