BACKGROUND AND HYPOTHESIS:A large body of literature suggests that neurocognitive processes underlying the sense of agency are disrupted in schizophrenia. We here tested the sense of agency in schizophrenia patients, by controlling for the potential confounding effect of temporal perception biases, antipsychotics, attentional-executive functioning, and illness duration. We also analyze the role of symptoms such as delusions, hallucinations, and passivity experiences. STUDY DESIGN:We capitalized on the intentional binding phenomenon, an implicit measure of the sense of agency. 30 schizophrenia patients and 30 healthy controls completed 2 tasks. Experimental task participants pressed a switch to turn a light bulb on (active condition) or let their finger be moved by an automated switch (passive condition). They then judged the interval between the action (active or passive) and the lighting of the bulb. Control task participants estimated the time interval between two light flashes presented in sequence. All participants underwent a comprehensive neuropsychological assessment, while schizophrenia patients were also evaluated for positive, negative symptoms, and passivity symptoms. STUDY RESULTS:Control participants showed the expected intentional binding effect, particularly at shorter action-outcome delays. In contrast, the effect was absent in schizophrenia patients. The alteration was significantly moderated by temporal perception biases, hallucinations, and delusions. CONCLUSIONS:The study provides the first evidence in favor of the relationship between agency disturbances, symptomatology, and temporal perception biases in schizophrenia while excluding putative confounding factors like neuroleptics. Results are discussed in the light of a recent predictive coding model of the sense of agency.

Electroconvulsive therapy (ECT) originally stems from the concept of Meduna at the beginning of the 1930s who utilized repeated generalized seizures as a therapeutic agent for schizophrenic disorders. The method has continuously evolved in technical and nontechnical aspects. The ECT could consistently overcome numerous adversities. It has recently been integrated into various guidelines and position papers for severe mental illnesses. The German Institute for Medical Documentation and Information (DIMDI) has established the term Elektrokonvulsionstherapie in Germany to replace older stigmatizing names. Better patient education contributes to a decline in skepticism and reluctance. The rising number of treatments in Germany resulted in capacity shortages in existing ECT centers. Numerous preclinical and clinical research studies are contributing to a better understanding of the mechanism of action. In parallel, innovative forms of anesthesia and muscle relaxation are becoming established.

BACKGROUND:The COVID-19 pandemic significantly impacted child mental health, but data on long-term outcomes are limited. This study explored the course of psychiatric symptoms in patients with pre-existing psychopathology, assessed from both the child's and parents' perspectives. METHODS:A three-year multicentre-longitudinal study involving patients aged 5-18 years and their parents across 10 Italian sites. Data were collected at three time points (2020, 2021 and 2022). Statistical analyses included Exploratory Factor Analysis (EFA), Confirmatory Factor Analysis (CFA) and Linear Mixed Models (LMM) via REML. RESULTS:A total of 523 families participated. Factor analysis validated 3 factors for parents and 4 for children. Parents reported a low emotional well-being, positively correlated with socioeconomic status (SES); children reported better emotional well-being correlated with higher SES in 2020-2021 but not in 2022. During the pandemic, children perceived the quality of care as unsatisfactory; however, the association between SES and the perceived quality of care was less pronounced. CONCLUSION:SES may have differentially influenced the long-term mental health outcomes in children and parents. Social disadvantage may be especially evident during acutely stressful periods. During the pandemic, the advantages of a higher SES in mental health care were less pronounced than expected. IMPACT:The multi-informant perspective is extremely important to understand the impact of pandemic on the well-being of the entire family. Both youths with pre-existing psychopathology and their parents show consistently low emotional well-being throughout the pandemic, indicating a persistent vulnerability that does not spontaneously normalize. Youths report low satisfaction with, and perceived quality of, mental health support during the pandemic. Socioeconomic status shows a dynamic and informant-specific pattern. The advantage of higher SES is less evident for care satisfaction, In at risk populations family-based interventions should also address caregivers' emotional involvement and burden. CATEGORY OF STUDY:Clinical Research Article.

BackgroundThe introduction of innovative oncological therapies, such as immune checkpoint inhibitors (ICIs) and multikinase inhibitors (TKIs), has improved the prognosis of many malignancies but has introduced complex neuropsychiatric adverse events. This case report describes the management of a complex psycho-organic syndrome occurring in a patient treated with the combination of pembrolizumab and lenvatinib.Case presentationA 69-year-old woman, with a history of anxious-depressive disorder and recurrent endometrial carcinoma, was admitted for the onset of a sub-confusional state, severe psychomotor retardation, akathisia, and tremors. These symptoms appeared in temporal relationship with the initiation of combined pembrolizumab-lenvatinib therapy. Diagnostic investigations (CT, MRI, FDG-PET, and CSF analysis) excluded brain metastases or primary neuroinflammatory processes, revealing diffuse cortical hypometabolism consistent with metabolic-iatrogenic encephalopathy.ManagementThe therapeutic strategy involved a multidisciplinary approach based on the precautionary suspension of oncological drugs and a structured pharmacological washout. Flumazenil was administered with diagnostic-therapeutic success to correct GABAergic redundancy, and pramipexole was introduced to treat extrapyramidal manifestations and akathisia.ConclusionsThis case highlights how overlapping immunological, vascular, and neuropharmacological effects can generate reversible encephalopathic patterns in complex oncological patients. Symptom resolution through psychopharmacological modulation and suspension of targeted treatment alone underscores the critical importance of active neuropsychiatric surveillance and close interdisciplinary collaboration between oncologists and psychopharmacologists.

Modern psychiatry is transitioning from an entity-based taxonomy toward a systems-oriented science that integrates biological, psychological, social, and existential levels of analysis. We propose a conceptual framework that combines genetics and multi-omics approaches, synergetics, complex systems theory, and a neo-existentialist perspective. Within this framework, psychiatric illness is conceptualized as a crisis of regulation and meaning emerging across dynamically interacting multi-level networks. We discuss implications for clinical practice, including process-based psychotherapy, idiographic mapping, and neuromodulatory interventions, as well as consequences for service design, such as recovery-oriented integrated care ecosystems and ethical challenges in forensic settings. Finally, we outline key research directions, including multimodal clustering approaches and digital phenotyping, aimed at capturing non-linear trajectories of mental suffering and recovery. “In order to possess what you do not possess…” ― T.S. Eliot

Die Elektrokonvulsionstherapie (EKT) beruht auf dem Konzept von Meduna, der zu Beginn der 1930er-Jahre wiederholte generalisierte Anfälle als therapeutisches Agens bei schizophrenen Erkrankungen einsetzte. Die Methode wurde kontinuierlich weiterentwickelt. Stets hat sie sich gegen Widerstände behaupten können. In jüngster Zeit wurde das Verfahren in mehrere Leitlinien und Stellungnahmen für schwere psychische Erkrankungen integriert. Das Deutsche Institut für Medizinische Dokumentation und Information (DIMDI) hat die Bezeichnung Elektrokonvulsionstherapie in Deutschland etabliert, um ältere, stigmatisierende Namen zu ersetzen. Bessere Aufklärung geht mit dem Rückgang von Skepsis und Zurückhaltung einher. Steigende Behandlungszahlen in Deutschland führen teilweise zu Engpässen in den EKT-Zentren. Zahlreiche vorklinische und klinische Forschungsarbeiten tragen zum besseren Verständnis des Wirkmechanismus bei. Parallel etablieren sich innovative Formen der Narkose und Muskelrelaxierung.

Abstract:TDM involves measuring and interpreting drug concentrations in blood plasma or serum to optimize pharmacotherapy. In psychiatry and neurology, TDM is a well-established tool for personalized drug treatments. The AGNP-TDM task force initially published guidelines for best practice TDM in 2004, 2011, and 2017. A fundamental methodological revision has now been carried out on how to determine therapeutic reference ranges and dose-related reference ranges transparently and systematically. In the current edition, 50 experts in neuropsychopharmacology offer a complete update of both ranges for each substance following an evidence-based approach. Various types of data were considered for reference range determination, ranging from meta-analyses to drug concentrations expected under recommended doses. Therapeutic reference ranges are now listed for 160 neuropsychiatric drugs, newly included for 30 drugs and revised for 88 drugs. Expected drug concentrations can be calculated based on a revised formula for 162 drugs. Obligatory TDM (i.e. for dose titration) is strongly recommended for 15 neuropsychiatric drugs and recommended for 39 drugs. TDM is classified as useful for 49 drugs and potentially useful for 62 drugs, indicating that it is recommended in specific clinical situations, such as suspected non-adherence, insufficient clinical response despite recommended doses, relapse during maintenance treatment, and many more. The 2026 update includes practical pharmacogenetic recommendations that are directly relevant to TDM. This work integrates a combination of strategies to guide drug treatments in clinical practice using all available tools. A consistent implementation of TDM and pharmacogenetic recommendations will enhance neuropsychopharmacotherapy, improve patient outcomes, and reduce healthcare costs.

BackgroundThis study examined whether the COVID-19 pandemic produced diagnosis-specific and cross-nationally reproducible alterations in psychiatric admissions, or whether observed variations primarily reflected organizational responses. We compared psychiatric inpatient services from Austria and Germany—two hospital-centered systems with similar pre-pandemic structures—and used Italy as a contrasting community-based model.MethodsWe conducted a retrospective multicenter observational study including all psychiatric hospitalizations between 2017 and 2020. Temporal admission trends were analyzed bi-weekly for each ICD-10 diagnostic group. Generalized Linear Models (Poisson family) were used to model the effects of Diagnosis, Year (2020 vs. pre-2020), Week, and Country, and their interactions. Diagnostic categories were grouped following ICD-10, with F10 (alcohol-related disorders) analyzed separately from other substance-use disorders to capture differences between planned and emergency admissions.ResultsAcross Austria and Germany, 2020 was associated with a marked temporal distortion in admission patterns compared with previous years (Week × Year interaction, p < 0.05), consistent across diagnoses except for F10. Alcohol-related disorders showed country-specific trajectories, reflecting service reorganization—bed closures in Austria versus stable capacity in Germany. No other diagnosis exhibited reproducible temporal deviations across countries, indicating that the pandemic affected admission organization rather than disorder-specific psychopathology. A supplementary comparison including Italy showed that, while Austria and Germany experienced a decline in total hospitalizations (−16 and −10%, respectively), Italy remained stable (+12%), suggesting greater resilience of its community-based system.ConclusionThe pandemic did not induce diagnosis-specific increases in acute psychiatric admissions but substantially altered their temporal organization. Differences across countries highlight how healthcare structure—particularly the integration of territorial and inpatient services—modulates system resilience under crisis conditions.

The Global Burden of Disease studies have consistently highlighted the persisting burden of mental disorders worldwide. Public health emergencies such as the COVID-19 pandemic, war and conflict, and climate change have exacerbated many determinants of poor mental health, resulting in an increased prevalence of anxiety and depression worldwide. Despite substantial advancements in intervention and prevention programs, treatment gaps in depression and suicidal behavior persist. Addressing these gaps requires a multi-level approach involving both community and health services. This Perspective addresses the urgent need to strengthen mental health systems globally. The primary purpose of this Perspective is to discuss the four-level community-based approaches of the European Alliance Against Depression program, including evidence in support of its four-level intervention as a sustainable model for community-based mental health care that can be effectively adapted to various contexts, including current and future public health emergencies. In this Perspective, the authors provide an overview of the four-level community-based intervention by the European Alliance Against Depression and highlight the need for improved public mental health care for depression and suicide risk.

The bilateral interaction between the brain and the gut has recently been on the spectrum of researchers’ interests, including complex neural, endocrinological, and immunological signaling pathways. The first case reports and clinical studies have already reported that delivering microbes through fecal microbial transplantation (FMT) may alleviate symptoms of psychiatric disorders. Therefore, modifying the gut microbiota through FMT holds promise as a potential treatment for psychiatric diseases. This scoping review assessed studies from PubMed related to FMT in autism spectrum disorder and attention deficit hyperactivity disorder. The evaluation included nine clinical studies and case reports. The beneficial and persistent effect on the autism spectrum disorder (ASD) symptoms has been reported. Also, an increased microflora diversity and altered levels of neurometabolites in serum were identified, albeit with a tendency to return to baseline over time. The microbiome–gut–brain axis could provide new targets for preventing and treating psychiatric disorders. However, a recent large randomized clinical trial has shed light on the previously collected data and suggested a possible contribution of the placebo effect. This highlights the necessity of large randomized double-blind studies to reliably assess the effect of FMT in ASD.

BACKGROUND:Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections induce immunological and inflammatory reactions that may have an impact on cytochrome P450 activity, altering the metabolism of psychotropic drugs. In a cohort study, we prospectively investigated whether SARS-CoV-2 vaccination affects plasma levels of psychotropic agents in association with inflammatory parameter changes. METHODS:We analyzed data from a cohort of 13 psychiatric inpatients receiving psychotropic treatment who underwent two inoculations of a SARS-CoV-2 mRNA vaccination. Plasma levels of psychotropic drugs and inflammatory markers were measured before and after vaccination. RESULTS:In clozapine-treated patients, plasma levels remained by mean almost constant after both inoculations, although changes were larger in patients without vs. with co-medication with fluvoxamine (p < 0.001 at all timepoints except for timepoint T2; p = 0.9), with minor changes in interleukin 6 (IL-6) and C-reactive protein (CRP). For aripiprazole, quetiapine, olanzapine, lithium, sertraline, escitalopram, duloxetine, and paroxetine, no distinct plasma level patterns at post-vaccination emerged. CONCLUSION:SARS-CoV-2 vaccination was not associated with essential alterations of psychotropic drug levels. Observed CRP increases did not reach concentrations that may be associated with elevated drug levels. Nevertheless, monitoring of CRP and drug levels is recommended to capture post-vaccine plasma level changes, particularly in patients receiving clozapine.

OBJECTIVE:To investigate the pharmacokinetic correlates of clinical response to long acting injectable (LAI) antipsychotics in a naturalistic outpatient sample. METHODS:We conducted a retrospective cohort study of LAI-treated outpatients. Steady-state trough antipsychotic plasma concentrations were classified as subtherapeutic, within, or supratherapeutic based on established therapeutic reference ranges (TRRs). Clinical response was defined as Clinical Global Impression Improvement score ≤ 2. Generalized linear mixed models were used to analyze predictors of treatment response. RESULTS:In a total of 158 LAI-treated outpatients, responders (42.4 %) were significantly younger (50.5 vs. 55.6 years, p = 0.002) and more often treated with monotherapy (64.2 % vs. 44.0 %, p = 0.01). Half of the responders (51.1 %) had antipsychotic levels below the TRR (51.1 %), and 42.2 % had levels within TRR, while there were no responders with supratherapeutic concentrations (p = 0.01). After controlling for age, sex, body mass index, smoking, LAI monotherapy, and symptom severity, patients with subtherapeutic plasma concentrations (adjusted odds ratio (aOR): 31.97, 95 % confidence interval (CI): 1.74-588.55, p = 0.02) and with levels within the TRR (aOR: 23.01, 95 % CI: 1.28-414.48, p = 0.03) had higher probability of treatment response compared to those with supratherapeutic concentrations, while these estimates were limited by the small group size (n = 9). Younger age (aOR: 0.97, 95 % CI: 0.94-0.99, p = 0.04) and LAI monotherapy (aOR = 3.77, 95 % CI = 2.19-6.51, p = 0.001) were associated with better treatment response. CONCLUSIONS:Assessing antipsychotic concentrations combined with clinical characteristics such as LAI monotherapy and age may be useful for guiding pharmacotherapy with LAIs.

BackgroundOver the past years, the COVID-19 pandemic has caused significant disruptions in daily routines. Although the pandemic has affected almost everyone, it has been particularly challenging for people with pre-existing mental health conditions. Therefore, this study investigated the long-term impact of resilience and extraversion on psychological distress in individuals diagnosed with mental health disorders (MHD) compared to the general population. In addition, possible gender-specific differences were investigated.Methods123 patients with pre-existing MHD and 343 control subjects from Austria and Italy participated in three online surveys that had been conducted after the initial wave of the COVID-19 pandemic (t0), during the second lockdown in both countries (t1), and one year thereafter (t2). Participants completed standardized questionnaires on psychological distress (Brief-Symptom-Checklist), resilience (Resilience Scale), and extraversion (Big Five Inventory). A mediation model was employed to test the primary hypothesis. Possible gender-specific differences were analyzed using a moderated mediation model.ResultsThe prevalence of psychological distress was consistently higher in patients compared to controls (t0: 37.3% vs. 13.2%, t1: 38.2% vs 11.7%, t2: 37.4% vs. 13.1%). This between-group difference in psychological distress at the first follow-up was fully mediated by baseline resilience scores (65.4% of the total effect). During the second-follow up, extraversion accounted for 18% of the total effect, whereas resilience slightly decreased to 56% of the total effect. Gender was not a significant moderator in the model.ConclusionNext to showing that people with MHD were particularly affected by the pandemic, these findings indicate that higher degrees of resilience and extraversion are related to less long-term psychological distress. Our findings stress the relevance of strengthening resilience and extraversion and to provide mental health support in times of crises, both to patients with MHD and the general population.

Die psychiatrische Versorgung in Südtirol ist, wie überall in Italien, bis heute durch das Gesetz 180 geprägt, das 1978 unter Federführung von Franco Basaglia und Bruno Orsini in Kraft trat. Das Gesundheitsministerium legte in der Folge eine Sollbettenzahl von 10/100.000 Einwohner fest. Private Kliniken spielen in Südtirol, anders als in anderen Teilen Italiens, praktisch keine Rolle. Die „Psychiatrischen Dienste“ sind Teil des für alle Bürgerinnen und Bürger zuständigen staatlichen Gesundheitswesens und zugleich auch für die ambulante Pflichtversorgung zuständig. Dem Konzept der gemeindenahen Betreuung folgend, aber auch aufgrund der geringen Zahl stationärer Betten findet sehr viel Versorgung ambulant statt. Für die Legitimität von Zwangsbehandlungen ist ausschließlich die dringende Behandlungsbedürftigkeit eines Patienten maßgeblich, der die Behandlung ablehnt. Dabei wird kein Bezug auf die Tatbestände von Gefahren (Eigen- oder Fremdgefährdung) genommen. Eine stationäre Unterbringung ist nur möglich, wenn auch eine Behandlung stattfindet und auch in diesem Bereich gilt das Prinzip „ambulant vor stationär“, d. h. auch Zwangsbehandlungen dürfen nur dann stationär stattfinden, wenn sie ambulant nicht durchführbar sind. Die forensische Psychiatrie hat nur sehr wenige Plätze, psychisch kranke Straftäter befinden sich häufig im Strafvollzug oder belegen Betten in der Allgemeinpsychiatrie. Verglichen mit Deutschland sind weniger Betten verfügbar, die Personalausstattung insbesondere in der Pflege ist aber besser. Zwangsbehandlungen sind, bezogen auf die Einwohnerzahl, häufiger als in Deutschland, Unterbringungen (ist in Italien nur auf richterliche Anweisung möglich) und mechanische Freiheitsbeschränkungen dagegen deutlich seltener.

Geno- and phenotyping currently represent the main biological pillars for personalized medicine, particularly with regard to the prescription of psychotropic medications.. Nonetheless we are missing data regarding the usefulness of combining TDM with pharmacogenetics in patients treated with long-acting injectable antipsychotics (LAIs).

Mental healthcare in South Tyrol, as everywhere in Italy, is still characterized by Law 180, which came into force in 1978 under the leadership of Franco Basaglia and Bruno Orsini. The Ministry of Health subsequently set a target number of beds of 10/100,000 inhabitants. Unlike in other parts of Italy, private clinics play a minimal role in South Tyrol. The "Psychiatric Services" are part of the state healthcare system responsible for all citizens and are also responsible for compulsory outpatient care. According to the concept of community care, also due to the small number of inpatient beds, a great deal of care is provided on an outpatient basis. Coercive measures can only be used in the case of an illness requiring urgent treatment that the patient refuses, without recourse to endangering circumstances (self-endangerment or danger to a third party). Inpatient hospitalization is only possible if treatment also takes place and the principle of "outpatient before inpatient" also applies in this context, i.e., coercive treatment can only take place as an inpatient if it cannot be carried out as an outpatient. Forensic psychiatry has very few places and mentally ill offenders are often in prison or occupy beds in general psychiatric wards. Compared to Germany there are fewer beds available but staffing levels are better, particularly for nursing. In relation to the number of inhabitants, compulsory treatment is more frequent than in Germany, whereas involuntary hospitalization and physical restraint are much rarer (only possible in Italy by court order).

The positive effects of resilience on psychological distress has been found in previous studies in samples not including the seriously mentally ill. The present study aimed to investigate the course of psychological distress and resilience in the first two years of the Covid-19 pandemic in patients with severe mental illness (SMI) and major depressive disorder without psychotic features (MDD) compared to healthy control subjects. 141 patients with SMI or MDD who had been admitted to a psychiatric ward in Tyrol (Austria) or South Tyrol (Italy) in 2019 and 584 community controls participated in a longitudinal online survey. Next to collecting sociodemographic data, psychological distress was evaluated using the Brief Symptom Checklist (BSCL) and resilience by the 13-Item Resilience Scale (RS-13). Psychological distress was consistently significantly higher while resilience was consistently significantly lower among both patient groups compared to healthy controls. In the patient samples, those with MDD consistently exhibited a significantly higher prevalence and level of psychological distress and significantly lower resilience. Resilience had a moderating effect on psychological distress especially in the MDD group. Our results suggest that MDD patients represent a particularly vulnerable group and findings imply that these patients would profit the most from trainings fostering resilience.