Search Results (259)

Background: As glucagon-like peptide-1 (GLP-1) receptor agonist use expands globally, reports of psychiatric adverse events (AEs) have increased in spontaneous reporting databases. However, which case-level characteristics are associated with these reporting patterns remains insufficiently characterized. This study aimed to characterize case-level features associated with psychiatric AE reporting in GLP-1 receptor agonist users through pharmacovigilance and explainable machine learning methods. Methods: The FDA Adverse Event Reporting System (FAERS) data (2021 Q2–2025 Q3) were analyzed using a comparator-based approach comprising other antidiabetic and anti-obesity agents. Disproportionality analyses (PRR, ROR, and IC) were performed to detect consolidated safety signals at the Preferred Term (PT) level, with additional drug-specific analyses for individual GLP-1 receptor agonists. Three classification models (logistic regression, XGBoost, and LightGBM) were developed, and SHAP values were used to identify case-level features associated with psychiatric AE reporting patterns. Results: A total of 211,195 unique cases were included (111,105 for GLP-1 receptor agonists; 100,090 for comparators). Sixteen PTs met consolidated signal criteria, with suicidal ideation being the most frequently reported (ROR 2.95). Drug-specific analyses indicated that signal magnitudes were consistently higher for semaglutide than tirzepatide. The XGBoost model achieved an AUROC of 0.816. SHAP analysis showed that age ≥65 years had the highest mean |SHAP| value (0.57) with a negative direction, corresponding to a lower predicted probability of psychiatric AE reporting in older adults. Semaglutide use ranked second (0.35) and showed a positive direction. Absence of concomitant medications (0.20) and diabetes indication (0.10) showed negative directions, while younger age (19–44 years, 0.08) showed a positive direction. These patterns remained consistent in sensitivity analysis excluding concomitant psychotropic medication users (AUROC 0.797). Conclusions: Older age status was associated with decreased predicted probability of psychiatric AE reporting, while semaglutide use and younger age showed positive contributions. These case-level patterns, identified through pharmacovigilance analysis using a comparator-based approach and explainable machine learning, suggest that reporting patterns may differ across subgroups and that the observed reporting heterogeneity among younger adults and semaglutide users merits further investigation in prospective studies. Full article

Background/Objectives: The relationship between psychotropic medication use, prescribing appropriateness, and fall-related risk factors remains incompletely characterised. Gait speed is a key predictor of falls. We aimed to examine whether gait speed is associated with appropriately versus inappropriately prescribed psychotropic medication use among relatively healthy older adults. Methods: We conducted an observational cross-sectional study of 119 community-dwelling adults aged ≥ 70 years with low comorbidity burden (Charlson Comorbidity Index < 2) and preserved functional status (Barthel Index > 85). Gait speed was assessed over 6 metres. Psychotropic medication use was recorded and prescribing appropriateness was evaluated using STOPP/START and Beers criteria, supplemented by geriatric pharmacological considerations. Multivariable linear regression analyses adjusted for age, sex, waist-to-height ratio, and frailty status. Results: In the fully adjusted model, inappropriate psychotropic medication use was associated with significantly slower gait speed compared with no use (B = −0.109 m/s; p = 0.026). In contrast, appropriately prescribed psychotropic medication use was not associated with gait speed (B = −0.018 m/s; p = 0.699). Conclusions: In this cross-sectional sample of relatively healthy older adults, appropriate psychotropic medication use was not associated with gait speed impairment, whereas inappropriate use was associated with slower gait. Although causal inference is not supported, these findings may inform prescribing quality and fall-risk assessment in older populations. Full article

Background: Insomnia is common among people with mental health conditions and can exacerbate symptoms, impair functioning and negatively impact treatment outcomes. Community mental health services require practical data to quantify the burden of insomnia in routine care and to identify groups at a higher risk of experiencing clinically significant insomnia. Methods: We conducted a retrospective analysis of anonymized routinely collected clinical data from adult psychiatric outpatients attending the Community Mental Health Center in Bra (Department of Mental Health, Asl Cuneo 2, Italy). Consecutive patients were included over a three-month period (1 September to 30 November 2025). Insomnia severity was assessed using the Insomnia Severity Index (ISI). Diagnoses were established by psychiatrists using the Structured Clinical Interview for DSM-5 (SCID-5). Results: The sample included 506 patients (mean age: 45.1 ± 16.7 years; 265 women, 52.4%). The mean ISI total score was 12.18 ± 6.99. Clinically significant insomnia (ISI ≥ 15) was present in 205 out of 506 patients (40.5%), while severe insomnia (ISI ≥ 22) was present in 55 out of 506 patients (10.9%). The ISI score differed across diagnostic groups (ANOVA, F(8, 497) = 2.82, p = 0.0046, η² = 0.043). Post hoc comparisons revealed higher ISI scores in patients with depressive disorders than in those with anxiety disorders (Tukey, p = 0.0056). In a multivariable logistic regression model (outcome: ISI score of at least 15), adjusted for age, sex, education and the complexity of concurrent psychotropic medication (number of medication classes), depressive disorders were associated with clinically significant insomnia (OR: 1.99; 95% CI: 1.07–3.73). Attention deficit hyperactivity disorder (ADHD) also showed higher odds (OR: 3.64; 95% CI: 1.26–10.55). Medication complexity was also associated with an ISI score of at least 15 (OR: 1.43 per additional class; 95% CI: 1.16–1.77). In a sensitivity model additionally adjusting for benzodiazepine prescription (yes/no), benzodiazepine prescription was associated with ISI ≥ 15 (OR 1.82; 95% CI 1.13–2.95), while the estimate for medication complexity was attenuated using this association (OR 1.17; 95% CI 0.90–1.53). The eating disorders group was excluded from multivariable models due to the very small sample size (n = 4). Conclusions: Clinically significant insomnia was prevalent among this sample of psychiatric outpatients, with modest differences in insomnia severity across diagnostic groups. Sensitivity analyses suggested that the signal of medication complexity may be partly accounted for by benzodiazepine prescribing, supporting the cautious interpretation of medication-related correlates in routine cross-sectional data. These findings support routine insomnia screening in psychiatric outpatient care, while prospective studies are needed to clarify directionality and clinical implications. Full article

Growing evidence indicates that the gut microbiota is not a static ecosystem but a rhythmic metabolic organ whose oscillatory activity is tightly coordinated with host circadian biology. Disruption of this temporal alignment, through irregular diet, sleep disturbance, shift work, or social jet lag, may profoundly alter microbial composition and the production of neuroactive metabolites. These alterations have emerged as potential contributors to the pathophysiology of mood disorders. This review introduces the concept of chrono-metabolic psychiatry, a framework integrating circadian rhythms, gut microbiota dynamics, and host metabolic signaling in the development and course of depressive and bipolar disorders. In this framework, the term “chrono-metabolic” refers to the integration of biological timing, host metabolic regulation, and microbiota-derived metabolic signaling. Chrono-metabolic psychiatry therefore shifts the focus from static dysbiosis or neurotransmitter imbalance alone to the time-dependent interactions among circadian misalignment, microbial rhythmicity, immune regulation, metabolite production, and affective instability. Diurnal fluctuations in short-chain fatty acids, tryptophan–kynurenine metabolites, bile acids, and microbial-derived neurotransmitters interact with clock gene regulation, hypothalamic–pituitary–adrenal axis activity, neuroinflammation, and synaptic plasticity. Chrono-disruption may represent a transdiagnostic vulnerability factor and may confirm the bidirectional relationship between mood instability and microbiota rhythmicity. Emerging therapeutic implications, including chrono-nutrition, time-restricted feeding, targeted probiotic administration (“chronobiotics”), and the microbiota-modulating effects of psychotropic medications are discussed. By shifting from a compositional to a temporal–metabolic perspective, this model highlights the importance of microbial oscillations rather than static dysbiosis alone. Integrating circadian biology into microbiota research may enable metabolomic stratification and pave the way for precision psychiatry approaches grounded in host–microbe metabolic crosstalk. Future longitudinal and time-resolved multi-omics studies are needed to validate this framework and to translate it into clinically actionable interventions. Full article

Background: Chronic obstructive pulmonary disease (COPD) is commonly managed alongside multimorbidity, polypharmacy, recurrent treatment escalation, and older age, all of which increase vulnerability to drug–drug interactions (DDIs). We aimed to synthesize the main DDI domains relevant to COPD pharmacotherapy and to distinguish harmful DDIs from beneficial combination therapy and formal compatibility findings. Methods: We performed a narrative review using structured literature searches and citation tracking to evaluate COPD-related studies. We prioritized direct COPD-specific DDI evidence, while also including mechanistic, class-specific, and contextual studies when direct evidence was lacking. Retained evidence included observational cohorts, prescribing studies, pharmacokinetic trials, case reports, and systematic reviews. Results: The reviewed literature indicates that DDI vulnerability in COPD is driven less by isolated drug pairs than by overall regimen complexity, multimorbidity, aging, fragmented prescribing, and high-intensity treatment periods such as exacerbations, hospitalization, and discharge. Key DDI domains included cardiopulmonary co-treatment, QT-related vulnerability, and potential or clinically relevant interactions amplified during exacerbations. Inhaled therapies are not universally interaction-free, particularly with strong metabolic inhibitors. Psychotropics, frailty, dementia, and palliative care further increase clinical complexity. However, beneficial bronchodilator combinations and formal compatibility studies demonstrate that not all multidrug COPD regimens are harmful. Conclusions: In COPD, DDI assessment should focus on the full treatment regimen and not be limited to a set of iconic drug pairs. Clinicians must focus on exacerbation-related prescribing, QT-active drugs, theophylline exposure, psychotropic co-medication, and vulnerable subgroups such as older, frail, and palliative patients. Pharmacist-supported drug review, drug reconciliation, and selective deprescribing are key strategies for reducing clinically relevant DDI burden in COPD. Full article

Background: Antenatal depression has been associated with systemic inflammation, autonomic imbalance, and vascular dysfunction, yet its relationship with clinically relevant cardiovascular complications during pregnancy remains insufficiently defined. Objective: To evaluate whether antenatal depression diagnosed before cardiologic assessment is associated with gestational hypertension, preeclampsia, and clinically significant Holter-confirmed arrhythmias in a tertiary-care population of pregnant women referred for cardiology assessment. Methods: We conducted a retrospective secondary matched cohort analysis nested within a prospectively approved doctoral research protocol (approval no. 76/02.10.2023; approved study interval: 2 October 2023–10 February 2025), including deliveries from October 2023 to February 2025. During this 16-month interval, 12,436 deliveries were recorded. The index point was the first cardiology specialist evaluation performed between 22 + 0 and 36 + 6 weeks’ gestation. Pregnancies with a depressive disorder diagnosed by structured psychiatric interview (SCID-5) before cardiology evaluation were classified as exposed. Depression severity was categorized as mild (n = 44), moderate (n = 62), or severe (n = 24), and psychotropic medication class at index was recorded. Each depressed case was matched 1:3 with non-depressed controls by gestational age at index, calendar year, maternal age, BMI category, smoking status, and parity; adjusted models included BMI and psychotropic medication class. Results: The final referral-enriched cohort included 130 depressed pregnancies and 390 matched controls (n = 520), all of whom underwent cardiology evaluation. Between 22 + 0 and 36 + 6 weeks’ gestation, gestational hypertension occurred in 18.5% vs. 10.0% (p = 0.010), preeclampsia in 8.5% vs. 4.9% (p = 0.12), and clinically significant Holter-confirmed arrhythmias in 15.4% vs. 6.9% (p = 0.003) in depressed versus control groups, respectively. After adjustment, depression remained independently associated with gestational hypertension (aOR 1.85, 95% CI 1.12–3.05; p = 0.016) and arrhythmia (aOR 2.05, 95% CI 1.18–3.57; p = 0.011). A numerical, exploratory severity-response gradient was observed across mild, moderate, and severe depression strata, most clearly for Holter-confirmed arrhythmias; however, the severe-depression stratum was small (n = 24). Conclusions: Antenatal depression was associated with a modest but significant increase in gestational hypertension and clinically significant Holter-confirmed arrhythmias during late pregnancy among women referred for cardiology assessment. The higher preeclampsia rate in depressed pregnancies was not statistically significant. These findings support antenatal depression as a cardiovascular risk marker in gestation rather than proof of causality. Full article

Background: Religious affiliation has traditionally served as a coping strategy during stressful events such as the COVID-19 pandemic. Pregnant women faced heightened stress during the pandemic due to concerns about their health as well as that of their fetus. This study examined the prevalence of self-reported religious affiliation among SARS-CoV-2-positive pregnant women and investigated differences in psychiatric diagnoses and pregnancy outcomes based on religious affiliation. Methods: The study included all asymptomatic or mildly symptomatic SARS-CoV-2-positive pregnant women who received care at the Mayo Health System from March 2020 through October 2021 and completed the routine religious affiliation questionnaire. Those selecting “none” were categorized as having no religious affiliation (RA−), whereas those selecting a specific religion were categorized as religiously affiliated (RA+). Results: Among 609 women, 49.6% were RA+ and 50.4% were RA−. RA+ women were more likely to be white, married, college-educated, and have fewer prior abortions. There were no significant differences in rates of depression, anxiety, psychotropic medication use, substance use, or pregnancy and labor complications between RA+ and RA− groups. Conclusions: Half of the women in this cohort reported no religious affiliation. Previously reported protective associations between religiosity and mental health were not observed when religious affiliation alone was examined. Full article

Objective: This study examined psychological resilience (PR) as a potential moderator and mediator of the association between borderline personality symptoms (BPS) and suicidal ideation (SI) among university students. Method: A cross-sectional design was used with (N = 257) university students. Moderation and mediation were tested in separate, theory-guided models using the PROCESS macro for SPSS, version 28. The moderation model (Model 1) and the mediation model (Model 4) were estimated with heteroskedasticity-consistent standard errors (HC3). In the adjusted analyses, sex, age, previous psychological consultation, previous psychotropic medication use, and family history of mental illness were entered as covariates. The indirect effect was evaluated using percentile bootstrap confidence intervals based on (5000) resamples. Results: BPS was positively correlated with SI, whereas PR was negatively correlated with both BPS and SI. In the adjusted moderation model, BPS was positively associated with SI (b = 0.118, p < 0.001) and PR was negatively associated with SI (b = −0.204, p = 0.048), but the interaction term was not significant (b = −0.001, p = 0.820) with negligible explained variance (ΔR² = 0.0003). In the adjusted mediation model, BPS was significantly associated with lower PR (a: b = −0.135, p < 0.001), and PR was associated with lower SI while controlling for BPS and the covariates (b: b = −0.216, p = 0.028). The total effect of BPS on SI was significant (c: b = 0.146, p < 0.001), and the direct effect remained significant after including PR (c′: b = 0.117, p < 0.001). The indirect effect was significant (ab = 0.029; 95% bootstrap CI [0.005, 0.061]). Conclusions: Psychological resilience did not moderate the association between BPS and suicidal ideation, but it showed a statistically significant indirect association consistent with the proposed mediation model. Higher BPS were associated with lower resilience, which in turn was associated with higher suicidal ideation. These findings suggest that resilience-related targets may complement interventions addressing core BPS-related risk processes, while the cross-sectional design precludes causal conclusions. Full article

Background: Multimorbidity frequently involves overlapping neuro-psychic, cardiometabolic, and renal disturbances, yet clinical assessment often relies on diagnosis-based comorbidity counts that may not fully capture cumulative physiological stress. We developed the Neuro–Cardio–Renal Stress Index (NCR-SI) as a pragmatic composite framework to describe multisystem burden using routinely available clinical data. Methods: This cross-sectional study analyzed electronic medical record data from adult patients with chronic conditions. NCR-SI integrates three domains: neuro-psychic burden (text-derived indicators and psychotropic medication use), cardiometabolic stress (triglyceride–glucose index and cardiometabolic diagnoses), and renal function (MDRD-estimated eGFR staging). Importantly, this study is not intended to demonstrate incremental predictive value over individual components or established comorbidity indices. Rather, it presents NCR-SI as a transparent, domain-based descriptive framework and reports its internal coherence and distribution across clinically recognizable multimorbidity contexts. Results: A total of 148 patient records were screened; 143 patients met complete-case criteria and were included in the main NCR-SI analyses. NCR-SI ranged from 0 to 10 (median 5). Higher scores were observed in renometabolic profiles. NCR-SI showed expected structural associations with declining renal function (eGFR; ρ ≈ −0.71), moderately with the TyG index (ρ ≈ 0.42), and weakly with medication burden. Correlation with age-adjusted CCI was minimal (ρ ≈ 0.09), indicating limited overlap with diagnosis-based comorbidity counts. Domain-specific correlations were consistent with predefined score construction rules, particularly between the renal domain and eGFR, and between the cardiometabolic domain and TyG. Conclusions: NCR-SI provides a pragmatic, integrative descriptor of neuro-cardio-renal stress using routinely collected clinical data. Rather than replacing established comorbidity indices, NCR-SI may complement them by summarizing multidimensional physiological burden patterns. NCR-SI is proposed as a research-oriented, hypothesis-generating descriptive framework. External validation in independent cohorts and longitudinal evaluation against clinically meaningful outcomes (e.g., hospitalization, mortality, functional status, healthcare utilization) are required before any claims of clinical performance can be made. Full article

Background: It is well known that the university period is an important stage for young adults, involving significant academic and psychosocial adjustments. Students with greater Mental Health Literacy (MHL), which is defined as the knowledge, beliefs, and skills individuals have regarding mental health and mental illness, are better able to identify difficulties, seek help, and adopt healthier coping strategies. This study aims to describe the MHL levels of undergraduate health students and identify associated factors related to academic life, mental health and psychological state. Methods: A cross-sectional, self-administered, web-based survey was conducted using a non-probability sampling strategy among undergraduate students in health-related degrees at a Portuguese higher-education institution. Data was collected using a general characterization questionnaire and the following instruments: MHL Questionnaire, Academic Life Satisfaction, Subjective Happiness Scale, Psychological Well-Being Scale (PWBS), and Depression Anxiety Stress Scale. Bivariate and linear regression analyses were employed to identify factors associated with MHL. Results: A total of 306 students (79% female, mean age = 21.6 years; 59% nursing students) participated. The median MHL score was 70 (range: 30–80). The linear regression model explained 17.5% of the variance in MHL. Higher MHL levels were associated with having the course as a first choice, holding a previous degree, reporting taking psychotropic medication use (which may reflect previous mental health service utilization), and higher levels of psychological well-being. Conclusions: This study provides evidence on factors associated with MHL among undergraduate health students, suggesting that higher MHL is associated with greater psychological well-being, highlighting the potential importance of integrating strategies to promote MHL and psychological well-being in health and nursing education. However, these findings should be interpreted with caution due to the single-institution convenience sample, potential self-selection and reporting biases, and cross-sectional design, which limits causal inferences. Full article

Background: Decades of randomized controlled trials (RCTs) support cognitive behavioral therapy (CBT) for pediatric anxiety, but exclusion criteria may limit generalizability to routine settings. We examined common exclusion criteria in recent CBT RCTs for pediatric anxiety, trends in these criteria over time, and whether meeting RCT exclusion criteria affects outcomes in a naturalistic sample. Methods: We reviewed 81 RCTs from the past 25 years assessing CBT for pediatric anxiety or related disorders to identify common exclusion criteria. We examined how often youth seeking exposure-based treatment for anxiety or OCD at an urban community health center met these exclusion criteria and whether this impacted treatment response, using three-year retrospective chart review data (n = 94). Results: Common exclusion criteria in identified RCTs included psychotropic medication use (66.7%), autism spectrum disorder (63.0%), and other psychiatric comorbidities. Suicidal ideation increased as an exclusion criterion over time (p < 0.05, Cramér’s V = 0.23). Based on these criteria, 53% of participants in our naturalistic sample would have been excluded from one or more RCTs. Excluded patients did not differ in baseline characteristics. Excluded youth required nearly twice as many treatment sessions and had more than double the rate of case management utilization (all ps < 0.01). Conclusions: Youth who would have been excluded from at least one RCT had poorer prognoses. Findings support continued emphasis on pragmatic trials to advance understanding of how to augment treatments to better meet the diverse needs of youth. Full article

Background/Objectives: An extensive body of data suggests that inflammation may contribute to the pathophysiological mechanisms of psychiatric illness. Circumstantial evidence implied that low-dose aspirin (LDA) may enhance the therapeutic efficacy of psychotropic drugs. We examined whether LDA administration with psychotropic medications is associated with medication regimen stability and other therapeutic effects in patients with bipolar disorder (BD), schizophrenia, and schizoaffective disorder (SAD). Methods: This retrospective study analyzed data from Clalit Health Services’ Southern District database in Israel, including 1924 patients treated between 2017 and 2019. The Study Group consisted of patients treated with LDA plus psychotropic medications, whereas the Control Group included patients treated only with psychotropic medications. Study outcomes included suicide attempts and pharmacotherapy-related negative events, defined as psychotropic dose escalation, augmentation, or switching. Results: The study group included 137 patients (55% males, age 63.3 ± 12.3 years), and the control group included 1787 patients (60% males, age 47 ± 16.9 years). Significant differences were observed across nearly all outcomes, favoring the LDA co-treatment group. Patients in the study group exhibited lower rates of medication dosage increase (40 [29%] vs. 726 [40.5%], p = 0.01); fewer changes and/or additions of psychotropic medications (37 [26.9%] vs. 778 [43.5%], p < 0.001); and a non-significantly lower rate of suicide attempts (0 [0%] vs. 16 [0.9%], p = 0.53). Conclusions: Overall, LDA co-treatment was associated with better clinical outcomes among patients with BD, schizophrenia, and SAD. Follow-up large-scale epidemiological studies and prospective randomized clinical trials are needed to examine the therapeutic potential of add-on LDA to psychotropic medications. Full article

Background: Treating depression and anxiety in adolescents can be challenging due to interindividual variability in medication response. With current trial-and-error prescribing practices, adolescents may undergo multiple medication changes over months or years before an effective and tolerated drug and dose are identified. Pharmacogenomic (PGx) testing can identify interindividual differences in drug metabolism, and evidence supporting PGx-guided prescribing in adults with mental disorders is growing. However, its impact on pediatric psychotropic prescribing remains underexplored. Methods: This is a protocol for a parallel-arm, multicentre, randomized controlled trial. Canadian adolescents aged 12–17 years who are initiating or switching a selective serotonin reuptake inhibitor (SSRI) for depression and/or an anxiety disorder under physician care are eligible. A total of 452 participants will be randomized 1:1 to PGx-guided SSRI prescribing (experimental) or SSRI prescribing based on current practice guidelines (control). Participants, caregivers, prescribing clinicians, outcome assessors, and investigators will be blinded to treatment allocation. Dual primary outcomes are symptom remission at 12 weeks, measured with the Quick Inventory of Depressive Symptomatology–Adolescent (QIDS-A17-SR) and the Screen for Child Anxiety Related Disorders (SCARED). Secondary outcomes, assessed at 4, 8, and 12 weeks, include participant- and physician-rated changes in depressive and anxiety symptoms, role functioning, health-related quality of life, health care utilization, cost-effectiveness, side-effect burden, medication burden, and adherence. Multiple testing will be addressed using the Hochberg method, and a parallel gated analysis will account for non-actionable genotypes. Secondary analysis will estimate minimal clinically important differences for symptom and role-functioning change with PGx-guided therapy. Discussion: At the time of writing, 36 participants have consented and been randomized to an intervention. This trial will evaluate whether PGx-guided prescribing improves symptom remission in adolescents treated with SSRIs. If efficacious, results should be interpreted with existing pediatric pharmacokinetic, observational, and adult trial data to inform PGx use in managing pediatric anxiety and depressive disorders. Full article

Background: 47,XYY syndrome is a relatively common sex chromosome aneuploidy that remains largely underdiagnosed. While its somatic phenotype is often mild, growing evidence indicates a substantial burden of neurodevelopmental and psychiatric morbidity. However, the characterization of the neuropsychiatric phenotype across development, particularly during adolescence, and the associated treatment challenges remain incomplete. Objectives: To provide a comprehensive narrative review of the neuropsychiatric phenotype of 47,XYY syndrome and to illustrate clinical complexity and treatment response through a case series of adolescents. Methods: A narrative review of the literature was conducted focusing on genetics, neurodevelopmental and psychiatric features, neuroimaging and neurophysiology findings, clinical course, and management strategies in 47,XYY syndrome. This review is complemented by a case series of adolescents with confirmed 47,XYY karyotype, evaluated for developmental history, psychiatric comorbidity and response to pharmacological and non-pharmacological interventions. Results: The literature consistently describes increased risks of language impairment, executive dysfunction, ADHD, autism spectrum traits, and emotional and behavioral dysregulation in males with 47,XYY syndrome. Psychiatric vulnerability appears to increase during adolescence and adulthood, with elevated rates of mood, psychotic, and substance use disorders. The presented cases illustrate a convergent clinical trajectory marked by early developmental delays, progressive behavioral dysregulation in adolescence and limited or inconsistent response to multiple classes of psychotropic medications, suggesting a pattern of pharmacoresistance in a subset of patients. Conclusions: 47,XYY syndrome is associated with a distinct and heterogeneous neuropsychiatric phenotype that extends beyond early neurodevelopmental disorders. Early diagnosis alone may be insufficient to prevent severe psychiatric outcomes, highlighting the need for long-term monitoring and integrated, multidisciplinary management. Further research is required to identify early predictors of high-risk trajectories and to optimize treatment strategies for this population. Full article

The primary and secondary objectives of this article are, respectively, to measure the effect of habitual physical activity on total medication expenditures and on expenditures specifically related to psychotropic drugs among primary healthcare users in a large Brazilian city. This cross-sectional study with a retrospective component was conducted using Propensity Score Matching (PSM). PSM is a robust and widely utilized method in studies evaluating the impact of public policies, particularly in observational data settings where randomization is infeasible. Medication expenditures and habitual physical activity data referring to the past 12 months were collected from 250 users of both sexes, aged over 40 years, across seven primary healthcare units. The average medication expenditure was USD 6.33 (95% CI: −206.64 to −31.02), and for psychotropics, USD 0.63 (95% CI: −217.75 to −11.87). The effect of physical activity on expenditures showed that more active individuals spent on average USD 34.83 less on all medications and USD 4.34 less on psychotropics compared to less active individuals. The findings of this study reinforce the importance of the physical activity as a health promotion strategy and as a means to reduce public health expenditures. Full article