Schizophrenia (Heidelberg, Germany)最新文献

Identifying predictors of clinical and functioning outcomes in individuals at clinical high risk (CHR) for psychosis is essential to early intervention and symptom monitoring. While motor abnormalities have been established as core features of psychosis vulnerability, the prognostic value of social motor behavior, particularly head movements during social interactions, remains underexplored despite being readily accessible and measurable by clinicians. We analyzed 10-minute of video recordings from virtual clinical interviews involving 72 individuals at CHR using an open-access video-based head tracking tool to quantify spontaneous head movements. In a longitudinal study, we examined associations between head movements, symptom severity, and global functioning at baseline and 12-month follow-up. At baseline, results showed that total amount of head movements were positively correlated with positive symptoms (ρ = 0.37), negative symptoms (ρ = 0.28), particularly social anhedonia (ρ = 0.30) and avolition (ρ = 0.31), and social functioning (ρ = -0.33). Head movements at baseline also predicted worsening of avolition (R² = 0.36, β = 0.0002, p = <0.05), and disorganized symptoms (trouble with focus and attention; R² = 0.24, β = 0.0002, p = <0.05) at 12-months, controlling for baseline symptomatology. Taken together, the results suggested that spontaneous head movements captured during virtual clinical interviews represent a sensitive social behavioral marker of symptom severity and future clinical course in individuals at CHR. The automated and ecological nature of the assessment offers a promising avenue for scalable and objective risk prediction and monitoring.

Semantic language dysfunction is a hallmark of early psychosis, yet the underlying brain structural correlates are largely unexplored. In particular, it is unclear whether core deficits arise from disruptions to semantic representation, which refers to the stored knowledge of word meanings, or to semantic control, which entails top-down mechanisms that guide the retrieval and selection of context-appropriate semantic information. By dissociating semantic representation-related from semantic control-related performance, we aimed to identify the preferential impairment in early psychosis and its structural correlates in the ventral and dorsal language streams. We investigated N = 120 individuals across the psychosis spectrum: N = 40 individuals with early psychosis, N = 40 individuals with high schizotypy, and N = 40 individuals with low schizotypy. Participants with high and low schizotypy constituted the non-clinical comparison group. All participants completed tasks designed to isolate semantic representation-related and semantic control-related processes. Given the importance of accurate delineation, this study employed meticulous manual fiber tractography of diffusion tensor imaging (DTI) data to ensure reliable evaluation of ventral and dorsal pathway microstructure. Compared to individuals with high and low schizotypy, individuals with early psychosis showed pronounced deficits in semantic control-related performance, while the semantic representation-related measure remained largely intact. Mean diffusivity in the left inferior fronto-occipital fasciculus and left uncinate fasciculus was lower in the early psychosis group than in individuals with schizotypy. In the early psychosis group, fractional anisotropy in the left arcuate fasciculus was negatively correlated with semantic control-related performance, but no DTI measure was associated with the semantic representation-related measure. These results underscore semantic control-related performance as a core deficit in early psychosis and extend the conventional view that semantic processing is subserved primarily by ventral pathways. The arcuate fasciculus appears implicated in semantic control-related processes, indicating a more integrated interplay of dorsal and ventral streams in semantic language processing.

Older adults with schizophrenia face a significantly elevated risk of dementia. However, recent trends remain unclear within South Korea's rapidly aging schizophrenia population. This study aimed to quantify the burden of dementia in older schizophrenia patients by examining prevalence, incidence, dementia subtypes, pharmacologic treatment, and healthcare utilization. Using nationwide Health Insurance Review and Assessment (HIRA) data from 2010 to 2021, we identified 220,378 individuals aged ≥50 with schizophrenia. Dementia was diagnosed in 14.6% of patients, with 20.7% of cases occurring before age 60. Patients with dementia were more likely to be female and to have a higher comorbidity burden. Age-standardized all-cause dementia prevalence rose from 11.8% (2010) to 15.8% (2021) in those aged ≥50, and from 24.2% to 32.8% in those aged ≥65-exceeding estimates in the general population. In contrast, incidence declined from 3.4% to 1.7% over the same period. Alzheimer's disease (AD) was the most prevalent subtype (12.2%), followed by vascular dementia (VD, 2.4%), and frontotemporal dementia (0.5%). A lower AD/VD prevalence ratio in schizophrenia (5.3 vs. 8.6 in the general population) suggests a relatively higher burden of vascular pathology. Cognitive enhancer prescriptions increased from 62% to 77% in patients with dementia, compared to 4% to 10% in those without dementia. In 2021, those with dementia were more likely to live in nursing homes (68% vs. 56%) and had greater annual increases in psychiatric hospitalization duration (+2.30 vs. +1.11 days/year). These findings underscore growing care demands and need for integrated treatment strategies for aging schizophrenia patients with dementia.

Numerous aspects of depressive symptomatology in first-episode schizophrenia spectrum disorders (FES) remain unclear. Based on data from the FES OPTiMiSE trial, we estimated the prevalence of depression (Calgary Depression Scale for Schizophrenia (CDSS) total score ≥7) at baseline (n = 122, 27.5%) and at weeks 4 (n = 57, 15.9%) and 10 (n = 14, 21.5%). Baseline depression was cross-sectionally associated with more severe extrapyramidal symptoms (p = 0.036) and poorer subjective wellbeing (p < 0.001). At week 4, baseline depression was linked to poorer psychosocial functioning (p < 0.001) and subjective wellbeing (p < 0.001). At week 10, baseline depression was associated with psychosis non-remission (p = 0.042) and worse subjective wellbeing (p = 0.011). There was a significant correlation between decrease in CDSS and PANSS total scores (p < 0.001) at weeks 4 and 10. Depressive symptomatology in the FES OPTiMiSE trial was prevalent and associated with poorer objectively- and subjectively-measured outcomes over a 10-week follow-up. Early intervention for depression may improve outcomes in FES.

Cognitive dysfunction is a defining characteristic impairing social functioning in schizophrenia (SZ). N-methyl-D-aspartate receptor (NMDAR) hypofunction may underlie these impairments. This study explored the association between peripheral blood levels of the NMDAR subunits NR1 and NR2 and cognitive improvement in SZ, evaluating their potential as biomarkers for the efficacy of cognitive intervention. This secondary analysis of a randomized controlled trial included 60 clinically stable SZ patients and 30 healthy controls (HCs). Patients received five-day transcranial direct current stimulation (tDCS) during cognitive tasks across three groups: the active dorsolateral prefrontal cortex (DLPFC), the active posterior parietal cortex (PPC), and the sham stimulation group. Cognition was evaluated, and blood samples were collected at baseline, week 1, and week 2. Baseline blood samples were also obtained from HCs. NR1 and NR2 concentrations were quantified using enzyme-linked immunosorbent assay (ELISA). We found that baseline NR1 concentration was significantly lower in the patient group than in HCs, with no NR2 differences observed. Compared to the other two groups, the active PPC group demonstrated significant working memory improvements. In the active PPC group, baseline NR1 and NR2 concentrations were negatively correlated with working memory improvements at week 1. Moreover, changes in NR1 at weeks 1 and 2, and NR2 at week 1, were positively associated with working memory improvements at week 1 in the active PPC group. Peripheral NR1 and NR2 levels may serve as biomarkers for predicting cognitive improvement in SZ, supporting the role of NMDAR dysfunction in SZ-related cognitive deficits.

Early identification of individuals with clinical high risk (CHR) for psychosis relies heavily on subjective assessments, necessitating the exploration of objective markers to enhance diagnostic accuracy. This study aimed to evaluate the temporal integration window (TIW) of sensory processing in individuals with CHR, first-episode schizophrenia (FES), and healthy controls (HC) to assess its utility as an objective neuropsychological marker for identifying CHR individuals. Ninety participants (30 CHR, 30 FES, 30 HC) completed temporal order judgment of visual and auditory(TOJV and TOJA) and simultaneity judgment of the flash-beep (SJF) tasks. Unisensory (visual and auditory) thresholds and TIW were measured and compared across groups. Cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB). The associations between cognition with unisensory thresholds and TIW were analyzed. The TIW was significantly prolonged in both the CHR (336.95 ± 108.30 ms) and FES (413.15 ± 121.27 ms) groups compared to the HC group (229.95 ± 54.53 ms) (P < 0.05). Visual and auditory thresholds and TIW were negatively correlated with information processing speed and attention (both P < 0.05). Notably, TIW effectively discriminates across three groups. Compared to HC, each 50 ms increase in TIW was associated with a 2.3-fold increased risk of CHR (95% CI 1.27-4.28, P = 0.01; AUC = 0.81, 95% BCa CI 0.65-0.91). Similarly, it was associated with a 3.3-fold increased risk of FES (95% CI 1.78-6.34, P < 0.01; AUC = 0.94, 95% BCa CI 0.81-0.99). No correlations were observed between TIW and symptom severity in FES and CHR. Prolonged TIW in multisensory integration may serve as a promising objective neuropsychological marker for identifying individuals at CHR for psychosis.

Schizophrenia ranks among the top ten causes of disability worldwide. The provision of healthcare services requires estimates on the epidemiology of schizophrenia, but recent data for Germany are lacking. Based on a large German health claims database (GePaRD), we identified persons aged 0-64 years with treated schizophrenia, i.e., persons having at least one inpatient/outpatient ICD-10 diagnosis (F20) with at least one prescription for a schizophrenia-recommended antipsychotic in the same calendar year. For each year from 2012 (eligible persons: 9,589,084) to 2021 (eligible persons: 12,450,531), we calculated the standardized incidence proportion (SIP) and the prevalence of schizophrenia. Analyses were stratified by sex, age, and population density in the region of residence. The SIP of treated schizophrenia remained stable from 2012 to 2017 (46.0-46.5/100,000) and subsequently declined to 41.3/100,000 in 2021, with higher SIP in men (45.3/100,000) than in women (37.1/100,000). In 2021, the SIP was comparable in urban, rural, and sparsely populated rural districts (36.3-38.5/100,000) and higher in large urban cities (48.3/100,000). SIP estimates among children and adolescents (aged 0-17 years) varied between 3.5/100,000 and 4.1/100,000 over the study period. The standardized prevalence of schizophrenia declined from 366.1/100,000 in 2012 to 334.0/100,000 in 2021. Similar to other Western countries, there has been a decline in the incidence and prevalence of schizophrenia in Germany over the last few years. The higher incidence in males and those living in large urban areas highlights the health care needs of these populations.

Disruptions in language processing observed in Individuals diagnosed with schizophrenia (ISZ) are likely to impair turn-taking fluency and social functioning. While turn-taking research in ISZ is limited and mostly interview-based, this study examines fluency differences between ISZ and controls in free conversations and their links to social outcomes and symptoms. We recruited 20 ISZ, 20 healthy interacting partners (IP), and 20 matched controls (MAT). Each IP, unaware of the ISZ diagnosis, had a 6-min conversation with an ISZ and a MAT, and then rated their willingness to interact again. Voice recordings were analyzed for pauses, gaps, and overlaps. Results revealed that conversations with ISZ featured fewer overlaps, more and longer gaps, and extended pauses. Additionally, the gap duration influenced participants' willingness to engage in future interactions. ISZ symptoms disrupted their speech and were linked to longer gaps and pauses in their partner's speech. This study extends fluency research in ISZ by shedding light on natural conversational dynamics.

Current preventative measures for clozapine-induced agranulocytosis (CIA) include indefinite haematological monitoring. Another safeguard against CIA is patient and carer education to identify and respond to potential symptoms of this adverse effect. Our aim was to explore how informed patients and carers are about the potential symptoms of CIA and what actions to take. An anonymous cross-sectional survey was distributed electronically to patients or family/carers prescribed clozapine across England. A mixed methods approach was used to assess how informed patients and carers are about CIA, identifying potential symptoms of CIA and the appropriate actions to take. Quantitative data were analysed using descriptive and inferential statistics, and qualitative responses were analysed thematically. A total of 354 individuals participated in the survey (310 patients and 44 unrelated family carers). Overall, 122 (35%) were aware that clozapine can cause agranulocytosis. The odds of awareness were significantly higher among carers (AOR = 2.90; 95% CI, 1.45-5.88) and lower among males (AOR = 0.60; 95% CI, 0.36-1.00), Black individuals (AOR = 0.33; 95% CI, 0.17-0.61) and individuals in the other ethnicity group (AOR = 0.39; 95% CI, 0.16-0.89). Among those who reported CIA awareness, 45 (37%) participants could name at least one of the signs or symptoms of CIA. A typology of responses to experiencing signs or symptoms of CIA were derived from the thematic analysis, categorised into seeking immediate medical attention (two subthemes), consulting healthcare professionals (four subthemes), uncertainty or lack of knowledge (two subthemes), involvement of family or care providers (two subthemes), self-care (three subthemes) and reluctance to seek help (two subthemes). Our results indicate that most patients and carers are unaware of CIA. There is a need to better inform patients and carers about CIA, about how to identify symptoms and the importance of consulting their treating clinician when suspicions arise. This is particularly important if calls for reduced haematological monitoring are implemented.

Early-onset schizophrenia (EOS) patients are at greater risk of poor long-term outcomes compared to later-onset patients, so it is essential to identify unique pathomechanisms and prognostic biomarkers for this EOS patient group. Deficits in neurotrophic and oxidative stress resistance are implicated in EOS, so this study investigated associations of EOS risk with peripheral blood platelet-derived growth factor (PDGF) subtype concentrations and superoxide dismutase (SOD) isoenzyme activities. Serum PDGF subtype concentrations and plasma SOD isoenzyme activities were measured in 99 first-episode drug-naïve EOS patients (ages 12-18 years) and 40 matched healthy controls (HCs). Disease severity was assessed using the five-factor model of the Positive and Negative Syndrome Scale (positive, negative, cognitive, excitement/hostility, and anxiety/depression). Serum PDGF-AB and PDGF-BB concentrations, as well as plasma total (T)-SOD and Mn-SOD activities, were significantly lower in EOS patients than HCs (all, P < 0.001 except for T-SOD, where P = 0.003). Serum PDGF-AB concentration was positively correlated with plasma Mn-SOD activity (r = 0.267, P = 0.007), while serum PDGF-BB concentration was negatively correlated with cognitive symptom severity (r = -0.406, P < 0.001), and T-SOD activity was negatively correlated with excitement/hostility symptom severity (r = -0.354, P < 0.001). Multivariate analysis with dichotomized factors identified low PDGF-AB (RR = 1.788, 95% CI: 1.226-2.608, P = 0.003), low PDGF-BB (RR = 1.758, 95% CI: 1.208-2.558, P = 0.003), and a significant PDGF-AB × Mn-SOD interaction (RR = 1.460, 95% CI: 1.044-2.042, P = 0.027) as independent EOS risk factors, with 44.1%, 43.1%, and 31.5% attributable risk, respectively, and population attributable risk fractions of 34.5%, 33.7%, and 23.6%, respectively. Reduced PDGF and SOD levels may contribute to the earlier onset of schizophrenia symptoms and exacerbate symptom severity. Peripheral blood PDGF concentrations and SOD activities may thus be valuable biomarkers for EOS detection.