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Background and Hypothesis: Abnormalities in the retina are observed in psychotic disorders, especially in schizophrenia., Study Design: Using spectral-domain optical coherence tomography, we investigated structural retinal changes in relatively metabolic risk-free youth with clinical high-risk (CHR, n = 34) and first-episode psychosis (FEP, n = 30) compared with healthy controls (HCs, n = 28)., Study Results: Total retinal macular thickness/volume of the right eye increased in FEP (effect sizes, Cohen's d = 0.69/0.66) and CHR (d = 0.67/0.76) compared with HCs. Total retinal thickness/volume was not significantly different between FEP and CHR. Macular retinal nerve fiber layer (RNFL) thickness/volume of the left eye decreased in FEP compared with HCs (d = -0.75/-0.66). Peripapillary RNFL thickness was not different between groups. The ganglion cell (GCL), inner plexiform (IPL), and inner nuclear (INL) layers thicknesses/volumes of both eyes increased in FEP compared with HCs (d = 0.70-1.03). GCL volumes of both eyes, IPL thickness/volume of the left eye, and INL thickness/volume of both eyes increased in CHR compared with HCs (d = 0.64-1.01). In the macula, while central sector thickness/volume decreased (d = -0.62 to -0.72), superior outer (peri-foveal) sector thickness/volume of both eyes increased (d = 0.81 to 0.86) in FEP compared with HCs., Conclusions: The current findings suggest that distinct regions and layers of the retina may be differentially impacted during the emergence and early phase of psychosis. Consequently, oculomics could play significant roles, not only as a diagnostic tool but also as a mirror reflecting neurobiological changes at axonal and cellular levels., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Abnormal connectivity in the brain has been linked to the pathophysiology of severe mental illnesses, including bipolar disorder and schizophrenia. The current study aimed to investigate large-scale functional networks and global network metrics in clinical high-risk for bipolardisorder (CHR-BD, n = 25), clinical high-risk for psychosis (CHR-P, n = 30), and healthy controls (HCs, n = 19). Help-seeking youth at CHR-BD and CHR-P were recruited from the early intervention program at Dokuz Eylul University, Izmir, Turkey. Resting-state functional magnetic resonance imaging scans were obtained from youth at CHR-BD, CHR-P, and HCs. Graph theoretical analysis and network-based statistics were employed to construct and examine the topological features of the whole-brain metrics and large-scale functional networks. Connectivity was increased (i) between the visual and default mode, (ii) between the visual and salience, (iii) between the visual and cingulo-opercular networks, and decreased (i) within the default mode and (ii) between the default mode and fronto-parietal networks in the CHR-P compared to HCs. Decreased global efficiency was found in CHR-P compared to CHR-BD. Functional networks were not different between CHR-BD and HCs. Global efficiency was negatively correlated with subthreshold positive symptoms and thought disorder in the high-risk groups. The current results suggest disrupted networks in CHR-P compared to HCs and CHR-BD. Moreover, transdiagnostic psychosis features are linked to functional brain networks in the at-risk groups. However, given the small, medicated sample, results are exploratory and hypothesis-generating., Competing Interests: Declaration of competing interest No potential conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In recent years, automated analyses using novel NLP methods have been used to investigate language abnormalities in schizophrenia. In contrast, only a few studies used automated language analyses in bipolar disorder. To our knowledge, no previous research compared automated language characteristics of first-episode psychosis (FEP) and bipolar disorder (FEBD) using NLP methods., Methods: Our study included 53 FEP, 40 FEBD and 50 healthy control participants who are native Turkish speakers. Speech samples of the participants in the Thematic Apperception Test (TAT) underwent automated generic and part-of-speech analyses, as well as sentence-level semantic similarity analysis based on SBERT., Results: Both FEBD and FEP were associated with the use of shorter sentences and increased sentence-level semantic similarity but less semantic alignment with the TAT pictures. FEP also demonstrated reduced verbosity and syntactic complexity. FEP differed from FEBD in reduced verbosity, decreased first-person singular pronouns, fewer conjunctions, increased semantic similarity as well as shorter sentence and word length. The mean classification accuracy was 82.45 % in FEP vs HC, 71.1 % in FEBD vs HC, and 73 % in FEP vs FEBD. After Bonferroni correction, the severity of negative symptoms in FEP was associated with reduced verbal output and increased 5th percentile of semantic similarity., Limitations: The main limitation of this study was the cross-sectional nature., Conclusion: Our findings demonstrate that both patient groups showed language abnormalities, which were more severe and widespread in FEP compared to FEBD. Our results suggest that NLP methods reveal transdiagnostic linguistic abnormalities in FEP and FEBD., Competing Interests: Declaration of competing interest The authors have no conflicts of interest regarding subject of this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Identifying individuals at clinical high risk for psychosis (CHRP) is crucial for preventing psychosis and improving the prognosis for schizophrenia. Individuals at CHR-P may exhibit mild forms of formal thought disorder (FTD), making it possible to identify them using natural language processing (NLP) methods. In this study, speech samples of 62 CHR-P individuals and 45 healthy controls (HCs) were elicited using Thematic Apperception Test images. The evaluation involved various NLP measures such as semantic similarity, generic, and part-of-speech (POS) features. The CHR-P group demonstrated higher sentence-level semantic similarity and reduced mean image-to-text similarity. Regarding generic analysis, they demonstrated reduced verbosity and produced shorter sentences with shorter words. The POS analysis revealed a decrease in the utilization of adverbs, conjunctions, and first-person singular pronouns, alongside an increase in the utilization of adjectives in the CHR-P group compared to HC. In addition, we developed a machine-learning model based on 30 NLP-derived features to distinguish between the CHR-P and HC groups. The model demonstrated an accuracy of 79.6 % and an AUC-ROC of 0.86. Overall, these findings suggest that automated language analysis of speech could provide valuable information for characterizing FTD during the clinical high-risk phase and has the potential to be applied objectively for early intervention for psychosis., Competing Interests: Declaration of competing interest The authors have no conflicts of interest regarding subject of this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Effort-based decision-making has been proposed as a potential mechanism contributing to transdiagnostic motivational deficits in psychotic disorder and bipolar disorder. However, very limited information is available about deficits in effort-cost-decision-making in the early stages of psychotic disorder and no study has investigated effort allocation deficits before the onset of bipolar disorder. Our aim was to investigate effort-based-decision-making in ultra-high-risk for psychosis (UHR-P) and bipolar disorder (UHR-BD)., Methods: Effort-cost decision-making performance was evaluated in UHR-P ( n = 72) and UHR-BD ( n = 68) and healthy controls ( n = 38). Effort-Expenditure for Reward Task (EEfRT) was used., Results: Compared to controls, both UHR-P and UHR-BD groups were associated with a reduced possibility to choose the harder task when the reward magnitudes and/or the likelihood of receiving the reward were high. In both groups, effort allocation abnormalities were associated with poor social functioning., Conclusions: The current findings suggest that difficulties in effort-cost computation are transdiagnostic markers of illness liability in psychotic and bipolar disorders. In early intervention services, effort-based decision-making abnormalities should be considered as a target for interventions to manage motivational deficits in individuals at high risk for psychosis and BD.

Abstract: Human rationality has a dual nature including analytic and common-sense thinking. Symptoms of schizophrenia have been suggested to be related to deficits in these aspects of logical reasoning. However, empirical studies investigating logical reasoning errors in schizophrenia and their clinical and neurocognitive correlates are scarce. Formal thought disorder and theory of mind (ToM) might be particularly important for understanding logical reasoning errors in schizophrenia. The current study compared the performances of 80 patients with schizophrenia with those of 49 healthy controls on syllogistic and counterfactual reasoning tasks and investigated clinical, neuropsychological, and social cognitive correlates of logical reasoning in schizophrenia. Patients with schizophrenia were impaired in both analytic and common-sense thinking. ToM impairment was a significant predictor of analytic reasoning abilities in schizophrenia. Executive functions and verbal memory were also significantly associated with analytic reasoning in schizophrenia. Further studies investigating logical reasoning errors in the early phases of the illness are needed., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Both structural and functional alterations in the retina and the choroid of the eye, as parts of the central nervous system, have been shown in psychotic disorders, especially in schizophrenia. In addition, genetic and imaging studies indicate vascular and angiogenesis anomalies in the psychosis spectrum disorders. In this ocular imaging study, choroidal structure and vascularity were investigated using enhanced depth imaging (EDI) optical coherence tomography (OCT) in first-episode psychosis (FEP), ultra-high risk for psychosis (UHR-P), and age- and gender- matched healthy controls (HCs). There were no significant differences between groups in central choroidal thickness, stromal choroidal area (SCA), luminal choroidal area (LCA) and total subfoveal choroidal area. The LCA/SCA ratio (p<0.001) and the choroidal vascularity index (CVI) (p<0.001) were significantly different between FEP, UHR-P and HCs. CVI and LCA/SCA ratio were significantly higher in patients with FEP compared to help-seeking youth at UHR-P. CVI and LCA/SCA ratio were not different between UHR-P and HCs. However, CVI was higher in UHR-P compared to HCs after excluding the outliers for the sensitivity analysis (p = 0.002). Current findings suggest that choroidal thickness is normal, but there are abnormalities in choroidal microvasculature in prodromal and first-episode psychosis. Further longitudinal studies are needed to investigate oculomics, especially CVI, as a promising biomarker for the prediction of conversion to psychosis in individuals at clinical high-risk., Competing Interests: Conflict of interest The authors have no conflicts of interest regarding subject of this manuscript., (Copyright © 2023 Elsevier B.V. and ECNP. All rights reserved.)

Executive dysfunction and language impairment are the most prominent neuropsychological models of formal thought disorder (FTD) in schizophrenia. However, available studies have provided contradictory findings regarding the accuracy of these models. Furthermore, specific neurocognitive underpinnings of positive FTD (PosFTD) and negative FTD (NegFTD) are not clear. Following the systematic review of schizophrenia studies, a random-effects meta-analysis of the relationship between FTD and neurocognition/language in schizophrenia was conducted in 52 reports including 2805 patients. Neurocognition was significantly associated with both PosFTD (r = -0.21, CI = -0.14 to -0.27) and NegFTD (r = -0.24, CI = -0.18 to -0.30). Both PosFTD (r = ranged from -0.18 to -0.27) and NegFTD (r = ranged from -0.19 to -0.23) were significantly correlated with verbal memory, visual memory, attention, and processing speed. In meta-analyses of executive functions, PosFTD was significantly associated with working memory (r = -0.21), planning (r = -0.19), and inhibition (r = -0.21) and NegFTD was significantly associated with planning (r = -0.27), fluency (r = -0.27), and working memory (r = -0.24). In meta-analyses of linguistic variables, PosFTD was associated with deficits in syntactic comprehension (r = -0.27) and semantic processing (r = -0.18). In contrast, NegFTD was associated only with semantic comprehension (r = -0.21). Both PosFTD and NegFTD were significantly associated with executive dysfunction, neurocognitive deficits and semantic dysfunction but syntactic deficits were more specific to PosFTD. There were also some distinct patterns of relationships between the pattern of executive dysfunction and types of FTD. Fluency deficit was associated more strongly with NegFTD and poor inhibition was more specifically related to PosFTD. Current findings suggest that neurocognitive and linguistic correlates of PosFTD and NegFTD might be partly different., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Neurocognitive impairment is a well-established feature of first-episode psychosis (FEP). Neurotoxicity hypothesis of psychosis suggests that untreated psychosis before the initiation of first effective treatment is associated with loss of acquired cognitive abilities. However, the outcome of the studies investigating the relationship between duration of untreated psychosis (DUP) and cognitive impairment in FEP remains inconclusive. No previous meta-analysis investigating the relationship between DUP and cognitive impairment in FEP has been published. Following the systematic review of FEP studies, a random-effects meta-analysis of the relationship between DUP and neurocognition in schizophrenia was conducted. Current meta-analysis included 27 studies including 3127 patients with first-episode psychosis. Overall, DUP and cognitive abilities were not significantly related, with the exception of evidence for a weak relationship with a single cognitive domain. There was a very small but significant association between longer DUP and reduced performance in planning/problem-solving ability (r=-0.09, CI=-0.14 to -0.03). Current findings do not provide support for the neurotoxicity hypothesis of psychosis., (Copyright © 2017. Published by Elsevier B.V.)

Historically, formal thought disorder has been considered as one of the distinctive symptoms of schizophrenia. However, research in last few decades suggested that there is a considerable clinical and neurobiological overlap between schizophrenia and bipolar disorder (BP). We conducted a meta-analysis of studies comparing positive (PTD) and negative formal thought disorder (NTD) in schizophrenia and BP. We included 19 studies comparing 715 schizophrenia and 474 BP patients. In the acute inpatient samples, there was no significant difference in the severity of PTD (d=-0.07, CI=-0.22-0.09) between schizophrenia and BP. In stable patients, schizophrenia was associated with increased PTD compared to BP (d=1.02, CI=0.35-1.70). NTD was significantly more severe (d=0.80, CI=0.52-0.1.08) in schizophrenia compared to BP. Our findings suggest that PTD is a shared feature of both schizophrenia and BP but persistent PTD or NTD can distinguish subgroups of schizophrenia from BP and schizophrenia patients with better clinical outcomes., (Copyright © 2016 Elsevier B.V. All rights reserved.)