{"title":"Insight as a Barrier to the Diagnosis and Treatment of Mental Illness.","authors":"Oliver Delgaram-Nejad","doi":"10.1093/schbul/sbaf024","DOIUrl":"https://doi.org/10.1093/schbul/sbaf024","url":null,"abstract":"","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Halil Aziz Velioglu, Julie Moehringer, Todd Lencz, Juan A Gallego, John Cholewa, Yevgeniy Kats, Anita D Barber, Michael L Birnbaum, Delbert G Robinson, Hengyi Cao, Anil K Malhotra
Background: The cerebellum has traditionally been associated with motor functions, but recent evidence highlights its critical role in cognitive and emotional regulation, contributing to the neuropathology of schizophrenia. Our previous data-driven research demonstrated that cerebellar-cortical functional connectivity can predict antipsychotic treatment outcomes in first-episode psychosis (FEP). The present study aimed to investigate specific cerebellar functional systems involved in treatment prediction.
Study design: This study included 127 patients with FEP who underwent 12 weeks of antipsychotic monotherapy (either risperidone or aripiprazole). Baseline resting-state functional MRI data were collected from two 3T scanners, and functional connectivity between 10 predefined cerebellar functional systems and the whole brain was analyzed. Psychotic symptom changes were measured using the Brief Psychiatric Rating Scale-Anchored version (BPRS-A). Connectivity patterns were examined in relation to treatment outcomes.
Study results: Higher baseline connectivity between the cerebellar auditory system and cortical regions, including the visual cortex, dorsolateral prefrontal cortex, and the hippocampus, predicted worse treatment outcome. In contrast, stronger connectivity between cerebellar cognitive systems (default mode and frontoparietal networks) and the anterior cingulate cortex (ACC) and medial prefrontal cortex was associated with better treatment outcome. These findings were consistently present in data acquired from both scanners and both drugs.
Conclusions: Our results identify specific cerebellar-cortical circuitries as prognostic biomarkers for predicting psychosis treatment outcomes, and suggest that cerebellar auditory and cognitive systems may be potential targets for future interventions aimed at improving treatment efficacy in FEP.
{"title":"Cerebellar-Cortical Connectivity and Prediction of Antipsychotic Treatment Response in First-Episode Psychosis.","authors":"Halil Aziz Velioglu, Julie Moehringer, Todd Lencz, Juan A Gallego, John Cholewa, Yevgeniy Kats, Anita D Barber, Michael L Birnbaum, Delbert G Robinson, Hengyi Cao, Anil K Malhotra","doi":"10.1093/schbul/sbaf021","DOIUrl":"https://doi.org/10.1093/schbul/sbaf021","url":null,"abstract":"<p><strong>Background: </strong>The cerebellum has traditionally been associated with motor functions, but recent evidence highlights its critical role in cognitive and emotional regulation, contributing to the neuropathology of schizophrenia. Our previous data-driven research demonstrated that cerebellar-cortical functional connectivity can predict antipsychotic treatment outcomes in first-episode psychosis (FEP). The present study aimed to investigate specific cerebellar functional systems involved in treatment prediction.</p><p><strong>Study design: </strong>This study included 127 patients with FEP who underwent 12 weeks of antipsychotic monotherapy (either risperidone or aripiprazole). Baseline resting-state functional MRI data were collected from two 3T scanners, and functional connectivity between 10 predefined cerebellar functional systems and the whole brain was analyzed. Psychotic symptom changes were measured using the Brief Psychiatric Rating Scale-Anchored version (BPRS-A). Connectivity patterns were examined in relation to treatment outcomes.</p><p><strong>Study results: </strong>Higher baseline connectivity between the cerebellar auditory system and cortical regions, including the visual cortex, dorsolateral prefrontal cortex, and the hippocampus, predicted worse treatment outcome. In contrast, stronger connectivity between cerebellar cognitive systems (default mode and frontoparietal networks) and the anterior cingulate cortex (ACC) and medial prefrontal cortex was associated with better treatment outcome. These findings were consistently present in data acquired from both scanners and both drugs.</p><p><strong>Conclusions: </strong>Our results identify specific cerebellar-cortical circuitries as prognostic biomarkers for predicting psychosis treatment outcomes, and suggest that cerebellar auditory and cognitive systems may be potential targets for future interventions aimed at improving treatment efficacy in FEP.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"What Constitutes the Personal Space in Schizophrenia? Converging Subjective Experience, Brain, and Social Environment.","authors":"Dusan Hirjak, Georg Northoff","doi":"10.1093/schbul/sbaf030","DOIUrl":"https://doi.org/10.1093/schbul/sbaf030","url":null,"abstract":"","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Living With Schizoaffective Disorder: Healthier Ways to Cope With Anxiety, Fear, and Depression.","authors":"Domenico Regonini","doi":"10.1093/schbul/sbaf027","DOIUrl":"https://doi.org/10.1093/schbul/sbaf027","url":null,"abstract":"","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background and Hypothesis Cognitive impairments in patients with schizophrenia initiate a cascade of effects on daily functioning. A single impairment can affect the functioning of the entire cognitive system. However, the relative interdependence among individual neuropsychological measures—whether the performance of a specific test depends on other tests—remains poorly understood. Study Design The study included a total of 1027 participants (522 patients with schizophrenia and 505 healthy controls) from China. All participants completed the comprehensive 9-test Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. To examine cognitive relationships, we employed Gaussian Graphical Models for undirected relationships and Bayesian networks for directed relationships among cognitive tests. Study Results Symbol Coding played a central role and exhibited downstream associations with other cognitive tests in both patients and controls. Network analysis showed significant between-group edge differences in undirected networks, particularly between Continuous Performance and Spatial Span (SS), and between Symbol Coding and Managing Emotions (P = .018). A consistent sequential pattern (Symbol Coding → SS → Maze → Trail Making) was identified in both networks. Notably, the Symbol Coding → Managing Emotions connection was uniquely present in the patient’s network. Importantly, Symbol Coding and SS were identified as central variables in schizophrenia, showing extensive connectivity with other cognitive tests. Conclusions Symbol Coding is a fundamental cognitive test in both patients and controls. The association between Symbol Coding and Managing Emotions appears to be a stable feature in schizophrenia. These findings may inform mechanistic insights into cognitive architecture.
{"title":"Clarifying Fundamental Role of Symbol Coding in Cognitive Networks in Schizophrenia and Healthy Controls Leveraging Gaussian Graphical Models and Bayesian Networks","authors":"Yuyanan Zhang, Yaoyao Sun, Zhe Lu, Guorui Zhao, Junyuan Sun, Xiao Zhang, Yang Yang, Zhewei Kang, Xiaoyang Feng, Rui Yuan, Yundan Liao, Yunqing Zhu, Jing Guo, Weihua Yue","doi":"10.1093/schbul/sbaf026","DOIUrl":"https://doi.org/10.1093/schbul/sbaf026","url":null,"abstract":"Background and Hypothesis Cognitive impairments in patients with schizophrenia initiate a cascade of effects on daily functioning. A single impairment can affect the functioning of the entire cognitive system. However, the relative interdependence among individual neuropsychological measures—whether the performance of a specific test depends on other tests—remains poorly understood. Study Design The study included a total of 1027 participants (522 patients with schizophrenia and 505 healthy controls) from China. All participants completed the comprehensive 9-test Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. To examine cognitive relationships, we employed Gaussian Graphical Models for undirected relationships and Bayesian networks for directed relationships among cognitive tests. Study Results Symbol Coding played a central role and exhibited downstream associations with other cognitive tests in both patients and controls. Network analysis showed significant between-group edge differences in undirected networks, particularly between Continuous Performance and Spatial Span (SS), and between Symbol Coding and Managing Emotions (P = .018). A consistent sequential pattern (Symbol Coding → SS → Maze → Trail Making) was identified in both networks. Notably, the Symbol Coding → Managing Emotions connection was uniquely present in the patient’s network. Importantly, Symbol Coding and SS were identified as central variables in schizophrenia, showing extensive connectivity with other cognitive tests. Conclusions Symbol Coding is a fundamental cognitive test in both patients and controls. The association between Symbol Coding and Managing Emotions appears to be a stable feature in schizophrenia. These findings may inform mechanistic insights into cognitive architecture.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"23 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143570437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eduardo Fonseca-Pedrero, Alicia Pérez-Albéniz, Beatriz Lucas-Molina, Susana Al-Halabí, Martin Debbané
Background New theoretical and measurement models related to Bayesian networks can usefully be implemented to enrich our understanding of psychosis risk. The present study aims to explore, using a directed acyclic graph (DAG), the putative causal relationship within schizotypal facets, as well as between schizotypal dimensions, psychopathology, and reflective functioning (RF) impairments, in a representative sample of non-clinical adolescents. Study Design A sample of 1476 adolescents from the general population participated in a cross-sectional survey. The Oviedo Schizotypy Assessment Questionnaire-Revised, the Strengths and Difficulties Questionnaire, and the Reflective Functioning Questionnaire (RFQ) were used. Study Results Schizotypal traits were positively associated with psychopathology and hypomentalizing. Putative causal relationships are presented between Reality distortion, Social disorganization, and Anhedonia. In addition, estimated DAG suggests that schizotypal dimensions influence psychopathology and RF impairments. Conclusions The findings suggest different pathways connecting schizotypal traits, mental health problems, and RF impairments during adolescence. The use of probabilistic DAG may allow us to make more robust conclusions about the direction of causation and to unravel potentially complex causal chains in the study of psychosis risk.
背景与贝叶斯网络相关的新理论和测量模型可以有效地丰富我们对精神病风险的理解。本研究的目的是利用有向无环图（DAG），在非临床青少年的代表性样本中，探讨精神分裂分型面之间的推定因果关系，以及精神分裂分型维度、精神病理学和反思功能（RF）障碍之间的推定因果关系。研究设计 共有1476名青少年参加了横断面调查。调查使用了奥维多分裂型评估问卷-修订版、优势与困难问卷和反思功能问卷（RFQ）。研究结果 人格分裂型特质与精神病理学和妄想症呈正相关。现实扭曲、社会混乱和失恋之间存在推测的因果关系。此外，估计的 DAG 表明，精神分裂症维度会影响精神病理学和射频损伤。结论 研究结果表明，青春期精神分裂症特质、心理健康问题和射频损伤之间存在不同的联系。使用概率 DAG 可以让我们对因果关系的方向做出更可靠的结论，并在研究精神病风险时解开潜在的复杂因果链。
{"title":"Schizotypal Traits, Psychopathology, and Reflective Functioning Impairments During Adolescence: A Bayesian Network Approach","authors":"Eduardo Fonseca-Pedrero, Alicia Pérez-Albéniz, Beatriz Lucas-Molina, Susana Al-Halabí, Martin Debbané","doi":"10.1093/schbul/sbae041","DOIUrl":"https://doi.org/10.1093/schbul/sbae041","url":null,"abstract":"Background New theoretical and measurement models related to Bayesian networks can usefully be implemented to enrich our understanding of psychosis risk. The present study aims to explore, using a directed acyclic graph (DAG), the putative causal relationship within schizotypal facets, as well as between schizotypal dimensions, psychopathology, and reflective functioning (RF) impairments, in a representative sample of non-clinical adolescents. Study Design A sample of 1476 adolescents from the general population participated in a cross-sectional survey. The Oviedo Schizotypy Assessment Questionnaire-Revised, the Strengths and Difficulties Questionnaire, and the Reflective Functioning Questionnaire (RFQ) were used. Study Results Schizotypal traits were positively associated with psychopathology and hypomentalizing. Putative causal relationships are presented between Reality distortion, Social disorganization, and Anhedonia. In addition, estimated DAG suggests that schizotypal dimensions influence psychopathology and RF impairments. Conclusions The findings suggest different pathways connecting schizotypal traits, mental health problems, and RF impairments during adolescence. The use of probabilistic DAG may allow us to make more robust conclusions about the direction of causation and to unravel potentially complex causal chains in the study of psychosis risk.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"19 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonas Hoffmann, Tina Meller, Carlo Maj, Per Hoffmann, Andreas J Forstner, Markus M Nöthen, Igor Nenadić
Objective Schizotypy as a psychosis proneness marker has facilitated the study of schizophrenia spectrum models, linking phenotypic psychosis risk to brain structural and functional variation. However, association studies to structural connectome markers are limited and often do not consider relations to genetic risk. We tested the hypothesis that dimensions of schizotypy (rather than overall phenotype risk burden) are related to fiber tract integrity and that this is moderated by polygenic schizophrenia risk (or resilience). Design In a cohort of 346 psychiatrically healthy subjects, we obtained diffusion tensor imaging, schizotypy using O-LIFE (Oxford-Liverpool Inventory of Feelings and Experiences), and polygenic risk scores (PRS) for schizophrenia risk and resilience to schizophrenia. Using FSL and TBSS (tract-based spatial statistics), we first analyzed the association between O-LIFE and fractional anisotropy (FA) for the anterior thalamic radiation, uncinate fascicle, and cingulum bundle, as well as moderation analyses with PRS scores. Results O-LIFE dimensions were differentially associated with structural connectivity, in particular, negative schizotypy positively to right uncinate FA, positive schizotypy negatively to right cingulum and disorganized schizotypy negatively to left cingulum. In disorganized schizotypy the association was moderated by schizophrenia PRS. Conclusions Our results support a neurobiological continuum model of structural connectivity across psychosis proneness, emphasizing differential association with different schizotypy facets. Genetic schizophrenia risk, however, appears to impact only some of these associations, highlighting the need for further studies to understand the contribution of other genetic and/or environmental factors.
{"title":"Differential Association of Schizotypy Dimensions With Brain Structural Connectivity and Moderation by Schizophrenia Polygenic Risk","authors":"Jonas Hoffmann, Tina Meller, Carlo Maj, Per Hoffmann, Andreas J Forstner, Markus M Nöthen, Igor Nenadić","doi":"10.1093/schbul/sbae160","DOIUrl":"https://doi.org/10.1093/schbul/sbae160","url":null,"abstract":"Objective Schizotypy as a psychosis proneness marker has facilitated the study of schizophrenia spectrum models, linking phenotypic psychosis risk to brain structural and functional variation. However, association studies to structural connectome markers are limited and often do not consider relations to genetic risk. We tested the hypothesis that dimensions of schizotypy (rather than overall phenotype risk burden) are related to fiber tract integrity and that this is moderated by polygenic schizophrenia risk (or resilience). Design In a cohort of 346 psychiatrically healthy subjects, we obtained diffusion tensor imaging, schizotypy using O-LIFE (Oxford-Liverpool Inventory of Feelings and Experiences), and polygenic risk scores (PRS) for schizophrenia risk and resilience to schizophrenia. Using FSL and TBSS (tract-based spatial statistics), we first analyzed the association between O-LIFE and fractional anisotropy (FA) for the anterior thalamic radiation, uncinate fascicle, and cingulum bundle, as well as moderation analyses with PRS scores. Results O-LIFE dimensions were differentially associated with structural connectivity, in particular, negative schizotypy positively to right uncinate FA, positive schizotypy negatively to right cingulum and disorganized schizotypy negatively to left cingulum. In disorganized schizotypy the association was moderated by schizophrenia PRS. Conclusions Our results support a neurobiological continuum model of structural connectivity across psychosis proneness, emphasizing differential association with different schizotypy facets. Genetic schizophrenia risk, however, appears to impact only some of these associations, highlighting the need for further studies to understand the contribution of other genetic and/or environmental factors.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"32 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qian Ren, Tian-xiao Yang, Yi Wang, Simon S Y Lui, Raymond C K Chan
Background and Hypothesis Evidence suggests that emotion regulation is related to schizotypal traits and negative affect in adults. Few studies examined the interplay among these constructs in school-aged children. We examined the complex relationship between schizotypal traits, emotion regulation, and negative affect in children aged 9–12 years. Study Design One-thousand-and-nineteen children completed the Schizotypal Personality Questionnaire—children (SPQ-C), the Depression Anxiety Stress Scales (DASS-21), and the Emotion Regulation Questionnaire for Children and Adolescence (ERQ-CA). Using subscales of these measures as nodes, we estimated a partial correlation network. We estimated a Directed Acyclic Graph to explore the putative directional relationship between schizotypal traits, emotion regulation, and negative affect. Node and bridge centrality indices were estimated. Results We found positive correlations between schizotypal dimensions and negative affect (depressed mood, anxiety, and stress) in the network. Emotion suppression was positively correlated with interpersonal and disorganized schizotypal dimensions, and negative affect. Emotion reappraisal was positively correlated with the cognitive–perceptual dimension and negatively correlated with interpersonal schizotypal traits, depressed mood, and stress. Stress showed higher strength than all nodes except depressed mood, and stress showed the highest expected influence (EI). The Bayesian network revealed that schizotypal traits appeared to be driven by stress. Network comparisons preliminarily showed higher EI for emotion reappraisal in girls’ than boys’ networks, and significant impacts of age and schizotypy levels on network patterns. Conclusion Children with higher levels of schizotypal traits may have more negative affect and suppression. Stress appears to drive schizotypal traits.
{"title":"Relationship Between Schizotypal Traits, Emotion Regulation, and Negative Affect in Children: A Network Analysis","authors":"Qian Ren, Tian-xiao Yang, Yi Wang, Simon S Y Lui, Raymond C K Chan","doi":"10.1093/schbul/sbae172","DOIUrl":"https://doi.org/10.1093/schbul/sbae172","url":null,"abstract":"Background and Hypothesis Evidence suggests that emotion regulation is related to schizotypal traits and negative affect in adults. Few studies examined the interplay among these constructs in school-aged children. We examined the complex relationship between schizotypal traits, emotion regulation, and negative affect in children aged 9–12 years. Study Design One-thousand-and-nineteen children completed the Schizotypal Personality Questionnaire—children (SPQ-C), the Depression Anxiety Stress Scales (DASS-21), and the Emotion Regulation Questionnaire for Children and Adolescence (ERQ-CA). Using subscales of these measures as nodes, we estimated a partial correlation network. We estimated a Directed Acyclic Graph to explore the putative directional relationship between schizotypal traits, emotion regulation, and negative affect. Node and bridge centrality indices were estimated. Results We found positive correlations between schizotypal dimensions and negative affect (depressed mood, anxiety, and stress) in the network. Emotion suppression was positively correlated with interpersonal and disorganized schizotypal dimensions, and negative affect. Emotion reappraisal was positively correlated with the cognitive–perceptual dimension and negatively correlated with interpersonal schizotypal traits, depressed mood, and stress. Stress showed higher strength than all nodes except depressed mood, and stress showed the highest expected influence (EI). The Bayesian network revealed that schizotypal traits appeared to be driven by stress. Network comparisons preliminarily showed higher EI for emotion reappraisal in girls’ than boys’ networks, and significant impacts of age and schizotypy levels on network patterns. Conclusion Children with higher levels of schizotypal traits may have more negative affect and suppression. Stress appears to drive schizotypal traits.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"68 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mélodie Derome, Suje Amir, Elodie Sprüngli-Toffel, George Salaminios, Eduardo FonsecaPedrero, Martin Debbané
Background Alterations of white matter microstructure have been reported in the psychosis spectrum. However, the development of these alterations during preclinical stages remains poorly understood. The framework proposed by schizotypy research as the personality base for liability to develop psychosis spectrum disorders offers 3 interconnected dimensions thought to impact neurodevelopment, affording an opportunity to investigate premorbid risk. Design In this study, 102 typically developing individuals aged between 12 and 20 y.o. at baseline were scanned longitudinally between 1 and 4 times, and schizotypy was assessed at each visit. Ten white matter tracts were reconstructed using TRACULA, and mixed model regression was used to characterize age-related changes in main diffusion parameters (ie, fractional anisotropy [FA]). Estimated longitudinal trajectories of the 3 dimensions of schizotypy were tested for different trajectories of diffusion parameters as a function of age. Results Positive schizotypy trajectory was the most strongly decreased when FA in the anterior thalamic radiation (atr-FA) increased in young adults compared with a moderate decrease in younger participants. Furthermore, in adolescents, disorganized schizotypy followed a steep increase when atr-FA increased, while in the older participants, it decreased as a function of atr-FA. Independent of age, intraindividual positive schizotypy was further longitudinally negatively associated with FA in the cingulate gyrus, and disorganized schizotypy was positively associated with FA in the superior longitudinal fasciculus. Conclusions Given that abnormalities in fronto-thalamo-cingulate subcircuit are present in schizophrenia and converters to psychosis, our results support the hypothesis of schizotypy as a personality base risk to develop psychosis.
{"title":"Longitudinal Associations Between Self-reported Schizotypy Dimensions and White Matter Integrity Development During Adolescence","authors":"Mélodie Derome, Suje Amir, Elodie Sprüngli-Toffel, George Salaminios, Eduardo FonsecaPedrero, Martin Debbané","doi":"10.1093/schbul/sbad147","DOIUrl":"https://doi.org/10.1093/schbul/sbad147","url":null,"abstract":"Background Alterations of white matter microstructure have been reported in the psychosis spectrum. However, the development of these alterations during preclinical stages remains poorly understood. The framework proposed by schizotypy research as the personality base for liability to develop psychosis spectrum disorders offers 3 interconnected dimensions thought to impact neurodevelopment, affording an opportunity to investigate premorbid risk. Design In this study, 102 typically developing individuals aged between 12 and 20 y.o. at baseline were scanned longitudinally between 1 and 4 times, and schizotypy was assessed at each visit. Ten white matter tracts were reconstructed using TRACULA, and mixed model regression was used to characterize age-related changes in main diffusion parameters (ie, fractional anisotropy [FA]). Estimated longitudinal trajectories of the 3 dimensions of schizotypy were tested for different trajectories of diffusion parameters as a function of age. Results Positive schizotypy trajectory was the most strongly decreased when FA in the anterior thalamic radiation (atr-FA) increased in young adults compared with a moderate decrease in younger participants. Furthermore, in adolescents, disorganized schizotypy followed a steep increase when atr-FA increased, while in the older participants, it decreased as a function of atr-FA. Independent of age, intraindividual positive schizotypy was further longitudinally negatively associated with FA in the cingulate gyrus, and disorganized schizotypy was positively associated with FA in the superior longitudinal fasciculus. Conclusions Given that abnormalities in fronto-thalamo-cingulate subcircuit are present in schizophrenia and converters to psychosis, our results support the hypothesis of schizotypy as a personality base risk to develop psychosis.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"12 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tina Meller, Clara Lundberg, Carlo Maj, Per Hoffmann, Andreas J Forstner, Markus M Nöthen, Igor Nenadić
Background and Hypothesis Schizotypy is a well-established phenotype for psychosis proneness and risk. Yet, its genetic underpinnings and relations to genetic bases of the schizophrenia spectrum are not well understood owing to conflicting findings. In a deep phenotyping approach, we hypothesized that genetic markers of risk for and to schizophrenia are differentially associated with (trait-level) dimensions of schizotypy and (state-level) prodromal symptoms. Study Design In 367 (130 male, 237 female) psychiatrically healthy young adults, we assessed multiple schizotypy instruments (OLIFE, SPQ-B, Multidimensional Schizotypy Scales), aggregated into composite scores, and a measure of prodromal symptoms (PQ-16). Those were tested for direct and interactive associations with the polygenic risk score (PRS) for schizophrenia and a novel PRS for resilience to schizophrenia. Study Results Both prodromal symptom number (rho = 0.16, pcorr = .018) and distress (rho = 0.14, pcorr = .027) were positively related to the schizophrenia PRS. Positive schizotypy showed a similar association but did not remain significant after correction (rho = 0.11, pcorr = .082). Schizophrenia PRS and disorganized schizotypy had a negative interactive effect on prodromal symptom distress (b = −0.10, pcorr = .048). The resilience score did not show any significant associations with any of the measures. Conclusions These results further support the idea of a (partially) shared genetic basis of schizophrenia and nonclinical, predominantly positive expressions of the psychosis spectrum but also indicate relevant distinctions between the 2, possibly related to other modulating factors or general (transdiagnostic) psychopathological risk. In line with previous findings, effects seem to be more robust for state- than trait-level markers, but these may also be influencing each other.
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