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Importance: Psilocybin has been proposed as a rapid-acting antidepressant (onset <2 weeks) with sustained effects (>6 weeks), but evidence from randomized clinical trials remains limited, particularly in the broader major depressive disorder (MDD) population.

Objective: To assess short-term and long-term antidepressant effects of psilocybin therapy in patients with MDD.

Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial of participants diagnosed with moderate to severe recurrent MDD was conducted at the Northern Stockholm Psychiatric Clinic between January 26, 2021, and February 19, 2024. Statistical analysis was performed from February 20, 2024, to June 20, 2025.

Interventions: Participants received a single dose of psilocybin (25 mg) or active placebo (niacin, 100 mg) and 5 psychotherapeutic support sessions during 17 days.

Main Outcomes and Measures: The primary end point was between-group difference in change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 8. Secondary end points included MADRS scores on days 15, 42, and 365, as well as monthly self-reports (MADRS-S) of depressive symptoms, disability, quality of life, and anxiety throughout the 365-day follow-up.

Results: The study included 35 participants (21 [60%] female; mean [SD] age, 41.0 [10.1] years) diagnosed with moderate to severe recurrent MDD, with 17 randomized to the psilocybin group and 18 to the niacin group. The study met its primary end point with a significant mean between-group difference (model estimated) in change in MADRS score on day 8 (-7.27; 95% CI, -12.89 to -1.65; P = .01) in favor of psilocybin. The between-group difference was significant also on days 15 (mean difference, -11.03; 95% CI, -16.65 to -5.42; P < .001) and 42 (mean difference, -8.33; -13.94 to -2.71; P = .004) but no longer on day 365 (mean difference, -3.68; -9.30 to 1.94; P = .20). For MADRS-S, the psilocybin group had a significantly greater reduction beginning at day 2 (mean difference, -9.58; 95% CI, -16.05 to -3.11; P = .004), with group differences persisting through day 102 (mean difference, -6.60; 95% CI, -13.01 to -0.19; P = .04) and then isolated effects at days 283 and 343. Most reported treatment-emergent adverse events were transient and of mild to moderate severity. No drug-related serious adverse events were reported. Two participants in the psilocybin group reported persistent, severe anxiety that required medical attention.

Conclusions and Relevance: In this randomized clinical trial of MDD, a single dose of psilocybin was associated with rapid antidepressant effects, observed by day 2 and persisting for more than 3 months on secondary outcomes; psilocybin was generally well tolerated, but some individuals required additional support after dosing due to anxiety. These results suggest that psilocybin may provide a rapid and relatively long-lasting antidepressant effect on major depressive disorder, warranting further investigation into repeated dosing or adjunctive treatment strategies.

Trial Registration: ClinicalTrials.gov Identifier: NCT04630964.

Background: Attention-deficit/hyperactivity disorder (ADHD) is characterized by emotional dysregulation, such as emotional instability, and by non-emotional symptoms, including inattention. These symptom domains are dimensionally distributed in the general population and are hypothesized to reflect both overlapping and distinct structural and functional features of cortical and subcortical brain networks.

Methods: We applied a dimensional symptom approach in a sample of adults with ADHD (n = 71) and healthy controls (n = 59) to investigate structural brain correlates of inattention and emotional instability, as measured by the Brown Attention-Deficit Disorder Scales. Structural magnetic resonance imaging (MRI) data were analysed to examine cortical and subcortical associations with these symptom dimensions. Performance in an emotional Stroop task was assessed in conjunction with MRI acquisition in a subsample to explore neural correlates of emotion-related cognitive control. Data were collected between 2012 and 2017.

Results: Emotional instability was negatively associated with nucleus accumbens volume, independent of inattention symptoms and ADHD diagnosis (beta = -0.29, p = 0.016). Additionally, while controlling for inattention symptoms, a negative correlation between emotional instability and cortical surface area was found in a cluster comprising the left dorsolateral prefrontal cortex and right medial/superior frontal cortex. Moreover, cortical thickness in the lateral orbitofrontal cortex was positively associated with performance in the Stroop task in ADHD (r = 0.44, p = 0.027) while being negatively associated in healthy controls (r = -0.40 p = 0.028).

Limitations: Medication use within the ADHD group might influence brain-symptom-associations. The cross-sectional design of the study precludes conclusions about causality.

Conclusions: These findings suggest that structural alterations in the nucleus accumbens are more strongly related to emotional, rather than attentional symptoms after accounting for their shared variance. Furthermore, altered prefrontal and orbitofrontal morphology may underlie impairments in emotional regulation, supporting the role of frontostriatal circuits in the dimensional expression of emotional instability across clinical and non-clinical populations.

Background: The challenges that the world faces to ensure good life for future generations are vast and complex. The United Nations Sustainable Development Goals (SDGs) aim to meet these challenges. A growing number of higher education institutions have integrated them within their curricula, but there are indications that health professional education has been lagging behind. Therefore, it is important to better understand the views of students in health professional education on the level and depth of their education on sustainable development.

Methods: This sequential exploratory mixed methods study was based on survey responses from N = 294 nursing (N = 137) and medical (N = 157) students of first and last semesters from three Swedish universities. From the full group of survey responders, 21 students participated in 5 focus group discussions (FGDs) and 9 individual interviews. The survey findings were summarized through descriptive statistics and the interviews and FGDs were analyzed by qualitative content analysis.

Results: The survey findings showed that most students (63%) perceived that they had not learned enough about the SDGs and Agenda 2030 during their education, or for the purposes of their future career. Most of the students (63%) also thought that Agenda 2030 and the SDGs should be a greater part of their education. The qualitative data gave a more in-depth understanding of the quantitative findings, forming two themes: The first theme revealed that the SDGs may be more relevant for health care practice than what the students initially thought, but that the education they had received was in most places superficial, or not tied to the SDGs. The second theme detailed what and how students wished to learn more about. Here, they called for a more in-depth understanding of how to promote equality, equity, inclusion and psychosocial aspects in health care. They also hoped for more knowledge about how to ensure a sustainable working life for themselves.

Conclusions: Nursing and medical students at three Swedish universities experience that they lack the knowledge necessary to face sustainability challenges they encounter in working life and give some suggestions about how this may be improved in future education.

Purpose: The objective of this study is to assess the psychometric properties and reliability of the Swedish Patient-Reported Outcomes Measurement Information System (PROMIS) item banks for anxiety and depressive symptoms with item response theory analysis and post-hoc computerized adaptive testing in a combined Swedish Child and Adolescent Psychiatry (CAP) and school sample.

Methods: Participants (n = 928, age 12–20) were recruited from junior and high schools and Child and Adolescent Psychiatry Clinics in the region of Västerbotten. Unidimensionality, local independence, and monotonicity was tested. We fitted a graded response model to the data and tested differential item functioning (DIF) for sex, age group, sample type, and language (Swedish vs. U.S.). Moreover, a post-hoc computer adaptive testing (CAT) simulation was performed. All analysis were made in R.

Results: Unidimensionality, local independence, and monotonicity were acceptable. The graded response model yielded acceptable item fit, discriminative, and threshold values for all items in both item banks. DIF for language (Swedish vs. U.S.) was found for two items from the anxiety and one item from the depressive symptoms item banks. A Stocking-lord transformation was used for the items displaying language DIF, and post-hoc CAT simulations were performed. The post-hoc CAT simulation showed reliability around 0.9 for both Swedish and official U.S. item parameters T-scores calibration from within normal limits to severe anxiety and depressive symptoms.

Conclusion: The Swedish pediatric PROMIS item banks of anxiety and depressive symptoms are appropriate to assess mild to severe symptoms of anxiety and depressive symptoms in Swedish school- and CAP samples.

Challenging experiences in ayahuasca use, childhood trauma, and posttraumatic growth have not been investigated systematically. This study aimed to explore whether a self-reported history of childhood trauma was associated with challenging experiences during acute ayahuasca effects and whether such challenging experiences were associated with beneficial long-term outcomes measured by posttraumatic growth. For this study, 231 individuals (mean age 40.29, 48% women) completed an online survey about traumatic experiences in childhood, challenges during acute ayahuasca effects, and perceived benefits of those challenges. This study found that people with histories of childhood trauma were not at greater risk of adverse or challenging experiences during acute ayahuasca effects than people without histories of childhood trauma (r = .080, p = .281, 95% CI [–.066, .223]). Additionally, there was no difference in posttraumatic growth among those who had history of childhood trauma versus those who did not (r = –.016, p = .837, 95% CI [–.166, .135]). People who have experienced more challenges during acute ayahuasca effects did not experience more ayahuasca-related posttraumatic growth (r = .137, p = .076, 95% CI [–.014, .281]). These findings are important, as they may indicate that childhood trauma exposure does not pose the same risk for a poor treatment response to ayahuasca, as it predicts in other forms of intervention.

Background: Depression is common and increasing in young people, who seem especially vulnerable, both in the probability of developing depression, and in the resulting negative consequences across the lifespan. Unfortunately, available treatments rarely lead to full remission and even in cases of remission relapse rates are high. Different explanatory models have been proposed, and research indicates a multifaceted etiology. The descriptive DSM-5 has low diagnostic validity in this age-group, especially for depressive disorders, and limited attention has been given to young people’s own experiences of becoming depressed. Hence, there is a risk of missing clinical information that is important for the therapeutic alliance and treatment.

Objective: This study aimed to explore young people’s experiences of becoming depressed.

Method: A qualitative study was performed. Six participants with clinical depression, currently in treatment at child and adolescent psychiatric outpatient clinics in northern Sweden were recruited. Interviews followed a semi-structured manual, and data was analyzed with inductive qualitative content analysis.

Results: Participants described different reasons for their depression, and from their stories four categories were identified: “Being subjected to violence”, “Suffering separation and loss”, “Feeling abandoned”, and “Feeling burdened and vulnerable”. These categories were interpreted in the theme: “Dealing with an overwhelming life situation”.

Conclusions: The participants presented mainly stressful external and relational events preceding their depression. A combination of overwhelming stressors, lack of support and lack of time for recovery was described. This points to the importance of validating the narratives of young patients with depression and to offer trauma-informed treatment approaches in mental health care.

Background: Insomnia is common in adolescents. This study evaluated feasibility and preliminary efficacy of a six-week internet-delivered cognitive-behavioral therapy for insomnia (ICBT-I) in adolescents.

Methods: In this uncontrolled pilot study, participants (n = 27, 78% female) completed assessments pre- and post intervention. Data on recruitment, adherence to treatment, treatment activity, satisfaction and credibility was collected to assess feasibility. Self-reported insomnia symptoms, sleep parameters as well as depression, anxiety and daytime function were also assessed.

Results: Participants showed good adherence to treatment and found the intervention overall credible and satisfactory. From pre- to post-assessment, statistically significant improvements were found for insomnia symptoms (p <.001; d = 1.02), sleep onset latency (p <.001; d =.39), wake after sleep onset (p =.001; d =.34), sleep efficiency (p <.001; d =.5) and depression (p =.01, d =.37). Changes in scores of total sleep time, generalized anxiety, daytime sleepiness and functional disability were not significant.

Conclusions: The present study indicates that ICBT-I is well accepted by adolescents, that insomnia symptoms and sleep parameters can improve following the intervention, and that co-morbid symptoms of depression can be reduced. Due to the limited sample size and the uncontrolled design, the suggested results need to be replicated in well-powered controlled clinical trials.

Introduction: This study evaluated changes in the white matter of the brain and psychological health variables, resulting from a neuroscience-based mindfulness intervention, the Training for Awareness, Resilience, and Action (TARA), in a population of healthy adolescents.

Methods: A total of 100 healthy adolescents (57 female, age ranges 14–18 years) were randomized into the 12-week TARA intervention or a waitlist-control group. All participants were imaged with diffusion MRI to quantify white matter connectivity between brain regions. Imaging occurred at baseline/randomization and after 12 weeks of baseline (pre- and post-intervention in the TARA group). We hypothesized that structural connectivity in the striatum and interoceptive networks would increase following the TARA intervention, and that, this increased connectivity would relate to psychological health metrics from the Strengths and Difficulties Questionnaire (SDQ) and the Insomnia Severity Index (ISI). The TARA intervention and all assessments, except for the MRIs, were fully remotely delivered using secure telehealth platforms and online electronic data capture systems.

Results: The TARA intervention showed high consistency, tolerability, safety, recruitment, fidelity, adherence, and retention. After 12 weeks, the TARA group, but not controls, also demonstrated significantly improved sleep quality (p = 0.02), and changes in the right putamen node strength were related to this improved sleep quality (r = −0.42, p = 0.006). Similarly, the TARA group, but not controls, had significantly increased right insula node strength related to improved emotional well-being (r = −0.31, p = 0.04). Finally, we used the network-based statistics to identify a white matter interoception network that strengthened following TARA (p = 0.009).

Discussion: These results suggest that the TARA mindfulness-based intervention in healthy adolescents is feasible and safe, and it may act to increase structural connectivity strength in interoceptive brain regions. Furthermore, these white matter changes are associated with improved adolescent sleep quality and emotional well-being. Our results suggest that TARA could be a promising fully remotely delivered intervention for improving psychological well-being in adolescents. As our findings suggest that TARA affects brain regions in healthy adolescents, which are also known to be altered during depression in adolescents, future studies will examine the effects of TARA on depressed adolescents.

Clinical trial registration: https://clinicaltrials.gov/study/NCT04254796.

Background: Depression in adolescence is a serious major global health problem with increasing rates of prevalence. Measures of depression that are valid for young people are clearly needed in clinical contexts.

Methods: The study included 577 patients from child and adolescent psychiatry (n = 471) and primary care (n = 106) aged 12–22 years in Sweden (Mage=16.7 years; 76% female). The reliability and validity for Montgomery–Åsberg Depression Rating Scale–Youth (MADRS-Y) were investigated. To confirm the latent structure, we used a single-factor confirmatory factor analysis (CFA). A Kruskal–Wallis test was performed to test total score differences between diagnostic groups. Using Spearman’s rho correlations, we examine whether single items in the MADRS-Y correlate with suicidal ideation measured by The Suicidal Ideation Questionnaire-JR (SIQ-JR).

Results: The internal consistency using McDonald’s coefficient omega was excellent. The CFA of the 12-item MADRS-Y supported a one factor structure. Evidence of convergent and discriminant validity was shown. There was a significant difference in MADRS-Y scores across diagnostic groups, with higher results for depressive disorders. A strong correlation with suicidal ideation was found for two items.

Conclusions: The results support MADRS-Y as a brief, reliable, and valid self-report questionnaire of depressive symptoms for young patients in a clinical setting.

Introduction: Depression constitutes one of our largest global health concerns and current treatment strategies lack convincing evidence of effectiveness in youth. We suggest that this is partly due to inherent limitations of the present diagnostic paradigm that may group fundamentally different conditions together without sufficient consideration of etiology, developmental aspects, or context. Alternatives that complement the diagnostic system are available yet understudied. The Power Threat and Meaning Framework (PTMF) is one option, developed for explanatory and practical purposes. While based on scientific evidence, empirical research on the framework itself is still lacking. This qualitative study was performed to explore the experiences of adolescents and young adults with depression from the perspective of the PTMF.

Methods: We conducted semi-structured interviews with 11 Swedish individuals aged 15– 22 years, mainly female, currently enrolled in a clinical trial for major depressive disorder. Interviews were transcribed verbatim and analyzed with framework analysis informed by the PTMF.

Results: A complex multitude of adversities preceding the onset of depression was described, with a rich variety of effects, interpretations, and reactions. In total, 17 themes were identified in the four dimensions of the PTMF, highlighting the explanatory power of the framework in this context. Not all participants were able to formulate coherent narratives.

Discussion: The PTMF provides a framework for understanding the complexities, common themes, and lived experiences of young individuals with depression. This may be essential for the development of new interventions with increased precision and effectiveness in the young.