Widespread Volumetric Reductions in Schizophrenia and Schizoaffective Patients Displaying Compromised Cognitive Abilities

Rheenen, Tamsyn E Van; Cropley, Vanessa; Zalesky, Andrew; Bousman, Chad; Wells, Ruth; Bruggemann, Jason; Sundram, Suresh; Weinberg, Danielle; Lenroot, R.; Pereira, Avril; Weickert, Cynthia Shannon; Weickert, Thomas; Pantelis, Christos

doi:10.1093/schbul/sbx109

Cited by 51 publications

(55 citation statements)

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“…The present results extend this literature, identifying two subgroups that differ in severity of executive dysfunction and a third subgroup exhibiting a relatively intact level of functioning as quantified through the WCST. Historically, schizophrenia spectrum disorder participants have been consistently documented as a single group to exhibit moderately impaired performance on the WCST relative to the HC population (Li, 2004;Van der Does & Van den Bosch, 1992). By applying exploratory cluster analysis, a small proportion of the schizophrenia spectrum participants were identified as having severe impairments on the WCST.…”

Section: Discussionmentioning

confidence: 99%

“…Individuals with schizophrenia spectrum disorder (SSD) are commonly reported not to successfully complete the WCST, attributed to an impaired ability to form concepts and engage in flexible thinking (Li, 2004;Polgár et al, 2010;Van der Does & Van den Bosch, 1992;Waford & Lewine, 2010). Previous studies have documented that participants with SSDs require a high number of trials to complete the first category, register a high proportion of perseverative and non-perseverative errors, and frequently break set, resulting in their failure to meet the six categories achieved discontinuation rule before the maximum numbers of trials are administered.…”

Section: Introductionmentioning

confidence: 99%

“…Broadly, two anchoring cognitive profiles repeatedly emerge, a severely impaired subgroup and a cognitively intact subgroup, with a varying number of intermediate profiles of mixed/specific cognitive deficits emerging in-between (Burdick et al, 2014;Lewandowski et al, 2018;Van Rheenen et al, 2017;Weickert et al, 2000;Wells et al, 2015). These subgroups can be identified at first episode (Reser et al, 2015;Uren et al, 2017), transcend the familial and psychosis spectrum (Burdick et al, 2014;Hoti et al, 2004;Lewandowski et al, 2014;Van Rheenen et al, 2017), exhibit distinctive brain structure (Czepielewski et al, 2017;Van Rheenen et al, 2018;Woodward & Heckers, 2015), and display altered response to treatment and functional outcomes (Gilbert et al, 2014;Uren et al, 2017). Together, this research indicates that while most individuals with SSD experience mild-to-severe cognitive dysfunction, a subset performs at similar-to-HC levels.…”

Section: Introductionmentioning

confidence: 99%

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Exploring Heterogeneity on the Wisconsin Card Sorting Test in Schizophrenia Spectrum Disorders: A Cluster Analytical Investigation

Carruthers

Gurvich

Meyer

et al. 2019

J Int Neuropsychol Soc

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Objectives: The Wisconsin Card Sorting Test (WCST) is a complex measure of executive function that is frequently employed to investigate the schizophrenia spectrum. The successful completion of the task requires the interaction of multiple intact executive processes, including attention, inhibition, cognitive flexibility, and concept formation. Considerable cognitive heterogeneity exists among the schizophrenia spectrum population, with substantive evidence to support the existence of distinct cognitive phenotypes. The within-group performance heterogeneity of individuals with schizophrenia spectrum disorder (SSD) on the WCST has yet to be investigated. A data-driven cluster analysis was performed to characterise WCST performance heterogeneity. Methods: Hierarchical cluster analysis with k-means optimisation was employed to identify homogenous subgroups in a sample of 210 schizophrenia spectrum participants. Emergent clusters were then compared to each other and a group of 194 healthy controls (HC) on WCST performance and demographic/clinical variables. Results: Three clusters emerged and were validated via altered design iterations. Clusters were deemed to reflect a relatively intact patient subgroup, a moderately impaired patient subgroup, and a severely impaired patient subgroup. Conclusions: Considerable within-group heterogeneity exists on the WCST. Identification of subgroups of patients who exhibit homogenous performance on measures of executive functioning may assist in optimising cognitive interventions. Previous associations found using the WCST among schizophrenia spectrum participants should be reappraised. (JINS, 2019, 25, 750–760)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exploring Heterogeneity on the Wisconsin Card Sorting Test in Schizophrenia Spectrum Disorders: A Cluster Analytical Investigation

Carruthers

Gurvich

Meyer

et al. 2019

J Int Neuropsychol Soc

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“…In this context, assessment of unaffected biological siblings of such patients (preferably in a discordant twin‐pair design) could help us to ascertain whether their cognition is truly “intact,” based on whether their performance deviates at all from their “genetic cognitive destiny” (see Ref. [] for a discussion of this notion in relation to SZ). A continued focus on testing and refining cognition—enhancing interventions will be important so long as they continue to be informed by growing knowledge of the biological and environmental correlates of cognitive functioning and their covariation over time and illness phases; it is likely that multi‐modal interventions will be among the most efficacious means by which to improve cognitive dysfunction in the illness.…”

Section: Future Perspectivesmentioning

confidence: 99%

Current understandings of the trajectory and emerging correlates of cognitive impairment in bipolar disorder: An overview of evidence

et al. 2019

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Objectives Cognitive dysfunction affects a significant proportion of people with bipolar disorder (BD), but the cause, trajectory and correlates of such dysfunction remains unclear. Increased understanding of these factors is required to progress treatment development for this symptom dimension. Methods This paper provides a critical overview of the literature concerning the trajectories and emerging correlates of cognitive functioning in BD. It is a narrative review in which we provide a qualitative synthesis of current evidence concerning clinical, molecular, neural and lifestyle correlates of cognitive impairment in BD across the lifespan (in premorbid, prodromal, early onset, post‐onset, elderly cohorts). Results There is emerging evidence of empirical links between cognitive impairment and an increased inflammatory state, brain structural abnormalities and reduced neuroprotection in BD. However, evidence regarding the progressive nature of cognitive impairment is mixed, since consensus between different cross‐sectional data is lacking and does not align to the outcomes of the limited longitudinal studies available. Increased recognition of cognitive heterogeneity in BD may help to explain some inconsistencies in the extant literature. Conclusions Large, longitudinally focussed studies of cognition and its covariation alongside biological and lifestyle factors are required to better define cognitive trajectories in BD, and eventually pave the way for the application of a precision medicine approach for individual patients in clinical practice.

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“…Heterogeneity of premorbid adjustment, illness course, and outcomes is the rule rather than the exception in psychotic disorders, (e.g., [62]), and identifiable subsamples may differ in neuroprogressive degree and trajectory (e.g., [111]). Recent reports suggest that abnormalities in brain structure and connectivity are associated with cognitive subtypes in psychosis [112][113][114]. A recent study found that baseline neurocognitive functioning predicted gray matter reductions in multiple brain regions two years later [115], suggesting that baseline profiles…”

Section: Heterogeneity In Cognition and Neurobiologymentioning

confidence: 99%

Neuroprogression across the Early Course of Psychosis

Lewandowski

Bouix

Öngür

et al. 2020

J Psychiatry Brain Sci

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Psychotic disorders are severe, debilitating, and even fatal. The development of targeted and effective interventions for psychosis depends upon on clear understanding of the timing and nature of disease progression to target processes amenable to intervention. Strong evidence suggests early and ongoing neuroprogressive changes, but timing and inflection points remain unclear and likely differ across cognitive, clinical, and brain measures. Additionally, granular evidence across modalities is particularly sparse in the "bridging years" between first episode and established illness-years that may be especially critical for improving outcomes and during which interventions may be maximally effective.Our objective is the systematic, multimodal characterization of neuroprogression through the early course of illness in a cross-diagnostic sample of patients with psychosis. We aim to (1) interrogate neurocognition, structural brain measures, and network connectivity at multiple assessments over the first eight years of illness to map neuroprogressive trajectories, and (2) examine trajectories as predictors of clinical and functional outcomes. We will recruit 192 patients with psychosis and 36 healthy controls. Assessments will occur at baseline and 8-and 16-month follow ups using clinical, cognitive, and imaging measures. We will employ an accelerated longitudinal design (ALD), which permits ascertainment of data across a longer timeframe and at more frequent intervals than would be possible in a single cohort longitudinal study. Results from this study are expected to hasten identification of actionable treatment targets that are closely associated with clinical outcomes, and identify subgroups who share common neuroprogressive trajectories toward the development of individualized treatments. Open Access

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Widespread Volumetric Reductions in Schizophrenia and Schizoaffective Patients Displaying Compromised Cognitive Abilities

Cited by 51 publications

References 43 publications

Exploring Heterogeneity on the Wisconsin Card Sorting Test in Schizophrenia Spectrum Disorders: A Cluster Analytical Investigation

Exploring Heterogeneity on the Wisconsin Card Sorting Test in Schizophrenia Spectrum Disorders: A Cluster Analytical Investigation

Current understandings of the trajectory and emerging correlates of cognitive impairment in bipolar disorder: An overview of evidence

Neuroprogression across the Early Course of Psychosis

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