Frontiers in Psychiatry
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Preprints posted in the last 30 days, ranked by how well they match Frontiers in Psychiatry's content profile, based on 87 papers previously published here. The average preprint has a 0.09% match score for this journal, so anything above that is already an above-average fit.
Harrison, H. V.; Gaillard, M.; Cook, R. R.; Sarparast, A.; Levander, X. A.
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Introduction: In 2020, Oregon became the first US state to legalize state-regulated psilocybin services. This study aims to examine: 1) the clinical and demographic characteristics, 2) psilocybin use motivations, and 3) differences in preparedness among patients seeking care in a Oregon- based pilot consult service specializing in psilocybin risk reduction. Methods: This retrospective chart review abstracted sociodemographics, trauma history, and medical and psychiatric risks of patients (November 2023 - September 2025). The Psychedelic Preparedness Scale (PPS), a validated self-report questionnaire, measured preparedness. Two sample t-tests examined associations of PPS scores by insurance, consult motivations, and prior psychedelic use. Results: Patients (N=29) had a mean age of 47.14 years (SD=15.9), were majority female (55.2%); White (82.8%); and privately insured (62.1%). Patients mostly sought psilocybin to address only a psychiatric concern (75.9%); 27.6% anticipated naturalistic (non-state regulated) use. Most patients were deemed low risk for adverse events. Prevalence of prior challenging psychedelic experiences (CPE) was 17.2%; 58.6% reported lifetime psilocybin use. 86.2% endorsed >1 form of lifetime trauma. Of PPS completers (N=23, 79%), mean score was 91.3 (SD = 23.99). Scores did not significantly differ by insurance; consultation motivation; CPE; prior psilocybin or psychedelic use. Conclusion: Patients utilizing a novel consultation service demonstrate a high prevalence of trauma, prior psilocybin use, and baseline preparedness. While preliminary, this is among the first descriptions of patients seeking medical and psychiatric consultation when considering psilocybin and highlight the potential role of healthcare systems in providing evidence-based patient education and risk reduction as interest in psychedelics grows.
Egami, H.; Rahman, S.; Egami, C.; Yamamoto, T.; Wakabayashi, T.; Horii, S.; Przybylski, A.
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IMPORTANCE With a growing global user base of 3.5 billion and users spending nearly as much time gaming as on social media, video gaming's effects on mental well-being have attracted scholarly and public interest. Despite the WHO's inclusion of gaming disorder in ICD-11 and government-mandated restrictions in multiple countries, the causal evidence supporting such policies remains limited. OBJECTIVE To investigate the causal effect of video gaming on mental well-being in the post-COVID period. DESIGN A natural experiment of game console lottery was used to identify the causal effect of video gaming on mental well-being. The intention-to-treat effect was estimated using multivariate regression and propensity score matching. Causal effects of game engagement were estimated using the instrumental variable method (two-stage least squares) and a causal machine learning algorithm, instrumental forest. SETTING Online surveys were conducted between September 2022 and March 2023, covering all 47 prefectures in Japan. PARTICIPANTS A total of 71,435 participants aged 10-69 answered the surveys. 6,911 individuals participated in the natural experiment. EXPOSURES Video game engagement, including video game console ownership, use of the console in the last 30 days, and video gaming duration. MAIN OUTCOMES AND MEASURES Psychological distress and life satisfaction. RESULTS The intention-to-treat effects of winning game console lotteries on mental well-being were positive (0.1 SD). Game console ownership improved mental well-being by 0.1-0.2 SD, and past-month play improved it by 0.2-0.3 SD. An extra hour of daily video game play led to 0.3-0.5 SD improvements in mental well-being. CONCLUSIONS AND RELEVANCE This study found that video gaming had a positive effect on mental well-being in the post-COVID period. The consistency of the effect size with that of a related COVID-period study adds robustness to our findings. Our findings add to the growing evidence that digital media screen time has diverse effects on well-being and support public health policies that recognize the potential mental well-being benefits of appropriate levels of video gaming.
Quigley, H.; Gardiner, B.; McDaid, L.; O'Donnell, C.
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Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition defined by differences in social communication and restricted, repetitive behaviours. As diagnostic criteria have broadened, ASD is now recognised across a wider range of individuals, raising key questions about its structure: does ASD have discrete sub-types, or is it better conceptualised as a continuous, possibly multidimensional, condition? We aim to explore whether a multidimensional continuum model more accurately captures the variability within ASD. We analysed a large SPARK phenotypic dataset of medical history and diagnostic surveys (background history, SCQ, RBS-R; n=36,710 individuals). We apply and compare two traditional statistical approaches, Factor Analysis and Gaussian Mixture Models, with a modern machine learning technique, the Variational Autoencoder (VAE). VAEs reconstructed unseen test data with ~4-fold better accuracy than Factor Analysis, and ~8-fold better accuracy than Gaussian Mixture Models. We identified four stable latent factors across 100 independently trained VAEs. These four dimensions provide an individual behavioural profile that can be visualized using radar-plots, offering a compact way to compare profiles at the person level. Through further analysis, we found evidence for 3 overlapping clusters or subtypes of ASD identified within the 4D latent space. This work aims to inform new ways of modelling ASD using a VAE that will be able to discern between a continuum or a clustered output and that go beyond binary diagnosis, instead reflecting the complex range of trait profiles, with implications for personalised diagnosis and intervention.
Packard, S. E.; Russo, T.; Parrott, J.; Sisti, J.; Lans, A.
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Objectives: To estimate the prevalence of Post-Exertional Malaise (PEM) among adults with prior COVID-19 and associated mental health and disability outcomes. Methods: We conducted a cross-sectional analysis of data from a survey of 9,620 adults with prior COVID-19 in New York City, collected May - June 2024. PEM was measured with the DePaul Symptom Questionnaire - Post Exertional Malaise, categorized by symptom duration (< 14 vs. [≥]14 hours). Weighted prevalence estimates were stratified by socio-demographic and clinical characteristics. Modified Poisson regression was used to assess the association of PEM with depression, anxiety, and disability. Results: The prevalence of PEM symptoms was 20.9% overall and 4.0% with symptom duration [≥]14 hours, representing over 800,000 New Yorkers affected and over 150,000 who meet a diagnostic criterion for ME/CFS. PEM prevalence was higher among women, transgender and non-binary adults, people of color, and lower educational attainment, chronic comorbidities, or disabilities. PEM was associated with 3 - 4 times higher prevalence of mental health outcomes and 4 - 5 times higher disability scores. Conclusions: PEM symptoms were common and strongly associated with disability and adverse mental health. Screening, pathways to care, and supportive policies are needed to mitigate long-term consequences, particularly among marginalized populations.
Heo, R.; McBride, L.; Parrish, E.; Fulginiti, A.; Taylor, C.; Depp, C.
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Background: Generative AI is evolving at a rapid pace, and many individuals are utilizing chatbots for mental health support. The safety of chatbots amid suicide disclosures is a major public health focus. However, the rate and correlates of intentions to seek help from chatbots for suicide thoughts is unknown. Objective: We sought to understand intentions to seek help from chatbots for suicide thoughts, compared to informal, formal, and anonymous online sources. Methods: Participants with clinically significant depression or anxiety (N=58) completed the General Help Seeking Questionnaire regarding help-seeking intentions for suicide thoughts and general emotional problems. Two questions were added to assess intentions to seek help from chatbots and anonymous online sources. Wilcoxon tests were used to compare intentions to use chatbots with intentions to use anonymous online sources and with groupings of informal (e.g., friends, family) and formal (e.g., therapist, general practitioner) sources. Kendall's correlations were used to examine correlations among groupings and individual informal and formal sources, and regression models further examined individual source associations adjusting for general help-seeking intentions. Exploratory analyses assessed whether demographic characteristics, mental health symptoms, and suicide risk were associated with help-seeking intentions for chatbots. Results: Participants endorsed lower help-seeking intentions for suicide thoughts from chatbots than from informal and formal sources. Intention to use chatbots for suicide thoughts was not correlated with informal and formal sources but was correlated with anonymous online sources. At the individual source level, chatbot intentions were positively associated with intimate partners but negatively associated with outreach to friends after adjustment for general help seeking tendency. Anxiety symptom severity was positively correlated with chatbot use intentions, but not with other sources of support. Conclusions: While preliminary, intentions to use chatbots for suicide thoughts appear mostly disconnected from intentions to seek help from other informal and formal supports. Future studies should evaluate the dynamics of help seeking for suicide thoughts via chatbots amidst and, perhaps in place of, other sources of support.
Thompson, S.; Effinger, D.; Novick, A.; Bates, S.; Conley, A.; Tobin-Cambell, C.; Epperson, N.; Skievaski, N.
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Oregon (OR) and Colorado (CO) were the first states to enact regulations for provision of psilocybin with support of licensed "facilitators." As more states and countries adopt similar policies, informed public policy decisions require that client characteristics and rationale for using psilocybin, psilocybin dosing practices, mental health outcomes, and adverse events are understood. We performed a retrospective observational study of responses for 2363 individuals receiving psilocybin at OR and CO regulated service centers. Clients and facilitators entered data before and after receiving psilocybin, including the Mystical Experience Questionnaire-30 (MEQ-30), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and World Health Organization Well-Being Index-5 (WHO-5). Preexisting mental health issues were common (66%) in participants. Psilocybin doses ranged from 1-95 mg, with a mean total of 28*8 mg. We observed improvements of 49% in PHQ-9 scores, 51% in GAD-7 scores, and 22% in WHO-5 scores at two-weeks after dosing. MEQ-30 scores were dose-dependent. Changes in PHQ-9 and GAD-7 scores were not different for psilocybin doses [≤]30 mg and >30 mg, and only weakly correlated with MEQ-30 scores. There were 94 mild adverse events during and after dosing, five more serious events not clearly related to treatment, and evidence of possible risk of increased suicidality. Study limitations include open label administration, self-reporting, loss of participants for follow-up, and a short 2-week post-dosing end-point. We conclude that psilocybin services, delivered within these regulated frameworks, is associated with improvements in mental health in real world populations, however, more robust monitoring is needed to ensure safety.
Amancio, R. T.; Cruz, L. N.; Dantas, R. d. S.; Gomes, M. P.; Silva, A. d. A. B. d.; Brasil, P. E.
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Background: Health and administrative professionals in tertiary hospitals face high levels of occupational stress, mental illness, and multimorbidity. The integrated measurement of these multidimensional health aspects is essential for informing effective workplace health promotion strategies. Objective: To describe the general health status of federal public hospital staff and correlate the measured health dimensions to inform institutional health promotion initiatives. Methods: A cross-sectional, online survey study was conducted at Hospital Universitario dos Servidores do Estado (HUSE) between November and December 2025. Data collection was performed via online REDCap questionnaires covering sociodemographic profiles and validated instruments (SRQ-20, MIDAS, AUDIT, WHOQOL-BREF, PHI, WHOQOL-SRPB BREF, CBI, GPAQ, and EPSO). Descriptive statistics, comparisons across employment ties (permanent vs. contracted staff), and Spearman correlation matrices were calculated. Results: Among 197 accesses, 117 completed the informed consent, and 86 finished all questionnaires. Participants were predominantly female, aged 40 to 60 years, and Christian. Screening positivity was 25% for common mental disorders, 21% for headache-related disability, and 10% for harmful drinking. Burnout scores clustered in the second quartile, while quality of life, happiness, and spirituality scores were in the upper third. Median physical activity was 670 min/week. Mental symptoms (SRQ-20), headache (MIDAS), and burnout (CBI) correlated positively with each other and negatively with quality of life, happiness, spirituality, and institutional support (EPSO). Conclusion: The set of instruments proved feasible for situational health diagnosis among hospital staff. Although the sample size was limited in this baseline wave, the initiative fostered workplace health awareness, driving concrete initiatives, including an on-site functional gym and workplace vaccination campaigns.
Ruiz-Grosso, P.; Macedo-Orrego, L.; Rodriguez-Vargas, D.; Rivera-Encinas, M.; Arosemena, A.; Carazas-Vera, M.; Sagastegui, A.; Zevallos-Bustamante, S.
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Objective. To estimate lifetime and 12 month mental health contact gaps among Peruvian adults with survey-defined mental disorders, and to describe inequalities in contact, perceived need for care, and mental health service use. Methods. We analyzed the information for adults of the 2022 Peruvian National Mental Health Survey, a cross-sectional household survey. The primary outcome was the survey-weighted proportion of adults with a 12 month mental disorder who reported no contact with an included source of mental health-related care during that period; the lifetime contact gap was descriptive. Perceived need was assessed using two derived 12 month perceived-need measures based on direct ENSM variables and service contact routing items. Analyses incorporated weights, strata, and clusters. Adjusted prevalence ratios were estimated using survey weighted Poisson models. Results. The dataset contained information on 13,840 individuals; 13,833 had complete survey-design information. Contact gap denominators were 3,927 for lifetime disorders and 1,649 for 12-month disorders. The lifetime and 12-month contact gaps were 61.0% (95% CI 58.4-63.7) and 84.5% (95% CI 81.5-87.6), respectively. Rural estimates exceeded urban estimates in both periods; after adjustment, poverty and rural residence were associated with the lifetime gap, and extreme poverty with the 12-month gap. Among individuals meeting survey-based criteria for one or more 12-month mental disorders, 37.3% (95% CI 33.4-41.4) reported self-perceived need, whereas 25.6% (95% CI 21.8-29.8) reported that need had been identified by others. Annual psychological and psychiatric service use was 3.7% and 1.1%, respectively. Conclusions. Mental health contact gaps were high, particularly for one or more 12-month mental disorders, and were associated with social and territorial variables. These contact measures do not establish adequate, continuous, or effective treatment, which needs to be addressed to understand the impact of the Peruvian mental health reform.
Streyma, D. H. B.; Gregersen, M.; Weye, N.; Hjorthoej, C.; Krantz, M. F.; Soendergaard, A.; Schiavon, M.; Rohd, S. B.; Wilms, M.; Ellergsaard, D.; Christiensen, S. B.; Enevoldsen, M.; Birk, M.; Nielsen, C. S.; Bundgaard, A. F.; Laursen, A. F.; Veddum, L.; Mors, O.; Greve, A. N.; Hemager, N.; Nordentoft, M.; Thorup, A. A. E.
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Background Children of parents with schizophrenia (SZ) or bipolar disorder (BP) show elevated rates of mental disorders. Longitudinal studies comparing offspring at familial risk with the background population are lacking. Method This study is an eight-year follow-up of the Danish High Risk and Resilience study. We examined four-year prevalence from age 11 to age15 (n=416), cumulative incidence by age 15 (n=516), persistency of mental disorders from age 11to age 15 (n=396) and global functioning in 15-year-old adolescents with familial high risk of SZ (FHR-SZ) or BP (FHR-BP) compared to population-based controls (PBC). We assessed mental disorders and global functioning with the Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version (K-SADS-PL) and the Childrens Global Assessment Scale (CGAS). Results Four-year prevalence of any mental disorder was higher in FHR-SZ (51.3%, OR=2.39, 95% CI 1.49-3.83) and FHR-BP (45.9%, OR=1.98, 95% CI 1.16-3.37) compared with PBC (30.5%). Cumulative incidence of mental disorders by age 15 was higher in FHR-SZ (67.2%, OR=3.19, 95% CI 2.11-4.82) and FHR-BP (64.4%, OR=2.82, 95% CI 1.75-4.54) than in PBC (39.1%). Adolescents with FHR-SZ showed the highest rate of persistent mental disorders (33.3%), followed by FHR-BP (24.5%), and PBC the lowest (12.9%). Global functioning at age 15 was lower in FHR-SZ than in both FHR-BP and PBC, and FHR-BP showed lower scores compared with PBC. Between-group differences in cumulative incidences of mental disorders and in global functioning scores remained stable across ages 7,11 and 15. Conclusion Adolescents at FHR-SZ or FHR-BP show elevated risks of a range of mental disorders, psychiatric comorbidity, and lower global functioning from childhood to mid-adolescence, not confined to the disorders for which they carry familial risk. This vulnerability underscores the need for early detection and support for FHR offspring and their families.
Diep, C.; Rosenbloom, B.; Goel, A.; Bosma, R.; Wijeysundera, D.; Clarke, H.; Ladha, K.
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Introduction: Self-rated health is an important patient-centred measure of health. The relationship between cannabis use and self-rated health has been previously studied, although with methodologic concerns which we aimed to address in this investigation. Methods: Propensity score weighted analyses of the National Health and Nutrition Examination Survey (NHANES) 2009-2018 were conducted. The primary exposure was self-reported cannabis use in the 30 days prior to survey response. The primary outcome was self-rated health measured on a five-level ordinal scale. Secondary outcomes included the number of days in the past months with: i) poor physical health, ii) poor mental health, and iii) activity limitations related to poor health. A weighted proportional odds regression model was used for the primary analysis and weighted zero-inflated negative binomial regression models were used for each secondary analysis. Results: Among 22,055 adults aged 20-59 responding to the NHANES cannabis questionnaire, 14.4% endorsed use in the past 30 days. After reweighting the sample to balance cannabis users and non-users across sociodemographic, medical, and lifestyle characteristics, there was no statistically significant association between recent cannabis use and higher levels of self-rated health (OR 0.90, 95% CI 0.80-1.01). Cannabis use was associated with poor mental health and activity limitations in the past month, but not poor physical health. Conclusions: Recent cannabis use was not associated with self-rated health but was associated with poor mental health and activity limitations in the past month. Cannabis users at risk of poor mental health should be connected with clinicians to help guide therapy.
Saarinen, A.; Asikainen, T.; Lehtimäki, T.; Raitakari, O.; Keltikangas-Järvinen, L.
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Background: Previous trauma research includes many limitations, such as the scarcity of pretraumatic health measurements and assessment of traumatic experiences with a broad scope across the lifespan. To respond to these gaps, we aimed to develop a new, prospective, population-based trauma dataset from childhood to middle age. Methods: We used the Young Finns Study that is a population-based, multi-generational, prospective study (n = 3596 for the main generation). It has started in 1980 (baseline assessment) and includes follow-ups in 1983, 1986, 1989, 1992, 1997, 2001, 2007, 2011/2012, and 2018-2020. From the 38-year follow-up and ten measurement points of the YFS, we collected all relevant trauma variables, including both free-format and structured questions that both the participants and their parents responded to. By a data-driven case-to-case analysis, we developed a scale to numerically capture variation in the quality of the experiences. Results: Our final dataset captured a total of 7769 traumatic experiences. We also developed the Traumatic Experience Severity Scale (TESS), including six subscales such as shamefulness, rarity, danger to life or health, effects on everyday life, human-made physical threat, and whether the target person was within or outside one's household. We also preprocessed the dataset to be later easily interleaved with other psychological, cardiovascular, and epigenetic variables of the YFS. Conclusions: We believe this new trauma dataset with thousands of experiences across the lifespan provides new opportunities to multidisciplinary, lifelong trauma research.
Zhang, Y.; Zhuang, X.; Niu, M.; Chen, T.; Luo, Y.; Luo, Y.; Almulla, A. F.; Carvalho, A. F.; Maes, M.; Li, J.
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Background: Major depressive disorder (MDD) is a severe mental illness associated with severe clinical consequences and substantial societal burden. It's characterized by immune-inflammatory dysregulation and immune sensitization. Objective: To determine whether in vitro ketamine attenuates phytohemagglutinin (PHA)/lipopolysaccharide (LPS)-induced immune sensitization in patients with MDD and healthy controls (HCs). Methods: Whole blood from 18 patients with MDD and 18 HCs was stimulated with PHA/LPS and exposed to ketamine (0.3 M, 0.6 M, and 6 M) for 72 hours. Cytokines, chemokines, growth factors, and composite immune profiles, including M1/M2 macrophages, T helper (Th)1/2/17, the immune-inflammatory response system (IRS), and compensatory immunoregulatory system (CIRS), were synthesized and determined. Results: Under PHA and LPS stimulation in vitro, the MDD group exhibited markedly elevated immune profiles, including M1, M2, Th1, Th2, Th17, IRS, CIRS, chemokines, and growth factors, consistent with immune sensitization. Significant group-by-treatment interactions were observed for Th1-Th2, M2, growth factors, IL-12(p70), M1, and chemokines. Ketamine produced minimal changes in HCs but broader suppression in MDD, particularly at the highest concentration, without normalizing the sensitized immune phenotype. Among the immune markers with no notable group-by-treatment interactions, ketamine exerted diagnosis-independent effects, decreasing MIP-1{beta}, IL-1&{beta}, Th1, TNF-{beta} IRS, IFN-{gamma}, and IL-2 compared to the control condition. Conclusions: Ketamine exhibited two distinct immunoregulatory patterns: selective, disease-dependent attenuation of sensitized immune pathways and broader, diagnosis-independent suppression of the stimulated immune response, predominantly at higher concentrations. However, these effects were insufficient to normalize the immune-sensitized phenotype of MDD.
Page, S.; Easey, K.; Sedgewick, F.; Rai, D.; Stergiakouli, E.
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Autistic individuals may be at an increased risk of hazardous drinking compared to non-autistic counterparts: potential motivations include facilitated social interactions and self-medication of co-occurring difficulties, and possible risk factors include being older and female. However, research remains limited and centred around clinical samples. Given the diversity of the autistic community, it is important to understand the intricacies of alcohol use to inform appropriate support. Eighteen autistic adults took part in semi-structured interviews about their drinking experiences. Data were analysed using reflexive thematic analysis. Three main themes were created (Autistic experiences, Managing expectations and coping by drinking and Recommendations for support). Autistic experiences was used to denote the ways in which participants described their own autistic features influenced their relationship with alcohol. Managing expectations and coping by drinking was chosen to reflect the pressures felt by participants to show up in social relationships and the co-occurring difficulties many of them managed using alcohol. Therapeutic preferences for alcohol services were captured under Recommendations for support. As expected, participants used alcohol to facilitate social interactions and self-medicate. However, additional nuances uncovered may provide clinical utility and highlight the need for further research in other demographics within the community.
Campion, J.-Y.; Desmidt, T.; Gross, J. J.; Tudorascu, D. L.; Andreescu, C.; Karim, H. T.
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Severe worry is a transdiagnostic syndrome associated with significant morbidity in older adults. In this study, we aim to infer worry-related mental states though brain activity timeseries. We acquired fMRI on two cohorts (N=116 and N=88), using an in-scanner worry induction and reappraisal task. We trained a recurrent long short-term memory (LSTM) neural network, using the first cohort as the train/validation and the second cohort as an independent test set. We predicted worry induction, reappraisal, and neutral states (area under the curve 0.89, 0.77, 0.91 for the test set and 0.78, 0.63, 0.81 for the independent set). The model was most accurate when participants reported high worry during the induction state. Dorsal attention network, and networks seeded on the anterior hippocampus, and supplementary motor area were most important for predicting worry states. The LSTM approach may have critical translational implications for identifying and treating severe worry in older adults.
O'Shea, A.; Mason, N. L.; Schreiber, R.; Verheijen, M.; Ramaekers, J.; Briede, J.; Krauskopf, J.
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BackgroundPsilocybin, a classic psychedelic, produces acute alterations in brain function, and has shown sustained therapeutic effects in psychiatric disorders. However, most studies focus on acute brain imaging readouts (e.g., fMRI) and rarely assess longer-term molecular changes. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression, are enriched in the brain, and can be released into blood, potentially indexing brain-relevant molecular processes. We hypothesised that a single psilocybin dose would show acute changes in miRNAs with predicted relevance to neuroplasticity related signalling and immune/inflammatory regulation in healthy adults. MethodsIn a randomised, double-blind, placebo-controlled study (N=62; 31 psilocybin, 31 placebo), volunteers received psilocybin (0.17 mg/kg) or placebo. Blood was collected at baseline, 360 minutes, and 7 days after dosing. Plasma miRNAs were quantified by small RNA sequencing. Elastic net regression was used for feature selection, followed by differential expression analysis and validation with linear mixed models. Pathway enrichment used Reactome and Gene Ontology. ResultsTwo circulating miRNAs (let-7g-5p and miR-150-5p) met criteria for differentially expressed at 360 minutes following psilocybin administration, with no significant differences detected at 7 days or in the placebo condition under the statistical thresholds used. Over representation analysis suggested enrichment of molecular processes involved in neuroplasticity (e.g., TrkA, MAPK), inflammation (e.g., IL-6, TGF-{beta}), and transcriptional regulation (e.g., RNA polymerase II, SMAD2/3/4). ConclusionsA single oral dose of psilocybin was associated with transient alterations in circulating miRNA expression, consistent with an acute shift in circulating gene-regulatory miRNA signals, without sustained miRNA changes at 7 days. These findings provide initial evidence that circulating miRNA changes after psilocybin may reflect acute molecular process responses and support further investigation of circulating miRNAs as potential biomarkers of psychedelic-induced molecular responses.
Admon, R.; Netzer, O.; Magal, N.; Simon, L.; Harduf, A.; Oren, M.; Radai, O.; Keren Cohen, S.; Bobek, M.; Grankin, M.; Menshes, R.; Stern, Y.; Mandelblit, N.; Shmueli, A.; Eldar, E.; Sand, D.; Polinsky, T.; Gross, R.; Salomon, R.
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Background: The October 7, 2023 attack in southern Israel was one of the deadliest terror attacks in modern history, with 1,182 fatalities, more than 4,000 wounded individuals, and 251 hostages. The Nova music festival, an all-night outdoor rave near the Gaza border, suffered the highest number of civilian casualties, with more than 370 festival attendees killed. Survivors were exposed to prolonged life-threatening trauma with similar characteristics and within a narrow time window. Many survivors also reported being under the acute influence of psychoactive substances during the attack and the following hours. This tragic combination of civilian mass trauma and naturalistic pharmacological exposure created a rare opportunity to study trauma processing prospectively. Objective: This paper describes the rationale, design, and methodology of the Nova Protocol, a multimodal longitudinal observational study of survivors of the October 7, 2023 Nova festival attack and a sociocultural comparison group. Methods: The protocol spans from the first weeks to approximately 24 months post-trauma and includes three major assessment time points. It integrates repeated online clinical assessments, prolonged wearable-sensor monitoring, ecological assessments, saliva-based endocrine and inflammatory markers, structural and functional MRI, cardiac interoception paradigms, online and in-scanner reinforcement-learning tasks, and semi-structured qualitative interviews. Primary outcomes are PTSD symptom severity (PCL-5) and general psychological distress (K6), supplemented by a rich battery of secondary measures. Conclusion: The Nova Protocol provides an unusually rich longitudinal framework for characterizing psychological, behavioral, physiological, inflammatory, neural, interoceptive, and subjective mechanisms that shape clinical trajectories after civilian mass trauma. Because psychoactive substance exposure was naturalistic and self-selected, findings will be interpreted as mechanistic and prognostic associations rather than causal effects. The protocol is expected to inform early risk detection and scalable post-disaster monitoring and intervention strategies, as well as unique insights into how psychoactive substances impact trauma processing.
West, C. L.; Baker, B.; Duran, A.; Nadeem, S.; Calhoun, V.; Hamm, J. P.
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Background. Serotonergic psychedelics show promise for treating psychiatric disorders, with symptom improvements lasting for weeks after a single dose. Clarifying the neural basis of these effects would benefit from an identification of empirical biomarkers of such lasting shifts in brain function. Resting state EEG offers a rapid (<5 minute), low-cost window into functional brain networks. However, connectivity is not static, but cycles between recurring semi-stable patterns that vary across frequency bands. Here we employed a dynamic function connectivity (dFC) framework to identify frequency-specific connectivity states and examine how they change in the weeks following psychedelic use. Methods. We collected resting-state EEG from individuals who had used one of two serotonergic psychedelic subclasses within the prior three weeks, psilocybin/LSD (typical; n=14) or 5-MeO-DMT (atypical; n=12), and age- and sex-matched controls (n=16). Frequency-band-specific spatial connectivity states (phase-lag index) were estimated across the full sample (5 per band). Groups were compared on proportion and dwell-time (per state) and state-to-state transitions. Results. A right frontoparietally-distributed beta synchrony state was dominant after both typical and atypical psychedelics use (proportion/dwell-time). This effect correlated with the number of days since using psychedelics. A globally-distributed theta-band state was prominent in recent users of typical psychedelics but occurred less often in atypical users. In contrast, neural entropy (Lempel-Ziv complexity; known to increase acutely during psychedelic dosing) was not altered in recent users of either subclass. Conclusion. These results reveal a beta-band signature of altered neural dynamics in the week following a psychedelic dose, consistent with a relaxation of brain network hierarchy after psychedelics.
Hansen, S.; Mollersen, S.; Spein, A. R.; Javo, A. C.
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Problematic Internet Use (PIU)--marked by compulsive or maladaptive online behavior--is an emerging public health issue among adolescents and is associated with psychological distress, social difficulties, and academic problems. In Finnmark County, Norways northernmost and ethnically diverse region, limited research has examined the underlying mechanisms of PIU among Sami and non-Sami youth, despite increasing levels of digital engagement. This study protocol outlines a population-based cross-sectional survey investigating the associations between social norms (descriptive and injunctive), ethnic identity, and ethnicity-based discrimination in relation to PIU among Sami and non-Sami adolescents in Finnmark. Guided by Social Norm Theory and Ethnic Identity Theory, the study aims to examine risk and resilience factors associated with adolescents digital behavior in a geographically sparsely populated, multiethnic region. A population-based, cross-sectional school survey will include all upper secondary school students in Finnmark County (N {approx} 2,230). A culturally adapted, bilingual questionnaire (Northern Sami - Norwegian) will measure problematic internet use, perceived social norms in family, peer, and school contexts, ethnic identity, ethnicity-based discrimination, positive internet use, and key covariates. Ethnicity will be classified based on indicators of Sami language use and self-identification. Data will be prepared using prespecified quality procedures and analyzed with partial least squares structural equation modeling (PLS-SEM) to examine associations between social norms, ethnic identity, ethnicity-based discrimination, and internet use outcomes, including mediation and moderation. Group differences between Sami and non-Sami adolescents will be assessed using PLS Multi-Group Analysis. The findings may inform the development of culturally appropriate approaches to screening, prevention, and early intervention, and are relevant for mental health services, school-based programs, and public health strategies targeting Indigenous youth in rural and semi-rural regions.
Ritter, M.; Bogadhi, A. R.
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"Revealing the structure of pharmacobehavioral space through motion sequencing" by Wiltschko et al. (2020) has been highly influential in behavioral phenotyping research. In a cohort of nearly 700 mice, the authors demonstrated that Motion Sequencing (MoSeq) could distinguish behavioral effects across a large and diverse set of neuroactive and psychoactive compounds. A central conclusion of the study is that MoSeq syllable features substantially outperform more traditional scalar behavioral features in treatment classification tasks. Although this comparison is not emphasized outside the Results section, the reported advantage corresponds to an increase in classification performance exceeding 50% relative to scalar feature representations. While reproducing parts of the analysis using the publicly available dataset, we found that much of this apparent performance difference can be attributed to differences in preprocessing, classifier selection, and hyperparameter optimization. Under alternative, but comparably standard, analytical choices, the performance gap between scalar features and MoSeq syllables was reduced to approximately 11%. Furthermore, in our reanalysis, the performance advantage of MoSeq syllables became statistically significant primarily in highly dense pharmacobehavioral spaces. These findings do not contradict the utility of MoSeq syllables. Rather, they suggest that the magnitude and generality of their advantage over simpler scalar features may depend strongly on analytical methodology and dataset structure. This distinction is practically relevant, as scalar feature approaches are substantially less computationally demanding and often easier to interpret biologically. Consequently, for laboratories with limited computational resources or for studies focused on specific treatment effects, conventional scalar representations may provide a competitive and more accessible alternative. Our findings highlight the importance of analytical standardization and reproducibility in comparative behavioral representation studies.
Nicolaidis, C.; Yang, L.-Q.; Uretsky, M.; Raymaker, D. M.; Baker-Ericzen, M.; Grillo, V.; Kapp, S. K.; Kripke-Ludwig, R.; Maslak, J.; Moura, I.; Scharer, M.; Wallington, A. F.
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Background: Autistic Chronic Energy Depletion Syndrome, commonly referred to as Autistic Burnout, is a debilitating condition characterized by exhaustion, loss of function, and reduced tolerance to stimuli. While several instruments attempt to measure it, validation studies have only used cross-sectional designs and/or convenience samples with low support needs, limiting understanding of their performance across heterogeneous, autistic populations and over time. Methods: Using a community-based participatory research (CBPR) approach, we revised the 27-item AASPIRE Autistic Burnout Measure (AABM) into a 14-item AASPIRE Autistic Burnout Measure-Revised (AABM-R) and tested it in a longitudinal study of 835 autistic adults recruited from healthcare systems, disability services, and the community. Participants completed surveys directly (with or without support) or via a caregiver. We assessed structural validity and measurement invariance using exploratory and confirmatory factor analysis, tested construct validity through a priori hypothesis testing, examined discriminant validity from depression using longitudinal factor analysis and cross-lagged panel models, and assessed criterion validity using ROC analysis. Results: The AABM-R demonstrated a clear single-factor structure among direct reporters, with and without support, and measurement invariance across these groups; findings were less conclusive for the smaller caregiver-report subsample. Autistic burnout correlated as hypothesized with stressors (e.g., discrimination, masking, adverse childhood experiences), supports (e.g., social support, receiving needed help with daily living activities), and broader outcomes (e.g., quality of life, depression, anxiety). Longitudinal modeling supported autistic burnout as empirically distinct from, though related to, depression. ROC analysis (AUC = 0.89) supported cut-offs distinguishing probable (33-56, LR 7.38), unsure, and unlikely (0-22, LR 0.15) burnout. Conclusions: The AABM-R is a brief, accessible, psychometrically sound measure of autistic burnout suitable for heterogeneous autistic populations, with preliminary clinical cut-offs to guide screening. Further research is needed on the caregiver-report version and on longitudinal predictors and outcomes of burnout.