Medicine and Pharmacology

Abstract: Background/Objectives: Professional burnout is widespread among surgeons. Despite the abundance of research on organizational factors, little attention has been paid to the resources developed during training that may protect against burnout. The aim of this study was to examine the relationship between involvement in student research and prac-tical clubs (SRPCs) during training and burnout symptoms during surgical practice, as well as subjective assessments of career progression in surgical graduates. Methods: A cross-sectional survey of 96 surgeons (32 women, 64 men; mean age 33.1 ± 6.4 years) who participated in the SRPC over a 20-year period was conducted. Burnout was assessed us-ing the Maslach Burnout Inventory (MBI) questionnaire. Involvement indicators (duration, activity) were combined into an integrative activity index using the principal component analysis. Multiple linear regression analysis and Spearman's rank correlation analysis were used. Results: The sample was characterized by a favorable burnout profile: emo-tional exhaustion at a medium/high level was detected in 71.9%, depersonalization at a low level was detected in 62.5% (high level in only 7.3%), and there was no reduction in professional achievements. Regression analysis revealed a strong negative relationship between the integrative activity index and depersonalization (β = –0.740, p < 0.001, R² = 0.535, f² = 1.15): higher involvement in SRPC was associated with a lower level of deper-sonalization. No significant connections were found with emotional exhaustion and re-duction in achievements. Subjective assessment of the impact of SRPC on one’s career was negatively correlated with depersonalization (rₛ = –0.517, p < 0.001) and emotional ex-haustion (rₛ = –0.319, p = 0.002). Conclusions: Engagement in student research can act as a protective resource against depersonalization, a key component of burnout, by promoting meaningful professional interactions and strengthening professional identity. The find-ings support the need to support SRPC in medical schools not only as a means of training research personnel but also as a tool for preventing professional strain and burnout among actively working surgeons.

Abstract: Background/Objectives: Assessment of Internet Gaming Disorder (IGD) relies largely on retrospective self-report and clinical interviews, which may be affected by recall bias, social desirability bias, and limited sensitivity to within-person behavioral change. This study evaluated an AI-enabled, privacy-preserving digital phenotyping framework for personalized IGD risk stratification under controlled simulation assumptions. Methods: A reproducible synthetic dataset of 1,000 virtual user profiles was generated; 20% were assigned to an elevated-risk class, and 5% balanced stochastic label noise was introduced to approximate imperfect ground truth. Four aggregated telemetry features were modeled: average session duration, sessions per week, Late-Night Index, and application-switching rate. Random Forest, Logistic Regression, and Gradient Boosting classifiers were evaluated against playtime-only baselines using a stratified 80:20 train–test split. Results: In the primary Random Forest model, accuracy was 0.880, balanced accuracy was 0.850, sensitivity was 0.800, specificity was 0.900, area under the receiver operating characteristic curve (ROC-AUC) was 0.909, area under the precision–recall curve (PR-AUC) was 0.779, and the Brier score was 0.089. All-feature models substantially outperformed playtime-only baselines. Feature-importance analyses recovered the known signal hierarchy encoded in the synthetic data-generating process, with application-switching rate and Late-Night Index showing the largest Gini-based and permutation-importance values. Performance degraded progressively as label noise increased from 0% to 20%. Conclusions: The framework demonstrates the methodological feasibility of transforming aggregated, privacy-preserving behavioral telemetry into interpretable simulated risk signals for IGD. The findings are hypothesis-generating and do not establish clinical validity or diagnostic performance. Longitudinal validation in clinically characterized cohorts using validated psychometric instruments and person-level calibration is required before practical deployment.

Abstract: Autism spectrum disorder is characterized by marked heterogeneity in developmental trajectories, functional regulation, therapeutic engagement, and intervention responsiveness. Although behavioral, developmental, educational, and family-centered interventions remain central to autism support, children with similar diagnostic labels and apparently comparable intervention exposure may show substantially different trajectories of engagement and benefit. This Hypothesis and Theory article proposes a neurodevelopmental regulation framework for examining whether multidomain biological burden may contribute to variability in therapeutic engagement and intervention responsiveness in autism. The framework is deliberately presented as a hypothesis-generating model rather than as a validated clinical tool. It organizes biological burden, energetic capacity, adaptive neurodevelopmental window accessibility, neuroplastic capacity, therapeutic engagement, and intervention responsiveness into a testable sequence of research constructs. Biological burden is conceptualized as a multidomain, state-sensitive and trait-influenced construct informed by sleep-circadian regulation, gastrointestinal symptoms, immune/allergic vulnerability, fatigue, pain or discomfort, autonomic regulation, sensory-physiological stress, and, where feasible, reproducible biological markers. Therapeutic engagement is conceptualized as a multidimensional functional construct reflecting regulatory availability, attentional and interactional access, responsiveness to support, persistence and adaptive effort, contextual transfer, and relational-motivational engagement. The manuscript distinguishes the proposed model from existing allostatic load, Research Domain Criteria, developmental systems, predictive processing, social motivation, and precision psychiatry approaches. It also provides candidate operational domains for biological burden and therapeutic engagement, proposes a staged validation roadmap, and discusses developmental confounds, state-trait variability, measurement limitations, and safeguards against overmedicalization. The framework does not recommend biomarker screening, biological treatment, or treatment selection at this stage. Its purpose is to support future feasibility studies, construct validation, longitudinal modeling, and ethically cautious precision-stratified autism research.

Abstract: Background/Objectives: Neuroinflammation is increasingly recognized as a key mechanism linking infectious diseases with psychiatric disorders through interactions between peripheral immune activation, metabolic pathways, and brain network alterations. This review aimed to synthesize current evidence on the neuroimmune mechanisms and biomarkers underlying infection-associated psychiatric disorders. Methods: A narrative literature review was conducted using the Web of Science Core Collection, PubMed/MEDLINE, Scopus and PsycINFO databases. Boolean search strategies identified studies investigating neuroinflammatory biomarkers, neuroimmune mechanisms, and psychiatric outcomes associated with infectious diseases. The search (2022–June 2025) included 71 studies in the final qualitative analyses. Results: The reviewed evidence consistently identified inflammatory cytokines and chemokines, complement proteins, blood–brain barrier markers, glial activation biomarkers, neuroaxonal injury markers, kynurenine pathway metabolites, and neuroimaging markers as complementary indicators of infection-induced neuroimmune dysfunction. Across diverse bacterial, viral, parasitic, and systemic infections, these mechanisms converged on peripheral immune activation, blood–brain barrier disruption, microglial activation, kynurenine pathway dysregulation, synaptic dysfunction, and altered brain network connectivity, contributing to depression, anxiety, psychosis, cognitive impairment, and fatigue. Based on these findings, a unified neuroimmune model integrating peripheral and central mechanisms is proposed. Conclusions: Neuroinflammation emerges as a shared biological pathway linking infections with transdiagnostic psychiatric phenotypes. Although no single biomarker currently demonstrates sufficient diagnostic specificity, integrated multimodal biomarker panels may improve biological stratification, facilitate earlier identification of high-risk patients, and support the development of mechanism-based precision approaches for infection-associated psychiatric disorders.

Abstract: Background: Autism spectrum disorder (ASD) is characterized by substantial biological and clinical heterogeneity that cannot be adequately explained by isolated biomarkers or single-system models. The Biological Burden Index (BBI) has been proposed as a hypothesis-generating multidimensional framework to organize convergent biological dysregulations that may contribute to interindividual variability in adaptive capacity, neurodevelopmental plasticity, and therapeutic responsiveness. Objective: This article examines how the BBI may be operationalized as a measurable, testable, and translational research construct rather than as a validated clinical instrument, providing a methodological foundation for future empirical investigation and precision stratification in autism. Methods and Conceptual Framework: Rather than representing a single biomarker, the BBI conceptualizes cumulative biological burden as an emergent multidomain property arising from the dynamic convergence of previously established physiological, molecular, immunological, metabolic, autonomic, and neurodevelopmental domains. Four complementary operational models are examined: (1) a weighted composite index, (2) a multidimensional burden profile, (3) a latent burden construct, and (4) a biological stratification framework for identifying clinically meaningful subgroups. Candidate biological domains, objective indicators, multimodal measurement layers, mathematical aggregation strategies, analytical approaches, and validation requirements are reviewed. Results and Translational Perspective: We argue that premature reduction of the BBI to a single summary score risks obscuring biologically meaningful heterogeneity, whereas multidimensional profile-based approaches provide a stronger foundation for early empirical validation, longitudinal characterization, biomarker integration, and precision stratification. Operationalization is presented as the critical methodological process through which the BBI can evolve from a conceptual framework into a scientifically usable research construct. Conclusions: By clarifying operational pathways, measurement architectures, and validation strategies, the BBI establishes a methodological foundation for future multimodal biomarker integration, translational autism research, and the progressive development of complementary precision frameworks addressing therapeutic engagement, intervention responsiveness, and human-supervised digital implementation while preserving the multidimensional complexity of biological burden.

Abstract: Background: Current screening instruments for problematic gaming primarily identify Gaming Disorder after clinically significant functional impairment has developed. However, pediatric clinical practice requires practical frameworks that facilitate earlier recognition of maladaptive gaming behaviors before substantial functional impairment becomes established. Objective: To propose and describe GAME-F (Gaming Addiction Monitoring and Evaluation with Functional Impairment), a prevention-oriented conceptual framework designed to support the early identification and clinical assessment of problematic gaming in children and adolescents. Methods: This conceptual study integrates evidence from addiction medicine, developmental neuroscience, pediatric public health, and the behavioral recognition philosophy underlying the CAGE questionnaire. Existing screening instruments and theoretical models of behavioral addiction were critically reviewed to identify conceptual gaps between diagnostic assessment and early preventive intervention. Results: GAME-F comprises five domains: Give Up, Angry, More, Everywhere in the Mind, and Functional Impairment. Unlike existing diagnostic instruments, GAME-F conceptually distinguishes addiction-related behavioral changes from functional impairment, thereby emphasizing prevention and early clinical recognition rather than diagnosis alone. The framework is operationalized through complementary components consisting of practical scoring principles, a clinical decision matrix, and representative clinical cases, thereby supporting a stepwise process from structured assessment to clinical interpretation and practical application. Conclusions: GAME-F provides a practical clinical framework for pediatric practice, school health, family education, and community-based prevention. By promoting earlier recognition of problematic gaming behaviors before significant functional impairment develops, the framework may facilitate timely preventive intervention and resilience-oriented care. Future studies should evaluate its reliability, validity, and clinical utility in diverse pediatric populations.

Abstract: Autism spectrum disorder is characterized by substantial heterogeneity in developmental trajectories, physiological regulation, participation, therapeutic engagement, and response to intervention. Although increasing attention has been given to biological burden, neuroplasticity, fatigue, sleep, and intervention responsiveness in autism, the construct linking these domains remains insufficiently defined. This manuscript proposes energetic capacity as a hypothesis-generating translational construct describing the dynamic biological and functional resources available to sustain regulation, participation, recovery, learning, and adaptive change. Energetic capacity is not intended to represent mitochondrial function alone, a fixed trait, a diagnostic marker, a global severity score, or a measure of motivation. Rather, it is conceptualized as a state-sensitive construct that may fluctuate across sleep quality, stress exposure, illness, sensory load, intervention intensity, environmental demands, and recovery conditions. Within the Framework for Integrated Autism Precision Care (FIAP), energetic capacity is positioned as one possible bridge between multidomain biological burden, adaptive reserve, neuroplastic accessibility, therapeutic engagement, and intervention responsiveness. However, energetic capacity is proposed as a standalone construct that can be evaluated independently of FIAP. The manuscript distinguishes energetic capacity from adaptive reserve, allostatic load, fatigue, self-regulation, motivation, and task engagement; outlines candidate physiological, behavioral, therapeutic-process, and contextual indicators; proposes testable hypotheses; and describes a staged pathway toward empirical validation. Energetic capacity remains an unvalidated conceptual research construct. Future studies should examine feasibility, reliability, construct validity, longitudinal variability, predictive value, fairness, and accessibility before any clinical or translational application is considered.

Abstract: Background/Objectives: The rates of obesity and binge-eating disorder (BED) have increased markedly over the last few decades. The onset of these conditions has been attributed in part to the disruption of neural pathways that regulate food reward. Existing literature has identified the endogenous opioid system as an important mediator of pleasure and reinforcing behaviors associated with food intake. While the relationship between opioids and food intake has been studied extensively, how dysregulated opioid signaling contributes to compulsive eating still remains unclear. Therefore, the aim of this review is to analyze the role of opioid peptides and receptors, and their interactions with dopamine in hedonic feeding. Methods: We conducted a narrative review of preclinical and clinical trials, incorporating studies that were relevant to opioid-mediated feeding and food reward. Results: β-endorphins modulate the hedonic value of food, but their effects appear to be context-dependent. Enkephalins regulate motivational drive toward food, while nociceptin signaling preferentially promotes the consumption of palatable foods under binge-like conditions. Consistent with these findings, NOP antagonism reduces binge on a high fat diet (HFD) without affecting homeostatic eating patterns. Lastly, chronic mu opioid receptor (MOR) activation by palatable foods may induce neuroadaptive changes, including receptor desensitization, dopamine D2 receptor downregulation, and reward hypofunctionality, paralleling mechanisms associated with substance use disorders. Conclusions: Altered MOR signaling disrupts the hedonic and behavioral mechanisms that regulate feeding behavior. Pharmacological therapies targeting opioid and opioid-dopamine interactions may show promise for treating obesity and BED. However, additional research is still needed to clarify peptide-specific mechanisms, sex differences, and long-term neurobiological consequences of hedonic and compulsive eating.

Abstract: Autism intervention responsiveness is highly heterogeneous, and current clinical approaches often remain insufficiently sensitive to dynamic fluctuations in biological, physiological, environmental, and behavioral readiness for therapeutic engagement and learning. This manuscript introduces NAI-Digital, a hypothesis-generating, human-supervised multimodal convergence architecture for investigating dynamic neuroplastic accessibility in autism. Neuroplastic accessibility is defined here not as neuroplasticity itself, but as the degree to which current conditions may support access to adaptive learning, engagement, consolidation, and therapeutic responsiveness at a given moment. NAI-Digital organizes candidate determinants of accessibility into four functional domains: Fuel, representing biochemical and systemic substrate; Support, representing physiological regulation, recovery, sleep, autonomic balance, and body-state stability; Trigger, representing environmental sensory load, predictability, transitions, contextual stress, and task demand; and Engine, representing behavioral priming, movement, preparatory routines, and activity-dependent readiness. The architecture proposes a dual-output logic combining a global accessibility state with domain-specific profiles, allowing constrained accessibility to be interpreted not as child failure or absence of intervention potential, but as a state requiring modulation, pacing, regulation, or restoration. The framework further introduces accessibility-oriented adaptation and neuroplastic readiness as translational targets for future feasibility research. NAI-Digital is not presented as a validated diagnostic tool, medical device, treatment-selection algorithm, or autonomous decision-support system. Rather, it is a conceptual and translational architecture intended to support future construct validation, measurement feasibility testing, stakeholder interpretation, longitudinal monitoring, and ethically governed pilot studies. The manuscript outlines testable hypotheses, falsifiability conditions, safety-aware safeguards, and a staged validation pathway for investigating whether multimodal convergence patterns can meaningfully inform timing-sensitive, individualized, and equity-aware autism intervention research.

Abstract: Background/Objectives: Antipsychotic drug utilization has changed substantially over recent decades, reflecting evolving prescribing practices, drug availability, and treatment guidelines. Methods: This study analyzed national antipsychotic consumption in Serbia from 2006 to 2024 using official data from the Medicines and Medical Devices Agency of Serbia. Utilization was expressed as defined daily doses per 1,000 inhabitants per day, and trends were assessed using linear and joinpoint regression analyses. Results: Total antipsychotic utilization increased from 4.35 to 14.42 DDD/1,000 inhabitants/day, representing a 231.5% increase. This growth was predominantly driven by atypical antipsychotics, whose utilization increased from 1.16 to 10.91 DDD/1,000 inhabitants/day (+840.2%). In contrast, typical antipsychotic utilization remained relatively stable in absolute terms. The share of atypical antipsychotics increased from 26.7% in 2006 to 75.6% in 2024, while the atypical : typical utilization ratio increased from 0.36 to 3.10. Atypical antipsychotics surpassed typical agents in 2013. Marked increases were observed for olanzapine, quetiapine, aripiprazole, paliperidone, risperidone, and clozapine, while chlorpromazine and fluphenazine declined. Conclusion: These findings demonstrate a substantial increase in overall antipsychotic utilization in Serbia and a pronounced structural shift toward atypical agents, highlighting the need for continued monitoring of prescribing trends, safety outcomes, and population-level treatment patterns.

Abstract: The therapeutic use of ketamine and other psychoactive substances in psychiatry is attracting growing research interest, particularly in treatment-resistant depression and related conditions refractory to conventional care. Ketamine exerts direct pharmacological antidepressant effects through NMDA receptor antagonism and downstream neuroplastic mechanisms; its combination with structured psychotherapy represents a promising augmentation strategy, though one that remains largely experimental and is currently recommended only for patients who have not responded to established treatments. By transiently attenuating self-referential processing and the dominance of habitual evaluative frameworks, psychoactive substances may enable new affective and cognitive connections — creating a window of opportunity for therapeutic change that is difficult to achieve through endogenous means alone. This potential appears transdiagnostic, extending beyond depression to trauma-related disorders, substance dependence, and other serious psychiatric conditions. The present article describes the theoretical and neurobiological foundations of altered states of consciousness relevant to this work, and presents preliminary clinical experience with ketamine-augmented hypnotherapy (KAHT) as a specific implementation of ketamine-assisted psychotherapy.

Abstract: Background/Objectives: According to current concepts, neuroinflammation is one of the putative causes of autism spectrum disorders (ASD) development. However, the role of neutrophils in neuroinflammation remains insufficiently studied. The study was aimed to determine the role of neutrophils in the neuroinflammatory mechanism of ASD development based on a comparative analysis of physiological and behavioral disturbances and the inflammatory response to early postnatal administration of valproic acid (VPA) to Wistar rats. Methods: The study was performed on 38 rat pups, half of which were injected intraperitoneally with aqueous solution of VPA at a dose of 150 mg/kg from 6 to 12 postnatal days (PND), control rats received water. Standard physiological and behavioral tests were used: weight monitoring, pain sensitivity (“hot plate” test) on 25 PND, and social behavior (sib/non-sib test) on 55 PND. Neutrophil elastase (NE) and alpha1-proteinase inhibitor (α1-PI) activity in serum and cerebellum homogenate was measured spectrophotometrically. Complement system (CS) activity was analyzed by the death rate of Tetrahymena pyriformis ciliates in the presence of rat serum. Results: Early postnatal administration of VPA to Wistar rats induces physiological and behavioral changes characteristic of ASD, confirming the validity of the experimental model used. These changes are accompanied by increased activity of inflammatory factors (CS, α1-PI, NE) in the rat serum, indicating an inflammation development. VPA treatment increased NE activity in the cerebellum, which may indicate neutrophil infiltration of the brain and neuroinflammation development. Conclusions: The data obtained indicate the role of neutrophils in neuroinflammatory mechanisms of ASD development.

Abstract: Background/Objectives: Cannabis use is prevalent in first-episode psychosis (FEP) and is associated with poor clinical outcomes. Cariprazine, a dopamine D3/D2 partial agonist with preferential D3 affinity, may offer clinical advantages for both psychotic symptoms and comorbid substance use; however, naturalistic data in FEP patients with active cannabis use are lacking. Methods: We conducted a retrospective naturalistic case series of eight FEP patients with active cannabis use treated with cariprazine for six months across two Greek Early Intervention Units (PNOES Athens and Thessaloniki, EPAPSY). Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) Five-Factor model and cannabis use using the Cannabis Experience Questionnaire (CEQ) at baseline and six months. Descriptive statistics only were applied. Results: At six months, lower mean PANSS scores were observed for positive symptoms (12.75 vs. 10.38), disorganization (11.25 vs. 9.13), and hostility (9.13 vs. 8.38). Negative symptoms showed a modest numerical change (16.00 vs. 15.12) and anxiety/depression remained unchanged (11.63 at both time points). Cannabis use frequency shifted toward lower categories in six of eight participants, with two reporting complete cessation. Conclusions: These preliminary, hypothesis-generating observations suggest that cariprazine may warrant further study in FEP with comorbid cannabis use. The findings cannot be interpreted as evidence of efficacy given the small, uncontrolled, diagnostically heterogeneous sample.

Abstract: Lithium remains the gold-standard maintenance treatment for bipolar disorder (BD) and is distinguished by its unique anti-suicidal and neuroprotective properties. Beyond its established psychiatric efficacy, growing evidence suggests that lithium may modulate fundamental mechanisms of biological aging. In parallel, cellular senescence has emerged as a central process linking oxidative stress, chronic inflammation, mitochondrial dysfunction, and impaired cellular resilience with neurodegeneration and psychiatric disease. Notably, BD is increasingly associated with features of accelerated aging, including telomere shortening, increased inflammatory burden, and structural brain changes consistent with premature brain aging. In this review, we discuss current evidence supporting lithium as a potential senostatic agent in the central nervous system, and specifically in BD. Experimental studies indicate that lithium attenuates several hallmarks of cellular senescence and promotes cellular resilience under conditions of oxidative, inflammatory, and genotoxic stress. These effects appear to involve coordinated modulation of neuroinflammatory signaling, mitochondrial function, oxidative stress responses, genomic stability, and neurotrophic pathways. Clinical findings further suggest that chronic lithium treatment may be associated with preserved telomere length and attenuated biological aging in the brain in BD. Collectively, the available data support a model in which lithium acts not only as a mood stabilizer but also as a broader regulator of aging-associated processes relevant to neuropsychiatric and neurodegenerative disorders. Although the senomodulatory effects of lithium appear context- and cell-type-dependent, its established clinical use and pleiotropic biological actions make it a promising candidate for translational senotherapeutic research.

Abstract: Background: Internalized stigma is progressively acknowledged as a key determinant of recovery in first-episode psychosis (FEP). Yet its interaction with quality of life, social anxiety, and illness insight remains insufficiently clarified. Objective: This study investigated the relationships between internalized stigma, quality of life, social anxiety, and insight in patients experiencing a first episode of psychosis. Methods: This observational cross-sectional study included 90 patients experiencing a first episode of psychosis recruited from a specialized early intervention service.The tools used for this study were the Internalized Stigma for Mental Illness Scale (ISMI), World Health Organization Quality of Life Assessment-BREF (WHOQoL-BREF), Liebowitz Social Anxiety Scale (LSAS-SR), Schedule for the Assessment of Insight-Expanded version (SAI-E), and Positive and Negative Syndrome Scale (PANSS). Results: The results of this study indicated that the Internalized Stigma for Mental Illness Scale showed statistically significant linear correlations with the LSAS-SR [anxiety (r=0.399, p <0.001) and Avoidance (r=0.421, p <0.001)], with positive correlations and approximately medium associations. In the multivariable analyses, ISMI was inversely associated with all WHOQoL-BREF domains (Physical health: -0.72 units 95% CI: -1.09 to -0.35, p<0.001; Mental health:-1.04, 95% CI: -1.45 to -0.63, p<0.001; social relationships:-0.79, 95% CI:-1.39 to -0.18, p=0.012; environmental health: -0.70, 95% CI: -1.00 to -0.39, p<0.001). Conclusion: Internalized stigma appears to represent a central clinical factor linked to poorer quality of life and increased social anxiety in FEP, drawing attention to the importance of early stigma-focused interventions within recovery-oriented care.

Abstract: This study aimed to compare antisaccade performance among adolescents with obsessive-compulsive disorder (OCD), their unaffected siblings, and healthy controls, and to examine whether this performance may serve as a candidate endophenotypic marker for OCD. The study included 48 adolescents aged 12–18 years with OCD, 35 unaffected siblings, and 39 healthy controls. Participants completed an antisaccade task using an eye-tracking device, and correct antisaccade percentage, latency, and saccadic velocity were measured to capture multiple components of oculomotor inhibitory control. The OCD group showed lower correct response rate and longer latency compared with healthy controls, while the sibling group demonstrated intermediate performance across these measures. Saccadic velocity was lower in both the OCD and sibling groups than in controls, with no significant difference observed between these two groups. Additional analyses indicated that both OCD diagnosis and sibling status were independently associated with antisaccade correct response rate and latency, whereas findings for antisaccade velocity should be considered exploratory. These findings suggest that impairments in antisaccade performance may not be specific to OCD but may also be present, to a milder extent, in unaffected siblings, supporting the view that oculomotor inhibitory control processes may represent a candidate endophenotypic marker associated with familial vulnerability to OCD and contribute to understanding the neurocognitive mechanisms underlying the disorder.

Abstract: Art therapy is a nonverbal form of therapy that can provide individuals a safe and supportive environment for expression and processing, particularly of trauma-related emotions and memories. For individuals who have experienced trauma, this nonverbal, creative, and tactile modality may serve as a beneficial complement, integrative aspect, or alternative to current gold-standard forms of care including exposure-based cognitive behavioral therapy, cognitive processing therapy, eye movement desensitization and reprocessing, and pharmacotherapy. In this narrative review, findings across the hier-archy of evidence, from theory and case studies to controlled trials and meta-analyses, in both adults and youth, are summarized to explore the benefits and limitations of art therapy to address trauma and related psychopathology. Findings are contextualized within the Expressive Therapies Continuum (ETC). We then provide directions for future research, to enhance the quality and diversity of evidence supporting art therapy in the trauma treatment space, with application of the ETC in research and treatment.

Abstract: Four clinical literatures — psychedelic-assisted therapy, accelerated transcranial magnetic stimulation, closed-loop deep brain stimulation, and reconsolidation-based trauma therapy — produce durable change from brief, often single, interventions in conditions the current standard of care has not solved. The convergence is not procedural. Each modality transiently induces a high-plasticity brain state — a window with roots in critical-period biology, memory reconsolidation, and the critical-brain literature in statistical physics — and the experience delivered into that state, not the intervention that opened it, is what produces the durable change. Stimulus and experience are co-equal active ingredients: the durable change is their product. Treatments that open the window without controlling what enters it, or deliver the right experience outside it, fail for reasons of timing and context rather than of the intervention itself. Naming the window as a measurable, manipulable variable turns these scattered results into one framework with testable predictions — about when to intervene, what to pair an opener with, and how to sequence treatments — and gives trial design and clinical practice a target the current paradigm does not provide.

Abstract: Background: University students are particularly vulnerable to elevated stress, anxiety, and reduced psychological well-being, especially in the post-pandemic period. Immer-sive virtual reality (VR) has emerged as a promising technology-supported approach for relaxation and stress reduction; however, evidence regarding its short-term psycho-physiological effects in academic populations remains limited. Objective: The aim of this study was to evaluate the effects of a short-term immersive VR relaxation intervention on perceived stress and autonomic nervous system activity in university students. Methods: A randomized controlled study with repeated measures was conducted among university students from Opole, Poland. Participants were allocated to an immersive VR group or a non-immersive screen-based control group. Both groups received identical relaxation content for 10 minutes daily over five consecutive days, differing only in the level of immersion. Heart rate variability (HRV) was recorded continuously during four consecutive 5-minute epochs within each session. Perceived stress was assessed using the Perceived Stress Scale-10 before and after the intervention. Cybersickness symptoms were assessed in the VR group. Results: Immersive VR elicited more pronounced favourable changes in HRV parameters than non-immersive exposure, including increased lnRMSSD, SDNN, and PNS index values, together with reduced mean heart rate, SNS index, and Stress index. Both groups showed significant reductions in perceived stress; however, the reduction was signifi-cantly greater in the VR group (p = 0.009, Cohen’s d = 0.78). Cybersickness symptoms were low and decreased across the intervention period. Conclusions: Short-term immersive VR relaxation appears to be a feasible, well-tolerated, and promising approach for reducing perceived stress and supporting autonomic reg-ulation in university students. Further studies with longer follow-up are warranted.

Abstract: Psychiatric decision-making frequently occurs under conditions of substantial uncertainty in which both intervention and non-intervention may carry clinically significant consequences. Although therapeutic inertia has been extensively studied in chronic medical conditions such as diabetes and cardiovascular disease, its implications for psychiatry remain comparatively underexplored despite the distinctive epistemological, emotional, and institutional challenges characterizing mental healthcare. This narrative review examines how cognitive biases, asymmetrical risk perception, defensive clinical cultures, institutional pressures, and uncertainty intolerance may contribute to therapeutic inertia in psychiatric practice. Particular attention is given to the tendency to perceive harms associated with active intervention as more salient and professionally consequential than the often slower and less visible harms associated with undertreatment, persistent suicidality, chronic suffering, psychosocial deterioration, and functional disability. The review discusses how therapeutic inertia may manifest through delayed treatment intensification, prolonged continuation of partially ineffective therapies, normalization of chronic symptoms, and hesitation toward interventions perceived as high risk or institutionally burdensome. Clozapine underutilization in treatment-resistant schizophrenia is examined as a paradigmatic example of the tension between fear of iatrogenic harm and the substantial risks associated with persistent severe mental illness. Finally, the article explores future directions for more balanced psychiatric risk–benefit models capable of incorporating both the risks of intervention and the risks of non-intervention within reflective, patient-centered approaches to clinical decision-making under uncertainty.