Schizophrenia bulletin open最新文献

Sleep disturbances are a risk factor for suicidal ideation and are commonly reported amongst individuals experiencing psychosis. Given elevated suicide risk in first episode psychosis (FEP), understanding associations between sleep and suicidality is imperative for informing risk management and intervention. This study explored associations between sleep, psychosis symptoms, and suicidal ideation and the perceptions of those with FEP regarding these experiences. Ten participants experiencing FEP were recruited from Early Intervention services. Participants wore an actigraph for 7 days, completed 3 measures (insomnia severity index, prodromal questionnaire brief, and Beck scale for suicidal ideation), and participated in a semi-structured interview. No significant associations were found between variables, however, descriptive statistics indicated variation in sleep duration, sleep timing, wake after sleep onset, and onset latency. Qualitatively, participants described an extended process of loss, from losing sleep to "losing themselves" and the ability to make safe decisions. Sleep disturbances were considered central to the meaning making of psychosis experiences prior to an acute episode, and as a "trigger" for subsequent experience. Participants discussed reduced emotional control and heightened self-harm or non-suicidal self-injury following sleep disturbances. Participants described a sense of entrapment in their experiences of poor sleep and described suicide as an escape from their current reality. The relationship between sleep and suicidality in FEP warrants further exploration, including understanding of how specific aspects of sleep relate to suicidality, and exploration of the psychological processes in this complex relationship.

Background: Extrapyramidal symptoms (EPS) are common side effects of antipsychotic medications and can contribute to medication non-adherence and subsequent relapse in schizophrenia. Recent research suggests that inflammatory markers, such as the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII), may serve as biomarkers for treatment response in schizophrenia. This exploratory study is a first look at the relationship between these inflammatory markers and EPS in patients with schizophrenia.

Study design: Fifty patients with schizophrenia spectrum disorders were recruited, with 28 completing bloodwork. EPS was assessed using the Extrapyramidal Symptom Rating Scale (ESRS), and overall side effects were evaluated using the Glasgow Antipsychotic Side-Effect Scale (GASS). Blood samples were analyzed to calculate NLR, PLR, MLR, and SII.

Study results: Monocyte count was negatively correlated with the ESRS akathisia subscale. Higher SII scores were significantly associated with self-reported parkinsonism and hyperkinesia. Patients on clozapine had significantly higher PLR and MLR compared to those on other antipsychotics. No significant association was found between total GASS scores and inflammatory markers.

Conclusions: These findings suggest that certain inflammatory markers may be associated with specific EPS subscales. Further research with larger samples is needed to validate these results.

Background: Long-acting injectable (LAI) antipsychotics improve adherence and reduce schizophrenia relapse rates vs oral antipsychotics (OAs) but remain underused. The ADVANCE study explored country-level differences in LAI use among healthcare professionals (HCPs), patients, and caregivers, to identify drivers of LAI use.

Study design: ADVANCE included participants from Australia, Canada, China, Germany, Israel, South Korea, Spain, and the United States. Eligible HCPs spent ≥25% of their time in direct patient care, managed an adult population of whom ≥10% have schizophrenia, and treated patients prescribed LAIs. Patients aged ≥18 years and caregivers of adults living with schizophrenia who had tried/been offered an LAI were included. Participants completed a 30-minute survey.

Study results: Systemic factors reported by HCPs (n = 791) associated with higher LAI use included being a physician vs nonphysician, having Hispanic/Latino/Spanish ethnicity, managing more adult patients with schizophrenia, and having more staff and nurse support. Nonadherence to OAs was the main HCP-reported reason for LAI recommendation. Patient characteristics, lack of available LAIs corresponding to OAs, and perceptions of patients' behavior were top reasons HCPs would not recommend an LAI. For patients (n = 470), symptom improvement and HCP recommendation, and for caregivers (n = 381), ease of injections, reduced hospitalizations, and fewer side effects were the main reasons for LAI acceptance. The top reason patients and caregivers declined LAIs was concern about side effects.

Conclusions: Results from ADVANCE demonstrate that systemic and attitudinal factors influence LAI use by HCPs, and these factors vary by country. Enhancing HCP-patient communication may improve LAI acceptance.

Background: Fidelity scales are designed to assess the degree to which a program delivers the core components of evidence-based programs. The degree to which scales can predict outcomes-its predictive validity-is an important psychometric property. Fidelity scales have multiple applications, including in quality assurance and improvement. The purpose of this study was to assess the degree to which the First Episode Psychosis Services Fidelity Scale (FEPS-FS) assesses the 6 domains of quality of care (QoC) described in the Institute of Medicine (IOM)'s QoC framework.

Study design: A quality thematic analysis using a theoretical (deductive) approach was used to categorize the 36 items of the FEPS-FS according to the framework for evaluating QoC outlined by the IOM. Two coders independently reviewed and coded each item in duplicate. Frequency counts were used to summarize the characteristics of the FEPS-FS items across the IOM's quality domains.

Study results: Most FEPS-FS items reflect effectiveness (47.2%), efficiency (19.59%), and patient-centeredness (18.56%). Safety (7.22%), timeliness (5.15%), and equity (2.06%) were relatively underrepresented.

Conclusions: The FEPS-FS can be considered as a measure of QoC that reflects all the IOM domains. As expected for a fidelity scale, the largest number of items assess effectiveness, while safety, timeliness, and equity were represented by fewer items. We identified potential items from the literature that could be used to increase the proportion of items in underrepresented quality domains in future iterations of the FEPS-FS or other fidelity scales.

Background and hypothesis: Most individuals at clinical high risk for psychosis (CHR) will not develop psychosis. Moreover, a proportion of individuals who meet the criteria for a CHR syndrome at one time point stop meeting the criteria at follow-up. It is unknown whether there are specific baseline resiliency factors associated with CHR-positive symptom remission. The literature suggests that among the possible resiliency factors premorbid social functioning may be particularly important. Here, we examine how social functioning at baseline is related to remission status among CHR participants.

Study design: A total of 146 CHR and 114 healthy controls were assessed at a baseline and 12 months later. Within the CHR group, 10 individuals transitioned to a psychotic disorder and were excluded, 96 remained CHR, and 40 were fully remitted from CHR status. We compared baseline social functioning between the remitted- and active-CHR groups and examined possible underlying mechanisms such as social anhedonia and severity of interpersonal problems.

Study results: CHR individuals who remitted had higher baseline levels of social functioning (t(92) = 3.3, P = .001). Social functioning was related to subsequent CHR group status when controlling for negative and positive symptoms and demographic variables (B = 0.46, SE = 0.19, P = .02). Remitted individuals had higher baseline levels of social pleasure (t(59) = 2.3, P = .03) and lower baseline levels of interpersonal problems (t(11) = 2.4, P = .03).

Conclusions: Our findings identify an important predictor of remission status in CHR patients and suggest that interventions to improve social functioning could have preventative effects.

Background and hypothesis: Adolescent stress has been linked to an increased risk of developing psychiatric disorders, including schizophrenia. Previous findings from our group suggest that adolescent stress causes redox imbalance and functional impairments in parvalbumin (PV) interneurons and their associated perineuronal nets (PNNs) in the ventral hippocampus (vHip). These changes are associated with behavioral abnormalities, vHip hyperactivity, and dopamine system overdrive, mirroring observations in people with schizophrenia. Thus, we hypothesized that the antioxidant N-acetylcysteine (NAC) could mitigate schizophrenia-related alterations induced by adolescent stress in adult rats.

Study design: Male Sprague-Dawley rats were subjected to a combination of daily footshock and restraint stress during adolescence [postnatal days (PD) 31-40]. NAC (900 mg/L) was administered through the drinking water either during (PD31-40) or after the adolescent stress (PD51-60). In adulthood (PD63), rats underwent behavioral tests to assess anxiety-like behaviors, social interaction, and cognition. From PD70, in vivo recordings of dopamine neurons in the ventral tegmental area (VTA) and immunostaining of PV, PNNs, and the oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-Oxo-dG) in the vHip were performed.

Study results: Adolescent stress causes, in adulthood, anxiety-like responses, deficits in sociability and cognitive function, increased VTA dopamine neuron population activity, reduced PV⁺ cells in the vHip, including those surrounded by PNNs, and enhanced expression of 8-Oxo-dG, particularly in PV⁺ cells. NAC treatment, whether administered during or after adolescent stress, significantly attenuated these alterations.

Conclusions: NAC effectively mitigates schizophrenia-related changes induced by adolescent stress and may serve as a pharmacological intervention for prevention and treatment strategies.

Background: Negative symptoms of schizophrenia are highly predictive of poor functional outcomes, and current treatment approaches have been minimally efficacious for these symptoms. CT-155/BI 3972080 (CT-155) is being developed as a smartphone-based digital therapeutic (DTx) rooted in evidence-based psychosocial interventions. Patient feedback on the usability, facilitators, and barriers to app use are of critical importance for long-term effectiveness of CT-155.

Study methods: This qualitative analysis explored user experiences with a beta version of CT-155 (CT-155 beta) following participation in an exploratory clinical study. Semistructured interviews were conducted with 42 participants at the end of a multicenter, 7-week, single-arm, open-label, study of CT-155 beta (NCT05486312). Thematic analysis was used to identify key patterns in participant experiences, focusing on usability, perceived benefits, and challenges.

Study results: Participant feedback revealed insights regarding: (1) usability of the app, (2) benefits of use, and (3) considerations for implementation. Participants described the app as accessible and easy to navigate, even among those with limited digital experience. The reported benefits included improved coping, increased motivation, increased social interest and skills, new thought patterns, and engagement with structured daily routines. Implementation considerations included technical issues, a desire for more personalization, and the influence of psychiatric symptoms.

Conclusions: This study provides early insights into patient experiences after using CT-155 beta. The findings support the acceptability of the app and offer user-informed direction for future development. These results informed updates to the study app, which has been evaluated in a phase III confirmatory study.

Background: Only a few studies have investigated the association of environmental factors with DNA methylation in schizophrenia (SZ). Our study sought to investigate differentially methylated positions (DMPs) and differentially methylated regions (DMRs) between patients with psychosis and healthy controls (HCs) and to explore associations of aberrant methylation levels with the Korea-polyenvironmental risk score-I (K-PERS-I), a comprehensive tool measuring polyenvironmental risk factors for psychosis.

Study design: Blood-based methylome-wide association study (MWAS) was conducted in patients with psychosis (n = 414) and HCs (n = 225). For MWAS, a new cutting-edge technique, Methyl-Seq was employed. Using the K-PERS-I, polyenvironmental risk factors were assessed. Psychosis-associated DMPs and DMRs were identified via beta-binomial regression, and their associations with K-PERS-I scores were examined.

Study results: We identified 1138 DMPs and 1611 DMRs associated with psychosis. In the correlation analysis, 12 DMPs-annotated genes and 11 DMRs-annotated genes were associated with childhood adversity. These genes were mainly implicated in neuronal development, neurotransmitter release, synaptic plasticity, immune response, and oxidative stress. For obstetric complications, most of top five DMPs-annotated genes were implicated in placenta function, embryonic development or gestation. For recent adult life events, top five DMPs- and DMRs-annotated genes were related to neurotransmitter production/release, oxidative stress, and stress regulation.

Conclusions: We identified new psychosis-associated DMPs and DMRs. More importantly, we demonstrated how environmental factors can be biologically embedded in DNA methylation of certain genes in patients with psychosis. Ultimately, establishing causal pathways between these risk factors and DNA methylation could lead to the discovery of novel therapeutic targets.

Background: Auditory verbal hallucinations (AVHs) are the most common hallucinations within the psychosis spectrum and are often accompanied by anxiety. Integrating mental imagery into current psychological theories may increase the understanding of working mechanisms and effectiveness of cognitive behavioral therapy for AVHs. Therefore, the current study examined associations over time between levels of anxiety, mental imagery, and AVHs in individuals with psychosis spectrum disorders.

Study design: Baseline data were analyzed from a replicated single-case series study using a within person mediation model approach and time-lagged multilevel analyses to examine associations over time between levels of anxiety, mental imagery, and AVHs. The baseline comprised a 2-week period before starting with an imagery intervention in 32 individuals diagnosed with psychosis spectrum disorders.

Study results: There was a positive but non-significant association between anxiety and subsequent mental imagery (P = .061, [Formula: see text] = 0.044). There was a significant positive association between mental imagery and AVHs (P < .001, [Formula: see text] = 0.042), and between anxiety and AVHs (P < .001, [Formula: see text] = 0.157). Additionally, anxiety was found to mediate the association between mental imagery and AVHs (P < .001 [Formula: see text] = 0.034).

Conclusion: The present findings suggest that mental imagery may play a role in the development and the maintenance of AVHs by intensifying anxiety, which then precedes an increase in AVHs. Capturing mental imagery alongside verbal interpretations of AVHs may help to understand the dynamic interplay between mental imagery, anxiety, and AVHs and to refine cognitive frameworks for more effective psychological treatments.