According to the World Health Organization (WHO), major depressive disorder (MDD) is the fourth leading cause of disability worldwide and the second most common disease after cardiovascular events. Approximately 280 million people live with MDD, with incidence varying by age and gender (female to male ratio of approximately 2:1). Although a variety of antidepressants are available for the different forms of MDD, there is still a high degree of individual variability in response and tolerability. Given the complexity and clinical heterogeneity of these disorders, a shift from “canonical treatment” to personalized medicine with improved patient stratification is needed. OPADE is a non-profit study that researches biomarkers in MDD to tailor personalized drug treatments, integrating genetics, epigenetics, microbiome, immune response, and clinical data for analysis. A total of 350 patients between 14 and 50 years will be recruited in 6 Countries (Italy, Colombia, Spain, The Netherlands, Turkey) for 24 months. Real-time electroencephalogram (EEG) and patient cognitive assessment will be correlated with biological sample analysis. A patient empowerment tool will be deployed to ensure patient commitment and to translate patient stories into data. The resulting data will be used to train the artificial intelligence/machine learning (AI/ML) predictive tool.

Background: The integration of digital health technologies has transformed mental healthcare, particularly for young adults with First-Episode Psychosis (FEP). Digital interventions, such as telepsychiatry and mobile applications, address barriers like social stigma, restricted access to services, and the urgency of timely care. Methods: A systematic literature review was conducted using PubMed and APA PsycINFO. Included studies focused on randomized controlled trials, cohort studies, and open studies of digital interventions for FEP rehabilitation. Exclusion criteria included meta-analyses, reviews, and irrelevant studies. Results: Smartphone applications like Horyzons-Canada facilitated peer support and symptom management, while tools such as My Journey 3 emphasized the need for better user engagement. Digital innovations, including Cognitive Behavioral Therapy for insomnia (CBT-I) and telepsychiatry, demonstrated improvements in recovery and treatment adherence. Discussion: Digital interventions significantly enhance the accessibility and quality of FEP care, supporting functional recovery and patient engagement. Future research should prioritize longitudinal studies, user engagement strategies, and advanced analytics to develop personalized, scalable solutions.

This review synthesises current knowledge to improve understanding of the pathophysiology of major depressive disorder (MDD) and optimise diagnostic, therapeutic and prognostic approaches. It examines the interplay between genetic, epigenetic, inflammatory, neurotransmitter and gut microbiome factors, together with environmental stressors and different clinical symptom presentations, in shaping MDD presentation and treatment response. Studies have revealed potential biomarkers predictive of treatment response, allowing differentiation of MDD subtypes and facilitating remission monitoring. While studies have identified potential biomarkers predictive of treatment response and enabling MDD subtype differentiation, significant challenges remain in achieving fully optimized therapeutic efficacy and widespread remission. A holistic, data-driven approach is key to addressing the complex aetiology of MDD, ultimately improving outcomes for patients and reducing the substantial burden of this prevalent disorder.

Background: Addictive disorders are characterized by the dysregulation of neural circuits involved in reward processing, salience attribution, emotional regulation, and cognitive control. Traditional neuroimaging paradigms based on static or two-dimensional stimuli show limited ecological validity and may fail to capture the contextual complexity of real-world addictive triggers. Immersive virtual reality (VR) offers a novel approach to simulate realistic, multisensory environments capable of eliciting craving and emotional responses. Although several reviews have examined VR in addictive disorders, most combined immersive and non-immersive tools and did not restrict inclusion to studies with brain-based outcomes. Methods: This systematic review with narrative synthesis was conducted in PubMed/MEDLINE and APA PsycINFO for studies published up to 30 December 2025. This systematic review followed PRISMA 2020 and was prospectively registered in PROSPERO; due to heterogeneity, findings were synthesized narratively. Eligible studies included human participants with substance-related or behavioral addictions and employed immersive VR paradigms (e.g., head-mounted display–based environments) combined with neuroimaging or neurophysiological measures (EEG, fMRI, fNIRS, PET, or DTI). Risk of bias was assessed using ROB-2 or ROBINS-I, and overall certainty of evidence was evaluated with the GRADE framework. Results: Ten studies met the inclusion criteria, encompassing over 1450 participants with alcohol, nicotine, methamphetamine, opioid use disorders, and internet gaming disorder. Immersive VR was associated with craving-related neural responses across modalities, involving prefrontal, insular, limbic, and striatal networks. EEG studies reported spectral power changes associated with craving and attentional salience, while fMRI, fNIRS, and PET studies demonstrated activation and modulation of executive control and reward-related circuits. Preliminary longitudinal and interventional studies indicate that repeated VR exposure may induce neurobiological changes consistent with therapeutic modulation. Conclusions: Immersive VR combined with neuroimaging supports the use of immersive VR as an ecologically grounded framework to probe addiction-related brain circuits; however, larger trials and standardized reporting are needed to strengthen clinical translation. Future studies should prioritize adequately powered randomized designs, harmonized VR cue-reactivity paradigms, and transparent neuroimaging reporting to enable reproducibility and cumulative inference.

Background: Gamification, the strategic application of game design elements in non-game environments, has become increasingly prominent in digital mental health. It aims to enhance user engagement, motivation, and adherence through mechanisms such as points, feedback systems, rewards, and narrative frameworks. While it shows promise in promoting therapeutic engagement, the empirical foundation of its use in psychiatric treatment remains limited. Aims: This section aims to explore the current state of evidence supporting gamification in psychiatric care, identify gaps in research, and highlight its potential role in improving treatment outcomes and user experience within digital mental health interventions. Method: We performed a comprehensive search of the PubMed database, covering articles published between January 1, 2014, and May 31, 2025. The search included only empirical studies that employed gamified interventions in mental health contexts. Articles were screened and selected following PRISMA guidelines. Quality assessment was conducted using the GRADE framework, while risk of bias in randomized controlled trials (RCTs) was assessed using the Cochrane RoB 2.0 tool. Due to heterogeneity in study designs and outcome measures, findings were synthesized narratively. Results: The review identified 7 eligible studies from an initial 109, all of which were randomized controlled trials (RCTs). These studies primarily used mobile or app-based platforms featuring gamified elements such as badges, levels, storylines, and points. The participants were largely adolescents and young adults experiencing mental health conditions, including depression, anxiety, and eating disorders. The studies reported positive effects on user engagement, adherence to therapeutic exercises, and symptom reduction. Conclusions: Gamification appears to be a viable and potentially effective adjunctive strategy for psychiatric and mental health interventions. Despite encouraging initial evidence, further research is needed to solidify its clinical relevance and optimize its theoretical integration.

Background: Anorexia nervosa (AN) is associated with extensive biochemical alterations at the time of clinical presentation. Despite distinct behavioural profiles, it remains unclear whether the restricting (AN-R) and binge–purge (AN-BP) subtypes differ in their biochemical profile at residential admission, a question with direct implications for clinical monitoring protocols. Methods: We conducted a retrospective cross-sectional study of 177 consecutive AN inpatients (AN-R: n = 130; AN-BP: n = 47; 98.3% female; mean BMI 15.8 ± 2.0 kg/m²; mean age 19.2 ± 5.5 years; 53.7% adolescents) admitted to a specialist residential unit (2018–2026). Thirty-five biochemical parameters were assessed. Unadjusted comparisons used Mann–Whitney U tests with rank-biserial effect sizes; multivariable logistic regression adjusted for BMI, age, and illness duration. Results: Overall, 98.3% of patients presented at least one biochemical anomaly (mean 4.4 ± 2.6 per patient). The most frequently abnormal parameters were LDH elevation (75.0%), vitamin D insufficiency (73.0%), low T3 syndrome (defined as low free triiodothyronine [FT3]) (58.0%), FT4 suppression (53.5%), ALT elevation (35.1%), and leucopenia (32.3%). AN subtype predicted none of these outcomes in unadjusted or multivariable analyses (all p > 0.10). The odds of presenting ≥3 simultaneous anomalies were not significantly associated with subtype, BMI, or illness duration in multivariable analysis. In contrast, older age independently predicted greater odds of low T3 syndrome (OR = 1.14 per year, 95% CI [1.00, 1.30], p = 0.045) and leucopenia (OR = 1.22 [1.06, 1.39], p = 0.004). No differences were observed between adolescents and adults in unadjusted comparisons. Conclusions: Despite their distinct behavioural profiles, no statistically significant biochemical differences were detected between AN-R and AN-BP at residential admission. These findings support routine standardised biochemical screening in all patients with anorexia nervosa admitted to residential care, regardless of behavioural subtype. Older age may identify a subgroup warranting closer endocrine and haematological monitoring.