Schizophrenia is a mental health disorder characterized by functional dysconnectivity. Eigenvector centrality mapping (ECM) has been employed to investigate alterations in functional connectivity in schizophrenia, yet the results lack consistency, and the genetic mechanisms underlying these changes remain unclear. In this study, whole-brain voxel-wise ECM analyses were conducted on resting-state functional magnetic resonance imaging data. A cohort of 91 patients with schizophrenia and 91 matched healthy controls were included during the discovery stage. Additionally, in the replication stage, 153 individuals with schizophrenia and 182 healthy individuals participated. Subsequently, a comprehensive analysis was performed using an independent transcriptional database derived from six postmortem healthy adult brains to explore potential genetic factors influencing the observed functional dysconnectivity, and to investigate the roles of identified genes in neural processes and pathways. The results revealed significant and reliable alterations in the ECM across multiple brain regions in schizophrenia. Specifically, there was a significant decrease in ECM in the bilateral superior and middle temporal gyrus, and an increase in the bilateral thalamus in both the discovery and replication stages. Furthermore, transcriptional analysis revealed 420 genes whose expression patterns were related to changes in ECM, and these genes were enriched mainly in biological processes associated with synaptic signaling and transmission. Together, this study enhances our knowledge of the neural processes and pathways involved in schizophrenia, shedding light on the genetic factors that may be linked to functional dysconnectivity in this disorder.
{"title":"Exploring functional dysconnectivity in schizophrenia: alterations in eigenvector centrality mapping and insights into related genes from transcriptional profiles.","authors":"Yuan Ji, Mengjing Cai, Yujing Zhou, Juanwei Ma, Yijing Zhang, Zhihui Zhang, Jiaxuan Zhao, Ying Wang, Yurong Jiang, Ying Zhai, Jinglei Xu, Minghuan Lei, Qiang Xu, Huaigui Liu, Feng Liu","doi":"10.1038/s41537-024-00457-1","DOIUrl":"10.1038/s41537-024-00457-1","url":null,"abstract":"<p><p>Schizophrenia is a mental health disorder characterized by functional dysconnectivity. Eigenvector centrality mapping (ECM) has been employed to investigate alterations in functional connectivity in schizophrenia, yet the results lack consistency, and the genetic mechanisms underlying these changes remain unclear. In this study, whole-brain voxel-wise ECM analyses were conducted on resting-state functional magnetic resonance imaging data. A cohort of 91 patients with schizophrenia and 91 matched healthy controls were included during the discovery stage. Additionally, in the replication stage, 153 individuals with schizophrenia and 182 healthy individuals participated. Subsequently, a comprehensive analysis was performed using an independent transcriptional database derived from six postmortem healthy adult brains to explore potential genetic factors influencing the observed functional dysconnectivity, and to investigate the roles of identified genes in neural processes and pathways. The results revealed significant and reliable alterations in the ECM across multiple brain regions in schizophrenia. Specifically, there was a significant decrease in ECM in the bilateral superior and middle temporal gyrus, and an increase in the bilateral thalamus in both the discovery and replication stages. Furthermore, transcriptional analysis revealed 420 genes whose expression patterns were related to changes in ECM, and these genes were enriched mainly in biological processes associated with synaptic signaling and transmission. Together, this study enhances our knowledge of the neural processes and pathways involved in schizophrenia, shedding light on the genetic factors that may be linked to functional dysconnectivity in this disorder.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141195","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}
Pub Date : 2024-03-15DOI: 10.1038/s41537-024-00449-1
Xishu Mu, Wenjing Wu, Sisi Wang, Xiuru Su, Hengyong Guan, Xiaoni Guan, Xiaobing Lu, Zezhi Li
Patients with schizophrenia (SCZ) smoke up to three times more than general people. However, there are conflicting results regarding the relationship between tobacco smoke and clinical symptom severity in SCZ. The aim of this study was to assess the impact of smoking on clinical symptoms after antipsychotic treatment in a 12-week cohort study after controlling for confounding factors. One hundred and forty-five male patients with drug-naïve first-episode (DNFE) SCZ received antipsychotic monotherapy for 12 weeks. Symptom severity was assessed at baseline and at week 12 by the Positive and Negative Syndrome Scale (PANSS). We found no differences in clinical symptoms among male smokers with SCZ compared with male nonsmokers. However, male smokers showed greater improvement in negative symptoms after 12 weeks of treatment, controlling for age, years of education, onset age, and baseline body mass index (BMI). Our study showed that after 12 weeks of treatment with antipsychotics, male smokers showed greater improvement in negative symptoms than male nonsmokers.
{"title":"Smoking affects symptom improvement in schizophrenia: a prospective longitudinal study of male patients with first-episode schizophrenia.","authors":"Xishu Mu, Wenjing Wu, Sisi Wang, Xiuru Su, Hengyong Guan, Xiaoni Guan, Xiaobing Lu, Zezhi Li","doi":"10.1038/s41537-024-00449-1","DOIUrl":"10.1038/s41537-024-00449-1","url":null,"abstract":"<p><p>Patients with schizophrenia (SCZ) smoke up to three times more than general people. However, there are conflicting results regarding the relationship between tobacco smoke and clinical symptom severity in SCZ. The aim of this study was to assess the impact of smoking on clinical symptoms after antipsychotic treatment in a 12-week cohort study after controlling for confounding factors. One hundred and forty-five male patients with drug-naïve first-episode (DNFE) SCZ received antipsychotic monotherapy for 12 weeks. Symptom severity was assessed at baseline and at week 12 by the Positive and Negative Syndrome Scale (PANSS). We found no differences in clinical symptoms among male smokers with SCZ compared with male nonsmokers. However, male smokers showed greater improvement in negative symptoms after 12 weeks of treatment, controlling for age, years of education, onset age, and baseline body mass index (BMI). Our study showed that after 12 weeks of treatment with antipsychotics, male smokers showed greater improvement in negative symptoms than male nonsmokers.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141261","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}
The gamma-band auditory steady-state response (ASSR), primarily generated from the auditory cortex, has received substantial attention as a potential brain marker indicating the pathophysiology of schizophrenia. Previous studies have shown reduced gamma-band ASSR in patients with schizophrenia and demonstrated correlations with impaired neurocognition and psychosocial functioning. Recent studies in clinical and healthy populations have suggested that the neural substrates of reduced gamma-band ASSR may be distributed throughout the cortices surrounding the auditory cortex, especially in the right hemisphere. This study aimed to investigate associations between the gamma-band ASSR and white matter alterations in the bundles broadly connecting the right frontal, parietal and occipital cortices to clarify the networks underlying reduced gamma-band ASSR in patients with schizophrenia. We measured the 40 Hz ASSR using electroencephalography and diffusion tensor imaging in 42 patients with schizophrenia and 22 healthy comparison subjects. The results showed that the gamma-band ASSR was positively correlated with fractional anisotropy (an index of white matter integrity) in the regions connecting the right frontal, parietal and occipital cortices in healthy subjects (β = 0.41, corrected p = 0.075, uncorrected p = 0.038) but not in patients with schizophrenia (β = 0.17, corrected p = 0.46, uncorrected p = 0.23). These findings support our hypothesis that the generation of gamma-band ASSR is supported by white matter bundles that broadly connect the cortices and that these relationships may be disrupted in schizophrenia. Our study may help characterize and interpret reduced gamma-band ASSR as a useful brain marker of schizophrenia.
伽马波段听觉稳态反应(ASSR)主要由听觉皮层产生,作为精神分裂症病理生理学的潜在脑标记已受到广泛关注。以往的研究表明,精神分裂症患者的伽马波段听觉稳态反应减弱,并与神经认知和社会心理功能受损有关。最近在临床和健康人群中进行的研究表明,伽马波段ASSR降低的神经基底可能分布在听觉皮层周围的皮层中,尤其是右半球。本研究旨在调查伽马波段ASSR与广泛连接右侧额叶、顶叶和枕叶皮层的白质束改变之间的关联,以明确精神分裂症患者伽马波段ASSR降低的基础网络。我们使用脑电图和弥散张量成像技术测量了42名精神分裂症患者和22名健康对比受试者的40赫兹ASSR。结果显示,伽马波段 ASSR 与健康受试者右侧额叶、顶叶和枕叶皮层连接区域的分数各向异性(白质完整性指数)呈正相关(β = 0.41,校正后 p = 0.075,未校正 p = 0.038),但与精神分裂症患者无关(β = 0.17,校正后 p = 0.46,未校正 p = 0.23)。这些发现支持了我们的假设,即伽马波段 ASSR 的产生是由广泛连接大脑皮层的白质束支持的,而精神分裂症患者的这些关系可能会被破坏。我们的研究可能有助于描述和解释伽马波段ASSR的减少,并将其作为精神分裂症的一个有用的脑标记。
{"title":"Cortical white matter microstructural alterations underlying the impaired gamma-band auditory steady-state response in schizophrenia.","authors":"Daisuke Koshiyama, Ryoichi Nishimura, Kaori Usui, Mao Fujioka, Mariko Tada, Kenji Kirihara, Tsuyoshi Araki, Shintaro Kawakami, Naohiro Okada, Shinsuke Koike, Hidenori Yamasue, Osamu Abe, Kiyoto Kasai","doi":"10.1038/s41537-024-00454-4","DOIUrl":"10.1038/s41537-024-00454-4","url":null,"abstract":"<p><p>The gamma-band auditory steady-state response (ASSR), primarily generated from the auditory cortex, has received substantial attention as a potential brain marker indicating the pathophysiology of schizophrenia. Previous studies have shown reduced gamma-band ASSR in patients with schizophrenia and demonstrated correlations with impaired neurocognition and psychosocial functioning. Recent studies in clinical and healthy populations have suggested that the neural substrates of reduced gamma-band ASSR may be distributed throughout the cortices surrounding the auditory cortex, especially in the right hemisphere. This study aimed to investigate associations between the gamma-band ASSR and white matter alterations in the bundles broadly connecting the right frontal, parietal and occipital cortices to clarify the networks underlying reduced gamma-band ASSR in patients with schizophrenia. We measured the 40 Hz ASSR using electroencephalography and diffusion tensor imaging in 42 patients with schizophrenia and 22 healthy comparison subjects. The results showed that the gamma-band ASSR was positively correlated with fractional anisotropy (an index of white matter integrity) in the regions connecting the right frontal, parietal and occipital cortices in healthy subjects (β = 0.41, corrected p = 0.075, uncorrected p = 0.038) but not in patients with schizophrenia (β = 0.17, corrected p = 0.46, uncorrected p = 0.23). These findings support our hypothesis that the generation of gamma-band ASSR is supported by white matter bundles that broadly connect the cortices and that these relationships may be disrupted in schizophrenia. Our study may help characterize and interpret reduced gamma-band ASSR as a useful brain marker of schizophrenia.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10933284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140112402","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}
Schizophrenia (SCZ), a highly heritable mental disorder, is characterized by cognitive impairment, yet the extent of the shared genetic basis between schizophrenia and cognitive performance (CP) remains poorly understood. Therefore, we aimed to explore the polygenic overlap between SCZ and CP. Specifically, the bivariate causal mixture model (MiXeR) was employed to estimate the extent of genetic overlap between SCZ (n = 130,644) and CP (n = 257,841), and conjunctional false discovery rate (conjFDR) approach was used to identify shared genetic loci. Subsequently, functional annotation and enrichment analysis were carried out on the identified genomic loci. The MiXeR analyses revealed that 9.6 K genetic variants are associated with SCZ and 10.9 K genetic variants for CP, of which 9.5 K variants are shared between these two traits (Dice coefficient = 92.8%). By employing conjFDR, 236 loci were identified jointly associated with SCZ and CP, of which 139 were novel for the two traits. Within these shared loci, 60 exhibited consistent effect directions, while 176 had opposite effect directions. Functional annotation analysis indicated that the shared genetic loci were mainly located in intronic and intergenic regions, and were found to be involved in relevant biological processes such as nervous system development, multicellular organism development, and generation of neurons. Together, our findings provide insights into the shared genetic architecture between SCZ and CP, suggesting common pathways and mechanisms contributing to both traits.
{"title":"Genetic overlap between schizophrenia and cognitive performance.","authors":"Jianfei Zhang, Hao Qiu, Qiyu Zhao, Chongjian Liao, Yuxuan Guoli, Qi Luo, Guoshu Zhao, Nannan Zhang, Shaoying Wang, Zhihui Zhang, Minghuan Lei, Feng Liu, Yanmin Peng","doi":"10.1038/s41537-024-00453-5","DOIUrl":"10.1038/s41537-024-00453-5","url":null,"abstract":"<p><p>Schizophrenia (SCZ), a highly heritable mental disorder, is characterized by cognitive impairment, yet the extent of the shared genetic basis between schizophrenia and cognitive performance (CP) remains poorly understood. Therefore, we aimed to explore the polygenic overlap between SCZ and CP. Specifically, the bivariate causal mixture model (MiXeR) was employed to estimate the extent of genetic overlap between SCZ (n = 130,644) and CP (n = 257,841), and conjunctional false discovery rate (conjFDR) approach was used to identify shared genetic loci. Subsequently, functional annotation and enrichment analysis were carried out on the identified genomic loci. The MiXeR analyses revealed that 9.6 K genetic variants are associated with SCZ and 10.9 K genetic variants for CP, of which 9.5 K variants are shared between these two traits (Dice coefficient = 92.8%). By employing conjFDR, 236 loci were identified jointly associated with SCZ and CP, of which 139 were novel for the two traits. Within these shared loci, 60 exhibited consistent effect directions, while 176 had opposite effect directions. Functional annotation analysis indicated that the shared genetic loci were mainly located in intronic and intergenic regions, and were found to be involved in relevant biological processes such as nervous system development, multicellular organism development, and generation of neurons. Together, our findings provide insights into the shared genetic architecture between SCZ and CP, suggesting common pathways and mechanisms contributing to both traits.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10914834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041102","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}
Pub Date : 2024-03-01DOI: 10.1038/s41537-024-00451-7
Marina Mihaljevic, Yu-Ho Chang, Ashley M Witmer, Jennifer M Coughlin, David J Schretlen, Peter B Barker, Kun Yang, Akira Sawa
Understanding the biological underpinning of relapse could improve the outcomes of patients with psychosis. Relapse is elicited by multiple reasons/triggers, but the consequence frequently accompanies deteriorations of brain function, leading to poor prognosis. Structural brain imaging studies have recently been pioneered to address this question, but a lack of molecular investigations is a knowledge gap. Following a criterion used for recent publications by others, we defined the experiences of relapse by hospitalization(s) due to psychotic exacerbation. We hypothesized that relapse-associated molecules might be underscored from the neurometabolites whose levels have been different between overall patients with early-stage psychosis and healthy subjects in our previous report. In the present study, we observed a significant decrease in the levels of N-acetyl aspartate in the anterior cingulate cortex and thalamus in patients who experienced relapse compared to patients who did not. Altogether, decreased N-acetyl aspartate levels may indicate relapse-associated deterioration of neuronal networks in patients.
{"title":"Reduction of N-acetyl aspartate (NAA) in association with relapse in early-stage psychosis: a 7-Tesla MRS study.","authors":"Marina Mihaljevic, Yu-Ho Chang, Ashley M Witmer, Jennifer M Coughlin, David J Schretlen, Peter B Barker, Kun Yang, Akira Sawa","doi":"10.1038/s41537-024-00451-7","DOIUrl":"10.1038/s41537-024-00451-7","url":null,"abstract":"<p><p>Understanding the biological underpinning of relapse could improve the outcomes of patients with psychosis. Relapse is elicited by multiple reasons/triggers, but the consequence frequently accompanies deteriorations of brain function, leading to poor prognosis. Structural brain imaging studies have recently been pioneered to address this question, but a lack of molecular investigations is a knowledge gap. Following a criterion used for recent publications by others, we defined the experiences of relapse by hospitalization(s) due to psychotic exacerbation. We hypothesized that relapse-associated molecules might be underscored from the neurometabolites whose levels have been different between overall patients with early-stage psychosis and healthy subjects in our previous report. In the present study, we observed a significant decrease in the levels of N-acetyl aspartate in the anterior cingulate cortex and thalamus in patients who experienced relapse compared to patients who did not. Altogether, decreased N-acetyl aspartate levels may indicate relapse-associated deterioration of neuronal networks in patients.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013785","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}
Pub Date : 2024-02-29DOI: 10.1038/s41537-024-00448-2
Anne Rivelli, Veronica Fitzpatrick, Michael Nelson, Kimberly Laubmeier, Courtney Zeni, Srikrishna Mylavarapu
Schizophrenia is often characterized by recurring relapses, which are associated with a substantial clinical and economic burden. Early identification of individuals at the highest risk for relapse in real-world treatment settings could help improve outcomes and reduce healthcare costs. Prior work has identified a few consistent predictors of relapse in schizophrenia, however, studies to date have been limited to insurance claims data or small patient populations. Thus, this study used a large sample of health systems electronic health record (EHR) data to analyze relationships between patient-level factors and relapse and model a set of factors that can be used to identify the increased prevalence of relapse, a severe and preventable reality of schizophrenia. This retrospective, observational cohort study utilized EHR data extracted from the largest Midwestern U.S. non-profit healthcare system to identify predictors of relapse. The study included patients with a diagnosis of schizophrenia (ICD-10 F20) or schizoaffective disorder (ICD-10 F25) who were treated within the system between October 15, 2016, and December 31, 2021, and received care for at least 12 months. A relapse episode was defined as an emergency room or inpatient encounter with a pre-determined behavioral health-related ICD code. Patients' baseline characteristics, comorbidities and healthcare utilization were described. Modified log-Poisson regression (i.e. log Poisson regression with a robust variance estimation) analyses were utilized to estimate the prevalence of relapse across patient characteristics, comorbidities and healthcare utilization and to ultimately identify an adjusted model predicting relapse. Among the 8119 unique patients included in the study, 2478 (30.52%) experienced relapse and 5641 (69.48%) experienced no relapse. Patients were primarily male (54.72%), White Non-Hispanic or Latino (54.23%), with Medicare insurance (51.40%), and had baseline diagnoses of substance use (19.24%), overweight/obesity/weight gain (13.06%), extrapyramidal symptoms (48.00%), lipid metabolism disorder (30.66%), hypertension (26.85%), and diabetes (19.08%). Many differences in patient characteristics, baseline comorbidities, and utilization were revealed between patients who relapsed and patients who did not relapse. Through model building, the final adjusted model with all significant predictors of relapse included the following variables: insurance, age, race/ethnicity, substance use diagnosis, extrapyramidal symptoms, number of emergency room encounters, behavioral health inpatient encounters, prior relapses episodes, and long-acting injectable prescriptions written. Prevention of relapse is a priority in schizophrenia care. Challenges related to historical health record data have limited the knowledge of real-world predictors of relapse. This study offers a set of variables that could conceivably be used to construct algorithms or models to proactively monitor demographic,
{"title":"Real-world predictors of relapse in patients with schizophrenia and schizoaffective disorder in a large health system.","authors":"Anne Rivelli, Veronica Fitzpatrick, Michael Nelson, Kimberly Laubmeier, Courtney Zeni, Srikrishna Mylavarapu","doi":"10.1038/s41537-024-00448-2","DOIUrl":"10.1038/s41537-024-00448-2","url":null,"abstract":"<p><p>Schizophrenia is often characterized by recurring relapses, which are associated with a substantial clinical and economic burden. Early identification of individuals at the highest risk for relapse in real-world treatment settings could help improve outcomes and reduce healthcare costs. Prior work has identified a few consistent predictors of relapse in schizophrenia, however, studies to date have been limited to insurance claims data or small patient populations. Thus, this study used a large sample of health systems electronic health record (EHR) data to analyze relationships between patient-level factors and relapse and model a set of factors that can be used to identify the increased prevalence of relapse, a severe and preventable reality of schizophrenia. This retrospective, observational cohort study utilized EHR data extracted from the largest Midwestern U.S. non-profit healthcare system to identify predictors of relapse. The study included patients with a diagnosis of schizophrenia (ICD-10 F20) or schizoaffective disorder (ICD-10 F25) who were treated within the system between October 15, 2016, and December 31, 2021, and received care for at least 12 months. A relapse episode was defined as an emergency room or inpatient encounter with a pre-determined behavioral health-related ICD code. Patients' baseline characteristics, comorbidities and healthcare utilization were described. Modified log-Poisson regression (i.e. log Poisson regression with a robust variance estimation) analyses were utilized to estimate the prevalence of relapse across patient characteristics, comorbidities and healthcare utilization and to ultimately identify an adjusted model predicting relapse. Among the 8119 unique patients included in the study, 2478 (30.52%) experienced relapse and 5641 (69.48%) experienced no relapse. Patients were primarily male (54.72%), White Non-Hispanic or Latino (54.23%), with Medicare insurance (51.40%), and had baseline diagnoses of substance use (19.24%), overweight/obesity/weight gain (13.06%), extrapyramidal symptoms (48.00%), lipid metabolism disorder (30.66%), hypertension (26.85%), and diabetes (19.08%). Many differences in patient characteristics, baseline comorbidities, and utilization were revealed between patients who relapsed and patients who did not relapse. Through model building, the final adjusted model with all significant predictors of relapse included the following variables: insurance, age, race/ethnicity, substance use diagnosis, extrapyramidal symptoms, number of emergency room encounters, behavioral health inpatient encounters, prior relapses episodes, and long-acting injectable prescriptions written. Prevention of relapse is a priority in schizophrenia care. Challenges related to historical health record data have limited the knowledge of real-world predictors of relapse. This study offers a set of variables that could conceivably be used to construct algorithms or models to proactively monitor demographic, ","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10904733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998478","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}
Pub Date : 2024-02-27DOI: 10.1038/s41537-024-00439-3
Kalyani B Karunakaran, Sanjeev Jain, Samir K Brahmachari, N Balakrishnan, Madhavi K Ganapathiraju
Genome-wide association studies suggest significant overlaps in Parkinson's disease (PD) and schizophrenia (SZ) risks, but the underlying mechanisms remain elusive. The protein-protein interaction network ('interactome') plays a crucial role in PD and SZ and can incorporate their spatiotemporal specificities. Therefore, to study the linked biology of PD and SZ, we compiled PD- and SZ-associated genes from the DisGeNET database, and constructed their interactomes using BioGRID and HPRD. We examined the interactomes using clustering and enrichment analyses, in conjunction with the transcriptomic data of 26 brain regions spanning foetal stages to adulthood available in the BrainSpan Atlas. PD and SZ interactomes formed four gene clusters with distinct temporal identities (Disease Gene Networks or 'DGNs'1-4). DGN1 had unique SZ interactome genes highly expressed across developmental stages, corresponding to a neurodevelopmental SZ subtype. DGN2, containing unique SZ interactome genes expressed from early infancy to adulthood, correlated with an inflammation-driven SZ subtype and adult SZ risk. DGN3 contained unique PD interactome genes expressed in late infancy, early and late childhood, and adulthood, and involved in mitochondrial pathways. DGN4, containing prenatally-expressed genes common to both the interactomes, involved in stem cell pluripotency and overlapping with the interactome of 22q11 deletion syndrome (comorbid psychosis and Parkinsonism), potentially regulates neurodevelopmental mechanisms in PD-SZ comorbidity. Our findings suggest that disrupted neurodevelopment (regulated by DGN4) could expose risk windows in PD and SZ, later elevating disease risk through inflammation (DGN2). Alternatively, variant clustering in DGNs may produce disease subtypes, e.g., PD-SZ comorbidity with DGN4, and early/late-onset SZ with DGN1/DGN2.
{"title":"Parkinson's disease and schizophrenia interactomes contain temporally distinct gene clusters underlying comorbid mechanisms and unique disease processes.","authors":"Kalyani B Karunakaran, Sanjeev Jain, Samir K Brahmachari, N Balakrishnan, Madhavi K Ganapathiraju","doi":"10.1038/s41537-024-00439-3","DOIUrl":"10.1038/s41537-024-00439-3","url":null,"abstract":"<p><p>Genome-wide association studies suggest significant overlaps in Parkinson's disease (PD) and schizophrenia (SZ) risks, but the underlying mechanisms remain elusive. The protein-protein interaction network ('interactome') plays a crucial role in PD and SZ and can incorporate their spatiotemporal specificities. Therefore, to study the linked biology of PD and SZ, we compiled PD- and SZ-associated genes from the DisGeNET database, and constructed their interactomes using BioGRID and HPRD. We examined the interactomes using clustering and enrichment analyses, in conjunction with the transcriptomic data of 26 brain regions spanning foetal stages to adulthood available in the BrainSpan Atlas. PD and SZ interactomes formed four gene clusters with distinct temporal identities (Disease Gene Networks or 'DGNs'1-4). DGN1 had unique SZ interactome genes highly expressed across developmental stages, corresponding to a neurodevelopmental SZ subtype. DGN2, containing unique SZ interactome genes expressed from early infancy to adulthood, correlated with an inflammation-driven SZ subtype and adult SZ risk. DGN3 contained unique PD interactome genes expressed in late infancy, early and late childhood, and adulthood, and involved in mitochondrial pathways. DGN4, containing prenatally-expressed genes common to both the interactomes, involved in stem cell pluripotency and overlapping with the interactome of 22q11 deletion syndrome (comorbid psychosis and Parkinsonism), potentially regulates neurodevelopmental mechanisms in PD-SZ comorbidity. Our findings suggest that disrupted neurodevelopment (regulated by DGN4) could expose risk windows in PD and SZ, later elevating disease risk through inflammation (DGN2). Alternatively, variant clustering in DGNs may produce disease subtypes, e.g., PD-SZ comorbidity with DGN4, and early/late-onset SZ with DGN1/DGN2.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984807","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}
Pub Date : 2024-02-22DOI: 10.1038/s41537-024-00433-9
Yuan-Jung Chen, Mong-Liang Lu, Yi-Hang Chiu, Chenyi Chen, Vitor Hugo Jesus Santos, Kah Kheng Goh
Childhood trauma has been linked to schizophrenia, but underlying biological mechanisms remain elusive. This study explored the potential role of plasma oxytocin as a mediator in the relationship between childhood trauma and the psychopathology of schizophrenia. 160 patients with schizophrenia and 80 age- and sex-matched healthy controls were assessed for childhood trauma experiences using the Childhood Trauma Questionnaire and structured interviews. Psychopathology was evaluated using the Positive and Negative Syndrome Scale and plasma oxytocin levels were measured. Results showed that patients with schizophrenia had lower oxytocin levels and higher childhood trauma scores than healthy controls. There was a significant correlation between childhood trauma scores and psychopathology, with plasma oxytocin levels being inversely associated with psychopathology, except for positive symptoms. Hierarchical regression analysis indicated that both childhood trauma scores and plasma oxytocin levels significantly predicted psychopathology. Plasma oxytocin levels partially mediated the relationship between childhood trauma and schizophrenia psychopathology. This study underscores the potential role of oxytocin in bridging the gap between childhood trauma and schizophrenia.
{"title":"Linking childhood trauma to the psychopathology of schizophrenia: the role of oxytocin.","authors":"Yuan-Jung Chen, Mong-Liang Lu, Yi-Hang Chiu, Chenyi Chen, Vitor Hugo Jesus Santos, Kah Kheng Goh","doi":"10.1038/s41537-024-00433-9","DOIUrl":"10.1038/s41537-024-00433-9","url":null,"abstract":"<p><p>Childhood trauma has been linked to schizophrenia, but underlying biological mechanisms remain elusive. This study explored the potential role of plasma oxytocin as a mediator in the relationship between childhood trauma and the psychopathology of schizophrenia. 160 patients with schizophrenia and 80 age- and sex-matched healthy controls were assessed for childhood trauma experiences using the Childhood Trauma Questionnaire and structured interviews. Psychopathology was evaluated using the Positive and Negative Syndrome Scale and plasma oxytocin levels were measured. Results showed that patients with schizophrenia had lower oxytocin levels and higher childhood trauma scores than healthy controls. There was a significant correlation between childhood trauma scores and psychopathology, with plasma oxytocin levels being inversely associated with psychopathology, except for positive symptoms. Hierarchical regression analysis indicated that both childhood trauma scores and plasma oxytocin levels significantly predicted psychopathology. Plasma oxytocin levels partially mediated the relationship between childhood trauma and schizophrenia psychopathology. This study underscores the potential role of oxytocin in bridging the gap between childhood trauma and schizophrenia.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10883944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934599","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}
Deficit schizophrenia (DS) is a subtype of schizophrenia (SCZ). The polygenic effects on the neuroimaging alterations in DS still remain unknown. This study aims to calculate the polygenic risk scores for schizophrenia (PRS-SCZ) in DS, and further explores the potential associations with functional features of brain. PRS-SCZ was calculated according to the Whole Exome sequencing and Genome-wide association studies (GWAS). Resting-state fMRI, as well as biochemical features and neurocognitive data were obtained from 33 DS, 47 NDS and 41 HCs, and association studies of genetic risk with neuroimaging were performed in this sample. The analyses of amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were performed to detect the functional alterations between DS and NDS. In addition, correlation analysis was used to investigate the relationships between functional features (ALFF, ReHo, FC) and PRS-SCZ. The PRS-SCZ of DS was significantly lower than that in NDS and HC. Compared to NDS, there was a significant increase in the ALFF of left inferior temporal gyrus (ITG.L) and left inferior frontal gyrus (IFG.L) and a significant decrease in the ALFF of right precuneus (PCUN.R) and ReHo of right middle frontal gyrus (MFG.R) in DS. FCs were widely changed between DS and NDS, mainly concentrated in default mode network, including ITG, PCUN and angular gyrus (ANG). Correlation analysis revealed that the ALFF of left ITG, the ReHo of right middle frontal gyrus, the FC value between insula and ANG, left ITG and right corpus callosum, left ITG and right PCUN, as well as the scores of Trail Making Test-B, were associated with PRS-SCZ in DS. The present study demonstrated the differential polygenic effects on functional changes of brain in DS and NDS, providing a potential neuroimaging-genetic perspective for the pathogenesis of schizophrenia.
缺陷型精神分裂症(DS)是精神分裂症(SCZ)的一种亚型。多基因对缺陷型精神分裂症神经影像学改变的影响仍然未知。本研究旨在计算缺陷型精神分裂症的多基因风险评分(PRS-SCZ),并进一步探讨其与大脑功能特征的潜在关联。PRS-SCZ是根据全外显子组测序和全基因组关联研究(GWAS)计算得出的。研究获得了 33 名 DS、47 名 NDS 和 41 名 HC 的静息态 fMRI 以及生化特征和神经认知数据,并在这些样本中进行了遗传风险与神经影像学的关联研究。研究人员对低频波动幅度(ALFF)、区域同质性(ReHo)和功能连接性(FC)进行了分析,以检测DS和NDS之间的功能改变。此外,研究人员还使用相关性分析来探讨功能特征(ALFF、ReHo和FC)与PRS-SCZ之间的关系。DS的PRS-SCZ明显低于NDS和HC。与NDS相比,DS左侧颞下回(ITG.L)和左侧额下回(IFG.L)的ALFF显著增加,右侧楔前回(PCUN.R)的ALFF和右侧额中回(MFG.R)的ReHo显著减少。FCs在DS和NDS之间发生了广泛变化,主要集中在默认模式网络,包括ITG、PCUN和角回(ANG)。相关分析表明,左侧ITG的ALFF、右侧额中回的ReHo、脑岛与ANG、左侧ITG与右侧胼胝体、左侧ITG与右侧PCUN的FC值以及Trail Making Test-B的得分均与DS的PRS-SCZ相关。本研究证明了多基因对 DS 和 NDS 脑功能变化的不同影响,为精神分裂症的发病机制提供了一个潜在的神经影像遗传学视角。
{"title":"Polygenic effects on brain functional endophenotype for deficit and non-deficit schizophrenia.","authors":"Jin Fang, Yiding Lv, Yingying Xie, Xiaowei Tang, Xiaobin Zhang, Xiang Wang, Miao Yu, Chao Zhou, Wen Qin, Xiangrong Zhang","doi":"10.1038/s41537-024-00432-w","DOIUrl":"10.1038/s41537-024-00432-w","url":null,"abstract":"<p><p>Deficit schizophrenia (DS) is a subtype of schizophrenia (SCZ). The polygenic effects on the neuroimaging alterations in DS still remain unknown. This study aims to calculate the polygenic risk scores for schizophrenia (PRS-SCZ) in DS, and further explores the potential associations with functional features of brain. PRS-SCZ was calculated according to the Whole Exome sequencing and Genome-wide association studies (GWAS). Resting-state fMRI, as well as biochemical features and neurocognitive data were obtained from 33 DS, 47 NDS and 41 HCs, and association studies of genetic risk with neuroimaging were performed in this sample. The analyses of amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were performed to detect the functional alterations between DS and NDS. In addition, correlation analysis was used to investigate the relationships between functional features (ALFF, ReHo, FC) and PRS-SCZ. The PRS-SCZ of DS was significantly lower than that in NDS and HC. Compared to NDS, there was a significant increase in the ALFF of left inferior temporal gyrus (ITG.L) and left inferior frontal gyrus (IFG.L) and a significant decrease in the ALFF of right precuneus (PCUN.R) and ReHo of right middle frontal gyrus (MFG.R) in DS. FCs were widely changed between DS and NDS, mainly concentrated in default mode network, including ITG, PCUN and angular gyrus (ANG). Correlation analysis revealed that the ALFF of left ITG, the ReHo of right middle frontal gyrus, the FC value between insula and ANG, left ITG and right corpus callosum, left ITG and right PCUN, as well as the scores of Trail Making Test-B, were associated with PRS-SCZ in DS. The present study demonstrated the differential polygenic effects on functional changes of brain in DS and NDS, providing a potential neuroimaging-genetic perspective for the pathogenesis of schizophrenia.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10873412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747936","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}