Pub Date : 2024-07-10DOI: 10.1038/s41537-024-00483-z
Alex Hatzimanolis, Stefania Foteli, Lida-Alkisti Xenaki, Mirjana Selakovic, Stefanos Dimitrakopoulos, Ilias Vlachos, Ioannis Kosteletos, Rigas-Filippos Soldatos, Maria Gazouli, Stylianos Chatzipanagiotou, Nikos Stefanis
The tryptophan-metabolizing kynurenine pathway (KP) can be activated by enhanced inflammatory responses and has been implicated in the pathophysiology of schizophrenia. However, there is little evidence for KP dysregulation in the early course of psychotic illness. We aimed to investigate the potential immune-mediated hyperactivity of KP in individuals with first-episode psychosis (FEP) and the relationship with symptom severity and treatment response outcomes. Serum immunoassays were performed to measure peripheral levels of inflammatory cytokines (IL-1β, IL-10, TNF-a), KP rate-limiting enzymes (IDO/TDO), and kynurenic acid (KYNA) metabolite in 104 antipsychotic-naïve patients with FEP and 80 healthy controls (HC). The Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning Scale (GAF) were administered to assess psychopathology and functioning status at admission and following 4-week treatment with antipsychotics. Cytokine and KP components levels were substantially increased in FEP patients compared to HC, before and after antipsychotic treatment. A significant positive correlation between pro-inflammatory IL-1β and KYNA levels was observed among FEP patients, but not in HC. Importantly, within-patient analysis revealed that those with higher baseline KYNA experienced more severe negative symptoms and poorer clinical improvement at follow-up. These findings suggest that KP is upregulated in early psychosis, likely through the induction of IL-1β-dependent pathways, and raised peripheral KYNA might represent a promising indicator of non-response to antipsychotic medication in patients with FEP.
{"title":"Elevated serum kynurenic acid in individuals with first-episode psychosis and insufficient response to antipsychotics.","authors":"Alex Hatzimanolis, Stefania Foteli, Lida-Alkisti Xenaki, Mirjana Selakovic, Stefanos Dimitrakopoulos, Ilias Vlachos, Ioannis Kosteletos, Rigas-Filippos Soldatos, Maria Gazouli, Stylianos Chatzipanagiotou, Nikos Stefanis","doi":"10.1038/s41537-024-00483-z","DOIUrl":"10.1038/s41537-024-00483-z","url":null,"abstract":"<p><p>The tryptophan-metabolizing kynurenine pathway (KP) can be activated by enhanced inflammatory responses and has been implicated in the pathophysiology of schizophrenia. However, there is little evidence for KP dysregulation in the early course of psychotic illness. We aimed to investigate the potential immune-mediated hyperactivity of KP in individuals with first-episode psychosis (FEP) and the relationship with symptom severity and treatment response outcomes. Serum immunoassays were performed to measure peripheral levels of inflammatory cytokines (IL-1β, IL-10, TNF-a), KP rate-limiting enzymes (IDO/TDO), and kynurenic acid (KYNA) metabolite in 104 antipsychotic-naïve patients with FEP and 80 healthy controls (HC). The Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning Scale (GAF) were administered to assess psychopathology and functioning status at admission and following 4-week treatment with antipsychotics. Cytokine and KP components levels were substantially increased in FEP patients compared to HC, before and after antipsychotic treatment. A significant positive correlation between pro-inflammatory IL-1β and KYNA levels was observed among FEP patients, but not in HC. Importantly, within-patient analysis revealed that those with higher baseline KYNA experienced more severe negative symptoms and poorer clinical improvement at follow-up. These findings suggest that KP is upregulated in early psychosis, likely through the induction of IL-1β-dependent pathways, and raised peripheral KYNA might represent a promising indicator of non-response to antipsychotic medication in patients with FEP.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581788","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 : 2024-07-04DOI: 10.1038/s41537-024-00478-w
Julia Gallucci, Maria T Secara, Oliver Chen, Lindsay D Oliver, Brett D M Jones, Tulip Marawi, George Foussias, Aristotle N Voineskos, Colin Hawco
Depressive symptoms in Schizophrenia Spectrum Disorders (SSDs) negatively impact suicidality, prognosis, and quality of life. Despite this, efficacious treatments are limited, largely because the neural mechanisms underlying depressive symptoms in SSDs remain poorly understood. We conducted a systematic review to provide an overview of studies that investigated the neural correlates of depressive symptoms in SSDs using neuroimaging techniques. We searched MEDLINE, PsycINFO, EMBASE, Web of Science, and Cochrane Library databases from inception through June 19, 2023. Specifically, we focused on structural and functional magnetic resonance imaging (MRI), encompassing: (1) T1-weighted imaging measuring brain morphology; (2) diffusion-weighted imaging assessing white matter integrity; or (3) T2*-weighted imaging measures of brain function. Our search yielded 33 articles; 14 structural MRI studies, 18 functional (f)MRI studies, and 1 multimodal fMRI/MRI study. Reviewed studies indicate potential commonalities in the neurobiology of depressive symptoms between SSDs and major depressive disorders, particularly in subcortical and frontal brain regions, though confidence in this interpretation is limited. The review underscores a notable knowledge gap in our understanding of the neurobiology of depression in SSDs, marked by inconsistent approaches and few studies examining imaging metrics of depressive symptoms. Inconsistencies across studies' findings emphasize the necessity for more direct and comprehensive research focusing on the neurobiology of depression in SSDs. Future studies should go beyond "total score" depression metrics and adopt more nuanced assessment approaches considering distinct subdomains. This could reveal unique neurobiological profiles and inform investigations of targeted treatments for depression in SSDs.
{"title":"A systematic review of structural and functional magnetic resonance imaging studies on the neurobiology of depressive symptoms in schizophrenia spectrum disorders.","authors":"Julia Gallucci, Maria T Secara, Oliver Chen, Lindsay D Oliver, Brett D M Jones, Tulip Marawi, George Foussias, Aristotle N Voineskos, Colin Hawco","doi":"10.1038/s41537-024-00478-w","DOIUrl":"10.1038/s41537-024-00478-w","url":null,"abstract":"<p><p>Depressive symptoms in Schizophrenia Spectrum Disorders (SSDs) negatively impact suicidality, prognosis, and quality of life. Despite this, efficacious treatments are limited, largely because the neural mechanisms underlying depressive symptoms in SSDs remain poorly understood. We conducted a systematic review to provide an overview of studies that investigated the neural correlates of depressive symptoms in SSDs using neuroimaging techniques. We searched MEDLINE, PsycINFO, EMBASE, Web of Science, and Cochrane Library databases from inception through June 19, 2023. Specifically, we focused on structural and functional magnetic resonance imaging (MRI), encompassing: (1) T1-weighted imaging measuring brain morphology; (2) diffusion-weighted imaging assessing white matter integrity; or (3) T2*-weighted imaging measures of brain function. Our search yielded 33 articles; 14 structural MRI studies, 18 functional (f)MRI studies, and 1 multimodal fMRI/MRI study. Reviewed studies indicate potential commonalities in the neurobiology of depressive symptoms between SSDs and major depressive disorders, particularly in subcortical and frontal brain regions, though confidence in this interpretation is limited. The review underscores a notable knowledge gap in our understanding of the neurobiology of depression in SSDs, marked by inconsistent approaches and few studies examining imaging metrics of depressive symptoms. Inconsistencies across studies' findings emphasize the necessity for more direct and comprehensive research focusing on the neurobiology of depression in SSDs. Future studies should go beyond \"total score\" depression metrics and adopt more nuanced assessment approaches considering distinct subdomains. This could reveal unique neurobiological profiles and inform investigations of targeted treatments for depression in SSDs.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499836","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 : 2024-07-04DOI: 10.1038/s41537-024-00481-1
Laurin Plank, Armin Zlomuzica
The extraction of linguistic markers from social media posts, which are indicative of the onset and course of mental disorders, offers great potential for mental healthcare. In the present study, we extracted over one million posts from the popular social media platform Reddit to analyze speech coherence, which reflects formal thought disorder and is a characteristic feature of schizophrenia and associated psychotic disorders. Natural language processing (NLP) models were used to perform an automated quantification of speech coherence. We could demonstrate that users who are active on forums geared towards disorders with a higher degree of psychotic symptoms tend to show a lower level of coherence. The lowest coherence scores were found in users of forums on dissociative identity disorder, schizophrenia, and bipolar disorder. In contrast, a relatively high level of coherence was detected in users of forums related to obsessive-compulsive disorder, anxiety, and depression. Users of forums on posttraumatic stress disorder, autism, and attention-deficit hyperactivity disorder exhibited medium-level coherence. Our findings provide promising first evidence for the possible utility of NLP-based coherence analyses for the early detection and prevention of psychosis on the basis of posts gathered from publicly available social media data. This opens new avenues for large-scale prevention programs aimed at high-risk populations.
{"title":"Reduced speech coherence in psychosis-related social media forum posts.","authors":"Laurin Plank, Armin Zlomuzica","doi":"10.1038/s41537-024-00481-1","DOIUrl":"10.1038/s41537-024-00481-1","url":null,"abstract":"<p><p>The extraction of linguistic markers from social media posts, which are indicative of the onset and course of mental disorders, offers great potential for mental healthcare. In the present study, we extracted over one million posts from the popular social media platform Reddit to analyze speech coherence, which reflects formal thought disorder and is a characteristic feature of schizophrenia and associated psychotic disorders. Natural language processing (NLP) models were used to perform an automated quantification of speech coherence. We could demonstrate that users who are active on forums geared towards disorders with a higher degree of psychotic symptoms tend to show a lower level of coherence. The lowest coherence scores were found in users of forums on dissociative identity disorder, schizophrenia, and bipolar disorder. In contrast, a relatively high level of coherence was detected in users of forums related to obsessive-compulsive disorder, anxiety, and depression. Users of forums on posttraumatic stress disorder, autism, and attention-deficit hyperactivity disorder exhibited medium-level coherence. Our findings provide promising first evidence for the possible utility of NLP-based coherence analyses for the early detection and prevention of psychosis on the basis of posts gathered from publicly available social media data. This opens new avenues for large-scale prevention programs aimed at high-risk populations.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11224262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536162","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 : 2024-06-24DOI: 10.1038/s41537-024-00479-9
Sunny X Tang, Katrin Hänsel, Lindsay D Oliver, Erin W Dickie, Colin Hawco, Majnu John, Aristotle Voineskos, James M Gold, Robert W Buchanan, Anil K Malhotra
Functional impairments contribute to poor quality of life in schizophrenia spectrum disorders (SSD). We sought to (Objective I) define the main functional phenotypes in SSD, then (Objective II) identify key biopsychosocial correlates, emphasizing interpretable data-driven methods. Objective I was tested on independent samples: Dataset I (N = 282) and Dataset II (N = 317), with SSD participants who underwent assessment of multiple functioning areas. Participants were clustered based on functioning. Objective II was evaluated in Dataset I by identifying key features for classifying functional phenotype clusters from among 65 sociodemographic, psychological, clinical, cognitive, and brain volume measures. Findings were replicated across latent discriminant analyses (LDA) and one-vs.-rest binomial regularized regressions to identify key predictors. We identified three clusters of participants in each dataset, demonstrating replicable functional phenotypes: Cluster 1-poor functioning across domains; Cluster 2-impaired Role Functioning, but partially preserved Independent and Social Functioning; Cluster 3-good functioning across domains. Key correlates were Avolition, anhedonia, left hippocampal volume, and measures of emotional intelligence and subjective social experience. Avolition appeared more closely tied to role functioning, and anhedonia to independent and social functioning. Thus, we found three replicable functional phenotypes with evidence that recovery may not be uniform across domains. Avolition and anhedonia were both critical but played different roles for different functional domains. It may be important to identify critical functional areas for individual patients and target interventions accordingly.
功能障碍导致精神分裂症谱系障碍(SSD)患者生活质量低下。我们试图(目标一)定义精神分裂症谱系障碍的主要功能表型,然后(目标二)确定关键的生物-心理-社会相关因素,强调可解释的数据驱动方法。目标 I 在独立样本上进行了测试:数据集 I(N = 282)和数据集 II(N = 317)中的 SSD 参与者接受了多个功能领域的评估。根据功能对参与者进行分组。目标 II 在数据集 I 中进行了评估,从 65 个社会人口、心理、临床、认知和脑容量测量指标中识别出功能表型集群分类的关键特征。研究结果在潜在判别分析(LDA)和一vs.-rest二项式正则回归中得到了重复,以确定关键的预测因素。我们在每个数据集中发现了三个参与者集群,展示了可复制的功能表型:第 1 组--各领域功能较差;第 2 组--角色功能受损,但独立和社交功能部分保留;第 3 组--各领域功能良好。与之相关的主要因素包括逃避、失乐症、左侧海马体积以及情商和主观社会体验的测量。逃避似乎与角色功能更密切相关,而失乐症则与独立和社会功能更密切相关。因此,我们发现了三种可复制的功能表型,有证据表明不同领域的恢复可能并不一致。逃避和失乐症都很关键,但在不同的功能领域发挥着不同的作用。确定个体患者的关键功能领域并有针对性地进行干预可能非常重要。
{"title":"Functional phenotypes in schizophrenia spectrum disorders: defining the constructs and identifying biopsychosocial correlates using data-driven methods.","authors":"Sunny X Tang, Katrin Hänsel, Lindsay D Oliver, Erin W Dickie, Colin Hawco, Majnu John, Aristotle Voineskos, James M Gold, Robert W Buchanan, Anil K Malhotra","doi":"10.1038/s41537-024-00479-9","DOIUrl":"10.1038/s41537-024-00479-9","url":null,"abstract":"<p><p>Functional impairments contribute to poor quality of life in schizophrenia spectrum disorders (SSD). We sought to (Objective I) define the main functional phenotypes in SSD, then (Objective II) identify key biopsychosocial correlates, emphasizing interpretable data-driven methods. Objective I was tested on independent samples: Dataset I (N = 282) and Dataset II (N = 317), with SSD participants who underwent assessment of multiple functioning areas. Participants were clustered based on functioning. Objective II was evaluated in Dataset I by identifying key features for classifying functional phenotype clusters from among 65 sociodemographic, psychological, clinical, cognitive, and brain volume measures. Findings were replicated across latent discriminant analyses (LDA) and one-vs.-rest binomial regularized regressions to identify key predictors. We identified three clusters of participants in each dataset, demonstrating replicable functional phenotypes: Cluster 1-poor functioning across domains; Cluster 2-impaired Role Functioning, but partially preserved Independent and Social Functioning; Cluster 3-good functioning across domains. Key correlates were Avolition, anhedonia, left hippocampal volume, and measures of emotional intelligence and subjective social experience. Avolition appeared more closely tied to role functioning, and anhedonia to independent and social functioning. Thus, we found three replicable functional phenotypes with evidence that recovery may not be uniform across domains. Avolition and anhedonia were both critical but played different roles for different functional domains. It may be important to identify critical functional areas for individual patients and target interventions accordingly.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447737","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 : 2024-06-17DOI: 10.1038/s41537-024-00477-x
Sung Woo Joo, Young Tak Jo, Woohyeok Choi, Sun Min Kim, So Young Yoo, Soohyun Joe, Jungsun Lee
A morphometric similarity (MS) network can be constructed using multiple magnetic resonance imaging parameters of each cortical region. An MS network can be used to assess the similarity between cortical regions. Although MS networks can detect microstructural alterations and capture connections between histologically similar cortical areas, the influence of schizophrenia on the topological characteristics of MS networks remains unclear. We obtained T1- and diffusion-weighted images of 239 healthy controls and 190 individuals with schizophrenia to construct the MS network. Group comparisons of the mean MS of the cortical regions and subnetworks were performed. The strengths of the connections between the cortical regions and the global and nodal network indices were compared between the groups. Clinical associations with the network indices were tested using Spearman's rho. Compared with healthy controls, individuals with schizophrenia had significant group differences in the mean MS of several cortical regions and subnetworks. Individuals with schizophrenia had both superior and inferior strengths of connections between cortical regions compared with those of healthy controls. We observed regional abnormalities of the MS network in individuals with schizophrenia regarding lower centrality values of the pars opercularis, superior frontal, and superior temporal areas. Specific nodal network measures of the right pars opercularis and left superior temporal areas were associated with illness duration in individuals with schizophrenia. We identified regional abnormalities of the MS network in schizophrenia with the left superior temporal area possibly being a key region in topological organization and cortical connections.
利用每个皮层区域的多个磁共振成像参数,可以构建一个形态计量相似性(MS)网络。MS 网络可用于评估皮质区域之间的相似性。虽然MS网络可以检测微观结构的改变并捕捉组织学上相似的皮质区域之间的联系,但精神分裂症对MS网络拓扑特征的影响仍不清楚。我们获取了 239 名健康对照组和 190 名精神分裂症患者的 T1 和弥散加权图像来构建 MS 网络。我们对皮质区域和子网的平均 MS 进行了分组比较。比较了各组之间皮质区域之间的连接强度以及整体和节点网络指数。使用Spearman's rho检验了网络指数与临床的关联性。与健康对照组相比,精神分裂症患者在几个皮层区域和子网的平均MS方面存在显著的群体差异。与健康对照组相比,精神分裂症患者大脑皮层区域之间的连接强度有高有低。我们观察到精神分裂症患者的 MS 网络存在区域性异常,其中眼旁、额叶上部和颞叶上部区域的中心性值较低。在精神分裂症患者中,右侧眼旁和左侧颞上区的特定节点网络测量值与病程有关。我们发现精神分裂症患者的多发性硬化症网络存在区域性异常,而左侧颞上区可能是拓扑组织和皮层连接的关键区域。
{"title":"Topological abnormalities of the morphometric similarity network of the cerebral cortex in schizophrenia.","authors":"Sung Woo Joo, Young Tak Jo, Woohyeok Choi, Sun Min Kim, So Young Yoo, Soohyun Joe, Jungsun Lee","doi":"10.1038/s41537-024-00477-x","DOIUrl":"10.1038/s41537-024-00477-x","url":null,"abstract":"<p><p>A morphometric similarity (MS) network can be constructed using multiple magnetic resonance imaging parameters of each cortical region. An MS network can be used to assess the similarity between cortical regions. Although MS networks can detect microstructural alterations and capture connections between histologically similar cortical areas, the influence of schizophrenia on the topological characteristics of MS networks remains unclear. We obtained T1- and diffusion-weighted images of 239 healthy controls and 190 individuals with schizophrenia to construct the MS network. Group comparisons of the mean MS of the cortical regions and subnetworks were performed. The strengths of the connections between the cortical regions and the global and nodal network indices were compared between the groups. Clinical associations with the network indices were tested using Spearman's rho. Compared with healthy controls, individuals with schizophrenia had significant group differences in the mean MS of several cortical regions and subnetworks. Individuals with schizophrenia had both superior and inferior strengths of connections between cortical regions compared with those of healthy controls. We observed regional abnormalities of the MS network in individuals with schizophrenia regarding lower centrality values of the pars opercularis, superior frontal, and superior temporal areas. Specific nodal network measures of the right pars opercularis and left superior temporal areas were associated with illness duration in individuals with schizophrenia. We identified regional abnormalities of the MS network in schizophrenia with the left superior temporal area possibly being a key region in topological organization and cortical connections.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11183129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422177","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 : 2024-06-15DOI: 10.1038/s41537-024-00476-y
Orsolya Lányi, Boróka Koleszár, Alexander Schulze Wenning, David Balogh, Marie Anne Engh, András Attila Horváth, Péter Fehérvari, Péter Hegyi, Zsolt Molnár, Zsolt Unoka, Gábor Csukly
Cortical excitation-inhibition (E/I) imbalance is a potential model for the pathophysiology of schizophrenia. Previous research using transcranial magnetic stimulation (TMS) and electromyography (EMG) has suggested inhibitory deficits in schizophrenia. In this meta-analysis we assessed the reliability and clinical potential of TMS-EMG paradigms in schizophrenia following the methodological recommendations of the PRISMA guideline and the Cochrane Handbook. The search was conducted in three databases in November 2022. Included articles reported Short-Interval Intracortical Inhibition (SICI), Intracortical Facilitation (ICF), Long-Interval Intracortical Inhibition (LICI) and Cortical Silent Period (CSP) in patients with schizophrenia and healthy controls. Meta-analyses were conducted using a random-effects model. Subgroup analysis and meta-regressions were used to assess heterogeneity. Results of 36 studies revealed a robust inhibitory deficit in schizophrenia with a significant decrease in SICI (Cohen's d: 0.62). A trend-level association was found between SICI and antipsychotic medication. Our findings support the E/I imbalance hypothesis in schizophrenia and suggest that SICI may be a potential pathophysiological characteristic of the disorder.
{"title":"Excitation/inhibition imbalance in schizophrenia: a meta-analysis of inhibitory and excitatory TMS-EMG paradigms.","authors":"Orsolya Lányi, Boróka Koleszár, Alexander Schulze Wenning, David Balogh, Marie Anne Engh, András Attila Horváth, Péter Fehérvari, Péter Hegyi, Zsolt Molnár, Zsolt Unoka, Gábor Csukly","doi":"10.1038/s41537-024-00476-y","DOIUrl":"10.1038/s41537-024-00476-y","url":null,"abstract":"<p><p>Cortical excitation-inhibition (E/I) imbalance is a potential model for the pathophysiology of schizophrenia. Previous research using transcranial magnetic stimulation (TMS) and electromyography (EMG) has suggested inhibitory deficits in schizophrenia. In this meta-analysis we assessed the reliability and clinical potential of TMS-EMG paradigms in schizophrenia following the methodological recommendations of the PRISMA guideline and the Cochrane Handbook. The search was conducted in three databases in November 2022. Included articles reported Short-Interval Intracortical Inhibition (SICI), Intracortical Facilitation (ICF), Long-Interval Intracortical Inhibition (LICI) and Cortical Silent Period (CSP) in patients with schizophrenia and healthy controls. Meta-analyses were conducted using a random-effects model. Subgroup analysis and meta-regressions were used to assess heterogeneity. Results of 36 studies revealed a robust inhibitory deficit in schizophrenia with a significant decrease in SICI (Cohen's d: 0.62). A trend-level association was found between SICI and antipsychotic medication. Our findings support the E/I imbalance hypothesis in schizophrenia and suggest that SICI may be a potential pathophysiological characteristic of the disorder.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11180212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141328204","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}
Phospholipase A2(PLA2) superfamily is recognized as being involved in the pathogenesis of schizophrenia by affecting lipid homeostasis in cell membranes. We hypothesized that PLA2 gene copy number variation (CNV) may affect PLA2 enzyme expression and be associated with schizophrenia risk. This study indicated that in the discovery stage, an increased copy number of PLA2G6 and the deletion of PLA2G3, PLA2G4A, PLA2G4F and PLA2G12F was associated with increased risk of schizophrenia. CNV segments involving six PLA2 genes were detected in publicly available datasets, including two deletion segments specific to the PLA2G4A gene. The relationship between the deletion of PLA2G4A and susceptibility to schizophrenia was then reaffirmed in the validation group of 806 individuals. There was a significant correlation between PLA2G4A deletion and the symptoms of poverty of thought in male patients and erotomanic delusion in females. Furthermore, ELISA results demonstrate a significant decrease in peripheral blood cytosolic PLA2(cPLA2) levels in patients with the PLA2G4A deletion genotype compared to those with normal and copy number duplicate genotypes. These data suggest that the functional copy number deletion in the PLA2G4A gene is associated with the risk of schizophrenia and clinical phenotypes by reducing the expression of cPLA2, which may be an indicator of susceptibility to schizophrenia.
{"title":"Copy number deletion of PLA2G4A affects the susceptibility and clinical phenotypes of schizophrenia.","authors":"Zibo Gao, Xinru Guo, Zhouyang Sun, Songyu Wu, Qianyi Wang, Qianlong Huang, Wei Bai, Changgui Kou","doi":"10.1038/s41537-024-00474-0","DOIUrl":"10.1038/s41537-024-00474-0","url":null,"abstract":"<p><p>Phospholipase A2(PLA2) superfamily is recognized as being involved in the pathogenesis of schizophrenia by affecting lipid homeostasis in cell membranes. We hypothesized that PLA2 gene copy number variation (CNV) may affect PLA2 enzyme expression and be associated with schizophrenia risk. This study indicated that in the discovery stage, an increased copy number of PLA2G6 and the deletion of PLA2G3, PLA2G4A, PLA2G4F and PLA2G12F was associated with increased risk of schizophrenia. CNV segments involving six PLA2 genes were detected in publicly available datasets, including two deletion segments specific to the PLA2G4A gene. The relationship between the deletion of PLA2G4A and susceptibility to schizophrenia was then reaffirmed in the validation group of 806 individuals. There was a significant correlation between PLA2G4A deletion and the symptoms of poverty of thought in male patients and erotomanic delusion in females. Furthermore, ELISA results demonstrate a significant decrease in peripheral blood cytosolic PLA2(cPLA2) levels in patients with the PLA2G4A deletion genotype compared to those with normal and copy number duplicate genotypes. These data suggest that the functional copy number deletion in the PLA2G4A gene is associated with the risk of schizophrenia and clinical phenotypes by reducing the expression of cPLA2, which may be an indicator of susceptibility to schizophrenia.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11139948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181323","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 : 2024-05-21DOI: 10.1038/s41537-024-00464-2
Jenna M Reinen, Pablo Polosecki, Eduardo Castro, Cheryl M Corcoran, Guillermo A Cecchi, Tiziano Colibazzi
The prospective study of youths at clinical high risk (CHR) for psychosis, including neuroimaging, can identify neural signatures predictive of psychosis outcomes using algorithms that integrate complex information. Here, to identify risk and psychosis conversion, we implemented multiple kernel learning (MKL), a multimodal machine learning approach allowing patterns from each modality to inform each other. Baseline multimodal scans (n = 74, 11 converters) included structural, resting-state functional imaging, and diffusion-weighted data. Multimodal MKL outperformed unimodal models (AUC = 0.73 vs. 0.66 in predicting conversion). Moreover, patterns learned by MKL were robust to training set variations, suggesting it can identify cross-modality redundancies and synergies to stabilize the predictive pattern. We identified many predictors consistent with the literature, including frontal cortices, cingulate, thalamus, and striatum. This highlights the advantage of methods that leverage the complex pathophysiology of psychosis.
{"title":"Multimodal fusion of brain signals for robust prediction of psychosis transition.","authors":"Jenna M Reinen, Pablo Polosecki, Eduardo Castro, Cheryl M Corcoran, Guillermo A Cecchi, Tiziano Colibazzi","doi":"10.1038/s41537-024-00464-2","DOIUrl":"10.1038/s41537-024-00464-2","url":null,"abstract":"<p><p>The prospective study of youths at clinical high risk (CHR) for psychosis, including neuroimaging, can identify neural signatures predictive of psychosis outcomes using algorithms that integrate complex information. Here, to identify risk and psychosis conversion, we implemented multiple kernel learning (MKL), a multimodal machine learning approach allowing patterns from each modality to inform each other. Baseline multimodal scans (n = 74, 11 converters) included structural, resting-state functional imaging, and diffusion-weighted data. Multimodal MKL outperformed unimodal models (AUC = 0.73 vs. 0.66 in predicting conversion). Moreover, patterns learned by MKL were robust to training set variations, suggesting it can identify cross-modality redundancies and synergies to stabilize the predictive pattern. We identified many predictors consistent with the literature, including frontal cortices, cingulate, thalamus, and striatum. This highlights the advantage of methods that leverage the complex pathophysiology of psychosis.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11109212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077461","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 : 2024-05-18DOI: 10.1038/s41537-024-00463-3
Tomer Ben Moshe, Ido Ziv, Nachum Dershowitz, Kfir Bar
We show how acoustic prosodic features, such as pitch and gaps, can be used computationally for detecting symptoms of schizophrenia from a single spoken response. We compare the individual contributions of acoustic and previously-employed text modalities to the algorithmic determination whether the speaker has schizophrenia. Our classification results clearly show that we can extract relevant acoustic features better than those textual ones. We find that, when combined with those acoustic features, textual features improve classification only slightly.
{"title":"The contribution of prosody to machine classification of schizophrenia.","authors":"Tomer Ben Moshe, Ido Ziv, Nachum Dershowitz, Kfir Bar","doi":"10.1038/s41537-024-00463-3","DOIUrl":"10.1038/s41537-024-00463-3","url":null,"abstract":"<p><p>We show how acoustic prosodic features, such as pitch and gaps, can be used computationally for detecting symptoms of schizophrenia from a single spoken response. We compare the individual contributions of acoustic and previously-employed text modalities to the algorithmic determination whether the speaker has schizophrenia. Our classification results clearly show that we can extract relevant acoustic features better than those textual ones. We find that, when combined with those acoustic features, textual features improve classification only slightly.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11102498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961174","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 prolonged usage of atypical antipsychotic drugs (AAPD) among individuals with schizophrenia often leads to metabolic side effects such as dyslipidemia. These effects not only limit one's selection of AAPD but also significantly reduce compliance and quality of life of patients. Recent studies suggest that bilirubin plays a crucial role in maintaining lipid homeostasis and may be a potential pre-treatment biomarker for individuals with dyslipidemia. The present study included 644 schizophrenia patients from two centers. Demographic and clinical characteristics were collected at baseline and 4 weeks after admission to investigate the correlation between metabolites, episodes, usage of AAPDs, and occurrence of dyslipidemia. Besides, we explored the combined predictive value of genotypes and baseline bilirubin for dyslipidemia by employing multiple PCR targeted capture techniques to sequence two pathways: bilirubin metabolism-related genes and lipid metabolism-related genes. Our results indicated that there existed a negative correlation between the changes in bilirubin levels and triglyceride (TG) levels in patients with schizophrenia. Among three types of bilirubin, direct bilirubin in the baseline (DBIL-bl) proved to be the most effective in predicting dyslipidemia in the ROC analysis (AUC = 0.627, p < 0.001). Furthermore, the odds ratio from multinomial logistic regression analysis showed that UGT1A1*6 was a protective factor for dyslipidemia (ß = -12.868, p < 0.001). The combination of baseline DBIL and UGT1A1*6 significantly improved the performance in predicting dyslipidemia (AUC = 0.939, p < 0.001). Schizophrenia patients with UGT1A1*6 mutation and a certain level of baseline bilirubin may be more resistant to dyslipidemia and have more selections for AAPD than other patients.
{"title":"Combination of UGT1A1 polymorphism and baseline plasma bilirubin levels in predicting the risk of antipsychotic-induced dyslipidemia in schizophrenia patients.","authors":"Chenquan Lin, Shuangyang Zhang, Ping Yang, Bikui Zhang, Wenbin Guo, Renrong Wu, Yong Liu, Jianjian Wang, Haishan Wu, Hualin Cai","doi":"10.1038/s41537-024-00473-1","DOIUrl":"10.1038/s41537-024-00473-1","url":null,"abstract":"<p><p>The prolonged usage of atypical antipsychotic drugs (AAPD) among individuals with schizophrenia often leads to metabolic side effects such as dyslipidemia. These effects not only limit one's selection of AAPD but also significantly reduce compliance and quality of life of patients. Recent studies suggest that bilirubin plays a crucial role in maintaining lipid homeostasis and may be a potential pre-treatment biomarker for individuals with dyslipidemia. The present study included 644 schizophrenia patients from two centers. Demographic and clinical characteristics were collected at baseline and 4 weeks after admission to investigate the correlation between metabolites, episodes, usage of AAPDs, and occurrence of dyslipidemia. Besides, we explored the combined predictive value of genotypes and baseline bilirubin for dyslipidemia by employing multiple PCR targeted capture techniques to sequence two pathways: bilirubin metabolism-related genes and lipid metabolism-related genes. Our results indicated that there existed a negative correlation between the changes in bilirubin levels and triglyceride (TG) levels in patients with schizophrenia. Among three types of bilirubin, direct bilirubin in the baseline (DBIL-bl) proved to be the most effective in predicting dyslipidemia in the ROC analysis (AUC = 0.627, p < 0.001). Furthermore, the odds ratio from multinomial logistic regression analysis showed that UGT1A1*6 was a protective factor for dyslipidemia (ß = -12.868, p < 0.001). The combination of baseline DBIL and UGT1A1*6 significantly improved the performance in predicting dyslipidemia (AUC = 0.939, p < 0.001). Schizophrenia patients with UGT1A1*6 mutation and a certain level of baseline bilirubin may be more resistant to dyslipidemia and have more selections for AAPD than other patients.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11101411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961109","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}