Anneliese E Spiteri-Staines, Alison R Yung, Ashleigh Lin, Jessica A Hartmann, Paul Amminger, Patrick D McGorry, Andrew Thompson, Stephen J Wood, Barnaby Nelson
{"title":"Non-psychotic Outcomes in Young People at Ultra-High Risk of Developing a Psychotic Disorder: A Long-Term Follow-up Study.","authors":"Anneliese E Spiteri-Staines, Alison R Yung, Ashleigh Lin, Jessica A Hartmann, Paul Amminger, Patrick D McGorry, Andrew Thompson, Stephen J Wood, Barnaby Nelson","doi":"10.1093/schbul/sbae005","DOIUrl":"10.1093/schbul/sbae005","url":null,"abstract":"<p><strong>Background: </strong>The majority of individuals at ultra-high risk (UHR) for psychosis do not transition to a full threshold psychotic disorder. It is therefore important to understand their longer-term clinical and functional outcomes, particularly given the high prevalence of comorbid mental disorders in this population at baseline.</p><p><strong>Aims: </strong>This study investigated the prevalence of non-psychotic disorders in the UHR population at entry and long-term follow-up and their association with functional outcomes. Persistence of UHR status was also investigated.</p><p><strong>Study design: </strong>The sample comprised 102 UHR young people from the Personal Assessment and Crisis Evaluation (PACE) Clinic who had not transitioned to psychosis by long-term follow-up (mean = 8.8 years, range = 6.8-12.1 years since baseline).</p><p><strong>Results: </strong>Eighty-eight percent of participants at baseline were diagnosed with at least one mental disorder, the majority of which were mood disorders (78%), anxiety disorders (35%), and substance use disorders (SUDs) (18%). This pattern of disorder prevalence continued at follow-up, though prevalence was reduced, with 52% not meeting criteria for current non-psychotic mental disorder. However, 35% of participants developed a new non-psychotic mental disorder by follow-up. Presence of a continuous non-psychotic mental disorder was associated with poorer functional outcomes at follow-up. 28% of participants still met UHR criteria at follow-up.</p><p><strong>Conclusions: </strong>The study adds to the evidence base that a substantial proportion of UHR individuals who do not transition to psychosis experience persistent attenuated psychotic symptoms and persistent and incident non-psychotic disorders over the long term. Long-term treatment and re-entry into services is indicated.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747346","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}
Anthony J Deo, Victor M Castro, Ashley Baker, Devon Carroll, Joseph Gonzalez-Heydrich, David C Henderson, Daphne J Holt, Kimberly Hook, Rakesh Karmacharya, Joshua L Roffman, Emily M Madsen, Eugene Song, William G Adams, Luisa Camacho, Sarah Gasman, Jada S Gibbs, Rebecca G Fortgang, Chris J Kennedy, Galina Lozinski, Daisy C Perez, Marina Wilson, Ben Y Reis, Jordan W Smoller
{"title":"Validation of an ICD-Code-Based Case Definition for Psychotic Illness Across Three Health Systems.","authors":"Anthony J Deo, Victor M Castro, Ashley Baker, Devon Carroll, Joseph Gonzalez-Heydrich, David C Henderson, Daphne J Holt, Kimberly Hook, Rakesh Karmacharya, Joshua L Roffman, Emily M Madsen, Eugene Song, William G Adams, Luisa Camacho, Sarah Gasman, Jada S Gibbs, Rebecca G Fortgang, Chris J Kennedy, Galina Lozinski, Daisy C Perez, Marina Wilson, Ben Y Reis, Jordan W Smoller","doi":"10.1093/schbul/sbae064","DOIUrl":"10.1093/schbul/sbae064","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Psychosis-associated diagnostic codes are increasingly being utilized as case definitions for electronic health record (EHR)-based algorithms to predict and detect psychosis. However, data on the validity of psychosis-related diagnostic codes is limited. We evaluated the positive predictive value (PPV) of International Classification of Diseases (ICD) codes for psychosis.</p><p><strong>Study design: </strong>Using EHRs at 3 health systems, ICD codes comprising primary psychotic disorders and mood disorders with psychosis were grouped into 5 higher-order groups. 1133 records were sampled for chart review using the full EHR. PPVs (the probability of chart-confirmed psychosis given ICD psychosis codes) were calculated across multiple treatment settings.</p><p><strong>Study results: </strong>PPVs across all diagnostic groups and hospital systems exceeded 70%: Mass General Brigham 0.72 [95% CI 0.68-0.77], Boston Children's Hospital 0.80 [0.75-0.84], and Boston Medical Center 0.83 [0.79-0.86]. Schizoaffective disorder PPVs were consistently the highest across sites (0.80-0.92) and major depressive disorder with psychosis were the most variable (0.57-0.79). To determine if the first documented code captured first-episode psychosis (FEP), we excluded cases with prior chart evidence of a diagnosis of or treatment for a psychotic illness, yielding substantially lower PPVs (0.08-0.62).</p><p><strong>Conclusions: </strong>We found that the first documented psychosis diagnostic code accurately captured true episodes of psychosis but was a poor index of FEP. These data have important implications for the case definitions used in the development of risk prediction models designed to predict or detect undiagnosed psychosis.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904760","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":"Anti-LGI1 Antibody-Associated Encephalitis Misdiagnosed as Schizophrenia: A Case Report.","authors":"Jin-He Zhang, Bing-Bing Fu, Wei Wang, Cong-Cong Sun, Jin-Jie Xu","doi":"10.1093/schbul/sbae155","DOIUrl":"10.1093/schbul/sbae155","url":null,"abstract":"<p><p>Anti-leucine-rich glioma-inactivated 1 (LGI1) antibody-associated encephalitis is a rare but clinically significant form of autoimmune encephalitis, predominantly affecting middle-aged men. Its heterogeneous clinical presentation often leads to misdiagnosis, commonly as other neurological or psychiatric disorders. This report details the case of a 46-year-old male who initially presented with depressive symptoms, personality changes, and visual hallucinations. Over time, his condition progressed to include memory impairment, disorganized behavior, and seizures. Initially misdiagnosed with schizophrenia, the correct diagnosis of LGI1 antibody-associated encephalitis was eventually established through positive serum and cerebrospinal fluid (CSF) tests for LGI1 antibodies. Neuroimaging findings revealed characteristic bilateral temporal lobe lesions. The patient demonstrated marked improvement following treatment with methylprednisolone and intravenous immunoglobulin, ultimately achieving significant recovery. This case highlights the critical importance of comprehensive antibody testing and neuroimaging in patients presenting with nonspecific psychiatric and neurological symptoms to prevent misdiagnosis and delays in appropriate treatment. The article also reviews the pathogenesis, clinical manifestations, diagnostic approaches, and therapeutic strategies for LGI1 antibody-associated encephalitis, aiming to enhance clinical awareness and optimize patient outcomes.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111581","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}
Chen Shen, Olivia L Calvin, Eric Rawls, A David Redish, Scott R Sponheim
{"title":"Clarifying Cognitive Control Deficits in Psychosis via Drift Diffusion Modeling and Attractor Dynamics.","authors":"Chen Shen, Olivia L Calvin, Eric Rawls, A David Redish, Scott R Sponheim","doi":"10.1093/schbul/sbae014","DOIUrl":"10.1093/schbul/sbae014","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Cognitive control deficits are prominent in individuals with psychotic psychopathology. Studies providing evidence for deficits in proactive control generally examine average performance and not variation across trials for individuals-potentially obscuring detection of essential contributors to cognitive control. Here, we leverage intertrial variability through drift-diffusion models (DDMs) aiming to identify key contributors to cognitive control deficits in psychosis.</p><p><strong>Study design: </strong>People with psychosis (PwP; N = 122), their first-degree biological relatives (N = 78), and controls (N = 50) each completed 120 trials of the dot pattern expectancy (DPX) cognitive control task. We fit full hierarchical DDMs to response and reaction time (RT) data for individual trials and then used classification models to compare the DDM parameters with conventional measures of proactive and reactive control.</p><p><strong>Study results: </strong>PwP demonstrated slower drift rates on proactive control trials suggesting less efficient use of cue information. Both PwP and relatives showed protracted nondecision times to infrequent trial sequences suggesting slowed perceptual processing. Classification analyses indicated that DDM parameters differentiated between the groups better than conventional measures and identified drift rates during proactive control, nondecision time during reactive control, and cue bias as most important. DDM parameters were associated with real-world functioning and schizotypal traits.</p><p><strong>Conclusions: </strong>Modeling of trial-level data revealed that slow evidence accumulation and longer preparatory periods are the strongest contributors to cognitive control deficits in psychotic psychopathology. This pattern of atypical responding during the DPX is consistent with shallow basins in attractor dynamic models that reflect difficulties in maintaining state representations, possibly mediated by excess neural excitation or poor connectivity.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139973349","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}
Rose Tinch-Taylor, Andrew Pickles, Dominic Stringer, Emese Csipke, Matteo Cella, Paul McCrone, Clare Reeder, Max Birchwood, David Fowler, Kathryn Greenwood, Sonia Johnson, Jesus Perez, Rosa Ritunnano, Andrew Thompson, Rachel Upthegrove, Jon Wilson, Alex Kenny, Iris Isok, Eileen M Joyce, Til Wykes
{"title":"Understanding the Mechanisms of Cognitive Remediation on Recovery in People With Early Psychosis: A Mediation and Moderation Analysis.","authors":"Rose Tinch-Taylor, Andrew Pickles, Dominic Stringer, Emese Csipke, Matteo Cella, Paul McCrone, Clare Reeder, Max Birchwood, David Fowler, Kathryn Greenwood, Sonia Johnson, Jesus Perez, Rosa Ritunnano, Andrew Thompson, Rachel Upthegrove, Jon Wilson, Alex Kenny, Iris Isok, Eileen M Joyce, Til Wykes","doi":"10.1093/schbul/sbae021","DOIUrl":"10.1093/schbul/sbae021","url":null,"abstract":"<p><strong>Background: </strong>To provide precision cognitive remediation therapy (CR) for schizophrenia, we need to understand whether the mechanism for improved functioning is via cognition improvements. This mechanism has not been rigorously tested for potential moderator effects.</p><p><strong>Study design: </strong>We used data (n = 377) from a randomized controlled trial using CIRCuiTS, a therapist-supported CR, with participants from first-episode psychosis services. We applied structured equation modeling to test whether: (1) CR hours explain the goal attainment functional outcome (GAS) at posttreatment, (2) global cognitive improvement mediates GAS, and if (3) total symptoms moderate the CR hours to cognitive improvement pathway, and/or negative symptoms moderate the cognition to functioning pathway, testing moderator effects via the mediator or directly on CR hours to functioning path.</p><p><strong>Study results: </strong>CR produced significant functioning benefit for each therapy hour (Coeff = 0.203, 95% CI 0.101-0.304, P < .001). The mediated path from CR hours to cognition and cognition to functioning was small and nonsignificant (Coeff = 0.014, 95% CI = -0.010, 0.037, P = .256). Total symptoms did not moderate the path to cognition (P = .211) or the direct path to outcome (P = .896). However, negative symptoms significantly moderated the effect of cognitive improvements on functioning (P = .015) with high negative symptoms reducing the functional gains of improved cognition.</p><p><strong>Conclusions: </strong>Although cognitive improvements were correlated with functioning benefit, they did not fully explain the positive effect of increased therapy hours on functioning, suggesting additional CR factors also contribute to therapy benefit. Negative symptoms interfere with the translation of cognitive improvements into functional gains so need consideration.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013212","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}
Qiao-Xia Zhang, Shan-Shan Wu, Peng-Jie Wang, Rui Zhang, Robert K Valenzuela, Shan-Shan Shang, Ting Wan, Jie Ma
{"title":"Schizophrenia-Like Deficits and Impaired Glutamate/Gamma-aminobutyric acid Homeostasis in Zfp804a Conditional Knockout Mice.","authors":"Qiao-Xia Zhang, Shan-Shan Wu, Peng-Jie Wang, Rui Zhang, Robert K Valenzuela, Shan-Shan Shang, Ting Wan, Jie Ma","doi":"10.1093/schbul/sbae120","DOIUrl":"10.1093/schbul/sbae120","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Zinc finger protein 804A (ZNF804A) was the first genome-wide associated susceptibility gene for schizophrenia (SCZ) and played an essential role in the pathophysiology of SCZ by influencing neurodevelopment regulation, neurite outgrowth, synaptic plasticity, and RNA translational control; however, the exact molecular mechanism remains unclear.</p><p><strong>Study design: </strong>A nervous-system-specific Zfp804a (ZNF804A murine gene) conditional knockout (cKO) mouse model was generated using clustered regularly interspaced short palindromic repeat/Cas9 technology and the Cre/loxP method.</p><p><strong>Results: </strong>Multiple and complex SCZ-like behaviors, such as anxiety, depression, and impaired cognition, were observed in Zfp804a cKO mice. Molecular biological methods and targeted metabolomics assay validated that Zfp804a cKO mice displayed altered SATB2 (a cortical superficial neuron marker) expression in the cortex; aberrant NeuN, cleaved caspase 3, and DLG4 (markers of mature neurons, apoptosis, and postsynapse, respectively) expressions in the hippocampus and a loss of glutamate (Glu)/γ-aminobutyric acid (GABA) homeostasis with abnormal GAD67 (Gad1) expression in the hippocampus. Clozapine partly ameliorated some SCZ-like behaviors, reversed the disequilibrium of the Glu/GABA ratio, and recovered the expression of GAD67 in cKO mice.</p><p><strong>Conclusions: </strong>Zfp804a cKO mice reproducing SCZ-like pathological and behavioral phenotypes were successfully developed. A novel mechanism was determined in which Zfp804a caused Glu/GABA imbalance and reduced GAD67 expression, which was partly recovered by clozapine treatment. These findings underscore the role of altered gene expression in understanding the pathogenesis of SCZ and provide a reliable SCZ model for future therapeutic interventions and biomarker discovery.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580747","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}
Stéphanie Astrid Dijkstra, Jennifer Rijkeboer, Arjen Noordhof, Lindy-Lou Boyette, Steven Berendsen, Mariken de Koning, Romy Liza Japien Bennen, Tim Hofman, Lieuwe de Haan
{"title":"Making Sense of Recovery From First Psychosis With Antipsychotic Medication: A Qualitative Phenomenological Study.","authors":"Stéphanie Astrid Dijkstra, Jennifer Rijkeboer, Arjen Noordhof, Lindy-Lou Boyette, Steven Berendsen, Mariken de Koning, Romy Liza Japien Bennen, Tim Hofman, Lieuwe de Haan","doi":"10.1093/schbul/sbae104","DOIUrl":"10.1093/schbul/sbae104","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Recovering from a first psychosis is a highly individual process and requires the person to make sense of their experiences. Clinicians, in turn, need to comprehend these first-person perspectives, creating a mutual sense-making dynamic. Antipsychotic medication is a substantial part of psychosis treatment. Providing insight in the lived experience of recovery with antipsychotics could improve the mutual understanding and help bridge the gap between the perspective of the clinician and that of the person recovering from psychosis.</p><p><strong>Study design: </strong>14 persons in recovery from a first psychosis with the use of antipsychotics were interviewed. Their narratives were analyzed using Interpretative Phenomenological Analysis (IPA).</p><p><strong>Study results: </strong>Five overarching themes were found, representing important and meaningful experiences in recovering with antipsychotic medication. Theme 1: antipsychotics as external dampening (4 subthemes); Theme 2: shifting of realities; Theme 3: pace of recovery; Theme 4: antipsychotics' influence on identity; and Theme 5: is it truly the antipsychotics?</p><p><strong>Conclusions: </strong>Our findings show that recovery from psychosis with antipsychotics is an all-encompassing, multi-faceted, and ambivalent experience. The themes found in this research could inspire clinicians to discuss less obvious aspects of the experience of recovering with antipsychotics. Even more so, paying attention to the first-person perspective could lead to a more thorough understanding and benefit therapeutic relationships.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617106","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}
Fan Mo, Han Zhao, Yifan Li, Huanhuan Cai, Yang Song, Rui Wang, Yongqiang Yu, Jiajia Zhu
{"title":"Network Localization of State and Trait of Auditory Verbal Hallucinations in Schizophrenia.","authors":"Fan Mo, Han Zhao, Yifan Li, Huanhuan Cai, Yang Song, Rui Wang, Yongqiang Yu, Jiajia Zhu","doi":"10.1093/schbul/sbae020","DOIUrl":"10.1093/schbul/sbae020","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Neuroimaging studies investigating the neural substrates of auditory verbal hallucinations (AVH) in schizophrenia have yielded mixed results, which may be reconciled by network localization. We sought to examine whether AVH-state and AVH-trait brain alterations in schizophrenia localize to common or distinct networks.</p><p><strong>Study design: </strong>We initially identified AVH-state and AVH-trait brain alterations in schizophrenia reported in 48 previous studies. By integrating these affected brain locations with large-scale discovery and validation resting-state functional magnetic resonance imaging datasets, we then leveraged novel functional connectivity network mapping to construct AVH-state and AVH-trait dysfunctional networks.</p><p><strong>Study results: </strong>The neuroanatomically heterogeneous AVH-state and AVH-trait brain alterations in schizophrenia localized to distinct and specific networks. The AVH-state dysfunctional network comprised a broadly distributed set of brain regions mainly involving the auditory, salience, basal ganglia, language, and sensorimotor networks. Contrastingly, the AVH-trait dysfunctional network manifested as a pattern of circumscribed brain regions principally implicating the caudate and inferior frontal gyrus. Additionally, the AVH-state dysfunctional network aligned with the neuromodulation targets for effective treatment of AVH, indicating possible clinical relevance.</p><p><strong>Conclusions: </strong>Apart from unifying the seemingly irreproducible neuroimaging results across prior AVH studies, our findings suggest different neural mechanisms underlying AVH state and trait in schizophrenia from a network perspective and more broadly may inform future neuromodulation treatment for AVH.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944390","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}
Henry R Cowan, Trevor F Williams, Vijay A Mittal, Jean Addington, Carrie E Bearden, Kristin S Cadenhead, Tyrone D Cannon, Barbara A Cornblatt, Matcheri Keshevan, Diana O Perkins, Daniel H Mathalon, William Stone, Scott W Woods, Elaine F Walker
{"title":"The Complex Latent Structure of Attenuated Psychotic Symptoms: Hierarchical and Bifactor Models of SIPS Symptoms Replicated in Two Large Samples at Clinical High Risk for Psychosis.","authors":"Henry R Cowan, Trevor F Williams, Vijay A Mittal, Jean Addington, Carrie E Bearden, Kristin S Cadenhead, Tyrone D Cannon, Barbara A Cornblatt, Matcheri Keshevan, Diana O Perkins, Daniel H Mathalon, William Stone, Scott W Woods, Elaine F Walker","doi":"10.1093/schbul/sbae042","DOIUrl":"10.1093/schbul/sbae042","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>The Structured Interview for Psychosis-Risk Syndromes (SIPS) and other assessments of psychosis risk define clinical high risk for psychosis (CHR) by the presence of attenuated psychotic symptoms. Despite extensive research on attenuated psychotic symptoms, substantial questions remain about their internal psychometric structure and relationships to comorbid non-psychotic symptoms.</p><p><strong>Study design: </strong>Hierarchical and bifactor models were developed for the SIPS in a large CHR sample (NAPLS-3, N = 787) and confirmed through preregistered replication in an independent sample (NAPLS-2, N = 1043). Criterion validity was tested through relationships with CHR status, comorbid symptoms/diagnoses, functional impairment, demographics, neurocognition, and conversion to psychotic disorders.</p><p><strong>Study results: </strong>Most variance in SIPS items (75%-77%) was attributable to a general factor. Hierarchical and bifactor models included a general factor and five specific/lower-order factors (positive symptoms, eccentricity, avolition, lack of emotion, and deteriorated thought process). CHR participants were elevated on the general factor and the positive symptoms factor. The general factor was associated with depressive symptoms; functional impairment; and mood, anxiety, and schizotypal personality diagnoses. The general factor was the best predictor of psychotic disorders (d ≥ 0.50). Positive symptoms and eccentricity had specific effects on conversion outcomes. The deteriorated thought process was least meaningful/replicable.</p><p><strong>Conclusions: </strong>Attenuated psychotic symptoms, measured by the SIPS, have a complex hierarchical structure with a strong general factor. The general factor relates to internalizing symptoms and functional impairment, emphasizing the roles of general psychopathological distress/impairment in psychosis risk. Shared symptom variance complicates the interpretation of raw symptom scores. Broad transdiagnostic assessment is warranted to model psychosis risk accurately.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904802","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}
Alexander Denissoff, Heidi Taipale, Jari Tiihonen, Marta Di Forti, Ellenor Mittendorfer-Rutz, Antti Tanskanen, Antti Mustonen, Solja Niemelä
{"title":"Antipsychotic Use and Psychiatric Hospitalization in First-Episode Non-affective Psychosis and Cannabis Use Disorder: A Swedish Nationwide Cohort Study.","authors":"Alexander Denissoff, Heidi Taipale, Jari Tiihonen, Marta Di Forti, Ellenor Mittendorfer-Rutz, Antti Tanskanen, Antti Mustonen, Solja Niemelä","doi":"10.1093/schbul/sbae034","DOIUrl":"10.1093/schbul/sbae034","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>There is a paucity of research on treatment outcomes of patients with psychosis and cannabis use disorder (CUD). We aimed to compare the effectiveness of antipsychotics in reducing the risk of hospitalization in patients with first-episode psychosis (FEP) and co-occurring CUD.</p><p><strong>Study design: </strong>We utilized a nationwide Swedish cohort of patients with longitudinal register data from the year 2006 to 2021. Participants were patients with FEP and co-occurring CUD (n = 1820, 84.73% men, mean age 26.80 years, SD 8.25 years). The main outcome was hospitalization due to psychotic relapse. Hospitalization due to any psychiatric disorder or substance use disorder (SUD) were examined as secondary outcomes. Within-individual Cox regression models were used to study these associations.</p><p><strong>Study results: </strong>Use of any antipsychotic was associated with a 33% risk reduction of psychotic relapse (aHR = 0.67; 95% CI 0.60-0.75). Clozapine (0.43; 0.29-0.64), long-acting injectable (LAI) formulations of risperidone (0.40; 0.22-0.71), aripiprazole (0.42; 0.27-0.65), and paliperidone (0.46; 0.30-0.69) were associated with the lowest risk of relapse. The association between the LAI formulation of olanzapine and hospitalization due to psychosis was statistically non-significant (0.61; 0.35-1.05). Clozapine was associated with an 86% risk reduction of hospitalization due to SUD (0.14; 0.05-0.44). Of oral non-clozapine antipsychotics, aripiprazole was associated with the lowest risk of hospitalization due to psychotic relapse (0.61; 0.45-0.83).</p><p><strong>Conclusions: </strong>These findings support the use of clozapine, LAI formulations of second-generation antipsychotics other than olanzapine, or oral aripiprazole to prevent hospitalization in FEP and co-occurring CUD.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140294460","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}