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  • Rosen, Marlene  (7)
  • Salokangas, Raimo K R  (7)
  • Medicine  (7)
  • 1
    In: Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 46, No. Supplement_1 ( 2020-05-18), p. S122-S122
    Abstract: Psychotic disorders are associated with serious deterioration in functioning even before the first psychotic episode. Also on clinical high risk (CHR) states of developing a first psychotic episode, several studies reported a decreased global functioning. In a considerable proportion of CHR individuals, functional deterioration remains even after (transient) remission of symptomatic risk indicators. Furthermore, deficits in functioning cause immense costs for the health care system and are often more debilitating for individuals than positive symptoms. However in the past, CHR research has mostly focused on clinical outcomes like transition. Prediction of functioning in CHR populations has received less attention. Therefore, the current study aims at predicting functioning in CHR individuals at a single subject level applying multi pattern recognition to clinical data. Patients with a first depressive episode who frequently have persistent functional deficits comparable to patients in the CHR state were investigated in addition. Methods PRONIA (‘Personalized Prognostic Tools for Early Psychosis Management’) is a prospective collaboration project funded by the European Union under the 7th Framework Programme (grant agreement n°602152). Considering a broad set of variables (MRI, clinical data, neurocognition, genomics and other blood derived parameters) as well as advanced statistical methods, PRONIA aims at developing an innovative multivariate prognostic tool enabling an individualized prediction of illness trajectories and outcome. 11 university centers in five European countries and in Australia (Munich, Basel, Birmingham, Cologne, Düsseldorf, Münster, Melbourne, Milan, Udine, Bari, Turku) participate in the evaluation of three clinical groups (subjects clinically at high risk of developing a psychosis [CHR], patients with a recent onset psychosis [ROP] and patients with a recent onset depression [ROD]) as well as healthy controls. In the current study, we analysed data of 114 CHR and 106 ROD patients. Functioning was measured by the ‘Global Functioning: Social and Role’ Scales (GF S/R). In a repeated, nested cross validation framework we trained a l1-regularized SVM to predict good versus bad outcome. Multivariate pattern recognition analysis allowed to identify most predictive variables from a multitude of clinical, environmental as well as sociodemographic potential predictors assessed in PRONIA. Results Based on the 5 to 20 identified most predictive features, prediction models revealed a balanced accuracy (BAC) up to 77/72 for social functioning in CHR/ROD patients and up to 73/69 for role functioning. These models showed satisfying performance of BACs up to 69/63 for social functioning and 67/60 for role functioning in an independent test sample. As expected, prior functioning levels were identified as main predictive factor but also distinct protective and risk factors were selected into the prediction models. Discussion Results suggest that especially prediction of the multi-faceted construct of role functioning could benefit from inclusion of a rich set of clinical variables. To the best of our knowledge this is the first study that has validated clinical prediction models of functioning in an independent test sample. Identification of predictive variables enables a much more efficient prognostic process. Moreover, understanding the mechanisms underlying functional decline and its illness related pattern might enable an improved definition of targets for intervention. Future research should aim at further maximisation of prediction accuracy and cross-centre generalisation capacity. In addition, other functioning outcomes as well as clinical outcomes need to be focused on.
    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
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 2
    In: Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 46, No. Supplement_1 ( 2020-05-18), p. S15-S16
    Abstract: Precise prognosis of clinical outcomes in individuals at clinical high-risk (CHR) of developing psychosis is imperative to guide treatment selection. While much effort has been put into the prediction of transition to psychosis in CHR individuals, prognostic models focusing on negative symptom progression in this population are widely missing. This is a major oversight bearing in mind that 82% of CHR individuals exhibit at least one negative symptom in the moderate to severe range at first clinical presentation, whereas 54% still meet this criteria after 12 months. Negative symptoms are strong predictors of poor functional outcome irrespective of other symptoms such as depression or anxiety. Prognostic tools are therefore urgently required to track negative symptom progression in CHR individuals in order to guide early personalized interventions. Here, we applied machine-learning to multi-site data from five European countries with the aim of predicting negative symptoms of at least moderate severity 9-month after study inclusion. Methods We analyzed data from the ‘Personalized Prognostic Tools for Early Psychosis Management’ (PRONIA; www.pronia.eu) study, which consisted of 94 individuals at clinical high-risk of developing psychosis (CHR). Predictive models either included baseline level of negative symptoms, measured with the Structured Interview for Prodromal Syndromes, whole-brain gyrification pattern, or both to forecast negative symptoms of moderate severity or above in CHR individuals. Using data from the clinical and gyrification model, further sequential testing simulations were conducted to stratify CHR individuals into different risk groups. Lastly, we assessed the models’ ability to predict functional outcomes in CHR individuals. Results Baseline negative symptom severity alone predicted moderate to severe negative symptoms with a balanced accuracy (BAC) of 68%, whereas predictive models trained on gyrification measures achieved a BAC of 64%. Stacking the two modalities allowed for an increased BAC of 72%. Additional sequential testing simulations suggested, that CHR patients could be stratified into a high risk group with 83% probability of experiencing at least moderate negative symptoms at follow-up and a medium/low risk group with a risk ranging from 25 to 38%, when using the two models sequentially. Furthermore, the models trained to predict negative symptom severity from baseline symptoms were less predictive of role (60% BAC) and social (62% BAC) functioning at follow-up. However, the model trained on gyrification data also predicted role (74% BAC) and social (73% BAC) functioning later on. The stacking model predicted role, and social functioning with 64% BAC and 66% BAC respectively. Discussion To the best of our knowledge this is the first study using state-of-the-art predictive modelling to prospectively identify CHR subjects with negative symptoms in the moderate to above moderate severity range who potentially require further therapeutic consideration. While the predictive performance will need to be validated in other samples and may be improved by expanding the models with additional predictors, we believe that this pragmatic approach will help to stratify individual risk profiles and optimize personal interventions in the future.
    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
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 3
    In: Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 47, No. 4 ( 2021-07-08), p. 1130-1140
    Abstract: Diagnostic heterogeneity within and across psychotic and affective disorders challenges accurate treatment selection, particularly in the early stages. Delineation of shared and distinct illness features at the phenotypic and brain levels may inform the development of more precise differential diagnostic tools. We aimed to identify prototypes of depression and psychosis to investigate their heterogeneity, with common, comorbid transdiagnostic symptoms. Analyzing clinical/neurocognitive and grey matter volume (GMV) data from the PRONIA database, we generated prototypic models of recent-onset depression (ROD) vs. recent-onset psychosis (ROP) by training support-vector machines to separate patients with ROD from patients with ROP, who were selected for absent comorbid features (pure groups). Then, models were applied to patients with comorbidity, ie, ROP with depressive symptoms (ROP+D) and ROD participants with sub-threshold psychosis-like features (ROD+P), to measure their positions within the affective-psychotic continuum. All models were independently validated in a replication sample. Comorbid patients were positioned between pure groups, with ROP+D patients being more frequently classified as ROD compared to pure ROP patients (clinical/neurocognitive model: χ2 = 14.874; P & lt; .001; GMV model: χ2 = 4.933; P = .026). ROD+P patient classification did not differ from ROD (clinical/neurocognitive model: χ2 = 1.956; P = 0.162; GMV model: χ2 = 0.005; P = .943). Clinical/neurocognitive and neuroanatomical models demonstrated separability of prototypic depression from psychosis. The shift of comorbid patients toward the depression prototype, observed at the clinical and biological levels, suggests that psychosis with affective comorbidity aligns more strongly to depressive rather than psychotic disease processes. Future studies should assess how these quantitative measures of comorbidity predict outcomes and individual responses to stratified therapeutic interventions.
    Type of Medium: Online Resource
    ISSN: 0586-7614 , 1745-1701
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2180196-4
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 4
    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
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 5
    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
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 6
    In: Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 47, No. 1 ( 2021-01-23), p. 249-258
    Abstract: Depression frequently occurs in first-episode psychosis (FEP) and predicts longer-term negative outcomes. It is possible that this depression is seen primarily in a distinct subgroup, which if identified could allow targeted treatments. We hypothesize that patients with recent-onset psychosis (ROP) and comorbid depression would be identifiable by symptoms and neuroanatomical features similar to those seen in recent-onset depression (ROD). Data were extracted from the multisite PRONIA study: 154 ROP patients (FEP within 3 months of treatment onset), of whom 83 were depressed (ROP+D) and 71 who were not depressed (ROP−D), 146 ROD patients, and 265 healthy controls (HC). Analyses included a (1) principal component analysis that established the similar symptom structure of depression in ROD and ROP+D, (2) supervised machine learning (ML) classification with repeated nested cross-validation based on depressive symptoms separating ROD vs ROP+D, which achieved a balanced accuracy (BAC) of 51%, and (3) neuroanatomical ML-based classification, using regions of interest generated from ROD subjects, which identified BAC of 50% (no better than chance) for separation of ROP+D vs ROP−D. We conclude that depression at a symptom level is broadly similar with or without psychosis status in recent-onset disorders; however, this is not driven by a separable depressed subgroup in FEP. Depression may be intrinsic to early stages of psychotic disorder, and thus treating depression could produce widespread benefit.
    Type of Medium: Online Resource
    ISSN: 0586-7614 , 1745-1701
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2180196-4
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 7
    In: Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 46, No. Supplement_1 ( 2020-05-18), p. S133-S133
    Abstract: Childhood trauma (CT) is associated with an increased risk for psychiatric disorders like major depression and psychosis. However, the pathophysiological relationship between CT, psychiatric disease and structural brain alterations is still unknown. Methods PRONIA (‘Personalized Prognostic Tools for Early Psychosis Mangement’) is a prospective collaboration project funded by the European Union under the 7th Framework Programme (grant agreement n° 602152). Considering a broad set of variables (sMRI, rsMRI, DTI, psychopathological, life event related and sociobiographic data, neurocognition, genomics and other blood derived parameters) as well as advanced statistical methods, PRONIA aims at developing an innovative multivariate prognostic tool enabling an individualized prediction of illness trajectories and outcome. Seven clinical centers in five European countries and in Australia participate in the evaluation of three clinical groups (subjects clinically at high risk of developing a psychosis (CHR), patients with a recent onset psychosis (ROP) and patients with a recent onset depression (ROD)) as well as healthy controls (HC). To investigate the high-dimensional patterns of CT experience, measured by the childhood trauma questionnaire (CTQ), in HC and our three patient groups (PAT) (n=643), we used a Support Vector Machine (SVM). Furthermore, we tested whether patient-specific CT exposure is associated with structural brain changes by VBM analyses. Results We found that patients and HC could be separated very well by their CTQ pattern, whereas the different patient groups showed no specific CTQ pattern. Furthermore, an association with extensive grey matter changes suggests an impact on brain maturation which may put individuals at increased risk for mental disease. Discussion We have demonstrated in this large multi-center cohort that adverse experiences in childhood contribute transdiagnostically to the riskr for developing a psychiatric disease. The observed association between CTQ scores and structural changes suggests an impact of adverse childhood experiences on brain development. Resulting alterations may add to a neurobiological vulnerability for depression and psychosis. A role of both features for other mental disorders could be assumed and warrants further investigation.
    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
    SSG: 15,3
    Location Call Number Limitation Availability
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