Background and Hypothesis Disorganized thinking is a prominent feature of schizophrenia that becomes persistent in the presence of treatment resistance. Disruption of the default mode network (DMN), which regulates self-referential thinking, is now a well-established feature of schizophrenia. However, we do not know if DMN disruption affects disorganization and contributes to treatment-resistant schizophrenia (TRS). Study Design This study investigated the DMN in 48 TRS, 76 non-TRS, and 64 healthy controls (HC) using a spatiotemporal approach with resting-state functional magnetic resonance imaging. We recovered DMN as an integrated network using multivariate group independent component analysis and estimated its loading coefficient (reflecting spatial prominence) and Shannon Entropy (reflecting temporal variability). Additionally, voxel-level analyses were conducted to examine network homogeneity and entropy within the DMN. We explored the relationship between DMN measures and disorganization using regression analysis. Results TRS had higher spatial loading on population-level DMN pattern, but lower entropy compared to HC. Non-TRS patients showed intermediate DMN alterations, not significantly differing from either TRS or HC. No voxel-level differences were noted between TRS and non-TRS, emphasizing the continuum between the two groups. DMN's loading coefficient was higher in patients with more severe disorganization. Conclusions TRS may represent the most severe end of a spectrum of spatiotemporal DMN dysfunction in schizophrenia. While excessive spatial contribution of the DMN (high loading coefficient) is specifically associated with disorganization, both excessive spatial contribution and exaggerated temporal stability of DMN are features of schizophrenia that become more pronounced with refractoriness to first-line treatments.
{"title":"Default Mode Network, Disorganization, and Treatment-Resistant Schizophrenia","authors":"Huan Huang, Xuan Qin, Rui Xu, Ying Xiong, Keke Hao, Cheng Chen, Qirong Wan, Hao Liu, Wei Yuan, Yunlong Peng, Yuan Zhou, Huiling Wang, Lena Palaniyappan","doi":"10.1093/schbul/sbaf018","DOIUrl":"https://doi.org/10.1093/schbul/sbaf018","url":null,"abstract":"Background and Hypothesis Disorganized thinking is a prominent feature of schizophrenia that becomes persistent in the presence of treatment resistance. Disruption of the default mode network (DMN), which regulates self-referential thinking, is now a well-established feature of schizophrenia. However, we do not know if DMN disruption affects disorganization and contributes to treatment-resistant schizophrenia (TRS). Study Design This study investigated the DMN in 48 TRS, 76 non-TRS, and 64 healthy controls (HC) using a spatiotemporal approach with resting-state functional magnetic resonance imaging. We recovered DMN as an integrated network using multivariate group independent component analysis and estimated its loading coefficient (reflecting spatial prominence) and Shannon Entropy (reflecting temporal variability). Additionally, voxel-level analyses were conducted to examine network homogeneity and entropy within the DMN. We explored the relationship between DMN measures and disorganization using regression analysis. Results TRS had higher spatial loading on population-level DMN pattern, but lower entropy compared to HC. Non-TRS patients showed intermediate DMN alterations, not significantly differing from either TRS or HC. No voxel-level differences were noted between TRS and non-TRS, emphasizing the continuum between the two groups. DMN's loading coefficient was higher in patients with more severe disorganization. Conclusions TRS may represent the most severe end of a spectrum of spatiotemporal DMN dysfunction in schizophrenia. While excessive spatial contribution of the DMN (high loading coefficient) is specifically associated with disorganization, both excessive spatial contribution and exaggerated temporal stability of DMN are features of schizophrenia that become more pronounced with refractoriness to first-line treatments.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"67 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546202","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}
Jun-yan Ye, Xiao-jing Qin, Ji-fang Cui, Jia-li Liu, Hai-song Shi, Tian-xiao Yang, Ya Wang, Raymond C K Chan
Background and Hypothesis Mental time travel (MTT) is a crucial ability for daily life. Personal goal-related MTT events has stronger phenomenological characteristics than personal goal-unrelated ones, ie, the “personal goal-advantage effect”. However, it remains unclear whether this effect is impacted in individuals with high schizotypal traits (HST) and the neural correlates of this effect have yet to be elucidated. The present study aimed to fill these knowledge gaps. We hypothesized that HST would show a reduced “personal goal-advantage effect” in MTT and would exhibit altered relationships with resting-state functional connectivity. Study Design In Study 1, 37 HST and 40 individuals with low schizotypal traits (LST) were recruited. Participants generated MTT events with personal goal-related and personal goal-unrelated cues. In Study 2, 39 HST and 38 LST were recruited, they completed the same behavioral task and resting-state functional magnetic resonance imaging (fMRI) scanning. Study Results Both Study 1 and Study 2 revealed that HST exhibited reduced “personal goal-advantage effect” on MTT specificity. Moreover, Study 2 showed that compared with LST, HST exhibited altered association between the “personal goal-advantage effect” and functional connectivity (ie, between the right precuneus and the left postcentral gyrus and “personal goal-advantage effect” on emotional valence, between the left hippocampus and the right temporal fusiform gyrus and “personal goal-advantage effect” on emotional intensity). Conclusions These findings suggest that HST exhibit a reduced “personal goal-advantage effect” in MTT specificity and altered neural correlates related to this effect. The “personal goal-advantage effect” may be a potential target for intervention in HST.
{"title":"Personal Goal-Related Mental Time Travel and Its Association With Resting-State Functional Connectivity in Individuals With High Schizotypal Traits","authors":"Jun-yan Ye, Xiao-jing Qin, Ji-fang Cui, Jia-li Liu, Hai-song Shi, Tian-xiao Yang, Ya Wang, Raymond C K Chan","doi":"10.1093/schbul/sbad183","DOIUrl":"https://doi.org/10.1093/schbul/sbad183","url":null,"abstract":"Background and Hypothesis Mental time travel (MTT) is a crucial ability for daily life. Personal goal-related MTT events has stronger phenomenological characteristics than personal goal-unrelated ones, ie, the “personal goal-advantage effect”. However, it remains unclear whether this effect is impacted in individuals with high schizotypal traits (HST) and the neural correlates of this effect have yet to be elucidated. The present study aimed to fill these knowledge gaps. We hypothesized that HST would show a reduced “personal goal-advantage effect” in MTT and would exhibit altered relationships with resting-state functional connectivity. Study Design In Study 1, 37 HST and 40 individuals with low schizotypal traits (LST) were recruited. Participants generated MTT events with personal goal-related and personal goal-unrelated cues. In Study 2, 39 HST and 38 LST were recruited, they completed the same behavioral task and resting-state functional magnetic resonance imaging (fMRI) scanning. Study Results Both Study 1 and Study 2 revealed that HST exhibited reduced “personal goal-advantage effect” on MTT specificity. Moreover, Study 2 showed that compared with LST, HST exhibited altered association between the “personal goal-advantage effect” and functional connectivity (ie, between the right precuneus and the left postcentral gyrus and “personal goal-advantage effect” on emotional valence, between the left hippocampus and the right temporal fusiform gyrus and “personal goal-advantage effect” on emotional intensity). Conclusions These findings suggest that HST exhibit a reduced “personal goal-advantage effect” in MTT specificity and altered neural correlates related to this effect. The “personal goal-advantage effect” may be a potential target for intervention in HST.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"24 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546198","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}
Emsal Llapashtica, John L Barbur, Corinna Haenschel
Background and Hypothesis Visual impairments have been proposed as risk factors for psychotic symptoms and illnesses. Visual impairments can considerably impact people’s daily lives, but little is known about the impact and diagnostic sensitivity of such abnormalities for schizotypal personality traits. This study aims to explore possible relationships between schizotypy and visual acuity (VA), contrast sensitivity, and parameters that describe eye movements and visual processing times. Study Design Schizotypy was assessed in 37 participants with the Multidimensional Schizotypy Scale-Brief (MSS-B). For the visual function measures, we used the Acuity-Plus test and the new Eye Movement and Integrated Saccade Latency (EMAIL) test. The latter measures oculomotor performance during an eye movement task, including the visual processing time at the end of each saccade. Study Results The disorganized dimension of the schizotypy scores predicted VA when measured with black optotypes. Additionally, we found that participants who had higher disorganized scores showed an increased response variability, as assessed through the goodness of fit measure from the EMAIL test. Conclusions These results from this exploratory study extend upon earlier findings from both general and patient samples, highlighting the clinical and subclinical importance of understanding how spatial vision can be affected in people with schizotypal disorganized behavior.
{"title":"Reduced Visual Function in Schizotypal Traits: An Exploratory Study","authors":"Emsal Llapashtica, John L Barbur, Corinna Haenschel","doi":"10.1093/schbul/sbae049","DOIUrl":"https://doi.org/10.1093/schbul/sbae049","url":null,"abstract":"Background and Hypothesis Visual impairments have been proposed as risk factors for psychotic symptoms and illnesses. Visual impairments can considerably impact people’s daily lives, but little is known about the impact and diagnostic sensitivity of such abnormalities for schizotypal personality traits. This study aims to explore possible relationships between schizotypy and visual acuity (VA), contrast sensitivity, and parameters that describe eye movements and visual processing times. Study Design Schizotypy was assessed in 37 participants with the Multidimensional Schizotypy Scale-Brief (MSS-B). For the visual function measures, we used the Acuity-Plus test and the new Eye Movement and Integrated Saccade Latency (EMAIL) test. The latter measures oculomotor performance during an eye movement task, including the visual processing time at the end of each saccade. Study Results The disorganized dimension of the schizotypy scores predicted VA when measured with black optotypes. Additionally, we found that participants who had higher disorganized scores showed an increased response variability, as assessed through the goodness of fit measure from the EMAIL test. Conclusions These results from this exploratory study extend upon earlier findings from both general and patient samples, highlighting the clinical and subclinical importance of understanding how spatial vision can be affected in people with schizotypal disorganized behavior.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"28 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546277","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}
Ding-ding Hu, Xiao-dong Guo, Simon S Y Lui, Yi Wang, Raymond C K Chan
Background and Hypothesis Previous studies on Empathic Accuracy Task (EAT) suggested patients with schizophrenia exhibited altered brain activations in the precuneus, middle frontal gyrus, and thalamus. However, it remains unclear whether individuals with schizotypy would exhibit similar alterations of brain activations associated with EAT. This study aimed to examine the relationships between schizotypy and intersubject correlation (ISC) during EAT. Study Design Forty-seven college students undertook the Chinese version of EAT in a 3T MRI scanner. The Chapman Social Anhedonia Scale (CSAS) and Perceptual Aberration Scale (PAS) were used to capture negative and positive schizotypy, respectively. We adopted GLM analysis, ISC analyses of brain activation, and dynamic functional connectivity during EAT to examine its association with dimensional schizotypy and self-report empathy. Study Results Regardless of schizotypy scores, brain activations in the middle occipital cortex, precuneus, lingual gyrus, paracentral gyrus, and anterior cingulate cortex (ACC) were associated with participants’ empathic accuracy, while strong ISC of brain activations were found in bilateral superior temporal gyri (STG). Negative schizotypy was associated with ISC of brain activation in the precentral gyrus and dynamic connectivity between the STG and ACC, both of which further mediated the associations between negative schizotypy and self-report affective empathy. Conclusions These preliminary findings suggest that weaker intersubject synchronization of brain activation in the precentral gyrus and dynamic connectivity between the STG and ACC is related to negative schizotypy. Our findings may shed light on the underlying neural mechanisms of impaired social cognition in patients with schizophrenia spectrum disorder.
{"title":"Negative Schizotypy Associated With Weaker Intersubject Correlation in Dynamic Functional Connectivity During Empathic Accuracy Task","authors":"Ding-ding Hu, Xiao-dong Guo, Simon S Y Lui, Yi Wang, Raymond C K Chan","doi":"10.1093/schbul/sbad182","DOIUrl":"https://doi.org/10.1093/schbul/sbad182","url":null,"abstract":"Background and Hypothesis Previous studies on Empathic Accuracy Task (EAT) suggested patients with schizophrenia exhibited altered brain activations in the precuneus, middle frontal gyrus, and thalamus. However, it remains unclear whether individuals with schizotypy would exhibit similar alterations of brain activations associated with EAT. This study aimed to examine the relationships between schizotypy and intersubject correlation (ISC) during EAT. Study Design Forty-seven college students undertook the Chinese version of EAT in a 3T MRI scanner. The Chapman Social Anhedonia Scale (CSAS) and Perceptual Aberration Scale (PAS) were used to capture negative and positive schizotypy, respectively. We adopted GLM analysis, ISC analyses of brain activation, and dynamic functional connectivity during EAT to examine its association with dimensional schizotypy and self-report empathy. Study Results Regardless of schizotypy scores, brain activations in the middle occipital cortex, precuneus, lingual gyrus, paracentral gyrus, and anterior cingulate cortex (ACC) were associated with participants’ empathic accuracy, while strong ISC of brain activations were found in bilateral superior temporal gyri (STG). Negative schizotypy was associated with ISC of brain activation in the precentral gyrus and dynamic connectivity between the STG and ACC, both of which further mediated the associations between negative schizotypy and self-report affective empathy. Conclusions These preliminary findings suggest that weaker intersubject synchronization of brain activation in the precentral gyrus and dynamic connectivity between the STG and ACC is related to negative schizotypy. Our findings may shed light on the underlying neural mechanisms of impaired social cognition in patients with schizophrenia spectrum disorder.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"3 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546272","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 Many patients with psychiatric disorders show increased temporal discounting (TD), ie, they discount future rewards more steeply than healthy controls. However, findings for schizophrenia and schizotypy, a personality constellation considered to be on the schizophrenia spectcrum, are less clear. Moreover, the role of future time representation in TD in the schizophrenia spectrum has not been examined. We hypothesized positive associations between schizotypal personality traits and TD and reduced TD when the timepoint of future rewards is represented in dates rather than delay units (the date/delay effect). Further, we explored associations between schizotypy and the magnitude of the date/delay effect. Study Design We conducted a large-scale, general-population online study (N = 1000) assessing TD with the Monetary Choice Questionnaire (MCQ) and schizotypal traits with the Short Oxford-Liverpool Inventory of Feelings and Experiences (sO-LIFE). Time representation in the MCQ (dates vs delays) was manipulated within subject. Study Results Associations between TD and sO-LIFE subscales were not significant after Bonferroni correction (all r ≤ .06). The date/delay effect was successfully replicated (P < .001, gav = 0.22). Interestingly, higher values in the sO-LIFE Unusual Experiences subscale predicted the magnitude of the date/delay effect when controlling for influences of other sO-LIFE subscales, age, education, and drug use. Conclusions TD was not associated with schizotypy, but individuals with higher levels of positive schizotypy were more sensitive to manipulations of the representation of future timepoints. Future studies should focus on these processes as potential mechanisms in the development and treatment of cognitive-perceptual deficits in the schizophrenia spectrum.
{"title":"The Relationship Between Schizotypal Personality Traits and Temporal Discounting: The Role of the Date/Delay Effect","authors":"Kristof Keidel, Carsten Murawski, Christos Pantelis, Ulrich Ettinger","doi":"10.1093/schbul/sbad110","DOIUrl":"https://doi.org/10.1093/schbul/sbad110","url":null,"abstract":"Background and Hypothesis Many patients with psychiatric disorders show increased temporal discounting (TD), ie, they discount future rewards more steeply than healthy controls. However, findings for schizophrenia and schizotypy, a personality constellation considered to be on the schizophrenia spectcrum, are less clear. Moreover, the role of future time representation in TD in the schizophrenia spectrum has not been examined. We hypothesized positive associations between schizotypal personality traits and TD and reduced TD when the timepoint of future rewards is represented in dates rather than delay units (the date/delay effect). Further, we explored associations between schizotypy and the magnitude of the date/delay effect. Study Design We conducted a large-scale, general-population online study (N = 1000) assessing TD with the Monetary Choice Questionnaire (MCQ) and schizotypal traits with the Short Oxford-Liverpool Inventory of Feelings and Experiences (sO-LIFE). Time representation in the MCQ (dates vs delays) was manipulated within subject. Study Results Associations between TD and sO-LIFE subscales were not significant after Bonferroni correction (all r ≤ .06). The date/delay effect was successfully replicated (P &lt; .001, gav = 0.22). Interestingly, higher values in the sO-LIFE Unusual Experiences subscale predicted the magnitude of the date/delay effect when controlling for influences of other sO-LIFE subscales, age, education, and drug use. Conclusions TD was not associated with schizotypy, but individuals with higher levels of positive schizotypy were more sensitive to manipulations of the representation of future timepoints. Future studies should focus on these processes as potential mechanisms in the development and treatment of cognitive-perceptual deficits in the schizophrenia spectrum.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"1 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546204","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}
Neus Barrantes-Vidal, Pilar Torrecilla, Patricia Mas-Bermejo, Sergi Papiol, Marian J Bakermans-Kranenburg, Araceli Rosa, Thomas R Kwapil
Background and Hypothesis Consistent with diathesis-stress models, psychosis research has focused on genetic moderation of adverse environmental exposures. In contrast, the Differential Susceptibility (DS) model suggests that the same genetic variants that increase risk-inducing effects of adverse experiences also enhance beneficial effects from positive experiences. This study examined whether individuals with high genetic susceptibility to the environment showed differential psychotic-like and affective reactivity in response to positive and negative events in daily life. Study Design Experience sampling methodology assessed context (positive and stressful) and momentary levels of paranoia, psychotic-like experiences (PLE), and positive (PA) and negative affect (NA) in 217 non-clinical adults oversampled for schizotypy. Linear mixed models examined whether Polygenic Risk Scores of Environmental Sensitivity (PRS-ES) moderated the impact of current context on subsequent experiences. Study Results PRS-ES moderated positive, but not stressful, context on subsequent levels of momentary paranoia, NA, and PA, but not PLE. Genetic and environmental (G × E) interactions indicated diathesis-stress at lower thresholds of PRS-ES, but a DS model at the highest threshold of the PRS-ES. Participants with elevated PRS-ES showed increased paranoia and NA and decreased PA in subsequent assessments when reporting low levels of positive situations, but also decreased paranoia and NA and increased PA when rating contexts as positive. Conclusions Findings support the influence of genetic sensitivity to the environment on psychotic-like and affective reactivity in daily life, particularly in response to positive contexts. This highlights the transdiagnostic protective role of positive experiences and informs ecological momentary interventions.
{"title":"Genetic Differences in Reactivity to the Environment Impact Psychotic-Like and Affective Reactivity in Daily Life","authors":"Neus Barrantes-Vidal, Pilar Torrecilla, Patricia Mas-Bermejo, Sergi Papiol, Marian J Bakermans-Kranenburg, Araceli Rosa, Thomas R Kwapil","doi":"10.1093/schbul/sbad162","DOIUrl":"https://doi.org/10.1093/schbul/sbad162","url":null,"abstract":"Background and Hypothesis Consistent with diathesis-stress models, psychosis research has focused on genetic moderation of adverse environmental exposures. In contrast, the Differential Susceptibility (DS) model suggests that the same genetic variants that increase risk-inducing effects of adverse experiences also enhance beneficial effects from positive experiences. This study examined whether individuals with high genetic susceptibility to the environment showed differential psychotic-like and affective reactivity in response to positive and negative events in daily life. Study Design Experience sampling methodology assessed context (positive and stressful) and momentary levels of paranoia, psychotic-like experiences (PLE), and positive (PA) and negative affect (NA) in 217 non-clinical adults oversampled for schizotypy. Linear mixed models examined whether Polygenic Risk Scores of Environmental Sensitivity (PRS-ES) moderated the impact of current context on subsequent experiences. Study Results PRS-ES moderated positive, but not stressful, context on subsequent levels of momentary paranoia, NA, and PA, but not PLE. Genetic and environmental (G × E) interactions indicated diathesis-stress at lower thresholds of PRS-ES, but a DS model at the highest threshold of the PRS-ES. Participants with elevated PRS-ES showed increased paranoia and NA and decreased PA in subsequent assessments when reporting low levels of positive situations, but also decreased paranoia and NA and increased PA when rating contexts as positive. Conclusions Findings support the influence of genetic sensitivity to the environment on psychotic-like and affective reactivity in daily life, particularly in response to positive contexts. This highlights the transdiagnostic protective role of positive experiences and informs ecological momentary interventions.","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":"143546278","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 Although the psychometric high-risk method based on schizotypy has proven to be a highly cost-effective strategy for unraveling etiological factors for schizophrenia-spectrum disorders, there is a paucity of longitudinal studies with nonclinical populations. This study analyzed the predictive validity of positive and negative schizotypy in a longitudinal project (Barcelona Longitudinal Investigation of Schizotypy; BLISS) spanning a total of 7.8 years. Study Design At Time 1 (T1), 547 college students completed the Wisconsin Schizotypy Scales. We re-assessed subsamples (oversampled for high schizotypy to ensure variability) at 4 re-assessments. This study reports psychopathology, psychological, and functional outcomes assessed with self-report and interview (CAARMS, Negative Symptom Manual, SCID-II Cluster A) measures at T4 (n = 89; 4.4 years after T1) and self-report measures at T5 (n = 169; 7.8 years after T1). T1 positive and negative schizotypy were entered simultaneously as predictors in linear regression models. Study Results Positive schizotypy predicted positive symptoms at T4, whereas negative schizotypy predicted interview-rated negative symptoms and schizoid personality traits (even when controlling for mood and avoidant personality), and impaired social and global functioning. Both dimensions predicted suspiciousness, and schizotypal and paranoid personality traits, as well as low self-esteem and depression. Similarly, both dimensions predicted suspiciousness, depression, and poor social support at T5, whereas only positive schizotypy predicted low self-esteem, anxiety, and perceived stress. Conclusions Both schizotypy dimensions consistently showed a meaningful pattern of hypothesized differential and overlapping predictions, which supports their validity as distinct dimensions and their predictive validity in nonclinical samples.
{"title":"Predictive Validity of Psychometrically Assessed Schizotypy for Psychopathology Dimensions and Functioning in an 8-Year Multiwave Study","authors":"Neus Barrantes-Vidal, Thomas R Kwapil","doi":"10.1093/schbul/sbae140","DOIUrl":"https://doi.org/10.1093/schbul/sbae140","url":null,"abstract":"Background and Hypothesis Although the psychometric high-risk method based on schizotypy has proven to be a highly cost-effective strategy for unraveling etiological factors for schizophrenia-spectrum disorders, there is a paucity of longitudinal studies with nonclinical populations. This study analyzed the predictive validity of positive and negative schizotypy in a longitudinal project (Barcelona Longitudinal Investigation of Schizotypy; BLISS) spanning a total of 7.8 years. Study Design At Time 1 (T1), 547 college students completed the Wisconsin Schizotypy Scales. We re-assessed subsamples (oversampled for high schizotypy to ensure variability) at 4 re-assessments. This study reports psychopathology, psychological, and functional outcomes assessed with self-report and interview (CAARMS, Negative Symptom Manual, SCID-II Cluster A) measures at T4 (n = 89; 4.4 years after T1) and self-report measures at T5 (n = 169; 7.8 years after T1). T1 positive and negative schizotypy were entered simultaneously as predictors in linear regression models. Study Results Positive schizotypy predicted positive symptoms at T4, whereas negative schizotypy predicted interview-rated negative symptoms and schizoid personality traits (even when controlling for mood and avoidant personality), and impaired social and global functioning. Both dimensions predicted suspiciousness, and schizotypal and paranoid personality traits, as well as low self-esteem and depression. Similarly, both dimensions predicted suspiciousness, depression, and poor social support at T5, whereas only positive schizotypy predicted low self-esteem, anxiety, and perceived stress. Conclusions Both schizotypy dimensions consistently showed a meaningful pattern of hypothesized differential and overlapping predictions, which supports their validity as distinct dimensions and their predictive validity in nonclinical samples.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"10 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546192","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}
Igor Nenadić, Johannes Mosebach, Simon Schmitt, Tina Meller, Frederike Stein, Katharina Brosch, Kai Ringwald, Julia-Katharina Pfarr, Susanne Meinert, Hannah Lemke, Lena Waltemate, Katharina Thiel, Nils Opel, Jonathan Repple, Dominik Grotegerd, Olaf Steinsträter, Jens Sommer, Tim Hahn, Andreas Jansen, Udo Dannlowski, Axel Krug, Tilo Kircher
Background and Hypothesis Schizotypy is a risk phenotype for the psychosis spectrum and pilot studies suggest a biological continuum underlying this phenotype across health and disease. It is unclear whether this biological continuum might include brain structural associations in networks altered in schizophrenia spectrum disorders, such as the fronto-thalamo-striatal system or nodes of the default mode network, such as the precuneus. Study Design In this study, we analyze a large multi-center cohort of 673 nonclinical subjects phenotyped for schizotypal traits (using the Schizotypal Personality Questionnaire-Brief version) using tract-based spatial statistics of diffusion tensor imaging data, as well as voxel-based morphometry (VBM) analysis of regional brain volumes and gyrification analysis of early neurodevelopmental markers of cortical folding on T1-weighted MRI. Study Results We identify significant (P < .05 family-wise error corrected) associations of schizotypy with major fiber tract fractional anisotropy: positive (cognitive-perceptual) schizotypy correlated negatively with the left anterior thalamic radiation (a principal thalamo-frontal projection), left uncinate fasciculus and cingulum, while negative (interpersonal) schizotypy correlated positively with left anterior thalamic radiation, cingulum, and the anterior corpus callosum, and disorganized schizotypy correlated negatively with right cingulum, and superior and inferior longitudinal fasciculi. VBM analyses showed a negative correlation of gray matter with negative schizotypy in the left cerebellum, while gyrification in the inferior parietal cortex correlated positively with negative (interpersonal) schizotypy. Conclusions These findings pave the way for a neural network conceptualization of schizotypy as a psychosis proneness trait across the general population, showing associations with fronto-subcortical and frontotemporal systems as structural substrates of this risk phenotype.
{"title":"Fronto-Thalamic Structural Connectivity Associated With Schizotypy, a Psychosis Risk Phenotype, in Nonclinical Subjects","authors":"Igor Nenadić, Johannes Mosebach, Simon Schmitt, Tina Meller, Frederike Stein, Katharina Brosch, Kai Ringwald, Julia-Katharina Pfarr, Susanne Meinert, Hannah Lemke, Lena Waltemate, Katharina Thiel, Nils Opel, Jonathan Repple, Dominik Grotegerd, Olaf Steinsträter, Jens Sommer, Tim Hahn, Andreas Jansen, Udo Dannlowski, Axel Krug, Tilo Kircher","doi":"10.1093/schbul/sbad143","DOIUrl":"https://doi.org/10.1093/schbul/sbad143","url":null,"abstract":"Background and Hypothesis Schizotypy is a risk phenotype for the psychosis spectrum and pilot studies suggest a biological continuum underlying this phenotype across health and disease. It is unclear whether this biological continuum might include brain structural associations in networks altered in schizophrenia spectrum disorders, such as the fronto-thalamo-striatal system or nodes of the default mode network, such as the precuneus. Study Design In this study, we analyze a large multi-center cohort of 673 nonclinical subjects phenotyped for schizotypal traits (using the Schizotypal Personality Questionnaire-Brief version) using tract-based spatial statistics of diffusion tensor imaging data, as well as voxel-based morphometry (VBM) analysis of regional brain volumes and gyrification analysis of early neurodevelopmental markers of cortical folding on T1-weighted MRI. Study Results We identify significant (P &lt; .05 family-wise error corrected) associations of schizotypy with major fiber tract fractional anisotropy: positive (cognitive-perceptual) schizotypy correlated negatively with the left anterior thalamic radiation (a principal thalamo-frontal projection), left uncinate fasciculus and cingulum, while negative (interpersonal) schizotypy correlated positively with left anterior thalamic radiation, cingulum, and the anterior corpus callosum, and disorganized schizotypy correlated negatively with right cingulum, and superior and inferior longitudinal fasciculi. VBM analyses showed a negative correlation of gray matter with negative schizotypy in the left cerebellum, while gyrification in the inferior parietal cortex correlated positively with negative (interpersonal) schizotypy. Conclusions These findings pave the way for a neural network conceptualization of schizotypy as a psychosis proneness trait across the general population, showing associations with fronto-subcortical and frontotemporal systems as structural substrates of this risk phenotype.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"10 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546274","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}
Ling-ling Wang, Gai-ying Li, Chao Yan, Yi Wang, Yan Gao, Ya Wang, Simon S Y Lui, Jian-Qi Li, Raymond C K Chan
Background and Hypothesis Social anhedonia is a core feature of schizotypy and correlates significantly with social functioning and range adaptation. Range adaptation refers to representing a stimulus value based on its relative position in the range of pre-experienced values. This study aimed to examine the resting-state neural correlates of range adaptation and its associations with social anhedonia and social functioning. Study Design In study 1, 60 participants completed resting-state magnetic resonance spectroscopy and fMRI scans. Range adaptation was assessed by a valid effort-based decision-making paradigm. Self-reported questionnaires was used to measure social anhedonia and social functioning. Study 2 utilized 26 pairs of participants with high (HSoA) and low levels of social anhedonia (LSoA) to examine the group difference in range adaptation’s neural correlates and its relationship with social anhedonia and social functioning. An independent sample of 40 pairs of HSoA and LSoA was used to verify the findings. Study Results Study 1 showed that range adaptation correlated with excitation–inhibition balance (EIB) and ventral prefrontal cortex (vPFC) functional connectivity, which in turn correlating positively with social functioning. Range adaptation was specifically determined by the EIB via mediation of ventral-medial prefrontal cortex functional connectivities. Study 2 found HSoA and LSoA participants exhibiting comparable EIB and vPFC connectivities. However, EIB and vPFC connectivities were negatively correlated with social anhedonia and social functioning in HSoA participants. Conclusions EIB and vPFC functional connectivity is putative neural correlates for range adaptation. Such neural correlates are associated with social anhedonia and social functioning.
{"title":"The Relationship Among Range Adaptation, Social Anhedonia, and Social Functioning: A Combined Magnetic Resonance Spectroscopy and Resting-State fMRI Study","authors":"Ling-ling Wang, Gai-ying Li, Chao Yan, Yi Wang, Yan Gao, Ya Wang, Simon S Y Lui, Jian-Qi Li, Raymond C K Chan","doi":"10.1093/schbul/sbad116","DOIUrl":"https://doi.org/10.1093/schbul/sbad116","url":null,"abstract":"Background and Hypothesis Social anhedonia is a core feature of schizotypy and correlates significantly with social functioning and range adaptation. Range adaptation refers to representing a stimulus value based on its relative position in the range of pre-experienced values. This study aimed to examine the resting-state neural correlates of range adaptation and its associations with social anhedonia and social functioning. Study Design In study 1, 60 participants completed resting-state magnetic resonance spectroscopy and fMRI scans. Range adaptation was assessed by a valid effort-based decision-making paradigm. Self-reported questionnaires was used to measure social anhedonia and social functioning. Study 2 utilized 26 pairs of participants with high (HSoA) and low levels of social anhedonia (LSoA) to examine the group difference in range adaptation’s neural correlates and its relationship with social anhedonia and social functioning. An independent sample of 40 pairs of HSoA and LSoA was used to verify the findings. Study Results Study 1 showed that range adaptation correlated with excitation–inhibition balance (EIB) and ventral prefrontal cortex (vPFC) functional connectivity, which in turn correlating positively with social functioning. Range adaptation was specifically determined by the EIB via mediation of ventral-medial prefrontal cortex functional connectivities. Study 2 found HSoA and LSoA participants exhibiting comparable EIB and vPFC connectivities. However, EIB and vPFC connectivities were negatively correlated with social anhedonia and social functioning in HSoA participants. Conclusions EIB and vPFC functional connectivity is putative neural correlates for range adaptation. Such neural correlates are associated with social anhedonia and social functioning.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"58 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546275","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}
Igor Nenadić, Jonas Hoffmann, Andrea Federspiel, Sebastian Walther, Ahmad Abu-Akel, Andreas Jansen, Tina Meller
Background and Hypothesis Schizotypy can be utilized as a phenotypic risk marker for schizophrenia and its spectrum and might relate to putative dimensional biological markers of the psychosis spectrum. Among these are amygdala function and structure, which are impaired in schizophrenia, but possibly also correlated with subclinical expression of schizotypy in nonclinical samples. We tested whether different parameters relating to amygdala function would be different in healthy subjects with relatively higher vs lower schizotypy traits. Study Design Sixty-three psychiatrically healthy subjects (42 with higher vs 21 with lower schizotypy scores, selected on the basis of the Oxford-Liverpool Inventory of Feelings and Experiences positive schizotypy subscale) underwent a multimodal imaging protocol, including functional magnetic resonance imaging (fMRI) during a task-based emotional (fearful) face recognition paradigm, arterial spin labeling for measurement of regional cerebral blood flow (rCBF) at rest, and resting-state fMRI for functional connectivity (FC) analyses, as well as a T1-weighted structural MRI scan. Study Results The high schizotypy group showed significantly higher right amygdala activation during viewing of fearful emotional images and lower resting-state FC of the left amygdala with a cerebellum cluster, but no differences in resting-state amygdala rCBF or volume. Conclusions Our findings demonstrate a functionally relevant effect of schizotypy on amygdala activation in the absence of baseline rCBF or macroscopic structure. This suggests that while schizotypy might affect some functional or structural parameters in the brain, certain functionally relevant effects only emerge during cognitive or emotional triggers.
{"title":"Amygdala Function, Blood Flow, and Functional Connectivity in Nonclinical Schizotypy","authors":"Igor Nenadić, Jonas Hoffmann, Andrea Federspiel, Sebastian Walther, Ahmad Abu-Akel, Andreas Jansen, Tina Meller","doi":"10.1093/schbul/sbae171","DOIUrl":"https://doi.org/10.1093/schbul/sbae171","url":null,"abstract":"Background and Hypothesis Schizotypy can be utilized as a phenotypic risk marker for schizophrenia and its spectrum and might relate to putative dimensional biological markers of the psychosis spectrum. Among these are amygdala function and structure, which are impaired in schizophrenia, but possibly also correlated with subclinical expression of schizotypy in nonclinical samples. We tested whether different parameters relating to amygdala function would be different in healthy subjects with relatively higher vs lower schizotypy traits. Study Design Sixty-three psychiatrically healthy subjects (42 with higher vs 21 with lower schizotypy scores, selected on the basis of the Oxford-Liverpool Inventory of Feelings and Experiences positive schizotypy subscale) underwent a multimodal imaging protocol, including functional magnetic resonance imaging (fMRI) during a task-based emotional (fearful) face recognition paradigm, arterial spin labeling for measurement of regional cerebral blood flow (rCBF) at rest, and resting-state fMRI for functional connectivity (FC) analyses, as well as a T1-weighted structural MRI scan. Study Results The high schizotypy group showed significantly higher right amygdala activation during viewing of fearful emotional images and lower resting-state FC of the left amygdala with a cerebellum cluster, but no differences in resting-state amygdala rCBF or volume. Conclusions Our findings demonstrate a functionally relevant effect of schizotypy on amygdala activation in the absence of baseline rCBF or macroscopic structure. This suggests that while schizotypy might affect some functional or structural parameters in the brain, certain functionally relevant effects only emerge during cognitive or emotional triggers.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"6 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546203","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}
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