Background: The plasma level of antipsychotics and their metabolites depends on the activity of the cytochrome P450 (CYP) system in the liver. This research aims to test the individual response variability to atypical antipsychotic drugs, depending on the activity of the CYP2D6 enzyme. Methods: In a prospective, noninterventional study, we included 56 adolescents, 51.79% male, diagnosed with schizophrenia. The patients underwent DNA sampling for genotyping SNP by RT-PCR and CYP* allelic variants using Applied Bio-systems™ TaqMan^® Assays Foster City, CA, USA). and clinical and paraclinical assessments. The effectiveness of the therapy was evaluated with the PANSS scores at baseline and 3, 6, and 12 months after the initiation of an atypical antipsychotic treatment. Results: Based on the genotyping results, the patients were divided into slow metabolizers (Group 1), extensive metabolizers (Group 2), and intermediate metabolizers (Group 3). The PANSS score showed a significant decrease in Group 2, compared to Group 3 after 3 (p = 0.02), 6 (p = 0.0009), and 12 months (p < 0.0001). The patients in Group 1 showed high PANSS scores, and those in Group 2 had fewer adverse reactions than the other groups. Conclusions: Assessing the CYP2D6 polymorphism may be useful in clinical pediatric psychiatric practice towards improving clinical results and patients’ quality of life.

Pathogenic variants in the NEXMIF gene are associated with a broad neurodevelopmental phenotype, including autism spectrum disorder (ASD), intellectual disability (ID), and epilepsy. However, the role of NEXMIF in specific epileptic syndromes remains insufficiently explored. We present the case of an 11.9-year-old Romanian girl diagnosed with ASD, attention-deficit/hyperactivity disorder (ADHD), mild ID, and Jeavons syndrome (generalized epilepsy characterized by eyelid myoclonia, absence seizures, and photosensitivity). Genetic testing identified a pathogenic NEXMIF variant: c.1882C>T (p.Arg628*), a pathogenic variant rarely reported in the literature, with only two documented cases to date. To better understand the genotype–phenotype correlation, we conducted a systematic review of NEXMIF-associated disorders and compared our findings with previously reported cases. Our analysis suggests that NEXMIF variants may contribute to a broader spectrum of epileptic syndromes, including photosensitive epilepsy such as Jeavons syndrome. This highlights the need for a greater awareness of atypical seizure presentations in individuals with NEXMIF-related disorders. This study underscores the importance of genetic testing in individuals with overlapping ASD and epilepsy phenotypes as early diagnosis may facilitate targeted therapeutic interventions and genetic counseling. Further research is needed to clarify the molecular mechanisms linking NEXMIF dysfunction to epileptic syndromes and neurodevelopmental disorders.

Background and Objectives: Substance use disorders (SUDs) affect millions worldwide. Despite increasing drug use, treatment options remain limited. Psychedelic-assisted therapy (PAT), integrating psychedelic substances with psychotherapy, offers a promising alternative by addressing underlying neural mechanisms. Materials and Methods: This review’s purpose is to investigate the current understanding of psychedelic therapy for treating SUDs, including tobacco, alcohol, and drug addiction. The systematic review approach focused on clinical trials and randomized controlled trials conducted from 2013 to 2023. The search was performed using PubMed, Google Scholar, and Consensus AI, following PRISMA guidelines. Studies involving psychedelics like LSD, psilocybin, ibogaine, and ayahuasca for treating various addictions were included, excluding naturalistic studies and reviews. Results: Our results highlight the key findings from 16 clinical trials investigating psychedelic therapy for SUDs. Psychedelics like psilocybin and ayahuasca showed promise in reducing alcohol and tobacco dependence, with psilocybin being particularly effective in decreasing cravings and promoting long-term abstinence. The studies revealed significant improvements in substance use reduction, especially when combined with psychotherapy. However, the variability in dosages and study design calls for more standardized approaches. These findings emphasize the potential of psychedelics in SUD treatment, though further large-scale research is needed to validate these results and develop consistent protocols. Conclusions: This research reviewed the past decade’s international experience, emphasizing the growing potential of psychedelic therapy in treating SUDs pertaining to alcohol, tobacco, and cocaine dependence. Psychedelics such as psilocybin and ketamine can reduce cravings and promote psychological well-being, especially when combined with psychotherapy. However, regulatory barriers and specialized clinical training are necessary to integrate these therapies into mainstream addiction treatment safely. Psychedelics offer a promising alternative for those unresponsive to conventional methods.

Psychotic disorders in youth pose significant challenges for mental health services, necessitating a detailed understanding of the interplay between risk factors and resilience. This systematic review aimed to assess how resilience factors might buffer the adverse effects of risk factors on the development of psychosis among youth, thereby informing targeted interventions. Studies were selected based on criteria including a focus on individuals aged up to 25 years old at risk for psychosis, the examination of both risk factors and resilience, and the use of validated instruments for measuring outcomes. Literature searches were conducted across several databases, such as PubMed, Scopus, and Web of Science. Data extraction emphasized odds ratios (ORs) and hazard ratios (HRs) for risk factors, including familial, developmental, and socio-environmental influences. The review included and analyzed nine studies, encompassing a diverse sample of 140,972 participants. Significant findings indicate that highly supportive familial and community environments significantly reduce the risk of psychosis onset. For instance, children with strong family support and engagement in structured activities demonstrated a 40% lower incidence of developing psychotic symptoms [p < 0.05]. Furthermore, the presence of neurobehavioral deficits, such as impaired verbal memory and attention, emerged as significant predictors of psychosis, with these children exhibiting a threefold increase in risk compared to their peers [OR = 3.2, 95% CI: 2.1–4.8, p < 0.01]. Resilience factors play a critical role in mitigating the impact of psychosocial and neurobiological risks in the development of psychosis among youths. Interventions enhancing resilience could potentially alter the trajectory of psychosis development, emphasizing the need for early and targeted psychosocial interventions to support at-risk populations. This study underscores the importance of fostering resilience through both individual-focused and community-based strategies to prevent the onset of psychotic disorders in vulnerable young populations.

Background: Schizophrenia in adolescence disrupts neurodevelopment and long-term functioning. While symptom reduction remains a primary treatment goal, quality of life (QoL) represents a critical, patient-centered outcome. Pharmacogenetic variability, particularly in CYP2D6 metabolism of second-generation antipsychotics, may influence tolerability and subjective well-being beyond symptom control. Materials and Methods: Forty-seven adolescents (aged 14–18 years) diagnosed with schizophrenia (DSM-5) were followed in routine clinical care. CYP2D6 genotyping classified patients as normal metabolizers (NM, n = 27) or reduced-function metabolizers (RFM, including intermediate/poor, n = 20). Symptom severity was assessed with PANSS, QoL was assessed with the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q), and adverse effects (hyperprolactinemia, extrapyramidal symptoms, sedation, metabolic changes) were monitored. Non-parametric tests and multiple linear regression were applied. Results: At 12 months, RFM patients showed significantly higher PANSS scores, markedly more adverse reactions (95% vs. 48.1%), and lower PQ-LES-Q total and domain scores (all p < 0.0001) compared to NM patients. A regression analysis identified the metabolizer status (β = −0.410, p = 0.001), extrapyramidal symptoms (β = −0.248, p = 0.003), sedation (β = −0.193, p = 0.029), and hyperprolactinemia (β = −0.190, p = 0.012) as independent predictors of a reduced QoL, explaining 84% of the variance. The residual symptom severity was not independently associated. Conclusions: In adolescent schizophrenia, the CYP2D6-reduced metabolizer status is the strongest independent predictor of long-term QoL impairment, associated primarily through a substantially higher burden of treatment-related adverse effects (metabolic, endocrine, neurological, and sedative) rather than through persistence of psychotic symptoms alone. These findings support early pharmacogenetic testing to guide individualized dosing and improve tolerability and patient-reported outcomes.

Background and Objectives: AI- and extended reality (XR)-enabled telemedicine is increasingly relevant to clinical training, yet evidence from Central and Eastern Europe is limited. We assessed Romanian medical students’ acceptance of AI/XR-enabled telemedicine and examined whether health literacy moderates the association between AI/XR knowledge and acceptance. Methods: We conducted an anonymous cross-sectional online survey of 212 medical students (years 1–6) at a single Romanian university (March 2024–June 2025). Acceptance was measured using a study-specific Acceptance Index (mean of three 4-point items: trust in AI-assisted recommendations, perceived improvement in telemedicine quality with AI/XR, and willingness to participate in AI/XR-enabled teleconsultations; internal consistency acceptable, Cronbach’s α ≈ 0.8). Health literacy was assessed with the validated Romanian version of the European Health Literacy Survey Questionnaire (HLS-EU-Q16). We performed group comparisons, Spearman correlations, multivariable and hierarchical regression with a Knowledge × Health Literacy interaction, and k-means clustering. Results: Participants had a mean age of 22.5 ± 1.9 years; 66.0% were female. Overall acceptance was high (2.9 ± 0.6). Acceptance was higher in clinical vs. preclinical years (3.1 ± 0.6 vs. 2.8 ± 0.5; p < 0.001; Cohen’s d ≈ 0.55) and in prior AI/XR users vs. non-users (3.2 ± 0.5 vs. 2.7 ± 0.6; p < 0.001; d ≈ 0.89). Knowledge correlated strongly with acceptance (ρ = 0.68; p < 0.001). In multivariable models (R² = 0.61), knowledge, perceived educational value, prior AI/XR use, and clinical stage independently predicted acceptance, whereas privacy concern and gender did not. Health literacy was sufficient in 64.2% and significantly moderated the knowledge–acceptance link (interaction p = 0.012). Conclusions: Romanian medical students report favorable acceptance of AI/XR-enabled telemedicine. Findings support curriculum integration that combines structured AI/XR teaching with literacy-sensitive scaffolding to ensure knowledge translates into informed, critical acceptance across student subgroups.