Schizophrenia (Heidelberg, Germany)最新文献

Schizophrenia is a complex mental health condition characterized by a range of heterogenous symptoms. Cognitive impairment associated with schizophrenia (CIAS) interferes with individuals' ability to manage their daily activities and has a detrimental effect on everyday life. The Schizophrenia Cognition Rating Scale (SCoRS) is an interview-based assessment, which was developed to provide a detailed evaluation of the performance of everyday tasks in the real world. The assessment is completed by clinicians with input from patients with schizophrenia and caregivers. The scale has good psychometric properties and has been used across several trials. Nevertheless, the relevance of the SCoRS from the caregivers' perspective has not been confirmed. The aim of this study was to confirm the content of the SCoRS from the caregivers' perspective. A cross-sectional qualitative study was conducted with primary (live-in, for example, a family member) and secondary (professionally trained) caregivers in the US caring for patients with schizophrenia. The caregiver research confirmed the concepts that clinicians and patients had previously identified in the creation of the PRECIS scale as clear cognitive deficits of patients with schizophrenia. Understanding that family and professional caregivers confirm these cognitive impairments to be real, independently from the patient and clinicians, is helpful to determine the validity of the cognitive impairment concept. Overall, the findings confirmed that the SCoRS captures relevant aspects of cognitive functioning in patients with schizophrenia and support the relevance and clarity of instructions, domains, and items with primary and secondary informants.

Cognitive impairment associated with schizophrenia (CIAS) places a significant burden on patients and caregivers. This study explored the burden experienced by primary (informal) and secondary (formal) caregivers. A secondary qualitative analysis was performed on interviews from a Schizophrenia Cognition Rating Scale (SCoRS) confirmation study. Thematic analysis was utilised to investigate the characteristics of caregiver burden. Quotes were analysed across 3 levels (Level 1: caregiver experience of patient cognitive symptoms; Level 2: caregiver experience of patient burden; Level 3: overarching caregiver burden) to establish themes. Subsequently, themes were mapped to SCoRS domains. Twenty primary caregivers and 20 secondary caregivers were enrolled. Caregivers described patient difficulties with memory, learning, social communication, and everyday tasks. Caregivers assisted patients by engaging in sustained teaching for new activities, encouraging social communication and repeating reminders to accomplish tasks. Caregiver burden was substantial among both groups. Thematic analysis identified 2 main themes: caregiving difficulty and caregiving necessity. These themes reflected the extensive roles and responsibilities assumed by caregivers due to the impacts of CIAS symptoms. Illustrative quotes were reported for 60% of primary caregivers and 55% of secondary caregivers. Six of the 8 SCoRS domains (memory, learning, attention, problem-solving, language, social cognition)were mapped to themes identified at each level. A high level of objective caregiving burden was found in relation to CIAS symptoms among primary and secondary caregivers. The SCoRS domains of memory, learning, attention, problem-solving, language and social cognition are key areas to treat in patients with schizophrenia to reduce caregiver burden.

Speech-based detection of early psychosis is progressing at a rapid pace. Within this evolving field, the Accelerating Medicines Partnership® in Schizophrenia (AMP® SCZ) is uniquely positioned to deepen our understanding of how language and related behaviors reflect early psychosis. We begin with detailed standard operating procedures (SOPs) that govern every stage of collection. These SOPs specify how to elicit speech, capture facial expressions, and record acoustics in synchronized audio-video files-both on-site and through remote platforms. We then explain how we chose our sampling tasks, hardware, and software, and how we built streamlined pipelines for data acquisition, aggregation, and processing. Robust quality-assurance and quality-control (QA/QC) routines, along with standardized interviewer training and certification, ensure data integrity across sites. Using natural language processing parsers, large language models, and machine-learning classifiers, we analyzed Data Release 3.0 to uncover systematic grammatical markers of psychosis risk. Speakers at clinical high risk (CHR) produced more referential language but fewer adjectives, adverbs, and nouns than community controls (CC), a pattern that replicated across sampling tasks. Some effects were task-specific: CHR participants showed elevated use of complex syntactic embeddings in two elicitation conditions but not the third, underscoring the importance of the language sampling task. Together, these results demonstrate how computational linguistics can turn everyday speech into a scalable, objective biomarker, paving the way for earlier and more precise detection of psychosis.Video Link: https://vimeo.com/1112291965?fl=pl&fe=sh.

A growing body of evidence has indicated an increased risk of violence among patients with schizophrenia. While childhood trauma (CT) has been robustly associated with increased violent behavior in schizophrenia spectrum disorders, the neurobiological mechanisms underlying this relationship remain underexplored. The objectives of this study are to investigate the potential role of functional connectivity (FC) in the relationship between CT and violence. This study enrolled 55 patients with schizophrenia and 36 healthy controls. Seed-based functional connectivity between a predefined seed in the orbitofrontal cortex and other brain voxels was compared across groups, with significant results regarding FC used in further mediation analysis. The seed-based analysis revealed decreased FC between the right orbital part of the inferior frontal gyrus (ORBinf) and the right middle temporal gyrus as well as the right superior frontal gyrus in violent schizophrenia patients (VSP) compared to both healthy controls (HC) and non-violent schizophrenia patients (NVSP). VSP also exhibited decreased FC between the right ORBinf and the right middle frontal gyrus compared to NVSP. Furthermore, the mediation analysis indicated that the relationship between CT and violence was completely mediated by the strength of FC between the right ORBinf and the right MTG. The present study suggested that alterations of FC between certain brain regions may be associated with violence and offer valuable insights into potential neural targets for interventions aiming to address CT and violence in patients with schizophrenia.

Historically, large samples of individuals at clinical high risk (CHR) for psychosis have mirrored overt psychotic disorders in both sex (predominantly male) and age representation (adolescent to early adulthood onset). We report on a recent CHR sample suggesting a shift in these distributions and explore contributing factors and clinical implications. We hypothesized that demographic differences would be related to recruitment sources and that age, sex, and recruitment sources would be related to baseline clinical profiles. Baseline data were included from the recent computerized assessment of psychosis risk (CAPR) study and the second and third waves of the North American Prodrome Longitudinal Study (NAPLS-2 and 3). Hierarchical regression was used to examine differences in sex, age, and recruitment sources between samples and relationships with clinical characteristics. Univariate analyses revealed a significant shift to female predominance, older age, and a change in recruitment source from NAPLS to CAPR. Multivariate analyses indicated that between-study differences in sex and age were conditional on recruitment source, with the apparent study effect driven by differences in the non-self-referred groups. More than 60% of participants recruited through internet self-referrals were female across samples. Clinical heterogeneity was partly related to age, sex, and recruitment source differences. Internet-based self-referrals were older and showed less severe negative symptoms, disorganization, and general symptoms and higher role functioning than non-self-referred participants. Findings highlight the importance of recruitment sources for CHR sample characteristics. Recruitment source effects, including those from internet sources, should be investigated in other CHR samples.

While voice-hearing in psychosis has received much attention, perceptual experiences in other sensory modalities and psychiatric conditions have remained relatively overlooked. The present review aimed to address this gap by providing an overview of voices/altered perceptual experiences (APE) across psychotic, mood and anxiety disorders in terms of phenomenological characteristics, biopsychosocial mechanisms, etiological models and therapeutic interventions. Where possible, lived experience perspectives and transcultural considerations were embedded. A narrative literature review was conducted. Knowledge pertaining to voices in psychosis formed the foundation, broadened to include other sensory modalities and diagnostic conditions. Quality assessment demonstrated an excellent rating of 12/12. Notable findings related to: (i) phenomenological heterogeneity in voices/APE within individuals and across diagnostic conditions, with multisensory/multimodal experiences relatively widespread; (ii) existing mechanistic studies mainly focusing on the role of trauma and neurocognition in voices; (iii) prevailing explanatory models mostly focusing on voices; (iv) a need for emerging interventions to extrapolate to encompass broader therapeutic applications; and (v) wide-ranging specificity issues and transcultural considerations to be addressed. Future research should invest in appropriate assessment tools as well as ensuring methodological consistency in mechanistic studies. Incorporating lived experience perspectives and meaningfully embedding transcultural considerations in theoretical and empirical ways are also essential.

Schizophrenia (SCZ) is a complex neuropsychiatric disorder that profoundly disrupts daily life. Beyond its well-documented effects on the brain, SCZ is also associated with peripheral organ dysfunction, yet the underlying shared genetic mechanisms remain unclear. In this study, leveraging large-scale genome-wide association study (GWAS) data, we investigated the genetic architecture shared between SCZ and 47 common imaging phenotypes spanning three major peripheral organs: 28 cardiac magnetic resonance (CMR) phenotypes, eight skeletal dual-energy X-ray absorptiometry (DXA) phenotypes, and 11 abdominal magnetic resonance imaging (MRI) phenotypes. We identified seven significant causal associations between SCZ and peripheral organ imaging phenotypes, alongside 99 unique loci through local genetic correlation analysis. Additionally, we pinpointed 437 independent pleiotropic SNPs between SCZ and CMR phenotypes, 257 for skeletal DXA phenotypes, and 230 for abdominal MRI phenotypes. The shared genes were significantly enriched in synapse-related biological processes, underscoring their vital role in SCZ across various peripheral organ systems. Furthermore, we characterized the spatiotemporal expression patterns of shared genes in the brain across different peripheral imaging phenotype groups and identified drug-gene interactions, highlighting potential therapeutic targets for SCZ-related peripheral dysfunction. Our findings underscore the systemic nature of SCZ, emphasizing the need to integrate psychiatric and systemic health perspectives in its management. By revealing novel genetic links and potential therapeutic targets, this study provides valuable insights into SCZ's multifaceted impact beyond the brain.

Experiential negative symptoms (ENS) of schizophrenia, such as asociality, anhedonia, and avolition, are associated with poor outcomes, yet no FDA-approved pharmacotherapies currently exist specifically to target these symptoms. With the increasing use of smartphones, evidence-based digital interventions delivered by prescription digital therapeutics (DTx) may present an opportunity to address the unmet therapeutic need for ENS of schizophrenia. CT‑155/BI 3972080 (CT-155) is being developed as a smartphone-based prescription DTx for the treatment of ENS. A multicenter, 7-week, single-arm, open-label, exploratory study (NCT05486312) evaluated the engagement, adherence, potential effectiveness, acceptability, user experience, and safety of an abbreviated version of CT-155 (CT‑155 beta). Engagement and adherence with CT-155 beta were measured passively throughout the study using the study app. Change in ENS severity was assessed using the clinically administered clinical assessment interview for negative symptoms, motivation, and pleasure subscale (CAINS-MAP). Acceptability and user experience were assessed using the validated Mobile App Rating Scale (MARS) along with an episodic user experience survey, respectively. Fifty participants with a clinically confirmed schizophrenia diagnosis were enrolled; 80% were male, 58% were Black or African American, and the median (range) age was 53.5 (23-64) years. At baseline, participants' mean (SD) CAINS-MAP total score was 20.5 (8.3). Most participants (n = 43; 86%) completed the 7-week study. Participants readily engaged with CT-155 beta. Kaplan-Meier retention analysis showed that 84% of participants (N = 42/50) engaged with CT-155 beta (i.e., last app open) until the end of the study period. Daily app check-ins were completed on a median (IQR) of 43.0 (19-47) days of the 49 possible days (88%). The median (IQR) duration of engagement was 11.6 (8.1-16.1) min per session. Additionally, adherence with CT-155 was high, with participants completing a median of 18 (IQR 13-20) of the 21 therapeutic lessons available. After 7 weeks of CT-155 beta usage, the mean change in within-subject CAINS-MAP score was 3.6 points from baseline (95% CI 1.3, 5.8; p = 0.0026; baseline: 20.4 (8.6) Week 7: 16.8 (7.7)). Most participants (91%; n = 39/43) rated CT-155 beta functionality using MARS assessment as acceptable or higher, with an overall mean MARS functionality subscale score of 4.2 points out of 5 points, with 5 corresponding to "excellent" at Week 7. The end of study participant feedback survey showed that 95% (n = 42/44) of participants would recommend using CT-155 beta. No app-related adverse events nor severe adverse events leading to discontinuation of the study were reported. Overall, the study demonstrated the feasibility of CT-155 beta in participants with ENS of schizophrenia. Results from this feasibility study show the potential of evidence-based DTx approaches to address ENS of schizophrenia.

It has been proposed that dysfunctions in emotional multisensory integration (MSI) could contribute to the development of psychosis. To further substantiate this proposition, we investigated whether impaired MSI of emotional cues can be observed in people with high psychosis proneness without a diagnosis of psychosis and whether it is associated with aberrant perception and psychotic experiences. Adults scoring high vs. low on the positive subscale of the Community Assessment of Psychic Experiences (score ≥9 or <9, respectively; n = 36 each) categorized the perceived emotion and rated the intensity of unimodal, bimodal emotionally congruent and bimodal emotionally incongruent dynamic face-voice stimuli. In different blocks, participants were asked to attend to one modality and to ignore the other modality input. Additionally, participants completed self-report questionnaires on anomalous perceptual experiences, hallucinations and paranoia. Participants with high and low psychosis proneness did not differ in emotion categorization performance as indicated by similar inverse efficiency (IE) scores (i.e., mean reaction time divided by accuracy) in all conditions, nor did they differ in intensity ratings in any condition. Correlation analyses did not reveal significant associations between crossmodal (in)congruency effects and self-reported anomalous perceptual experiences, hallucinations or paranoia. Our findings, thus, do not provide support for the assumption that MSI of emotional cues is linked to altered perception or subclinical psychotic symptoms, nor for the notion that MSI of emotional cues is already altered at a very early stage in the developmental trajectory of psychosis.