Diurnal variation of cardiac autonomic activity in adolescent non-suicidal self-injury.

Heart rate (HR) and vagally mediated heart rate variability (HRV) are two distinct biomarkers of cardiac autonomic activity. Decreased cardiac vagal activity (or decreased HRV) in particular has been linked with impairments in the functional flexibility of the central autonomic network (CAN), resulting in impaired stress and emotion regulatory capacities. Decreased HRV is widely used as trait marker of psychopathology. Repetitive engagement in non-suicidal self-injury (NSSI) in adolescence correlates with both deficits in stress and emotion regulation, as well as decreased HRV. Existing research has, however, focused on short-term recordings of HR and HRV under resting and phasic conditions. In this study, we examined whether diurnal variation of cardiac autonomic activity, indexed by cosinor parameters of HR and HRV derived from 48 h of ambulatory ECG recording under natural conditions over a weekend, are altered in female adolescents with NSSI disorder compared to controls (HC; N = 30 per study group). Several important confounds, including physical activity, were controlled for. Female adolescents with NSSI show higher rhythm-adjusted 24 h mean levels and greater respective amplitude of HR, as well as lower rhythm-adjusted 24 h mean levels and smaller respective amplitude of HRV. Peak levels in both HR and HRV in the NSSI group were reached approximately 1 h later compared to HC. Severity of exposure to early life maltreatment might be linked with altered amplitudes of 24 h HR and HRV. Diurnal rhythms of cardiac autonomic activity might hold promise as objective indicators of disordered stress and emotion regulation in developmental psychopathology, and as such should be investigated in future studies with rigorous assessment and control of potential confounds.

Who Benefits from Acute Psychiatric Home Treatment? A Systematic Review.

Home treatment (HT) treats patients in an acute crisis through an interdisciplinary team with daily appointments for a short treatment period. The effectiveness of HT has already been confirmed. However, only few studies addressed specific patient characteristics associated outcome of treatment. This study aimed to identify patient characteristics associated with successful outcomes of HT. A systematic literature search was conducted according to the PRISMA guidelines. A total of 13 studies were included in the systematic review. Being employed, having a regular income, having an anxiety disorder and family involvement were associated with a successful treatment outcome in HT. High symptom severity and former hospital admissions were associated with unsuccessful treatment outcome in HT in the selected studies. HT seems to be especially beneficial for patients with paid employment or regular income, patients with anxiety disorders, and patients with familial or other social support.

Child maltreatment and hypothalamic-pituitary-adrenal axis functioning: A systematic review and meta-analysis.

Alterations in hypothalamic-pituitary-adrenal (HPA) axis and its effector hormone cortisol have been proposed as one possible mechanism linking child maltreatment experiences to health disparities. In this series of meta-analyses, we aimed to quantify the existing evidence on the effect of child maltreatment on various measures of HPA axis activity. The systematic literature search yielded 1,858 records, of which 87 studies (k = 132) were included. Using random-effects models, we found evidence for blunted cortisol stress reactivity in individuals exposed to child maltreatment. In contrast, no overall differences were found in any of the other HPA axis activity measures (including measures of daily activity, cortisol assessed in the context of pharmacological challenges and cumulative measures of cortisol secretion). The impact of several moderators (e.g., sex, psychopathology, study quality), the role of methodological shortcomings of existing studies, as well as potential directions for future research are discussed.

Introducing a Group Therapy Program (PLAN D) for Young Outpatients with Derealization and Depersonalization: A Pilot Study.

Depersonalization and derealization (DD) cause significant distress and are associated with poor role and social functional outcomes. Despite the relatively high prevalence of DD symptoms and the chronic course in those suffering from a DD disorder, there still exists a need for effective interventions. Preliminary evidence indicates that cognitive behavioral therapy (CBT) delivered in an individual setting demonstrates some positive intervention effects for patients with DD regarding their symptom levels. By considering DD-specific treatment needs, a group therapy program was developed as an add-on therapy based on CBT techniques called PLAN D comprising the following elements: psychoeducation, lifestyle interventions, acceptance and mindfulness training, and new patterns of DD-related cognitions. In a pilot study, we present an 8-week group intervention for adolescents and young adults with DD disorder. To our knowledge, no standardized group intervention program for DD exists so far. Thus, this novel intervention represents a promising opportunity to positively influence long-term outcomes and course of DD.

Age effects on basic symptoms in the community: A route to gain new insight into the neurodevelopment of psychosis?

Reports of limited clinical significance of attenuated psychotic symptoms before age 15/16 indicate an important role of neurodevelopment in the early detection of psychoses. Therefore, we examined if age also exerts an influence on the prevalence and clinical significance of the 14 cognitive and perceptive basic symptoms (BS) used in psychosis-risk criteria and conceptualized as the most direct self-experienced expression of neurobiological aberrations. A random representative general population sample of the Swiss canton Bern (N = 689, age 8-40 years, 06/2011-05/2014) was interviewed for BS, psychosocial functioning, and current mental disorder. BS were reported by 18% of participants, mainly cognitive BS (15%). In regression analyses, age affected perceptive and cognitive BS differently, indicating an age threshold for perceptive BS in late adolescence (around age 18) and for cognitive BS in young adulthood (early twenties)-with higher prevalence, but a lesser association with functional deficits and the presence of mental disorder in the below-threshold groups. Thereby, interaction effects between age and BS on functioning and mental disorder were commonly stronger than individual effects of age and BS. Indicating support of the proposed "substrate-closeness" of BS, differential age effects of perceptual and cognitive BS seem to follow normal brain maturation processes, in which they might occur as infrequent and temporary non-pathological disturbances. Their persistence or occurrence after conclusion of main brain maturation processes, however, might signify aberrant maturation or neurodegenerative processes. Thus, BS might provide important insight into the pathogenesis of psychosis and into differential neuroprotective or anti-inflammatory targets.

Childhood physical abuse and emotional neglect are specifically associated with adult mental disorders.

Background: Childhood adversities and trauma (CAT) are associated with adult mental disorders. Nevertheless, although CAT of different domains mostly co-occurs, and co-morbidity is common, the associations between CAT and mental disorders, when taking these interrelations into account, are not well known.Aims: We aimed to study differential associations between the five core domains of CAT and current axis-I disorders, taking into consideration their interrelations.Methods: Four hundred and fifteen outpatients attending adult primary (n = 255) and psychiatric care (n = 160) were assessed with the Trauma and Distress Scale (TADS) and the Mini International Neuropsychiatric Interview (MINI). Associations between CAT core domains and diagnostic categories were examined by path analyses.Results: At least some infrequent experience of CAT (83.6%), mostly of neglect, and current mental disorders (49.4%), mostly depression, was frequent, as were co-morbidities and co-occurrence of CAT domains. Considering these interrelations in a path model of excellent fit, physical abuse predicted depressive, manic, psychotic and anxiety disorders, whereas emotional neglect predicted depressive, anxiety and substance misuse disorders.Conclusions: Of all five CAT core domains, physical abuse and emotional neglect had the strongest association with adult psychiatric disorders and might have transmitted earlier reported main effects of other CAT domains onto mental disorders.

[Progress and challenges in the analysis of big data in social media of adolescents]. / Fortschritte und Herausforderungen für die Analyse von Big Data in sozialen Medien im Jugendalter.

Progress and challenges in the analysis of big data in social media of adolescents Abstract. Social media are ubiquitous today, and adolescents use them to express their thoughts, feelings, and behaviours. New interdisciplinary methods allow the automatic analysis of the massive amounts of data (big data) available on social networking websites using machine-learning tools to detect indicators of mental-health problems and disorders by identifying differences with common activity and communication patterns. This review first introduces the concept and potential fields of applications of big data in social media. It then discusses the first studies that used big data analyses and detected mental-health problems by identifying differences in the structure of social networks, in the use of certain words, and in the communication of opinions and sentiments. Future studies employing several assessment points could use longitudinal mediation analysis to model intraindividual changes in order to understand when and through which mechanisms social media use has an impact on mental health. Furthermore, future studies should include additional mental disorders, various sources of information, a broader age range, and additional social-networking websites to develop more precise models for the early detection of mental disorders. This would enable the development of personalised intervention programs to promote mental health and resilience in adolescents.

[Concepualization and promotion of resilience, well-being and mental health in children and adolescents]. / Konzeptualisierung und Förderung von Resilienz, Wohlbefinden und psychischer Gesundheit im Kindes- und Jugendalter.

Concepualization and promotion of resilience, well-being and mental health in children and adolescents Abstract. Resilience, mental health and well-being are commonplace terms in Positive Psychology and Psychiatry. However, many aspects regarding their definition, assessment and promotion still remain unclear. Therefore, this review provides an overview of recent studies and suggests that resilience is best understood as allostasis, i. e. as an interactive process between individuals and environment to achieve or maintain stability in the context of present or anticipated stressors through behavioral and / or physiological changes. Consequently, the degree of resilience of an individual depends on the context, population, stressor(s), risk or protective factors and outcome. Thus, resilience is a multidimensional construct only visible when a person is experiencing adversity or traumatic events. Preliminary results suggest that interventions targeting personal (assets) and environmental (resources) protective factors in children and adolescents produce some positive effects on symptom levels when assessed directly after the intervention. Similar to the concept of resilience, no consensus on the definition or measurement of well-being has been reached so far. Given the overlap between both constructs, well-being is often regarded as an indicator or element of resilience. Future cross- and longitudinal studies are therefore needed to uncover the composition and underlying mechanisms of these constructs, to reveal how they relate to each other and to determine the potential role of developmental and cultural peculiarities.

[Prevention of aversive childhood experiences: social and health policy consequences]. / Prävention aversiver Kindheitserfahrungen: gesellschaftliche und gesundheitspolitische Konsequenzen.

Prevention of aversive childhood experiences: social and health policy consequences Abstract. Neglect, as well as physical, psychological or sexual abuse increase the risk of developmental disorders and of long-term health consequences in adulthood. The prevention of maltreatment is therefore crucial. In Switzerland, a multi-layered prevention model mainly focuses on supporting the family. An improved social awareness of the importance of adequate childcare is in the interest of each individual as well as of the health care system and society as a whole.

Nature and Nurture: Brain Region-Specific Inheritance of Sleep Neurophysiology in Adolescence.

Sleep-specific oscillations of spindles and slow waves are generated through thalamocortical and corticocortical loops, respectively, and provide a unique opportunity to measure the integrity of these neuronal systems. Understanding the relative contribution of genetic factors to sleep oscillations is important for determining whether they constitute useful endophenotypes that mark vulnerability to psychiatric illness. Using high-density sleep EEG recordings in human adolescent twin pairs (n = 60; 28 females), we find that over posterior regions 80-90% of the variance in slow oscillations, slow wave, and spindle activity is due to genes. Surprisingly, slow (10-12 Hz) and fast (12-16 Hz) anterior spindle amplitude and σ power are largely driven by environmental factors shared among the twins. To our knowledge this is the first example of a neural phenotype that exhibits a strong influence of nature in one brain region, and nurture in another. Overall, our findings highlight the utility of the sleep EEG as a reliable and easy to measure endophenotype during adolescence. This measure may be used to measure disease risk in development before the onset of a psychiatric disorder; the location within the brain of deficits in sleep neurophysiology may suggest whether the ultimate cause is genetic or environmental.SIGNIFICANCE STATEMENT Two cardinal oscillations of sleep, slow waves and sleep spindles, play an important role in the core functions of sleep including memory consolidation, synaptic plasticity, and the recuperative function of sleep. In this study, we use a behavioral genetics approach to examine the heritability of sleep neurophysiology using high-density EEG in a sample of early adolescent twins. Our findings reveal a strong influence of both environmental and genetic factors in shaping these oscillations, dependent on brain region. Thus, during a developmental period when brain structure and function is in flux, we find that the sleep EEG is among the most heritable of human traits over circumscribed brain regions.

[Mediators of Problematic Social Media Use in Adolescence as Possible Mechanisms of Change in Psychotherapy]. / Mediatoren der problematischen Nutzung sozialer Medien im Jugendalter als mögliche Wirkmechanismen von psychotherapeutischen Interventionen.

Mediators of Problematic Social Media Use in Adolescence as Possible Mechanisms of Change in Psychotherapy Social media are omnipresent in the lives of adolescents. Problematic use of social media has been linked to adverse mental health outcomes including depression, anxiety, suicidality, self-harm, body dissatisfaction and eating pathology. Preliminary evidence suggests that interventions aiming at reducing the amount of time spent in social media and changing dysfunctional beliefs about social media use are promising. However, the mechanisms of change of these interventions with regard to mental health remain unclear. Therefore, this review first provides an overview of the association between social media and mental health and then identifies mediators of this relationship as potential mechanisms of change of interventions targeting problematic media use in adolescents. The identified mediators encompass social comparison, decreased self-esteem, fear of missing out, sleep problems and increased rumination. Future studies should apply a longitudinal design, should investigate additional confounding variables (e. g. age, level of psychopathology) and should also focus on positive effects of social media use on mental health. Thereby, this line of research has the potential to improve our understanding how social media use exerts its effects and based thereupon to develop new or optimize current interventions on problematic social media use to improve mental health in adolescents by targeting the identified mediators.

Negative symptoms, anxiety, and depression as mechanisms of change of a 12-month trial of assertive community treatment as part of integrated care in patients with first- and multi-episode schizophrenia spectrum disorders (ACCESS I trial).

Assertive community treatment (ACT) has shown to be effective in improving both functional deficits and quality of life (QoL) in patients with severe mental illness. However, the mechanisms of this beneficial effect remained unclear. We examined mechanisms of change by testing potential mediators including two subdomains of negative symptoms, i.e. social amotivation as well as expressive negative symptoms, anxiety, and depression within a therapeutic ACT model (ACCESS I trial) in a sample of 120 first- and multi-episode patients with a schizophrenia spectrum disorder (DSM-IV). Path modelling served to test the postulated relationship between the respective treatment condition, i.e. 12-month ACT as part of integrated care versus standard care, and changes in functioning and QoL. The final path model resulted in 3 differential pathways that were all significant. Treatment-induced changes in social amotivation served as a starting point for all pathways, and had a direct beneficial effect on functioning and an additional indirect effect on it through changes in anxiety. Expressive negative symptoms were not related to functioning but served as a mediator between changes in social amotivation and depressive symptoms, which subsequently resulted in improvements in QoL. Our results suggest that social amotivation, expressive negative symptoms, depression, and anxiety functioned as mechanisms of change of ACCESS. An integrated and sequential treatment focusing on these mediators may optimise the generalisation effects on functioning as well as on QoL by targeting the most powerful mechanism of change that fits best to the individual patient.

[Asperger Syndrome and/or Clinical High Risk of Psychosis? A Differential Diagnostic Challenge]. / Asperger-Syndrom und/oder klinisch erhöhtes Psychoserisiko? Eine differenzialdiagnostische Herausforderung.

Asperger Syndrome and/or Clinical High Risk of Psychosis? A Differential Diagnostic Challenge This case-study deals with the often difficult differential diagnosis of Asperger syndrome and a clinical high risk state of psychosis, in particular as indicated by attenuated psychotic symptoms, as well as with its therapeutic implications. The presented case is a 10-year old girl, who has not been diagnosed with an autism spectrum disorder before being referred to a specialized center for early detection of psychosis due to possible hallucinatory experiences and delusional ideas. We demonstrate how to perform a context-sensitive differential diagnosis to distinguish between specific interests as well as related behaviors and unusual thought content as well as perceptive abnormalities, between paranoid ideas and biased interpretations of the behaviors of others typical for autism, and between disorganized symptoms and autistic unusual communication and social behavior. The resulting dual diagnoses in our case-study formed the basis for a complex differential indication, which considered both the increased stress vulnerability associated with an increased risk for the development of psychosis as well as the rigid thinking style associated with autism. Our case-report shows that such a precise differential indication can lead to stabilization over the long-term, even in patients with dual diagnoses.

Opening the Black Box of Cognitive-Behavioural Case Management in Clients with Ultra-High Risk for Psychosis.

BACKGROUND: Cognitive-behavioural therapy (CBT) is the first-choice treatment in clients with ultra-high risk (UHR) for psychosis. However, CBT is an umbrella term for a plethora of different strategies, and little is known about the association between the intensity and content of CBT and the severity of symptomatic outcome. METHODS: A sample of 268 UHR participants received 6 months of CBT with case management (CBCM) in the context of the multi-centre NEURAPRO trial with monthly assessments of attenuated psychotic symptoms (APS). Using multilevel regressions and controlling for the initial severity of APS, the associations between (1) number of CBCM sessions received and severity of APS and (2) specific CBCM components and severity of APS were investigated. RESULTS: In month 1, a higher number of sessions and more assessment of symptoms predicted an increase in APS, while in month 3, a higher number of sessions and more monitoring predicted a decrease in the level of APS. More therapeutic focus on APS predicted an overall increase in APS. CONCLUSIONS: Our findings indicate that the association between intensity/content of CBCM and severity of APS in a sample of UHR participants depends on the length of time in treatment. CBCM may positively impact the severity of APS later in the course of treatment. Therefore, it would seem important to keep UHR young people engaged in treatment beyond this initial period. Regarding the specific content of CBCM, a therapeutic focus on APS may not necessarily be beneficial in reducing the severity of APS, a possibility in need of further investigation.

[Developmental Aspects in the Early Detection and Intervention in Clinical High Risk States for Psychosis]. / Entwicklungsspezifische Aspekte in der Früherkennung und Frühbehandlung eines erhöhten Psychoserisikos.

Developmental Aspects in the Early Detection and Intervention in Clinical High Risk States for Psychosis The early detection and intervention in psychoses, which are a main source of disability-adjusted life years already in children and adolescents, have made good progress within the past years. In particular the attenuated and transient positive symptoms of the ultra-high risk criteria and the basic symptom criterion "Cognitive Disturbances" open promising routes to an indicated prevention and have recently been considered as diagnostic criteria of a psychosis-risk syndrome by the European Psychiatric Association (EPA). However, because their association with a development of psychosis has been weaker in children and adolescents than in adults, only the assessment and monitoring of these risk symptoms was recommended for children and adolescents, while interventions aiming at the prevention of psychoses were discouraged. Furthermore, treatment of comorbid current mental disorders and psychosocial problems over the prevention of a potential future disorder also characterizes the intervention recommendations of the EPA. Furthermore, these give primacy to psychological, in particular cognitive-behavioral interventions over psychopharmacological treatments. Yet, also with regard to an early intervention, current evidence indicates that children and adolescents might benefit less than adults. Overall, age-related or developmental peculiarities in the early detection and intervention in psychoses become more and more apparent and should be more focused in future research in this field.

[Modular psychotherapy with children and adolescents]. / Modulare Psychotherapie im Kindes- und Jugendalter.

The implementation of evidence-based psychotherapy with children and adolescents has been limited so far. This is mainly due to the fact that patients in service settings tend to have higher rates of comorbidities and more frequently changing therapy needs than those in research settings. Thus, modular psychotherapies are promising, as they allow the treatment protocol to be adapted to patients' individual needs. Because no review on modular psychotherapy for children and adolescents exists, we conducted a systematic literature research. The results of the 15 randomized controlled trials identified demonstrate that modular psychotherapy is associated with significant reductions in symptom levels as well as with higher rates of diagnostic remission compared to control conditions. Because of the lack of evidence, future studies should investigate the incremental efficacy of modular approaches and test the validity of underlying theoretical models as well as of decision flowcharts. Modular psychotherapy approaches have the potential to personalize evidence-based interventions for children and adolescents across various therapeutical traditions, and to facilitate their implementation into clinical practice.

Prediction and prevention of psychosis: current progress and future tasks.

Prevention of psychoses has been intensively investigated within the past two decades, and particularly, prediction has been much advanced. Depending on the applied risk indicators, current criteria are associated with average, yet significantly heterogeneous transition rates of ≥30 % within 3 years, further increasing with longer follow-up periods. Risk stratification offers a promising approach to advance current prediction as it can help to reduce heterogeneity of transition rates and to identify subgroups with specific needs and response patterns, enabling a targeted intervention. It may also be suitable to improve risk enrichment. Current results suggest the future implementation of multi-step risk algorithms combining sensitive risk detection by cognitive basic symptoms (COGDIS) and ultra-high-risk (UHR) criteria with additional individual risk estimation by a prognostic index that relies on further predictors such as additional clinical indicators, functional impairment, neurocognitive deficits, and EEG and structural MRI abnormalities, but also considers resilience factors. Simply combining COGDIS and UHR criteria in a second step of risk stratification produced already a 4-year hazard rate of 0.66. With regard to prevention, two recent meta-analyses demonstrated that preventive measures enable a reduction in 12-month transition rates by 54-56 % with most favorable numbers needed to treat of 9-10. Unfortunately, psychosocial functioning, another important target of preventive efforts, did not improve. However, these results are based on a relatively small number of trials; and more methodologically sound studies and a stronger consideration of individual profiles of clinical needs by modular intervention programs are required.

The relationship between bullying victimization and impairment in personality functioning in a clinical adolescent sample.

Problematic interpersonal relationships may represent both, a risk factor for the development or trigger of personality disorder (PD) symptoms and its consequences. Since peer relationships become more and more important in adolescence, the current study explores the cross-sectional association between recent bullying experiences and levels of impairment in personality functioning according to the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) alternative model of personality disorders (AMPD; Criterion A) in help-seeking adolescents (N = 493). Logistic and multiple regression analyses revealed that patients who were frequently bullied in the past 3 months (i.e., at least once a week) were more likely to reach the diagnostic threshold for PD according to the AMPD (OR = 1.71, p = .025) and showed higher levels of impairment in identity (ß = .41, p < .001), empathy (ß = .26, p = .002), and intimacy (ß = .30, p = .001), but not self-direction, compared to patients who did not report any bullying experiences. Occasional bullying in the past 3 months (i.e., every few weeks) was neither associated with a greater likelihood to reach the diagnostic threshold for PD nor with greater impairments in identity, self-direction, empathy, or intimacy compared to no bullying. While the current study provides support for a correlation between bullying experiences and personality dysfunction (particularly in the elements identity and intimacy), longitudinal research is needed to clarify whether experiences of bullying cause or trigger personality dysfunction or/and vice versa. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Fostering resilience and well-being in emerging adults with adverse childhood experiences: study protocol for a randomized controlled trial to evaluate the FACE self-help app.

BACKGROUND: Adverse childhood experiences (ACE) are linked to an increased risk of psychological disorders and lower psychosocial functioning throughout life. This study aims to evaluate the FACE self-help app, designed to promote resilience and well-being in emerging adults with a history of ACE. The app is based on cognitive-behavioural principles and consists of two thematic components: (1) self- and emotion regulation (SER) and (2) social skills and biases in social information processing (SSIP). METHODS: The efficacy of the app will be tested through a single-centre, two-arm randomized controlled trial, comparing an active intervention group against a waiting list control group. The active group is divided into two subgroups, in which the two components are delivered in a different order to investigate differential effects in a crossover design. Up to 250 emerging adults aged 18 to 25 years with a history of ACE from a general population cohort study will be recruited. The primary objective is to test the efficacy of the app in improving resilience (primary outcome) and well-being (co-primary outcome) compared to a waiting list control group and to examine the stability of these effects. The secondary objectives include testing the efficacy of the app in improving the secondary outcomes, i.e., self-efficacy in managing emotions, problem solving, fear of evaluation, social avoidance, and self-esteem; examining the differential effects of the two components; and assessing the effect of the app on real-life data on resilience, affective states, distress in social interactions and coping strategies. Furthermore, the study will investigate potential moderators (e.g. ACE severity) and mediators of intervention outcomes (e.g. self-efficacy in managing emotions). DISCUSSION: The results will provide insights into the efficacy of the self-help intervention as well as mediators and moderators of outcomes. Furthermore, results will extend the existing knowledge by testing the differential effects of the SER and SSIP component on the outcomes. Findings can inform improvements to the FACE app and the development of other interventions for this target group and assess its potential as a scalable, low-threshold intervention to support emerging adults with a history of ACE in their transition to adulthood. TRIAL REGISTRATION NUMBER: NCT05824182.

N-Acetylcysteine and a Specialized Preventive Intervention for Individuals at High Risk for Psychosis: A Randomized Double-Blind Multicenter Trial.

Background and Hypothesis: Clinical high risk for psychosis (CHR-P) offers a window of opportunity for early intervention and recent trials have shown promising results for the use of N-acetylcysteine (NAC) in schizophrenia. Moreover, integrated preventive psychological intervention (IPPI), applies social-cognitive remediation to aid in preventing the transition to the psychosis of CHR-P patients. Study Design: In this double-blind, randomized, controlled multicenter trial, a 2 × 2 factorial design was applied to investigate the effects of NAC compared to placebo (PLC) and IPPI compared to psychological stress management (PSM). The primary endpoint was the transition to psychosis or deterioration of CHR-P symptoms after 18 months. Study Results: While insufficient recruitment led to early trial termination, a total of 48 participants were included in the study. Patients receiving NAC showed numerically higher estimates of event-free survival probability (IPPI + NAC: 72.7 ±â€…13.4%, PSM + NAC: 72.7 ±â€…13.4%) as compared to patients receiving PLC (IPPI + PLC: 56.1 ±â€…15.3%, PSM + PLC: 39.0 ±â€…17.4%). However, a log-rank chi-square test in Kaplan-Meier analysis revealed no significant difference of survival probability for NAC vs control (point hazard ratio: 0.879, 95% CI 0.281-2.756) or IPPI vs control (point hazard ratio: 0.827, 95% CI 0.295-2.314). The number of adverse events (AE) did not differ significantly between the four groups. Conclusions: The superiority of NAC or IPPI in preventing psychosis in patients with CHR-P compared to controls could not be statistically validated in this trial. However, results indicate a consistent pattern that warrants further testing of NAC as a promising and well-tolerated intervention for CHR patients in future trials with adequate statistical power.