Schizophrenia (Heidelberg, Germany)最新文献

{"title":"Addressing brain metabolic connectivity in treatment-resistant schizophrenia: a novel graph theory-driven application of ¹⁸F-FDG-PET with antipsychotic dose correction.","authors":"Giuseppe De Simone, Felice Iasevoli, Annarita Barone, Valeria Gaudieri, Alberto Cuocolo, Mariateresa Ciccarelli, Sabina Pappatà, Andrea de Bartolomeis","doi":"10.1038/s41537-024-00535-4","DOIUrl":"10.1038/s41537-024-00535-4","url":null,"abstract":"<p><p>Few studies using Positron Emission Tomography with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG-PET) have examined the neurobiological basis of antipsychotic resistance in schizophrenia, primarily focusing on metabolic activity, with none investigating connectivity patterns. Here, we aimed to explore differential patterns of glucose metabolism between patients and controls (CTRL) through a graph theory-based approach and network comparison tests. PET scans with ¹⁸F-FDG were obtained by 70 subjects, 26 with treatment-resistant schizophrenia (TRS), 28 patients responsive to antipsychotics (nTRS), and 16 CTRL. Relative brain glucose metabolism maps were processed in the automated anatomical labeling (AAL)-Merged atlas template. Inter-subject connectivity matrices were derived using Gaussian Graphical Models and group networks were compared through permutation testing. A logistic model based on machine-learning was employed to estimate the association between the metabolic signals of brain regions and treatment resistance. To account for the potential influence of antipsychotic medication, we incorporated chlorpromazine equivalents as a covariate in the network analysis during partial correlation calculations. Additionally, the machine-learning analysis employed medication dose-stratified folds. Global reduced connectivity was detected in the nTRS (p-value = 0.008) and TRS groups (p-value = 0.001) compared to CTRL, with prominent alterations localized in the frontal lobe, Default Mode Network, and dorsal dopamine pathway. Disruptions in frontotemporal and striatal-cortical connectivity were detected in TRS but not nTRS patients. After adjusting for antipsychotic doses, alterations in the anterior cingulate, frontal and temporal gyri, hippocampus, and precuneus also emerged. The machine-learning approach demonstrated an accuracy ranging from 0.72 to 0.8 in detecting the TRS condition.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"116"},"PeriodicalIF":3.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased GDF-15 in chronic male patients with schizophrenia: correlation with body mass index and cognitive impairment.","authors":"Tianming Guo, Lihua Chen, Wenxi Sun, Haidong Yang, Jin Li, Xiaobin Zhang, Peng Chen","doi":"10.1038/s41537-024-00541-6","DOIUrl":"10.1038/s41537-024-00541-6","url":null,"abstract":"<p><p>Growth Differentiation Factor-15 (GDF-15) is a pleiotropic cytokine that plays a significant role in metabolism and inflammation. Elevated serum levels of GDF-15 have been associated with mood disorders. We propose that GDF-15 may potentially influence cognitive impairment and metabolism in male patients with chronic schizophrenia (CS), although there is limited research on this topic. This study compared serum GDF-15 levels in 72 male patients with CS and 85 healthy controls (HC). The severity of psychotic symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS), while cognitive performance was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The male CS patients performed worse than the healthy controls in both the total score and all subscales of the RBANS. Serum GDF-15 concentrations were significantly higher in the male CS patients compared to the healthy controls. Furthermore, the log-transformed serum GDF-15 concentrations in male CS patients were positively correlated with BMI and negatively correlated with Delayed Memory scores, Immediate Memory, and the total RBANS score. This preliminary study suggests that elevated serum GDF-15 levels in male patients with chronic schizophrenia may play a role in cognitive function and BMI regulation.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"117"},"PeriodicalIF":3.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychomotor slowing in schizophrenia is associated with aberrant postural control.","authors":"Melanie G Nuoffer, Anika Schindel, Stephanie Lefebvre, Florian Wüthrich, Niluja Nadesalingam, Alexandra Kyrou, Hassen Kerkeni, Roger Kalla, Jessica Bernard, Sebastian Walther","doi":"10.1038/s41537-024-00534-5","DOIUrl":"10.1038/s41537-024-00534-5","url":null,"abstract":"<p><p>Motor abnormalities, including psychomotor slowing, are prevalent in a large proportion of individuals with schizophrenia. While postural control deficits have been observed in this population, the impact of motor abnormalities on postural stability remains unclear. This study aimed to objectively evaluate postural stability in patients with and without psychomotor slowing and healthy controls. Seventy-three schizophrenia patients with psychomotor slowing (PS; Salpêtrière Retardation Rating Scale (SRRS) ≥ 15), 25 schizophrenia patients without psychomotor slowing (non-PS; SRRS < 15), and 27 healthy controls (HC) performed four conditions on the Kistler force plate: eyes open (EO), eyes closed (EC), head reclined with eyes open (EOHR), and head reclined with eyes closed (ECHR). Larger sway areas and higher Root Mean Square (RMS) values indicate lower postural stability, while a lower Complexity Index (CI) reflects reduced adaptability, flexibility, and dynamic functioning of postural control. PS exhibited larger sway areas and higher RMS compared to the other groups. Both PS and non-PS showed reduced complexity in postural control compared to healthy controls, without differences between the two patient groups. Reduced postural stability and complexity were associated with greater expert-rated motor abnormalities, as well as more severe negative symptoms. Additionally, lower complexity was linked to reduced physical activity levels. These findings suggest that psychomotor slowing is associated with lower postural stability, potentially reflecting impaired cerebellar function. Furthermore, the loss of complexity in postural control highlights reduced flexibility, adaptability, and efficiency in the postural control network of individuals with schizophrenia.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"118"},"PeriodicalIF":3.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approximating the semantic space: word embedding techniques in psychiatric speech analysis.","authors":"Claudio Palominos, Rui He, Karla Fröhlich, Rieke Roxanne Mülfarth, Svenja Seuffert, Iris E Sommer, Philipp Homan, Tilo Kircher, Frederike Stein, Wolfram Hinzen","doi":"10.1038/s41537-024-00524-7","DOIUrl":"10.1038/s41537-024-00524-7","url":null,"abstract":"<p><p>Large language models provide high-dimensional representations (embeddings) of word meaning, which allow quantifying changes in the geometry of the semantic space in mental disorders. A pattern of a more condensed ('shrinking') semantic space marked by an increase in mean semantic similarity between words has been recently documented in psychosis across several languages. We aimed to explore this pattern further in picture descriptions provided by a transdiagnostic German sample of patients with schizophrenia spectrum disorders (SSD) (n = 42), major depression (MDD, n = 43), and healthy controls (n = 44). Compared to controls, both clinical groups showed more restricted dynamic navigational patterns as captured by the time series of semantic distances crossed, while also showing differential patterns in the total distances and trajectories navigated. These findings demonstrate alterations centred on the dynamics of the flow of meaning across the semantic space in SSD and MDD, preserving previous indications towards a shrinking semantic space in both cases.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"114"},"PeriodicalIF":3.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the heart-brain axis: shared genetic mechanisms in cardiovascular diseases and Schizophrenia.","authors":"Jing Shen, Chuang Jiang","doi":"10.1038/s41537-024-00533-6","DOIUrl":"10.1038/s41537-024-00533-6","url":null,"abstract":"<p><p>The comorbidity between cardiovascular diseases (CVD) and schizophrenia (SCZ) has attracted widespread attention from researchers, with shared genetic causes potentially providing important insights into their association. This study conducted a comprehensive analysis of genetic data from 17 types of CVD and SCZ using genome-wide multi-trait association studies (GWAS), employing statistical methods such as LDSC, MTAG, LAVA, and bidirectional Mendelian randomization to explore global and local genetic correlations and identify pleiotropic single nucleotide variants (SNVs). The analysis revealed a significant genetic correlation between CVD and SCZ, identifying 842 potential pleiotropic single nucleotide variants (SNVs) and multiple associated biological pathways. Notably, genes such as TRIM27, CENPM, and MYH7B played critical roles in the shared genetic variations of both types of diseases. This study reveals the complex genetic relationship between CVD and SCZ, highlighting potential shared biological mechanisms involving immune responses, metabolic factors, and neurodevelopmental processes, thereby providing new directions for future interventions and treatments.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"113"},"PeriodicalIF":3.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FMR1 genetically interacts with DISC1 to regulate glutamatergic synaptogenesis.","authors":"Takato Honda, Kazuki Kurita, Yuko Arai, Himani Pandey, Akira Sawa, Katsuo Furukubo-Tokunaga","doi":"10.1038/s41537-024-00532-7","DOIUrl":"10.1038/s41537-024-00532-7","url":null,"abstract":"<p><p>Synaptic development and functions have been hypothesized as crucial mechanisms of diverse neuropsychiatric disorders. Studies in past years suggest that mutations in the fragile X mental retardation 1 (FMR1) are associated with diverse mental disorders including intellectual disability, autistic spectrum disorder, and schizophrenia. In this study, we have examined genetical interactions between a select set of risk factor genes using fruit flies to find that dfmr1, the Drosophila homolog of the human FMR1 gene, exhibits functional interactions with DISC1 in synaptic development. We show that DISC1 overexpression in the dfmr1^null heterozygous background causes synaptic alterations at the larval neuromuscular junctions that are distinct from those in the wild-type background. Loss of dfmr1 modifies the DISC1 overexpression phenotype in synaptic formation, suppressing the formation of synapse boutons. Interaction between the two genes was further supported molecularly by the results that dfmr1 mutations suppress the DISC1-mediated upregulations of the postsynaptic expression of a glutamate receptor and the expression of ELKS/CAST protein, Bruchpilot, in presynaptic motoneurons. Moreover, DISC1 overexpression in the dfmr1^null heterozygous background causes downregulation of a MAP1 family protein, Futsch. These results thus suggest an intriguing converging mechanism controlled by FMR1 and DISC1 in the developing glutamatergic synapses.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"112"},"PeriodicalIF":3.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Individuals with psychosis receive less electric field strength during transcranial direct current stimulation compared to healthy controls.","authors":"Rebecca Kazinka, Da Som Choi, Alexander Opitz, Kelvin O Lim","doi":"10.1038/s41537-024-00529-2","DOIUrl":"10.1038/s41537-024-00529-2","url":null,"abstract":"<p><p>Recent research has examined the effectiveness of transcranial direct current stimulation (tDCS) as an adjunctive treatment for antipsychotics, finding mixed results on cognitive, positive, and negative symptoms. We tested if individuals with psychosis have reduced electric field strength compared to healthy controls and assessed the potential causal factors. We hypothesized that either cortical thinning due to the disorder or increased scalp thickness due to secondary effects of the disorder were causal factors. Using the Psychosis Human Connectome Project dataset, we simulated electric field models for 136 individuals with psychosis, 73 first-degree relatives, and 43 healthy controls. We compared group differences of electric field strength at bilateral dorsolateral prefrontal cortex (dlPFC), targeted with two montages (Fp1-Fp2 & F3-Fp2) commonly used to treat cognitive impairment. We additionally compared groups on scalp, skull, and cerebrospinal fluid thickness at bilateral dlPFC and the three electrode locations. Mediation analyses assessed if tissue thickness and BMI were causal factors for group differences while controlling for age and sex. Individuals with psychosis had lower electric field strength for bilateral dlPFC for both montages. Scalp thickness was also greater for individuals with psychosis, but cerebrospinal fluid thickness was not significantly different. BMI was a significant mediator for the group difference seen in both scalp thickness and electric field strength. Future treatment studies using tDCS in the psychosis population should include electric field modeling to assess its effectiveness given the increased risk of obesity. Individualized montages based on head models may also improve effectiveness.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"111"},"PeriodicalIF":3.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Onset age moderates the associations between neutrophil-to-lymphocyte ratio and clinical symptoms in first-episode patients with schizophrenia.","authors":"Kuiyuan Wang, Shaohua Liu, Dan Huang, Xiaoni Guan, Nan Chen, Meihong Xiu, Dianying Liu, Yuanyuan Huang","doi":"10.1038/s41537-024-00522-9","DOIUrl":"10.1038/s41537-024-00522-9","url":null,"abstract":"<p><p>Patients with schizophrenia with early onset age have been shown to exhibit more severe negative symptoms. Genetic, biomarker, postmortem brain, and imaging studies indicate the involvement of immune abnormalities in the pathophysiology of schizophrenia. In this study, we examined the moderating role of early onset on the associations between clinical symptoms and neutrophil-to-lymphocyte ratio (NLR) in medication-naïve first-episode schizophrenia (MNFES). A total of 97 MNFES patients were recruited. Neutrophil (NEU), LYM, and NLR values were compared between early-onset (EO) and non-early-onset (non-EO) patients with schizophrenia to explore the potential influence of EO on the correlations between NLR and symptoms. The results showed no differences in NEU and NLR values between the EO and non-EO groups. In the EO group, NEU and NLR values significantly correlated with general psychopathology and total score (all p < 0.05), whereas lymphocyte counts were not correlated with symptoms of schizophrenia. NEU and NLR were not associated with symptoms in the non-EO group. Linear regression analysis in the EO group revealed that NEU or NLR values were a predictive biomarker for the clinical symptoms. Our study indicates that EO patients had greater severe negative symptoms compared with non-EO patients. In addition, onset age mediates the relationships of NEU and NLR values with clinical symptoms, suggesting that an immune disturbance, particularly increased innate immune response in EO patients, may be involved in the psychophysiology of schizophrenia.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"110"},"PeriodicalIF":3.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Brain structural associations of syntactic complexity and diversity across schizophrenia spectrum and major depressive disorders, and healthy controls.","authors":"Katharina Schneider, Nina Alexander, Andreas Jansen, Igor Nenadić, Benjamin Straube, Lea Teutenberg, Florian Thomas-Odenthal, Paula Usemann, Udo Dannlowski, Tilo Kircher, Arne Nagels, Frederike Stein","doi":"10.1038/s41537-024-00530-9","DOIUrl":"10.1038/s41537-024-00530-9","url":null,"abstract":"","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"109"},"PeriodicalIF":3.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-analyses of epigenetic age acceleration and GrimAge components of schizophrenia or first-episode psychosis.","authors":"Toshiyuki Shirai, Satoshi Okazaki, Takaki Tanifuji, Shusuke Numata, Tomohiko Nakayama, Tomohiro Yoshida, Kentaro Mouri, Ikuo Otsuka, Noboru Hiroi, Akitoyo Hishimoto","doi":"10.1038/s41537-024-00531-8","DOIUrl":"10.1038/s41537-024-00531-8","url":null,"abstract":"<p><p>Schizophrenia is a common chronic psychiatric disorder that causes age-related dysfunction. The life expectancy in patients with schizophrenia is ≥10 years shorter than that in the general population because of the higher risk of other diseases, such as cardiovascular diseases. Aging studies based on DNA methylation status have received considerable attention. Several epigenetic age accelerations and predicted values of aging-related proteins (GrimAge and GrimAge2 components) have been analyzed in multiple diseases. However, no studies have investigated up to GrimAge and GrimAge2 components between patients with schizophrenia and controls. Therefore, we aimed to conduct multiple regression analyses to investigate the association between schizophrenia and epigenetic age accelerations and GrimAge and GrimAge2 components in seven cohorts. Furthermore, we included patients with first-episode psychosis whose illness duration was often shorter than schizophrenia in our analysis. We integrated these results with meta-analyses, noting the acceleration of GrimAge, GrimAge2, and DunedinPACE, and increase in adrenomedullin, beta-2 microglobulin, cystatin C, and plasminogen activation inhibitor-1 levels, in patients with schizophrenia or first-episode psychosis. These results corroborated the finding that patients with schizophrenia had an increased risk of diabetes, cardiovascular disease, and cognitive dysfunction from a biological perspective. Patients with schizophrenia and first-episode psychosis showed differences in the results when compared with controls. Such analyses may lead to the development of novel therapeutic targets to patients with schizophrenia or relevant diseases from the perspective of aging in the future.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"108"},"PeriodicalIF":3.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}