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  • 1
    In: Neuropsychopharmacology, Springer Science and Business Media LLC, Vol. 46, No. 8 ( 2021-07), p. 1484-1493
    Abstract: Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hitherto reported inconclusive findings. We investigated effects of age of cannabis initiation on psychosis using data from the multicentric Personalized Prognostic Tools for Early Psychosis Management (PRONIA) and the Cannabis Induced Psychosis (CIP) studies, yielding a total sample of 102 clinically-relevant cannabis users with recent onset psychosis. GM covariance underlies shared maturational processes. Therefore, we performed source-based morphometry analysis with spatial constraints on structural brain networks showing significant alterations in schizophrenia in a previous multisite study, thus testing associations of these networks with the age of cannabis initiation and with confounding factors. Earlier cannabis initiation was associated with more severe positive symptoms in our cohort. Greater gray matter volume (GMV) in the previously identified cerebellar schizophrenia-related network had a significant association with early cannabis use, independent of several possibly confounding factors. Moreover, GMV in the cerebellar network was associated with lower volume in another network previously associated with schizophrenia, comprising the insula, superior temporal, and inferior frontal gyrus. These findings are in line with previous investigations in healthy cannabis users, and suggest that early initiation of cannabis perturbs the developmental trajectory of certain structural brain networks in a manner imparting risk for psychosis later in life.
    Type of Medium: Online Resource
    ISSN: 0893-133X , 1740-634X
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2008300-2
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  • 2
    In: Neuropsychopharmacology, Springer Science and Business Media LLC, Vol. 46, No. 8 ( 2021-07), p. 1475-1483
    Abstract: In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated with neuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosis patients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means algorithm to cluster 108 psychosis patients from the multi-site EU PRONIA (Prognostic tools for early psychosis management) study based on cognitive performance and validated the solution independently ( N  = 53). Cognitive subgroups and healthy controls (HC; n  = 195) were classified based on gray matter volume (GMV) using Support Vector Machine classification. A cognitively spared ( N  = 67) and impaired ( N  = 41) subgroup were revealed and partially independently validated ( N spared  = 40, N impaired  = 13). Impaired patients showed significantly increased negative symptomatology ( p fdr  = 0.003), reduced cognitive performance ( p fdr   〈  0.001) and general functioning ( p fdr   〈  0.035) in comparison to spared patients. Neurocognitive deficits of the impaired subgroup persist in both discovery and validation sample across several domains, including verbal memory and processing speed. A GMV pattern (balanced accuracy = 60.1%, p  = 0.01) separating impaired patients from HC revealed increases and decreases across several fronto-temporal-parietal brain areas, including basal ganglia and cerebellum. Cognitive and functional disturbances alongside brain morphological changes in the impaired subgroup are consistent with a neurodevelopmental origin of psychosis. Our findings emphasize the relevance of tailored intervention early in the course of psychosis for patients suffering from the likely stronger neurodevelopmental character of the disease.
    Type of Medium: Online Resource
    ISSN: 0893-133X , 1740-634X
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2008300-2
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  • 3
    In: Neuropsychopharmacology, Springer Science and Business Media LLC
    Abstract: Cognitively impaired and spared patient subgroups were identified in psychosis and depression, and in clinical high-risk for psychosis (CHR). Studies suggest differences in underlying brain structural and functional characteristics. It is unclear whether cognitive subgroups are transdiagnostic phenomena in early stages of psychotic and affective disorder which can be validated on the neural level. Patients with recent-onset psychosis (ROP; N  = 140; female = 54), recent-onset depression (ROD; N  = 130; female = 73), CHR ( N  = 128; female = 61) and healthy controls (HC; N  = 270; female = 165) were recruited through the multi-site study PRONIA. The transdiagnostic sample and individual study groups were clustered into subgroups based on their performance in eight cognitive domains and characterized by gray matter volume (sMRI) and resting-state functional connectivity (rsFC) using support vector machine (SVM) classification. We identified an impaired subgroup ( N ROP  = 79, N ROD  = 30, N CHR  = 37) showing cognitive impairment in executive functioning, working memory, processing speed and verbal learning (all p   〈  0.001). A spared subgroup ( N ROP  = 61, N ROD  = 100, N CHR  = 91) performed comparable to HC. Single-disease subgroups indicated that cognitive impairment is stronger pronounced in impaired ROP compared to impaired ROD and CHR. Subgroups in ROP and ROD showed specific symptom- and functioning-patterns. rsFC showed superior accuracy compared to sMRI in differentiating transdiagnostic subgroups from HC (BAC impaired  = 58.5%; BAC spared  = 61.7%, both: p   〈  0.01). Cognitive findings were validated in the PRONIA replication sample ( N  = 409). Individual cognitive subgroups in ROP, ROD and CHR are more informative than transdiagnostic subgroups as they map onto individual cognitive impairment and specific functioning- and symptom-patterns which show limited overlap in sMRI and rsFC. Clinical trial registry name German Clinical Trials Register (DRKS). Clinical trial registry URL: https://www.drks.de/drks_web/ . Clinical trial registry number: DRKS00005042.
    Type of Medium: Online Resource
    ISSN: 0893-133X , 1740-634X
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2008300-2
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  • 4
    In: Neuropsychopharmacology, Springer Science and Business Media LLC, Vol. 46, No. 4 ( 2021-03), p. 828-835
    Abstract: Two decades of studies suggest that computerized cognitive training (CCT) has an effect on cognitive improvement and the restoration of brain activity. Nevertheless, individual response to CCT remains heterogenous, and the predictive potential of neuroimaging in gauging response to CCT remains unknown. We employed multivariate pattern analysis (MVPA) on whole-brain resting-state functional connectivity (rsFC) to (neuro)monitor clinical outcome defined as psychosis-likeness change after 10-hours of CCT in recent onset psychosis (ROP) patients. Additionally, we investigated if sensory processing (SP) change during CCT is associated with individual psychosis-likeness change and cognitive gains after CCT. 26 ROP patients were divided into maintainers and improvers based on their SP change during CCT. A support vector machine (SVM) classifier separating 56 healthy controls (HC) from 35 ROP patients using rsFC (balanced accuracy of 65.5%, P   〈  0.01) was built in an independent sample to create a naturalistic model representing the HC-ROP hyperplane. This model was out-of-sample cross-validated in the ROP patients from the CCT trial to assess associations between rsFC pattern change, cognitive gains and SP during CCT. Patients with intact SP threshold at baseline showed improved attention despite psychosis status on the SVM hyperplane at follow-up ( p   〈  0.05). Contrarily, the attentional gains occurred in the ROP patients who showed impaired SP at baseline only if rsfMRI diagnosis status shifted to the healthy-like side of the SVM continuum. Our results reveal the utility of MVPA for elucidating treatment response neuromarkers based on rsFC-SP change and pave the road to more personalized interventions.
    Type of Medium: Online Resource
    ISSN: 0893-133X , 1740-634X
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2008300-2
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  • 5
    In: Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 46, No. Supplement_1 ( 2020-05-18), p. S317-S318
    Abstract: Functional deficits associated with the Clinical High Risk (CHR) status very often lead to inability to attend school, unemployment, as well as social isolation, thus calling for predictors of individual functional outcomes which may facilitate the identification of people requiring care irrespective of transition to psychosis. Studies have revealed that a pattern of cortical and subcortical gray matter volumes (GMV) anomalies measured at baseline in CHR individuals could predict their functional abilities at follow up. Furthermore, literature is consistent in revealing the crucial role of several environmental adverse events in increasing the risk of developing either transition to psychosis, or a worse overall personal functioning. Therefore, the aim of this study is to employ machine learning to test the individual and combined ability of baseline GMV data and of history of environmental adverse events in predicting good vs. poor social and occupational outcome in CHR individuals at follow up. Methods 92 CHR individuals recruited from the 7 discovery PRONIA sites were included in this project. Social and occupational impairment at follow up (9–12 months) were respectively measured through the Global Functioning: Social (GF:S) and Role (GF:R) scale, and CHR with a follow up rating of 7 or below were labeled as having a poor functional outcome. This way, we could separate our cohort in 52 poor outcome CHR and 40 good outcome CHR. GMV data were preprocessed following published procedures which allowed also to correct for site effects. The environmental classifier was built based on Childhood Trauma Questionnaire, Bullying Scale, and Premorbid Adjustment Scale (childhood, early adolescence, late adolescence and adulthood) scores. Raw scores have been normalized according to the psychometric properties of the healthy samples used for validating these questionnaires and scale, in order to obtain individual scores of deviation from the normative occurrence of adverse environmental events. GMV and environmental-based predictive models were independently trained and tested within a leave-site-out cross validation framework using a Support Vector Machine algorithm (LIBSVM) through the NeuroMiner software, and their predictions were subsequently combined through stacked generalization procedures. Results Our GMV-based model could predict follow up social outcome with 67.4% Balanced Accuracy (BAC) and significance (p=0.01), while it could not predict occupational outcome (46.6% BAC). On the other hand, our environmental-based model could discriminate both poor vs. good social and occupational outcomes at follow up with, respectively, 71% and 66.4% BACs, and significance (both p=0.0001). Specifically, the most reliable features in the environmental classifier were scores reflecting deviations from the normative values in childhood trauma and adult premorbid adjustment, for social outcome prediction, and in bullying experiences and late adolescence premorbid adjustment, for occupational outcome prediction. Only for social outcome prediction, stacked models outperformed individual classifiers’ predictions (74.3% BAC, p=0.0001). Discussion Environmental features seem to be more accurate than GMV in predicting both social and occupational outcomes in CHR. Interestingly, the predictions of follow up social and occupational outcomes rely on different patterns of occurrence of specific environmental adverse events, thus providing novel insights about how environmental adjustment disabilities, bullying and traumatic premorbid experiences may impact on different bad outcomes associated with the CHR status.
    Type of Medium: Online Resource
    ISSN: 0586-7614 , 1745-1701
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2180196-4
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  • 6
    In: Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 46, No. Supplement_1 ( 2020-05-18), p. S14-S15
    Abstract: Formal thought disorder (FThD) has been associated with more severe illness courses and functional deficits in psychosis patients. Given these associations, it remains unclear whether the presence of FThD accounts for the heterogeneous presentation of psychoses, and whether it characterises a specific subgroup of patients showing prominent differential illness severity, neurocognitive and functional impairments already in the early stages of psychosis. Thus, our aim is 1) to evaluate whether there are stable subtypes of patients with Recent-Onset Psychosis (ROP) that are characterized by distinct FThD patterns, 2) to investigate whether this FThD-related stratification is associated with clinical, and neurocognitive phenotypes at an early stage of the disease, and 3) to explore correlation patterns among the FThD-related symptoms, functioning and neurocognition through network analysis. Methods 279 individuals experiencing ROP were recruited for this project as part of multi-site European PRONIA study. In the present study, FThD was assessed with conceptual disorganization, difficulty in abstract thinking, poverty of content of speech, increased latency of response and poverty of speech items from the Positive and Negative Symptom Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). We first applied a multi-step clustering protocol comparing three clustering algorithms: (i) k-means, (ii) hierarchical clustering, and (iii) partitioning around medoids with the number of clusters ranging from 2 to 10. Our protocol runs following four checkpoints; (i) validity [ClValid package], (ii) re-evaluation of validity results and unbiased determination of the winning algorithm [NbClust package] , (iii) stability test [ClusterStability package] and (iv) generalizability [predict.strength package] testing for the most optimal clustering solution. Thereafter, we investigated whether the identified FThD subgrouping solution was associated with neurocognitive performance, social and occupational functioning by using Welch’s two-sample t-test or Mann-Whitney-U test based on the distribution of data, and explored the interrelation of these domains with network analysis by using qgraph package with the spearman correlation matrix among variables. All analyses and univariate statistical comparisons were conducted with R version 3.5.2. We used the False Discovery Rate (FDR)37 to correct all P-values for the multiple comparisons. Results The k-means algorithm-based on two-cluster solution (FThD high vs. low) surviving these validity, stability and generalizability tests was chosen for further association tests and network analysis with core disease phenotypes. Patients in FThD high subgroup had lower scores in global (pfdr = 0.0001), social (pfdr & lt; 0.0001) and role (pfdr & lt; 0.0001) functioning, in semantic (pfdr & lt; 0.0001) and phonological verbal fluency (pfdr = 0.0004), verbal short-term memory (pfdr = 0.0018) and abstract thinking (pfdr = 0.0099). Cluster assignment was not informed by the global disease severity (pfdr = 0.7786) but was associated with more pronounced negative symptoms (pfdr = 0.0001) in the FThD high subgroup. Discussion Our findings highlight how the combination of unsupervised machine learning algorithms with network analysis techniques may provide novel insight about the mappings between psychopathology, neurocognition and functioning. Furthermore, they point how FThD may represent a target variable for individualized psycho-, socio-, logotherapeutic interventions aimed at improving neurocognition abilities and functioning. Prospective studies should further test this promising perspective.
    Type of Medium: Online Resource
    ISSN: 0586-7614 , 1745-1701
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2180196-4
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  • 7
    In: Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 46, No. Supplement_1 ( 2020-05-18), p. S20-S20
    Abstract: Childhood maltreatment (CM) is a major psychiatric risk factor and leads to long-lasting physical and mental health implications throughout the affected individual’s lifespan. Nonetheless, the neuroanatomical correlates of CM and their specific clinical impact remain elusive. This might be attributed to the complex, multidimensional nature of CM as well as to the restrictions of traditional analysis pipelines using nosological grouping, univariate analysis and region-of-interest approaches. To overcome these issues, we present a novel transdiagnostic and naturalistic machine learning approach towards a better and more comprehensive understanding of the clinical and neuroanatomical complexity of CM. Methods We acquired our dataset from the multi-center European PRONIA cohort (www.pronia.eu). Specifically, we selected 649 male and female individuals, comprising young, minimally medicated patients with clinical high-risk states for psychosis as well as recent-onset of depression or psychosis and healthy volunteers. As part of our analysis approach, we created a new Matlab Toolbox, which performs multivariate Sparse Partial Least Squares Analysis in a robust machine learning framework. We employed this algorithm to detect multi-layered associations between combinations of items from the Childhood Trauma Questionnaire (CTQ) and grey matter volume (GMV) and assessed their generalizability via nested cross-validation. The clinical relevance of these CM signatures was assessed by correlating them to a wide range of clinical measurements, including current functioning (GAF, GF), depressivity (BDI), quality of life (WHOQOL-BREF) and personality traits (NEO-FFI). Results Overall, we detected three distinct signatures of sexual, physical and emotional maltreatment. The first signature consisted of an age-dependent sexual abuse pattern and a corresponding GMV pattern along the prefronto-thalamo-cerebellar axis. The second signature yielded a sex-dependent physical and sexual abuse pattern with a corresponding GMV pattern in parietal, occipital and subcortical regions. The third signature was a global emotional trauma signature, independent of age or sex, and projected to a brain structural pattern in sensory and limbic brain regions. Regarding the clinical impact of these signatures, the emotional trauma signature was most strongly associated with massively impaired state- and trait-level characteristics. Both on a phenomenological and on a brain structural level, the emotional trauma pattern was significantly correlated with lower levels of functioning, higher depression scores, decreased quality of life and maladaptive personality traits. Discussion Our findings deliver multimodal, data-driven evidence for a differential impact of sexual, physical and emotional trauma on brain structure and clinical state- and trait-level phenotypes. They also highlight the multidimensional nature of CM, which consists of multiple layers of highly complex trauma-brain patterns. In broader terms, our study emphasizes the potential of machine learning approaches in generating novel insights into long-standing psychiatric topics.
    Type of Medium: Online Resource
    ISSN: 0586-7614 , 1745-1701
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2180196-4
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  • 8
    In: Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 46, No. Supplement_1 ( 2020-05-18), p. S181-S181
    Abstract: A multitude of clinical models to predict transition to psychosis in individuals at clinical high risk (CHR) have been proposed. However, only limited efforts have been made to systematically compare these models and to validate their performance in independent samples. Therefore, in this study we identified psychosis risk models based on information readily obtainable in general clinical settings, such as clinical and neuropsychological data, and compared their performance in the PRONIA study (Personalised Prognostic Tools for Early Psychosis Management, www.pronia.eu) as an independent sample. Methods Of the 278 CHR participants in the PRONIA sample, 150 had available data until month 18 and were included in the validation of eleven psychosis prediction models identified through systematic literature search. Discrimination performance was assessed with the area under the receiver operating characteristic curve (AUC), and compared to the performance of the prognosis of clinical raters. Psychosocial functioning was explored as an alternative outcome. Results Discrimination performance varied considerably across models (AUC ranging from 0.42 to 0.79). High model performance was associated with the inclusion of neurocognitive variables as predictors. Low model performance was associated with predictors based on dichotomized variables. Clinical raters performed comparable to the best data-driven models (AUC = 0.75). Combining raters’ prognosis and model-based predictions improved discrimination performance (AUC = 0.84), particularly for less experienced raters. One of the tested models predicted transition to psychosis and psychosocial outcomes comparably well. Discussion The present external validation study highlights the benefit of enriching clinical information with neuropsychological data in predicting transition to psychosis satisfactorily and with good generalizability across samples. Integration of data-driven risk models and clinical expertise may improve clinical decision-making in CHR for psychosis, particularly for less experienced raters. This external validation study provides an important step toward early intervention and the personalized treatment of psychotic disorders.
    Type of Medium: Online Resource
    ISSN: 0586-7614 , 1745-1701
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2180196-4
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  • 9
    In: Neuropsychopharmacology, Springer Science and Business Media LLC, Vol. 47, No. 12 ( 2022-11), p. 2051-2060
    Abstract: Subtle subjective visual dysfunctions (VisDys) are reported by about 50% of patients with schizophrenia and are suggested to predict psychosis states. Deeper insight into VisDys, particularly in early psychosis states, could foster the understanding of basic disease mechanisms mediating susceptibility to psychosis, and thereby inform preventive interventions. We systematically investigated the relationship between VisDys and core clinical measures across three early phase psychiatric conditions. Second, we used a novel multivariate pattern analysis approach to predict VisDys by resting-state functional connectivity within relevant brain systems. VisDys assessed with the Schizophrenia Proneness Instrument (SPI-A), clinical measures, and resting-state fMRI data were examined in recent-onset psychosis (ROP, n  = 147), clinical high-risk states of psychosis (CHR, n  = 143), recent-onset depression (ROD, n  = 151), and healthy controls (HC, n  = 280). Our multivariate pattern analysis approach used pairwise functional connectivity within occipital (ON) and frontoparietal (FPN) networks implicated in visual information processing to predict VisDys. VisDys were reported more often in ROP (50.34%), and CHR (55.94%) than in ROD (16.56%), and HC (4.28%). Higher severity of VisDys was associated with less functional remission in both CHR and ROP, and, in CHR specifically, lower quality of life (Qol), higher depressiveness, and more severe impairment of visuospatial constructability. ON functional connectivity predicted presence of VisDys in ROP (balanced accuracy 60.17%, p  = 0.0001) and CHR (67.38%, p  = 0.029), while in the combined ROP + CHR sample VisDys were predicted by FPN (61.11%, p  = 0.006). These large-sample study findings suggest that VisDys are clinically highly relevant not only in ROP but especially in CHR, being closely related to aspects of functional outcome, depressiveness, and Qol. Findings from multivariate pattern analysis support a model of functional integrity within ON and FPN driving the VisDys phenomenon and being implicated in core disease mechanisms of early psychosis states.
    Type of Medium: Online Resource
    ISSN: 0893-133X , 1740-634X
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2008300-2
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  • 10
    In: Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 44, No. suppl_1 ( 2018-04-01), p. S147-S148
    Type of Medium: Online Resource
    ISSN: 0586-7614 , 1745-1701
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2180196-4
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