ORCID Profile
0000-0003-1385-1050
Current Organisation
Mount Sinai Hospital
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Publisher: American Medical Association (AMA)
Date: 02-2021
Publisher: Elsevier BV
Date: 2019
Publisher: Elsevier BV
Date: 09-2022
Publisher: Elsevier BV
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 22-09-2023
Publisher: Springer Science and Business Media LLC
Date: 03-10-2020
Publisher: Springer Science and Business Media LLC
Date: 07-10-2020
DOI: 10.1038/S41386-020-00877-4
Abstract: Two decades of studies suggest that computerized cognitive training (CCT) has an effect on cognitive improvement and the restoration of brain activity. Nevertheless, in idual 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 in idual psychosis-likeness change and cognitive gains after CCT. 26 ROP patients were ided 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 s le to create a naturalistic model representing the HC-ROP hyperplane. This model was out-of-s le 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.
Publisher: Springer Science and Business Media LLC
Date: 17-09-2021
DOI: 10.1007/S00406-021-01327-Y
Abstract: Formal thought disorder (FTD) has been associated with more severe illness courses and functional deficits in patients with psychotic disorders. However, it remains unclear whether the presence of FTD characterises a specific subgroup of patients showing more prominent illness severity, neurocognitive and functional impairments. This study aimed to identify stable and generalizable FTD-subgroups of patients with recent-onset psychosis (ROP) by applying a comprehensive data-driven clustering approach and to test the validity of these subgroups by assessing associations between this FTD-related stratification, social and occupational functioning, and neurocognition. 279 patients with ROP were recruited as part of the multi-site European PRONIA study (Personalised Prognostic Tools for Early Psychosis Management www.pronia.eu). Five FTD-related symptoms (conceptual disorganization, poverty of content of speech, difficulty in abstract thinking, increased latency of response and poverty of speech) were assessed with Positive and Negative Symptom Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). The results with two patient subgroups showing different levels of FTD were the most stable and generalizable clustering solution (predicted clustering strength value = 0.86). FTD-High subgroup had lower scores in social ( p fdr 0.001) and role ( p fdr 0.001) functioning, as well as worse neurocognitive performance in semantic ( p fdr 0.001) and phonological verbal fluency ( p fdr 0.001), short-term verbal memory ( p fdr = 0.002) and abstract thinking ( p fdr = 0.010), in comparison to FTD-Low group. Clustering techniques allowed us to identify patients with more pronounced FTD showing more severe deficits in functioning and neurocognition, thus suggesting that FTD may be a relevant marker of illness severity in the early psychosis pathway.
Publisher: Springer Science and Business Media LLC
Date: 26-07-2022
DOI: 10.1038/S41398-022-02057-Y
Abstract: In iduals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P in iduals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P in iduals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or ergence of neuroanatomical profiles between in iduals. Second, using a normative modelling approach, to assess the ‘normativeness’ of neuroanatomical profiles in in iduals at CHR-P. CHR-P in iduals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical ergence in global SA, CT and SV profiles in CHR-P in iduals compared with HC. Normative PBSI analysis identified 11 CHR-P in iduals (0.70%) with marked deviation ( .5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater ergence in neuroanatomical profiles at an in idual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.
Publisher: American Medical Association (AMA)
Date: 07-2021
Publisher: American Medical Association (AMA)
Date: 07-2022
Publisher: Springer Science and Business Media LLC
Date: 24-05-2021
DOI: 10.1038/S41398-021-01409-4
Abstract: Negative symptoms occur frequently in in iduals at clinical high risk (CHR) for psychosis and contribute to functional impairments. The aim of this study was to predict negative symptom severity in CHR after 9 months. Predictive models either included baseline negative symptoms measured with the Structured Interview for Psychosis-Risk Syndromes (SIPS-N), whole-brain gyrification, or both to forecast negative symptoms of at least moderate severity in 94 CHR. We also conducted sequential risk stratification to stratify CHR into different risk groups based on the SIPS-N and gyrification model. Additionally, we assessed the models’ ability to predict functional outcomes in CHR and their transdiagnostic generalizability to predict negative symptoms in 96 patients with recent-onset psychosis (ROP) and 97 patients with recent-onset depression (ROD). Baseline SIPS-N and gyrification predicted moderate/severe negative symptoms with significant balanced accuracies of 68 and 62%, while the combined model achieved 73% accuracy. Sequential risk stratification stratified CHR into a high (83%), medium (40–64%), and low (19%) risk group regarding their risk of having moderate/severe negative symptoms at 9 months follow-up. The baseline SIPS-N model was also able to predict social (61%), but not role functioning (59%) at above-chance accuracies, whereas the gyrification model achieved significant accuracies in predicting both social (76%) and role (74%) functioning in CHR. Finally, only the baseline SIPS-N model showed transdiagnostic generalization to ROP (63%). This study delivers a multimodal prognostic model to identify those CHR with a clinically relevant negative symptom severity and functional impairments, potentially requiring further therapeutic consideration.
Publisher: Cold Spring Harbor Laboratory
Date: 18-01-2023
DOI: 10.1101/2023.01.17.523348
Abstract: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in the majority of in iduals at psychosis risk may be nested within the range observed in healthy in iduals. To quantify deviations from the normative range of neuroanatomical variation in in iduals at clinical high-risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. Clinical, IQ and FreeSurfer-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1,340 CHR-P in iduals [47.09% female mean age: 20.75 (4.74) years] and 1,237 healthy in iduals [44.70% female mean age: 22.32 (4.95) years] from 29 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. For each regional morphometric measure, z-scores were computed that index the degree of deviation from the normative means of that measure in a healthy reference population (N=37,407). Average deviation scores (ADS) for CT, SA, SV, and globally across all measures (G) were generated by averaging the respective regional z-scores. Regression analyses were used to quantify the association of deviation scores with clinical severity and cognition and two-proportion z-tests to identify case-control differences in the proportion of in iduals with infranormal (z -1.96) or supranormal (z .96) scores. CHR-P and healthy in iduals overlapped in the distributions of the observed values, regional z-scores, and all ADS vales. The proportion of CHR-P in iduals with infranormal or supranormal values in any metric was low ( %) and similar to that of healthy in iduals. CHR-P in iduals who converted to psychosis compared to those who did not convert had a higher percentage of infranormal values in temporal regions (5-7% vs 0.9-1.4%). In the CHR-P group, only the ADS SA showed significant but weak associations (|β| .09 P FDR .05) with positive symptoms and IQ. The study findings challenge the usefulness of macroscale neuromorphometric measures as diagnostic biomarkers of psychosis risk and suggest that such measures do not provide an adequate explanation for psychosis risk. Is the risk of psychosis associated with brain morphometric changes that deviate significantly from healthy variation? In this study of 1340 in iduals high-risk for psychosis (CHR-P) and 1237 healthy participants, in idual-level variation in macroscale neuromorphometric measures of the CHR-P group was largely nested within healthy variation and was not associated with the severity of positive psychotic symptoms or conversion to a psychotic disorder. The findings suggest the macroscale neuromorphometric measures have limited utility as diagnostic biomarkers of psychosis risk.
Publisher: Springer Science and Business Media LLC
Date: 15-03-2021
DOI: 10.1038/S41386-021-00963-1
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 s le 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.
Publisher: Springer Science and Business Media LLC
Date: 18-08-2022
DOI: 10.1038/S41386-022-01385-3
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 s le VisDys were predicted by FPN (61.11%, p = 0.006). These large-s le 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.
Location: United States of America
No related grants have been discovered for Shalaila Haas.