INTRODUCTION:Antidepressant overprescribing and unnecessary long-term use are common and can increase the risk of adverse effects and withdrawal symptoms on discontinuation. Although gradual tapering strategies have been proposed, empirical evidence from randomised trials is lacking. This study will compare the efficacy of two antidepressant discontinuation strategies-linear and hyperbolic tapering-in adults with remitted depressive disorders. METHODS AND ANALYSIS:This pragmatic, multicentre, open-label, parallel-group superiority randomised controlled trial will recruit adults (≥18 years) with remitted depressive disorders who have been taking an antidepressant for at least 6 months. During an 8-month recruitment period, participants in outpatient psychiatric and primary care settings will be randomised (1:1) to (a) linear tapering (dose reduced by 50% of the minimum effective dose every 2 weeks until cessation) or (b) hyperbolic tapering (dose reduced by 20-25% every 2 weeks until cessation). The primary outcome is the proportion of participants who fail to discontinue the antidepressant by the end of the predefined tapering schedule or who re-initiate antidepressant therapy within 16 weeks of discontinuation. Secondary outcomes include safety, tolerability (including withdrawal symptoms), acceptability, clinical effectiveness, social functioning, quality of life and cost-effectiveness. Recruiters and participants will be aware of their treatment allocation; however, outcome assessors and the biostatistician will remain blinded throughout follow-up. Validated rating scales measuring depression, anxiety, withdrawal symptoms and social functioning will be administered at baseline and at scheduled follow-up visits up to 36 weeks. Based on observational data, we aim to recruit 150 participants (75 per arm). ETHICS AND DISSEMINATION:The study was approved by institutional Ethics Committees and regulatory authorities. Written informed consent will be obtained from all participants and data processed in accordance with General Data Protection Regulation. Study insurance and pharmacovigilance procedures are in place. Findings will be published in open-access journals, presented at scientific meetings and communicated to policy and regulatory stakeholders. TRIAL REGISTRATION:NCT07393919.

BACKGROUND:Bipolar disorder (BD) involves immune-inflammatory dysregulation. This systematic review and meta-analysis assessed complete blood count-based inflammatory indices - neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios - in BD versus healthy controls (HCs), major depressive disorder (MDD), and across BD mood states. METHODS:Databases were searched through June 2025 for observational studies reporting at least one ratio in adults with BD and including as comparators either HCs, MDD, or within-BD mood-state contrasts (mania, bipolar depression, euthymia). Quality was appraised using BIOCROSS. Random-effects meta-analyses, sensitivity analyses, and meta-regressions were performed. GRADE was adapted to rate evidence certainty. RESULTS:Fifty-one studies (38,309 participants) met the inclusion criteria. Compared to HCs, BD showed higher NLR (SMD = 0.44, p < 0.001) and MLR (SMD = 0.28, p < 0.001). In mania, NLR (SMD = 0.62, p < 0.001), MLR (SMD = 0.51, p < 0.001), and PLR (SMD = 0.18, p = 0.014) were all elevated versus HCs. Depression showed lower PLR (SMD = -0.14, p < 0.001) and euthymia higher NLR (SMD = 0.37, p = 0.002). Compared to MDD, BD had higher NLR (SMD = 0.21, p < 0.001) and MLR (SMD = 0.18, p < 0.001). Similarly, mania showed higher NLR (SMD = 0.53, p < 0.001) and MLR (SMD = 0.41, p < 0.001), while bipolar depression lower PLR (SMD = -0.15, p < 0.001). Mania had higher NLR (SMD = 0.32, p < 0.001), MLR (SMD = 0.32, p < 0.001), and PLR (SMD = 0.14, p = 0.028) than depression and higher MLR than euthymia (SMD = 0.44, p = 0.027), while depression had lower NLR (SMD = -0.28, p = 0.012) and PLR (SMD = -0.22, p < 0.001). Evidence certainty was mixed. CONCLUSIONS:NLR, MLR, and PLR emerge as non-specific, group-level correlates of immune-inflammatory dysregulation in BD, however offering limited discrimination between bipolar and unipolar depression. Notwithstanding their potential role as trait- and state-related markers in BD, further studies are needed to support translation into clinically useful biomarkers.

BACKGROUND:Schizophrenia spectrum disorders (SSDs) show substantial clinical heterogeneity, potentially reflecting distinct pathophysiological mechanisms. Peripheral immune-inflammatory alterations have been implicated in SSDs, yet their links with specific clinical phenotypes remain largely unexplored. This study thus aimed to examine associations between complete blood count-derived inflammatory markers and symptom patterns in inpatients with SSDs. METHODS:This cross-sectional study included inpatients with SSDs. Hierarchical clustering was applied to Positive and Negative Syndrome Scale (PANSS) five-factor scores to identify symptom-based phenotypes. Six markers - neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) - were compared across clusters using analysis of variance and multivariable linear regressions. RESULTS:Among 454 inpatients with SSDs aged 18-65, three clusters emerged: Positive/excited-dominant (n = 185, 40.8%), Negative/disorganised/depressive-dominant (n = 133, 29.3%), and Balanced (n = 136, 30.0%). All inflammatory markers significantly differed across clusters: NLR (F = 3.29, p = 0.038), MLR (F = 11.13, p < 0.001), PLR (F = 3.71, p = 0.025), SII (F = 3.34, p = 0.036), SIRI (F = 7.42, p < 0.001), and AISI (F = 6.49, p = 0.002). The Negative/disorganised/depressive-dominant cluster exhibited the most pronounced inflammatory profile, with covariate-adjusted increases compared to the Balanced cluster of +30% for MLR (p = 0.001), +20% for PLR (p = 0.040), +32% for SII (p = 0.043), +43% for SIRI (p = 0.011), and +52% for AISI (p = 0.015). The Positive/excited-dominant cluster showed selective, covariate-adjusted elevations in MLR (+19%, p = 0.020) and SIRI (+29%, p = 0.028) versus the Balanced cluster. CONCLUSIONS:Distinct SSD phenotypes are associated with heterogeneous inflammatory profiles, with monocyte-driven inflammation particularly characterizing negative/disorganised/depressive presentations, probably supporting phenotype-stratified approaches in precision psychiatry.

AIMS:Unipolar mania (UM), defined by the occurrence of manic episodes without a history of depression, is a topic of debate within the classification of affective disorders. However, its epidemiological burden remains unclear. This systematic review and meta-analysis aimed to estimate the prevalence of UM among individuals with bipolar type I disorder (BD-I) while exploring potential sources of heterogeneity. METHODS:The study protocol was registered in Open Science Framework on 27 March 2025. Embase, MEDLINE and APA PsycInfo were searched. We included observational studies reporting data on UM prevalence rates in adults with BD-I. Pooled prevalence was estimated using the Freeman-Tukey double arcsine transformation, employing a restricted maximum likelihood random-effects model. Subgroup and meta-regression analyses were implemented to explore sources of heterogeneity. RESULTS:We included 26 studies, encompassing 35 independent samples and 17,716 individuals with BD-I. The pooled prevalence of UM was 21.1% (95% confidence interval: 15.5-27.4%). Although potential publication bias was detected (Egger's p = 0.010), the trim-and-fill method did not impute any missing studies. No differences were found between clinical and community-based studies (p = 0.966). However, prevalence estimates were influenced by both geographical area (p = 0.020) and study quality (p = 0.014). Rate differences across studies may also be attributable to variations in UM diagnostic definition. CONCLUSIONS:People with UM represent a significant subset of BD-I cases worldwide, warranting greater clinical awareness. The observed rate variability emphasizes the impact of sociocultural and methodological factors on UM diagnosis. Further research is necessary to refine diagnostic criteria and evaluate optimal treatment approaches for individuals with UM.

BACKGROUND:Mentalising skills may be conceptualised as composed by both personal and interpersonal competencies, in turn shaped by early adverse experiences and coping strategies. Although cross-sectional observations described a role for mentalising skills in burnout development, large-scale longitudinal studies on the topic remain limited, especially in relation to psychiatry training. AIMS:The primary aim was to investigate protective and risk factors for higher burnout scores across time. Secondary aims included testing whether psychiatry exhibited different burnout scores across time in comparison to other medical residents. METHOD:A cohort of 1803 medical residents (1131 psychiatry residents) was assessed for mentalising skills, conceptualised as composed of emotional regulation (Difficulties in Emotion Regulation Scale), interpersonal competencies (Interpersonal Competence Questionnaire), coping strategies (Coping Orientation to Problems Experienced) and burnout dimensions (Maslach Burnout Inventory). One-year follow-up was available for 520 psychiatry residents (73.03% response rate) and 234 other medical residents (35.94% response rate). Longitudinal mixed models and bivariate latent change models were employed. RESULTS:Across all residents, greater levels of burnout were associated with higher scores in insecure attachment, emotional dysregulation and maladaptive coping, as well as lower scores in interpersonal skills. Attending at least one supervision per month was associated with lower burnout scores across time. According to a bivariate latent change model, emotional regulation improvements through years were associated with lower burnout scores across time. In psychiatry residents, lower burnout scores across time were observed as compared to other medical residents. Psychiatry residents benefited from a higher protective effect of interpersonal competencies (group by moderator by time interaction) and coping strategies against burnout. CONCLUSIONS:Mentalising skills may mitigate burnout development. Training in psychiatry emerged as a potential mitigating factor against burnout increases. Structured supervisions may foster professional development and emotional resilience.

Mental disorders remain diagnosed primarily through symptom-based classification systems that overlook biological heterogeneity, preventing the identification of mechanistically distinct patient subgroups and precluding pathophysiology-guided treatment selection. Metabolomics offers a promising pathway towards precision psychiatry by capturing dynamic biochemical readouts at the functional endpoint of the omics cascade, integrating genetic, environmental, and pharmacological influences on cellular metabolism. Over the past 15 years, untargeted and targeted metabolomics studies using nuclear magnetic resonance spectroscopy and mass spectrometry have identified consistent patterns of metabolic dysregulation across psychiatric disorders, particularly involving amino acid metabolism, lipid signaling, energy homeostasis, and oxidative stress pathways. Schizophrenia presents disruptions in arginine and proline metabolism, glutathione metabolism, and energy-related processes. Bipolar disorder shows perturbations in branched-chain and aromatic amino acids, kynurenine pathway, and tricarboxylic acid cycle dysfunction with phase-specific metabolic signatures. Major depressive disorder exhibits widespread alterations in amino acid turnover, bioenergetic processes, membrane lipid homeostasis, and glutamate-GABA cycling, with treatment-responsive metabolic changes. Despite these advances, substantial challenges remain: heterogeneous findings with disorder overlap, limited replication cohorts, predominance of cross-sectional designs, confounding by medication and lifestyle factors, pre-analytical variability, and high-dimensional data complexity. Future research requires harmonized multi-site protocols, longitudinal validation studies, multi-platform analytical approaches, integration with genomics, proteomics, and digital phenotyping, and implementation of artificial intelligence frameworks to enhance phenotype discrimination and predictive accuracy. In this mini-review, we provide an overview of current methodologies, major findings, strengths, challenges, and emerging directions in psychiatric metabolomics, with the goal of facilitating the translation of metabolomic insights into clinically applicable, personalized psychiatric treatment.

Beyond specific training in Digital Mental Health (DMH)/Digital Psychiatry (DP), mental health professionals (MHp) should own basic digital abilities and competences and a general openness to integrating technology into both clinical practice and daily life. These digital drivers have not been adequately investigated among MHp in Italy. As part of the DIGIT-PSY project, a multicenter observational study was conducted using the EUSurvey® platform. From May to September 2023, a cohort of multiprofessional MHp from 27 Italian university centers was surveyed to assess digital literacy (DHL), readiness (TR) and acceptability (ATiPP). The main aim was identifying whether these digitally-derived variables could influence the level of digitalization proneness in MH care. Overall, 60

Carers of individuals with eating disorders (EDs) often experience high levels of psychological distress, which can lead to anxiety and depressive symptoms. While several interventions have been developed to support carers, the effectiveness on their mental health remains unclear. We performed a systematic review of randomized controlled trials (RCTs) assessing mental health interventions for carers of individuals with EDs, with anxiety and depressive symptoms defined as outcomes of interest. Searches were performed across major electronic databases up to 31 October 2025. Twelve RCTs met the inclusion criteria. Structured narrative synthesis indicated that statistically significant effects were infrequent, outcome-specific, and generally small in magnitude. Interventions based on the Cognitive-Interpersonal Maintenance Model (CIMM) were the most frequently evaluated. However, only one trial demonstrated significant improvements in depressive symptoms (p = 0.010), with no significant effect on the Depression Anxiety Stress Scale (DASS-21) total scores (p = 0.06) or on the anxiety subscale (p = 0.50). In addition, Cognitive Behavioural Therapy (CBT)-based interventions showed some promising effects on the Hospital Anxiety and Depression Scale (HADS) total score (p = 0.033), but these results were not consistently replicated across guided and unguided formats. Among the other approaches, a video-based skills-training intervention produced a measurable reduction in carer distress, but this effect was observed only when combined with professional support (p = 0.030). Overall, interventions incorporating professional or peer support appeared more promising than fully self-directed approaches, although direct comparisons between guided and unguided formats did not consistently show statistically significant differences. Quality assessment showed at least an average standard of quality for all the included trials. Interventions for carers of individuals with EDs are conceptually well-founded, yet current evidence provides only limited support for their effectiveness in reducing anxiety and depressive symptoms. Future research should prioritize interventions that combine more structured mental health strategies with guided self-help programmes and workshops, providing tailored support to address the various needs of carers. Caring for someone with an eating disorder can be emotionally overwhelming and may affect the carer’s own mental health. This review looked at whether support programmes for carers can help reduce feelings of anxiety, low mood, and emotional strain. We examined studies that tested different kinds of support for carers, including online programmes, workshops, guided self-help, and skills-based training. Overall, these interventions were often helpful in giving carers information, practical strategies, and a better understanding of how to support their loved one. However, the evidence that they improve carers’ own anxiety and depression was limited. Indeed, only a few studies showed significant benefits, and these were usually small, specific to one outcome, or observed only when additional professional support was provided. Programmes that included guidance from a professional or trained supporter seemed more helpful than those completed alone. This suggests that carers may benefit most from support that is not only informative, but also personal and interactive. More research is needed to develop programmes that directly support carers’ mental health, while also helping them care for someone with an eating disorder.

Cognitive impairment is a pervasive feature across severe mental illnesses (SMIs), including schizophrenia spectrum disorders (SSDs), major depressive disorder (MDD), and bipolar disorder (BD), and is associated with poor functional outcomes and reduced quality of life. Cognitive remediation (CR) is an evidence-based psychosocial intervention aimed at improving cognitive functioning and daily functioning in individuals with SMI. In recent years, virtual reality (VR) has emerged as a promising modality for delivering CR in a more immersive, engaging, and ecologically valid manner. This narrative review synthesizes the current literature on the effectiveness of fully immersive VR-based CR interventions in SMI populations. Preliminary findings suggest that VR-CR may enhance treatment engagement, facilitate transfer of cognitive gains to real-life functioning, and support remote delivery. Although early results are encouraging, most available studies are limited by small sample sizes, short follow-up periods, and lack of standardized outcome measures. Further large-scale randomized controlled trials are needed to establish the long-term effectiveness, generalizability, and cost-efficiency of VR-CR approaches.

OBJECTIVES:Poor adherence to psychopharmacological treatment may contribute to relapses in bipolar disorder (BD). We performed a systematic review and meta-analysis to identify factors associated with poor adherence in BD. METHODS:The protocol was registered in Open Science Framework Registries (https://doi.org/10.17605/OSF.IO/2KZFJ). We searched main electronic databases through March 2025. Random-effects meta-analyses were performed to obtain pooled odds ratios (ORs) and standardized mean differences (SMDs) for relevant correlates. RESULTS:We included 19 studies. Subjects with poor adherence were more likely to be younger (SMD = -0.22, 95% CI: -0.42--0.02) and to have lower education (SMD = -0.34, 95% CI: -0.55--0.12), and less likely to be in a relationship (OR = 0.54, 95% CI: 0.34-0.86). Moreover, earlier age at onset (SMD = -0.29, 95% CI: -0.53--0.04), psychotic features (OR = 1.58, 95% CI: 1.30-1.92), a history of suicide attempts (OR = 1.36, 95% CI: 1.03-1.78), a higher number of manic (SMD = 0.34, 95% CI: 0.08-0.61) and mixed (SMD = 0.16, 95% CI: 0.03-0.28) episodes, and more hospitalizations (SMD = 0.53, 95% CI: 0.32-0.73) all emerged as correlates of poor adherence. Also, cannabis (OR = 2.34, 95% CI: 1.79-3.07) and alcohol use disorders (OR = 1.71, 95% CI: 1.39-2.12), comorbid generalized anxiety disorder (OR = 3.70, 95% CI: 1.90-7.22), and comorbid personality disorders (OR = 5.54, 95% CI: 1.32-23.15) were associated with poor adherence. Finally, poorly adherent individuals had higher global severity (SMD = 0.21, 95% CI: 0.01-0.41), lower insight (SMD = -0.74, 95% CI: -1.08--0.41), and lower global functioning (SMD = -0.60, 95% CI: -0.87--0.34). No differences were estimated for other variables. CONCLUSIONS:This meta-analysis showed that poor adherence in people with BD is associated with specific correlates. Although evidence was generally weak due to small effect sizes, imprecision, inconsistency, and potential publication bias, our findings highlight the importance of strategies to improve adherence.

The predominant polarity in bipolar disorder (BD) is defined by the skewness of mood episodes towards either the manic or depressive pole. However, since the predominant polarity can only be established over the long term, it is crucial to identify predictors of illness trajectory. Among these factors, the polarity at onset has been suggested to hold important implications, even though research in this field is not entirely consistent so far. In this retrospective study, we thus explored whether the polarity of the first episode can predict the predominant polarity in BD. We included subjects with BD consecutively referred to two acute inpatient units in the Milan metropolitan area from May 2020 to January 2024. Following Barcelona criteria, a manic (mPP) and a depressive (dPP) predominant polarity were defined as having a ratio ≥ 2:1 of past manic/hypomanic or depressive episodes, respectively. The relationship between first episode polarity and either mPP or dPP was examined using multivariable logistic regression models. A path analysis was then performed to jointly test the associations between putative variables and the predominant polarity. This study included 128 participants. Regression models estimated an association between a manic onset and a mPP (β = 3.23, p < 0.001) as well as between a depressive onset and a dPP (β = 3.65, p < 0.001). Participants with a mPP showed a lower age at onset (β = − 0.13, p = 0.004), while subjects diagnosed with BD type I were less likely to show a dPP (β = − 2.09, p = 0.024). The path analysis highlighted an association between earlier onset and the likelihood of a first episode of manic polarity (coeff. = − 1.39, p = 0.021). A manic onset was associated with a higher likelihood of mPP (coeff. = 3.46, p < 0.001) and a lower likelihood of dPP (coeff. = − 3.71, p < 0.001). Consistently, participants with a manic onset were more likely to experience a lower number of depressive episodes (coeff. = − 1.36, p < 0.001). Finally, cannabis use disorder was associated with a lower number of depressive episodes (coeff. = − 0.57, p = 0.011). These results provide important insights into the likely predictive value of first episode polarity in relation to the predominant polarity in BD. Though future studies validating these findings are needed, the polarity at onset may serve as an early marker for illness trajectory.

INTRODUCTION:Various novel harm reduction services leverage technology to reduce the rising number of drug poisoning deaths, particularly among those who use drugs alone. There is significant variability in terminology and outcome measures in reporting these interventions, complicating efforts to build a comprehensive knowledge base. Thus, we conducted a Delphi study to establish consensus and heterogeneity in these metrics. METHODS:Panellists from three stakeholder groups (people who use drugs, virtual harm reduction service operators and academics) participated in a multi-round Delphi study. The first round included open-ended questions to propose items in three categories: terminology, demographic information and outcomes. Subsequent rounds included options from a previously conducted scoping review for consideration. Likert ratings were used to achieve consensus, with a 70% threshold. Final rounds involved ranking terminology that reached a consensus. RESULTS:Of 23 initial participants, 14 completed the fourth survey round. "Overdose response technology" was identified as the most appropriate term for these harm reduction technologies. This definition includes drug contamination alerts, overdose response hotlines and applications, wearable overdose detection technology and overdose detection tools. Fourteen demographic outcomes reached a consensus for data collection, including name or handle, neighbourhood, age, gender, past overdose experience, substance used, amount and route of use. Six service use outcomes were recommended: response type, service outcomes, morbidity and mortality, overdose events, responder arrival time and post-rescue care. DISCUSSION AND CONCLUSIONS:The study results are recommended to standardise terminology and guide future research and knowledge dissemination in the field, ensuring clear communication with a shared language.

Usual treatment approaches for late-life depression primarily involve selective serotonin reuptake inhibitors (SSRIs). Recently, the potential role of vortioxetine has garnered attention. This study aimed to investigate whether vortioxetine is superior to SSRIs in terms of efficacy and tolerability in older people with moderate-to-severe depression. The Vortioxetine in the Elderly versus SSRIs: a Pragmatic Assessment (VESPA) study was an assessor-blinded, randomized, parallel-group, superiority trial, comparing flexible doses of vortioxetine versus SSRIs in older adults with depression. This is a post-hoc analysis that excluded participants with milder symptoms of depression. The primary outcome was the change in Montgomery–Åsberg Depression Rating Scale (MADRS) scores. Secondary outcomes included clinical response (MADRS total score reduction of ≥ 50

In recent times, several longitudinal studies aimed at clarifying whether cannabis use during adolescence might play a causal role in the subsequent risk of developing bipolar disorder have been published. Although their methodological heterogeneity precludes any meta-analytic approaches, evidence from these studies can be systematically evaluated using the Bradford Hill criteria. A biological gradient is supported by evidence on the dose-response relationship between exposure severity and outcome. As such, the effect of cannabis use on bipolar disorder onset is likely to be strong, coherent, plausible, and based on a clear temporality. In addition, some analogies can be hypothesized between studies testing the possible causal role of cannabis in the development of bipolar disorder and those is schizophrenia. Cannabis may represent a precipitating agent inducing bipolar disorder in a multicausal model of individual vulnerability. However, this relationship seems to be only partially consistent and nonspecific, and the experimental evidence is strongly suggestive but, as yet, inconclusive. Nevertheless, in summary, it seems there is sufficient support for the hypothesis that cannabis use during adolescence may play a causal role in bipolar disorder, although further studies are needed to consolidate the evidence.

Black hairy tongue (BHT), a benign condition characterized by hypertrophy of the filiform papillae and discoloration of the dorsal tongue, is commonly associated with antibiotic use, poor oral hygiene, lifestyle factors, and general health issues. By contrast, psychotropic drug-induced BHT is rare and typically emerges weeks to months after treatment initiation. We report the case of a 42-year-old male patient with recurrent major depressive disorder and prior use of different psychotropic medications who developed BHT within days of initiating clomipramine on two separate occasions. In the first trial, BHT resolved shortly after clomipramine discontinuation. On the second occasion, considering the effectiveness of the treatment, the absence of concerning symptoms, and the exclusion of other causes through multidisciplinary evaluation, the patient remained on clomipramine. Despite oral hygiene measures, BHT persisted. Close temporal association, reproducibility upon re-challenge, resolution upon discontinuation during the first trial, and absence of alternative explanations supported a definite causal link, as indicated by the Expanded Naranjo Adverse Drug Reaction Probability Scale. Chronic smoking and prolonged chlorhexidine mouthwash use may have contributed, though these were unlikely the individual causes. To our knowledge, this is the first report of clomipramine-induced BHT with such rapid onset and recurrence. This case highlights the importance of recognizing BHT as a potential early-onset side effect of tricyclic antidepressants, particularly clomipramine. Prompt recognition, interdisciplinary assessment, and consideration of the risk-benefit balance are essential. Although an idiosyncratic reaction – independent of clomipramine-induced xerostomia – can be hypothesized, further research is needed to clarify the mechanisms underlying antidepressant-induced BHT.

Background Monitoring symptoms of bipolar disorder (BD) is a challenge faced by mental health services. Speech patterns are crucial in assessing the current experiences, emotions, and thought patterns of people with BD. Natural language processing (NLP) and acoustic signal processing may support ongoing BD assessment within a mobile health (mHealth) framework. Objective Using both acoustic and NLP-based features from the speech of people with BD, we built an app-based tool and tested its feasibility and performance to remotely assess the individual clinical status. Methods We carried out a pilot, observational study, sampling adults diagnosed with BD from the caseload of the Nord Milano Mental Health Trust (Italy) to explore the relationship between selected speech features and symptom severity and to test their potential to remotely assess mental health status. Symptom severity assessment was based on clinician ratings, using the Young Mania Rating Scale (YMRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) for manic and depressive symptoms, respectively. Leveraging a digital health tool embedded in a mobile app, which records and processes speech, participants self-administered verbal performance tasks. Both NLP-based and acoustic features were extracted, testing associations with mood states and exploiting machine learning approaches based on random forest models. Results We included 32 subjects (mean [SD] age 49.6 [14.3] years; 50% [16/32] females) with a MADRS median (IQR) score of 13 (21) and a YMRS median (IQR) score of 5 (16). Participants freely managed the digital environment of the app, without perceiving it as intrusive and reporting an acceptable system usability level (average score 73.5, SD 19.7). Small-to-moderate correlations between speech features and symptom severity were uncovered, with sex-based differences in predictive capability. Higher latency time (ρ=0.152), increased silences (ρ=0.416), and vocal perturbations correlated with depressive symptomatology. Pressure of speech based on the mean intraword time (ρ=–0.343) and lower voice instability based on jitter-related parameters (ρ ranging from –0.19 to –0.27) were detected for manic symptoms. However, a higher contribution of NLP-based and conversational features, rather than acoustic features, was uncovered, especially for predictive models for depressive symptom severity (NLP-based: R2=0.25, mean squared error [MSE]=110.07, mean absolute error [MAE]=8.17; acoustics: R2=0.11, MSE=133.75, MAE=8.86; combined: R2=0.16; MSE=118.53, MAE=8.68). Conclusions Remotely collected speech patterns, including both linguistic and acoustic features, are associated with symptom severity levels and may help differentiate clinical conditions in individuals with BD during their mood state assessments. In the future, multimodal, smartphone-integrated digital ecological momentary assessments could serve as a powerful tool for clinical purposes, remotely complementing standard, in-person mental health evaluations.

Background/Objectives: Both traumatic and stressful events, including major life changes, may contribute to post-traumatic stress symptoms (PTS), often associated with anxiety and depression. Feelings of loneliness may influence these relationships, whilst social support seems to mitigate the effects of stressful events on mental health. Our study thus aimed to evaluate the mediating role of loneliness in the relationships between PTS and both anxiety and depressive symptoms among university students. Methods: The data were from the CAMPUS study (0058642/21; FHMS 20-21 157), a survey on university students’ mental health in Italy and the UK. Using a logit model, mediation analyses were carried out to test whether the relationships between PTS and both anxiety and depressive symptoms might be mediated by loneliness. A path analysis was then performed to jointly test the associations between the Impact of Event Scale—Revised (IES-R)’s subscales and clinical domains. Results: Positive associations were found between PTS and both anxiety (p < 0.001) and depressive symptoms (p < 0.001). However, loneliness mediated approximately 22% of the effect of the PTS on anxiety symptoms (indirect effect: 1.04, 95% CI: 0.59; 1.48, p < 0.001) and approximately 33% of the effect of the PTS on depressive symptoms (indirect effect: 1.81, 95% CI: 1.22; 2.39, p < 0.001). Furthermore, the path analysis indicated associations between the IES-R’s hyperarousal subscale and both anxiety (coeff.: 0.34, p < 0.001) and depressive symptoms (coeff.: 0.27, p < 0.001). Conclusions: Along with the associations between PTS and both anxiety and depressive symptoms, our findings highlight the key role of loneliness in both these associations. Targeted interventions to reduce loneliness, especially for students exposed to traumatic events, may ultimately improve their mental health.

Digital health interventions (DHIs) show promise for the treatment of mental health disorders. However, existing meta-analytical research is methodologically heterogeneous, with studies including a mix of clinical, non-clinical, and transdiagnostic populations, hindering a comprehensive understanding of DHI effectiveness. Thus, we conducted an umbrella review of meta-analyses of randomised controlled trials investigating the effectiveness of DHIs for specific mental health disorders and evaluating the quality of evidence. We searched three public electronic databases from inception to February, 2024 and included 16 studies. DHIs were effective compared with active interventions for schizophrenia spectrum disorders, major depressive disorder, social anxiety disorder, and panic disorder. Notable treatment effects compared with a waiting list were also observed for specific phobias, generalised anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, and bulimia nervosa. Certainty of evidence was rated as very low or low in most cases, except for generalised anxiety disorder-related outcomes, which showed a moderate rating. To integrate DHIs into clinical practice, further high-quality studies with clearly defined target populations and robust comparators are needed.