Journal of Psychiatric Research

Introduction: Pesticide exposure has been associated with poorer mental health, yet little is known about whether seasonal fluctuations in agricultural pesticide use are associated with cyclical changes in mood among people living in agricultural communities. We evaluated associations between 10 peak and off-peak pesticide spray seasons and ecological momentary assessment (EMA)-derived mood in a floricultural region in Ecuador. Methods: 496 participants completed repeated EMA surveys across 10 assessment administrations over 2.5 years (2022-2024), including one single-assessment administration and nine 10-day bursts (Nobservations=14,332). Mood outcomes included negative affect (sadness, anxiety, stress, anger, tiredness, difficulty concentrating; overall mean=2.79, Standard Deviation [SD]=1.32), positive affect (happiness, motivation; overall mean=4.21, SD=1.60), and behavioral dysregulation (aggression and impulsivity, overall mean=1.86, SD=1.29). Generalized linear mixed models estimated pooled, between-person and within-person associations between peak pesticide spray seasons and mood, adjusting for demographic and longitudinal factors Effect modification by sex, floricultural occupation, and cohabitation with a floricultural worker was assessed. Results: Peak spray seasons were associated with higher negative affect ({beta}=0.11 [0.06, 0.16]) and behavioral dysregulation ({beta}=0.10 [0.05, 0.15]) but not positive affect ({beta}=0.01 [-0.05, 0.07]). Associations were driven by within-person changes. Sex modified associations with negative affect, which were stronger in males than females. Floricultural occupation modified associations, with poorer mood, greater behavioral dysregulation and lower positive affect among floricultural workers than non-workers. Discussion: Peak pesticide spray seasons were associated with worsening of negative affect and behavioral dysregulation. EMA may provide a sensitive approach for detecting short-term neurobehavioral changes associated with seasonal pesticide exposure.

Brief assessments reduce clinician and patient burden and increase utilization. Recently, five core depression symptoms (low mood, poor concentration, low self-worth, loss of interest, low energy) have been shown to be particularly sensitive to treatment effects in adults. How these core depressive symptom domains perform for screening or diagnostic purposes in youth is unknown. To address this question, we extracted five analogous symptom items from four widely used symptom assessment tools for children and adolescents (Child Behavior Checklist [CBCL], Youth Self Report [YSR], Parent General Behavior Inventory [P-GBI], and Adolescent General Behavior Inventory [A-GBI]) to create 5-item short forms. We evaluated their psychometric properties and diagnostic utility in a large (N=1185), racially diverse sample (48% Black youth) across community and academic outpatient mental health settings, with diagnoses established through LEAD consensus. All short forms correlated highly with full-length measures (r=.74-.92) and demonstrated comparable inter-item correlations (r =.19-.46). The short forms did not differ meaningfully from the full measures in correlations with psychiatric diagnoses, demographics, or diagnostic interviews. Area under the curve (AUC) values for identifying depression and any mood disorder diagnosis (determined by semi-structured diagnostic interviews) were fair to good (AUC=0.60-0.79), which were not worse than full measures, except for the P-GBI. The CBCL-5, YSR-5, P-GBI-5, and A-GBI-5 may be useful brief depression assessments in youth. How these five symptom domains perform as outcome measures in treatment deserves study.

Objective: Brief measures of depressive symptoms and family psychiatry history may support the identification of youth who warrant further assessment, but their interpretation requires population-based measurement evidence. This study evaluated the Very Quick Inventory of Depressive Symptomatology (VQIDS) and Family Index of Risk for Mood (FIRM) in the BENCHMARK 2025 national survey. Method: The sample consisted of 2,252 parent reports for children aged 6-18 years and 1,008 linked adolescent self-reports aged 12-18 years. Analyses examined VQIDS dimensionality, reliability, item functioning, age- and sex-based norms, and informant agreement, alongside FIRM score distributions, alternative scoring approaches, and associations with depressive symptoms. Results: VQIDS findings supported a single dimension and good internal consistency, with greatest IRT precision at elevated symptom levels and no practically meaningful differential item functioning across age or sex. Two-week stability was moderate, and parent-adolescent agreement was lower within more symptomatic subsets. FIRM totals showed stronger cross-informant agreement and retest stability. Family history scores were associated with higher VQIDS percentiles and discriminated scores at or above the 90th percentile across informants (AUROC = .670-.698). FIRMs associations were strongest with internalizing symptoms, although evidence was mixed for mood specificity. Conclusions: These findings provide a measurement and normative foundation for brief depressive symptom assessment and support family history as a complementary correlate of symptom elevation. Diagnostic and prospective prediction utility require further evaluation.

Objective: To identify speech features distinguishing adults with depression from healthy controls, evaluate whether these features track with depression severity during naturalistic treatment, and assess whether baseline speech features predict treatment response. Design: Cross-sectional group comparison (Objective A) followed by longitudinal evaluation in an independent sample (Objectives B and C). Candidate features surviving false discovery rate (FDR) correction in the cross-sectional analysis were carried forward to longitudinal and predictive analyses. Setting: A community mental health center in New York. Participants: Dataset I (cross-sectional): 82 adults with chart-diagnosed depressive disorders and 80 healthy controls (N=162), recruited via convenience sampling. Dataset II (longitudinal): 85 adults with depressive disorders followed for up to four timepoints over a mean of 10.4 weeks during naturalistic treatment; 63 with baseline PHQ-9 >=10 and at least one follow-up were included in prediction analyses. Recruitment occurred under protocols approved between 2020 and 2021. Interventions: None; participants received naturalistic clinical care. Outcome Measures: Cross-sectional: diagnostic group membership (depressive disorder vs. healthy control). Longitudinal: Patient Health Questionnaire-9 (PHQ-9) total score. Predictive: treatment response, defined as >=50% PHQ-9 reduction from baseline to last follow-up. Results: Across three speech tasks (journaling, picture description, phonemic fluency), 11 voice quality features, six shimmer variants and five harmonics-to-noise ratio (HNR) variants, survived FDR correction (all q<.05) in all tasks, with higher shimmer and lower HNR in the depressed group (largest adjusted effect beta=1.89, q<.001). In longitudinal analysis, one phonemic fluency voice quality feature was associated with PHQ-9 at FDR<.05 (maximum HNR beta=-1.43, SE=0.41, FDR=.006), with the remaining ten consistent in direction at FDR<.10; no speech x time interactions were significant. Sex moderated voice quality-depression associations in picture description and phonemic fluency. For treatment response prediction, phonemic fluency voice quality features achieved cross-validated AUC=0.727 [95% CI: 0.662, 0.792], comparable to clinical features alone (AUC=0.700-0.715); the combined model across all tasks and clinical features achieved AUC=0.730 [0.639, 0.820]. No pairwise AUC comparisons between predictor configurations reached significance after correction (all corrected p>.54). Conclusions: Voice quality features, particularly shimmer and HNR, were the most consistent speech correlates of depression across cross-sectional, longitudinal, and predictive analyses and across multiple speech tasks. These features are computationally simple to extract from brief recordings and showed preliminary predictive utility comparable to standard clinical variables. However, the modest sample sizes, chart-based diagnoses and heterogeneous treatment exposures preclude clinical application at this stage. Larger, prospectively designed studies with standardized recording protocols, structured diagnostic assessment, and recruitment at treatment initiation are needed before voice quality features can be recommended as clinical biomarkers.

Background: Major depressive disorder (MDD) is a heterogeneous condition characterized by neuro-immune-metabolic-oxidative stress (NIMETOX) pathways. A systems-biology approach may help elucidate how these interconnected NIMETOX disturbances relate to early-life adversity and multidimensional clinical phenomes in adolescent MDD. Objectives: This study aimed to define the peripheral metabolic, vascular, and acute-phase, oxidative, and lipid biomarker profiles of adolescent MDD and to investigate associations with ACEs and clinical phenotypes. Methods: This cross-sectional study recruited 80 adolescents with MDD and 53 matched healthy controls and assessed C-peptide and insulin, vascular tone markers, the acute-phase inflammatory axis, oxidative stress, and lipid profiles. Results: MDD adolescents exhibited significant reductions in C-peptide, NO, ApoE, ApoA1, HDL-C, albumin, and transferrin, together with increased ApoB/ApoA1 ratio. These biomarkers correlated significantly with family dysfunction, childhood trauma, bullying exposure, and maladaptive parenting. These biomarkers and stressors accounted for 46.2% to 61.2% of the variance in psychological resilience, and major affective, physiosomatic, self-injurious, suicidal, and self-regulation phenomes. ACEs and bullying exposure, together with relevant socio-demographic data, explained 10.5% to 28.4% of the variance in selected metabolic, vascular, and acute-phase biomarkers. Multivariable classification models showed adequate discrimination between MDD and healthy controls, achieving up to 88.5% classification accuracy and an AUC of 0.948. Conclusion: Adolescent MDD is characterized by coordinated reductions in negative acute-phase proteins, metabolic and lipoprotein protective factors, and endothelial NO, without overt CRP-defined inflammation or conventional dyslipidemia. These findings support a systems-biology model of impaired peripheral homeostatic protection associated with developmental adversity and multidimensional depressive phenomes.

Negative emotional bias, including reduced processing of positive information and negative interpretation of ambiguous stimuli, is a core feature of depression. Esketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist with rapid antidepressant effects in treatment-resistant depression (TRD), reduces depressive symptoms, but its effects on distinct components of emotional processing remain unclear. Fifty-three patients with TRD and 53 healthy controls performed an Emotional Facial Expression Morphing task. Patients were assessed at baseline, 24 hours after the first esketamine administration, and after 4 weeks of treatment. Statistical models examined detection thresholds for happy and sad faces, negative categorisation of neutral faces, and signal detection indices separating emotion-neutral discrimination sensitivity (d') from response criterion (c), indexing the evidence required to report the presence of an emotion. At baseline, patients required greater happy-face intensity for emotion detection and were more likely to categorise detected neutral faces as negative. They also showed a more conservative response criterion without group difference in discrimination sensitivity. Responders showed an early increase in d'; and, by week 4, less negative categorisation of neutral faces than non-responders. A lower baseline response criterion was associated with responder status and, in secondary continuous analyses, with greater subsequent MADRS improvement. These findings indicate that TRD involves abnormalities across detection-related, valence-related, and decisional aspects of facial-emotion processing that are differently associated with esketamine response: baseline response criterion emerged as a candidate prognostic marker, whereas negative categorisation of neutral faces tracked clinical response. Assessing these domains may inform clinical evaluation, pending independent replication.

Individuals with major depressive disorder (MDD) show an attentional bias toward negatively valenced stimuli and thoughts. In this study, we applied a closed-loop neurofeedback procedure designed to reduce this bias. Participants were shown composite negative faces and neutral scenes with variable opacity and were instructed to attend to the neutral scene while ignoring the negative face. Internal attentional states were decoded in real time from functional magnetic resonance imaging (fMRI) data. When a participant's decoded attentional state indicated a failure to ignore the negative faces, the faces became more visible (higher opacity), thus externalizing the brain's attentional lapse in that moment. Forty-eight individuals with MDD were randomly assigned to a real neurofeedback training group (N = 24) or a sham control group (N = 24); the control group received feedback yoked to a participant in the real group. All participants completed three fMRI neurofeedback sessions. The main outcome quantified the extent to which participants got ``stuck'' in the most negative attentional state of focusing strongly on the negative faces. We hypothesized that the real neurofeedback group would learn to escape that state by the end of training, relative to the sham control group. Consistent with our hypothesis, neurofeedback training reduced the probability of getting stuck in the most negative attentional state. In offline analyses, training reduced fMRI activity in the precuneus/posterior cingulate and the medial prefrontal cortex when participants successfully attended to scenes and ignored faces. These results demonstrate the efficacy of remediating the negative attentional bias in depression with closed-loop neurofeedback from real-time fMRI.

Objective: To evaluate the psychometric properties, factor structure, validity, and age- and sex-specific norms of the 21- and 10-item parent-report Child Mania Rating Scale (CMRS-P) in a nationally representative U.S. sample of youth aged 6-18 years. Method: Parents of 2,229 youth aged 6-18 years [weighted M(SD)=12.0(3.3) years; 45.9% female] completed the CMRS-P and related measures between July 2025 and March 2026. Data were weighted to represent U.S. demographics. A clinical comparison sample included parents of 522 youth seeking outpatient mental health services. Complete-case analyses evaluated reliability, factor structure, item response theory, measurement equivalence, retest stability, and convergent and discriminant validity. GAMLSS estimated age- and sex-specific norms. Results: Weighted mean scores were 8.5(SD=9.0) for CMRS-P-21 and 4.0(4.3) for CMRS-P-10. Internal consistency was high ({omega}=.97/.93), and forms correlated .95. A general severity factor explained most reliable variance ({omega}H=.94). Three items differed in response thresholds across samples, with an average impact below one point on expected total scores. Both forms correlated strongly with attention problems, suicidality, depression, externalizing symptoms, and emotion dysregulation (r=.51-.63 for CMRS-P-21) and negligibly with pubertal status. Reliable-change thresholds were 14.5 (CMRS-P-21) and 6.8 (CMRS-P-10) points. Weighted GAMLSS CMRS-P-21 95th percentiles declined with age in males (30-23) and increased in females (22-30), with wide bootstrap intervals at age extremes; the female trend was not replicated without weights. Conclusions: Findings support both CMRS-P forms for assessing youth manic symptoms. The first nationally representative U.S. norms provide age- and sex-adjusted benchmarks for interpreting scores and informing further clinical assessment.

Home-based 2 mA transcranial direct current stimulation (tDCS) was recently approved by the US Food and Drug Administration for depression, but tDCS amplitude has been limited largely by skin tolerance, and higher-intensity, accelerated dosing may be more efficacious or faster-acting. Using a novel high-capacity tDCS (HC-tDCS) stimulator and hydrogel electrodes, we evaluated the safety, tolerability and feasibility of accelerated HC-tDCS (20-minute bifrontal 6 mA sessions, twice daily for five days) in 20 patients with major depressive disorder. A Safety Review Committee reviewed data from the first three participants, who completed a within-day escalation to 6 mA, before the remaining 17 were enrolled. Retention and adherence were 100% (203 of 203 sessions), and 19/20 tolerated the full 6 mA amplitude without dose reduction. There were no serious adverse events. The most common symptoms were fatigue (49% of sessions), burning (46%) and tingling (43%) at the electrode, and difficulty concentrating (40%). Electrode-site erythema occurred in all participants, with no severe reaction or skin breakdown. At 1 week, 7 of 20 reported a residual skin change, mostly peeling or redness, none painful; at 1 month, hyperpigmentation at the electrode site persisted in 2 participants, both Black. At the end of the five-day course, PHQ-9 scores decreased from 15.8 to 7.2 (Hedges g = 1.62); 50% of participants responded, 45% remitted, and improvement was maintained at 1-month follow-up. Accelerated HC-tDCS was feasible, well tolerated, and warrants a sham-controlled trial.

Music is a central component of psychedelic settings, yet little experimental work has examined how psilocybin and musical composition influence music-evoked emotional responses in healthy volunteers. This exploratory, double-blind, placebo-controlled study assessed these effects during the plateau phase of psilocybin and the corresponding time window in placebo sessions following oral administration of psilocybin (0.26 mg/kg) or placebo. The study consisted of two parts. In Part 1 (n = 19), a pilot stage, the first half of participants rated music-induced affective valence for eight compositions representing different genres/subgenres (Rock/Punk, Metal/Industrial Metal, Metal/Industrial Metal, Classical/Baroque, Electronic/Dub, Folk/Nordic Folk, Electronic/Techno, Electronic/Trance, Electronic/Psytrance) using a visual analogue scale (VAS). Based on Part 1, the classical composition with the highest overall affective valence and the psytrance composition with the largest psilocybin-placebo contrast (i.e., the composition most responsive to psilocybin) were selected for Part 2 (n = 17), in which the second half of participants assessed emotional responses to music using the Geneva Emotional Music Scale (GEMS-9). Psilocybin increased wonder, transcendence, and joyful activation across both contrasting compositions. Relative to each other, the classical composition elicited greater peacefulness, tenderness, and nostalgia, whereas the psytrance composition elicited greater tension across both psilocybin and placebo conditions. A composition x condition interaction was observed for sadness: under psilocybin, sadness increased during the classical composition and decreased during the psytrance composition. These findings suggest that psilocybin and contrasting musical compositions independently influence different aspects of music-evoked emotional responses, with limited interaction effects, and point to potential implications for protocol design and music selection in psychedelic settings.

Importance. Suicide is a leading cause of mortality, yet its prevention remains a challenge. Suicide attempters exhibit disrupted decision-making, but the specific cognitive processes driving this impairment and their utility for risk stratification are unclear. Objective. To determine which computational decision-making mechanisms are disrupted in high-risk suicide attempters, and whether they distinguish attempters from depressed and healthy controls. Design. This cross-sectional study fit reinforcement-learning models to Iowa Gambling Task performance across two independent studies: SPAD (August 2017 to May 2020); SUICIDE-DECIDE (March 2021 to September 2023). Data was analyzed between January 2025 and July 2026. Setting. SPAD was conducted in Nimes (France). SUICIDE-DECIDE was a muticenter study across Jena (Germany) and Nimes. Clinical groups were recruited from academic inpatient psychiatry units and outpatient clinics, and healthy controls through local advertisement. Participants. SPAD included adults aged 60 years or older; SUICIDE-DECIDE middle-aged adults stratified by attempt means (violent/nonviolent). Consecutive participants were recruited into three groups: suicide attempters, patient controls, healthy controls. Main outcomes and measures. The primary outcomes were group differences on parameters reflecting learning from rewards and losses, sensitivity to win frequency, choice perseverance, and forgetting of past choices. We trained a multinomial logistic regression model in the SUICIDE-DECIDE study using self-reported depression and parameters that differentiated attempters from controls across studies, and evaluated its performance in the SPAD sample. Results. SPAD included 57 participants (40 females [70.2%]; mean [SD] age, 70.1 [8.2]). SUICIDE-DECIDE included 124 participants (77 females [62.1%]; 32.1 [11.0]). Suicide attempters forgot past choices faster than controls (SPAD: F(2,36) = 13.5; P < .001; SUICIDE-DECIDE: F(3,57) = 46.6; P < .001). No other parameter specifically differed in attempters across studies. In SUICIDE-DECIDE, greater forgetting of past choices was associated with attempter status only (RRR = 4.2, 95% CI [1.5, 11.5]). This parameter paired with depression severity correctly classified 87.2% of participants in SPAD (95% CI [74.3%, 95.2%], 41/47). Conclusions and relevance. Short-sighted decision-making may represent a cognitive phenotype associated with suicide in high-risk populations and a potential target for prevention and treatment.

Objective This study aimed at analyzing changes in the prevalence of excessive internet use and to analyze its associations with mental and cognitive health problems among adolescents. Method We used repeated cross-sectional data from the School Health Promotion study, a population-based nationwide classroom survey in Finland. All adolescents in grades 8-11 were invited, with a total of 602,226 responses in 2017-2023. Excessive internet use was measured with the five-item Excessive Internet Use Scale covering core behavioral addiction symptoms. Depressive symptoms, generalized anxiety, and social anxiety were measured with validated questionnaires. Problems in cognitive functioning were assessed with one-item indicators. Analyses were done with Chi-square tests and logistic regression. Results From 2017 to 2023, the prevalence of excessive internet use increased, especially among girls. The increasing trend was significantly (p<0.001) steeper among girls, with the OR for time (in years) being 1.12 in grades 8-9 and 1.14 in grades 10-11, while among boys the corresponding ORs were 1.00 and 1.04, respectively. Excessive internet use associated with short sleep, depressive, generalized anxiety, and social anxiety symptoms (ORs between 1.73-2.42 in boys; 1.92-2.26 in girls; p<0.001) and with difficulties in tasks requiring reading, writing, and mathematics, and difficulties in concentrating (ORs 1.84-2.31 in boys; 1.83-1.98 in girls; p<0.001). Conclusion The prevalence of excessive internet use showed an increasing trend, especially among girls. The associations of excessive internet use with mental health symptoms and cognitive challenges were clear.

ObjectiveThe Concise Health Risk Tracking (CHRT) assessment has utility in suicide risk prediction in adults and adolescents. Because multi-informant assessment is the gold standard in pediatric populations, a parent report version of the CHRT may enhance evaluation of youth suicide risk. We adapted the self-report version of the 16-item CHRT as a parent report version (CHRT-PR16) and evaluated the psychometric properties and continuous age- and sex-specific norms in a nationally representative sample of parents. MethodParents of youth aged 6-18 years (N=2,236; 2,235 in sex-stratified analyses) completed the CHRT-PR16, enabling evaluation of both the 16- and 14-item (CHRT-PR14) version. Psychometric analyses included internal consistency, factor structure, Item Response Theory, measurement invariance, criterion validity, and continuous norming using Generalized Additive Models for Location, Scale and Shape (GAMLSS). ResultsInternal consistency was excellent for both CHRT-PR16 and CHRT-PR14 (both{omega} t =.98, =.96), although general factor variance was higher for CHRT-PR14 ({omega}H=.83) than CHRT-PR16 ({omega}H=.68). Mokken scale analysis confirmed zero monotonicity violations for CHRT-PR14. CHRT-PR16 showed a clinically trivial edge in criterion correlations with other measures of psychopathology. In GAMLSS modeling, a zero-inflated negative binomial distribution achieved optimal fit for both scales. Score trajectories diverged by age and sex around age 10, with males scoring slightly higher at upper percentiles. ConclusionsCHRT-PR16 and CHRT-PR14 demonstrate strong psychometric support, essential unidimensionality, measurement invariance, and optimal GAMLSS fit. Age- and sex-specific percentile lookup tables provide population-level benchmarks to guide measurement-based care, symptom tracking, and suicide risk stratification in pediatric settings.

Background: Social difficulties in alcohol use disorder (AUD) have been linked to alterations in social cognition, including increased egocentric bias. Psychedelics such as psilocybin have been proposed to modulate self-related processing, but their effects on specific socio-cognitive mechanisms remain unclear. Methods: In this randomized controlled pilot study, recently detoxified individuals with AUD with persistent depressive symptoms completed a visual perspective-taking task before and after a psilocybin session (25 mg dose vs active placebo 1 mg psilocybin). Results: The 25 mg psilocybin group showed a significant reduction in egocentric bias and egocentric superiority on reaction times, with no effect on altercentric bias nor on accuracy. Between-group comparisons confirmed greater reductions in the high-dose relative to the low-dose group. The high-dose group reported more intense subjective psychedelic experiences, and greater subjective intensity was associated with lower egocentric superiority in accuracy. Conclusions: These findings provide preliminary evidence that psilocybin may selectively reduce egocentric interference in individuals with AUD, suggesting a decrease in egocentricity rather than enhanced sensitivity to others. Although replication in larger samples is needed, reduced egocentricity may represent one mechanism through which psilocybin influences social cognition in AUD. Clinical trial registration: ClinicalTrials.gov, https://clinicaltrials.gov/study/NCT06235411, NCT06235411.

Importance: Obsessive-Compulsive Disorder (OCD) has a 2% global prevalence, but only about 50% of patients respond to conventional treatment, underscoring the need for additional effective interventions. Objective: To assess the feasibility, safety, and preliminary evidence for efficacy of repeated psilocybin administration in OCD patients who had previously attempted psychotherapy or pharmacotherapy. Design: Waitlist-controlled open label randomized clinical trial. Setting: Data were collected at the Johns Hopkins University School of Medicine. Participants: Data were analyzed from 30 participants (total randomized N=37, by age, sex and OCD severity) with a failed previous attempt at either pharmacotherapy or evidence-based psychotherapies such as exposure response prevention (ERP). Intervention: Participants received two psilocybin doses over two weeks (20 mg followed by 30 mg, if well-tolerated) under supportive conditions. The immediate-treatment arm received the drug within a month following enrollment, and the waitlist-control arm received identical support and dosing after an 8-week waiting period. Main Outcomes: Clinician-administered Y-BOCS scores was collected one week post each drug administration and one month post session 2. Self-assessed reports were collected for acute subjective effects (Mystical Experience Questionnaire (MEQ), Challenging Experience Questionnaire (CEQ), and 11-Dimensional Altered States of Consciousness (11D-ASC)), State-Trait Anxiety Inventory (STAI), Beck Depression Inventory-II (BDI-II), and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Results: A total of 37 participants were enrolled in the study (age[SD] years:38.4[11.6] years; 21 [56.75%] female), with 30 [81.08%] completing the 1-month follow-up. We show that two successive doses of psilocybin over two weeks were well-tolerated, leading to improvements in OCD symptoms. Compared with the waitlist group (N=14), the immediate-treatment group (N=16) showed a greater reduction in the Y-BOCS scores (F(2,56)=16.17, p<0.001). After crossover, this improvement persisted one month after the second psilocybin dose for both groups (F(3,84)=29.91, p<0.001). Reductions in Y-BOCS score post sessions were correlated with several acute subjective effects measures, including total scores on MEQ, and individual factors on CEQ and 11D-ASC. Conclusions and Relevance: Repeated psilocybin administration is tolerable and potentially efficacious in reducing OCD symptoms. These results support further investigation of multidose psilocybin protocols as a viable therapeutic approach. Trial Registration: ClinicalTrials.gov Identifier NCT05546658

Background: Psychological health is an important aspect of health and well-being among adults with irritable bowel syndrome, yet the interrelationships among individual vulnerabilities, social experiences, perceived stress, and psychological health outcomes remain poorly understood. Objective: To characterize psychological health and examine direct and indirect associations of childhood adversity and adult attention-deficit/hyperactivity disorder-related symptoms within an adapted Stress Process Model. Design: Cross-sectional secondary analysis. Setting: The United States All of Us Research Program. Participants: 2,417 adults with electronic health record-documented irritable bowel syndrome and complete data on the primary analysis variables and covariates. Methods: Separate structural equation models examined childhood adversity and adult attention-deficit/hyperactivity disorder-related symptoms in relation to perceived stress, anxiety and depressive symptoms, and positive psychological well-being, with loneliness and perceived social support as psychosocial pathways. Models adjusted for sociodemographic and social-context factors. Results: The median age was 54.39 years; 80.7% were female and 84.4% were White. Moderate-to-high perceived stress was reported by 56.2%, at least moderate anxiety symptoms by 21.0%, and at least moderate depressive symptoms by 24.3%. Higher ACE-8 scores were associated with greater perceived stress, anxiety symptoms, and depressive symptoms and lower psychological well-being ({beta} = 0.063, 0.089, 0.116, and -0.100, respectively); corresponding associations for higher ASRS-6 scores were {beta} = 0.299, 0.355, 0.390, and -0.260. Loneliness-specific indirect associations were positive for perceived stress, anxiety, and depressive symptoms (ACE-8: {beta} = 0.023-0.034; ASRS-6: {beta} = 0.043-0.075) and negative for psychological well-being (ACE-8: {beta} = -0.039; ASRS-6: {beta} = -0.089; all p < .001). Social support-specific indirect associations were not significant in the ACE-8 model and were small and significant only for anxiety and depression in the ASRS-6 model ({beta} = 0.003-0.004). Conclusions: Psychological health among adults with irritable bowel syndrome was associated with interconnected individual and social factors within an adapted Stress Process Model. Childhood adversity and adult attention-deficit/hyperactivity disorder-related symptoms showed direct and indirect associations with psychological health, with loneliness emerging as the most consistent social factor. These findings support prospective investigation of individual vulnerabilities and social experiences in psychological health. The cross-sectional design does not establish temporal ordering or causal mediation.

Objective: Parent-adolescent disagreement in ratings of attention-deficit/hyperactivity disorder (ADHD) symptoms can complicate clinical assessment. This study examined parent - adolescent agreement in ADHD symptom ratings and characteristics associated with disagreement. Method: Participants were 1,008 parent-adolescent dyads recruited from a nationally stratified U.S. community sample. Adolescents were 12--18 years old (49.6% female) and along with their parents completed measures of ADHD and depressive symptoms. Agreement on Inattention (IN), Hyperactivity/Impulsivity (HI), and Total ADHD scores was examined. Item-level agreement was assessed using weighted kappa, Gwet 's AC2, percent agreement, and polychoric correlations. Associations between age, sex, and severity of ADHD and depression with levels of agreement were analyzed. Results: Agreement for ADHD factor and total symptom scores was moderate (intraclass correlations = 0.67--0.71), with moderate-to-strong rank-order correspondence. Adolescents reported slightly higher ADHD symptom levels than parents, although the mean difference was small. Item-level agreement was moderate to high (Gwet 's AC2 = 0.79--0.95). Several HI items demonstrated the kappa's paradox, with relatively low kappa values despite high Gwet's AC2 and percent agreement. Q-correlations revealed low agreement on relative strengths and weaknesses. Age and sex were not associated with disagreement and parent-reported ADHD severity and adolescent-reported depressive symptoms were associated with disagreement. Conclusions: Parent and adolescent ratings showed moderate agreement across boys and girls ages 12-- 18; however, disagreement related to relative strengths and weaknesses. Disagreement was associated with ADHD and depressive symptom severity. Findings suggest that ratings from parents and adolescents offer unique perspectives on the assessment of ADHD symptoms.

BackgroundPsychotic-like experiences (PLEs) have been shown to increase the risk for mental health problems in later life, especially psychosis. Following previously raised methodological concerns about the assessment of PLEs in adolescents, this study sought to differentiate subtypes of PLEs and to explore their trajectories. MethodsLongitudinally matched data of 671 German adolescents from three surveys over the time span of one year were analysed. Four trajectories were identified, including persisting, subsiding, and emerging highly indicative PLEs (HIPs), and non-highly indicative PLEs (non-HIPs), and longitudinally compared in terms of associated distress, psychopathology, and substance use. A differentiated never PLEs group was considered as a control. ResultsThe persisting HIPs group reported greater distress than the non-HIP group over time and was consistently associated with higher rates of internalising symptoms. The subsiding HIP group showed significant reductions in distress and internalising symptoms over time, but no significant changes regarding externalising symptoms and substance use. There was no difference in the extent of substance use between the groups. ConclusionsScreenings of PLEs should be mindful of different subtypes of PLEs that indicate a greater associated risk of poor mental health. PLE screening should not stop at whether PLEs are present but ask which ones.

Background: Short-form video elicits a stimulus-driven, passive neural state, yet existing interventions target time of use alone and cannot show whether the mechanism of cognitive control has changed. Objective: This pilot study developed BrainPT, a mini-game-based cognitive intervention, and evaluated whether a single insertion alters the neural state during short-form viewing (Study 1) and whether repeated use improves behavioral self-regulation (Study 2). Methods: Study 1 used a within-subject design (n=9) in which electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) were recorded in the same session across short-form viewing, a single BrainPT set, and goal-directed tasks. Study 2 used a nonrandomized 2-week pretest-posttest design comparing an experimental group that used BrainPT daily (n=13) with a control group (n=8). Both visits followed the same in-laboratory protocol, and app logs and self-report indices were collected over the intervention period. Results: In Study 1, short-form viewing was accompanied by prefrontal deactivation: EEG power fell below baseline in all four bands and most in alpha (-1.72 dB, P=.01; q=.054 after correction). Prefrontal activation was opposite in sign between the goal-directed tasks and viewing (+0.180 vs -0.093, P=.002), and the viewing block immediately after a BrainPT insertion exceeded the block before it (+0.110 vs -0.093, P=.02). The same condition ordering appeared in an independent preintervention sample (n=18). In Study 2, daily short-form use fell from 143.5 to 50.9 min in the experimental group and rose from 104.8 to 132.9 min in the control group, a between-group difference in change of 120.7 min (P=.004). The Adult ADHD Self-Report Scale did not differ between groups (P=.39), and no neural index separated the groups after 2 weeks. Conclusions: A single insertion produced a measurable neural change: prefrontal state during the viewing that followed moved toward the goal-directed task. After 2 weeks of use that neural difference was not detectable between groups although behavior differed, so repeated use may act through the momentary state during viewing rather than by reorganizing the resting state. Both samples were small and nonrandomized, the primary outcome was self-reported, and the analyses were exploratory and not preregistered, so these estimates require confirmation in a preregistered randomized trial with objectively logged use.

Abstract Background: Insomnia is highly prevalent in major depressive disorder (MDD), yet the clinical and biological significance of dysfunctional beliefs and attitudes about sleep (DBAS) in MDD remains poorly understood. We examined whether distinct DBAS dimensions are associated with insomnia severity, depressive phenotypes, and neuroimmune-metabolic-oxidative (NIMETOX) biomarkers. Methods: DBAS-30 dimensions, clinical phenotypes, and NIMETOX biomarkers were assessed in 87 hospitalized patients with MDD and 31 healthy controls. Principal component analysis (PCA) was used to ascertain DBAS cognitive dimensions, and associations were examined using multivariable analyses. Results: Compared with controls, MDD patients showed lower scores on "perceived consequences of insomnia," "sleep-related worry and helplessness," and "medication-related beliefs," but higher "causal attributions to aging or biochemical imbalance" scores. A composite DBAS score reflecting these 4 MDD-associated cognitive dimensions was constructed, labeled DBAS dimensional index (DBAS-DI). This score was lower in MDD and inversely associated with Insomnia Severity Index (ISI) scores, overall MDD severity, physiosomatic symptoms, current suicidal ideation, and recurrence of illness. DBAS-DI and the expectations domain jointly explained 35.4% of the variance in ISI scores, with inverse and positive associations, respectively. The DBAS-DI score was inversely associated with indices of the acute-phase inflammatory response, oxidative stress, fecal branched-chain short-chain fatty acids (SCFAs) and positively associated with serum antioxidant capacity and protective SCFAs, such as acetate, propionate, and butyrate. Conclusions: DBAS abnormalities in MDD extend beyond insomnia-related cognitions and are associated with illness severity, suicidality, recurrence, and NIMETOX alterations. These findings suggest that dysfunctional sleep-related cognitions are embedded within broader immune-oxidative and gut microbial-metabolic processes that may contribute to the insomnia-depression interface.