Deconstructing Bipolar Disorder and Schizophrenia: A cross-diagnostic cluster analysis of cognitive phenotypes

Lee, Jung‐Hee; Rizzo, Shemra; Altshuler, Lori L.; Glahn, David C.; Miklowitz, David J.; Sugar, Catherine A.; Wynn, Jonathan K.; Green, Michael F.

doi:10.1016/j.jad.2016.11.030

Cited by 54 publications

(33 citation statements)

References 60 publications

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“…Impairments have been reported in many cognitive domains, including verbal learning and memory, verbal fluency, working memory, processing speed, and executive function (Bilder et al, 2002; Hill et al, 2013, 2004a; Saykin et al, 1994). Similar neuropsychological deficits, albeit less severe, are reported in other psychotic disorders (Hill et al, 2013, 2009, 2008; Lee et al, 2016). Cognitive impairment relates directly to functional outcomes in patients such as psychosocial skill acquisition, performing daily activities, and vocational attainment and contributes to poor quality of life (Green et al, 2000; Leifker et al, 2009).…”

Section: Introductionsupporting

confidence: 72%

Cognitive burden of anticholinergic medications in psychotic disorders

Eum

Hill

Rubin

et al. 2017

Schizophrenia Research

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Background Patients with psychotic disorders are often treated with numerous medications, many of which have anticholinergic activity. We assessed cognition in relation to the cumulative anticholinergic burden of multiple drugs included in treatment regimens of participants from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study. Method Clinically stable participants with schizophrenia (n=206), schizoaffective disorder (n=131), and psychotic bipolar disorder (n=146) were examined. Anticholinergic properties of all scheduled drugs were quantified using the Anticholinergic Drug Scale (ADS). ADS scores were summed across individual drugs to create a total ADS burden score for each participant and examined in relation to the Brief Assessment of Cognition in Schizophrenia (BACS). Results Anticholinergic burden aggregated across all medications was inversely related to cognitive performance starting at ADS scores of 4 in participants with schizophrenia. Those with ADS scores ≥4 had lower composite BACS scores compared to those with ADS<4 (p=0.004). Among BACS subtests, Verbal Memory was the most adversely affected by high anticholinergic burden. Despite similar anticholinergic burden scores across groups, a significant effect of anticholinergic burden was not detected in schizoaffective or psychotic bipolar disorder. Conclusion We identified an adverse effect threshold of anticholinergic burden on cognition in clinically stable participants with schizophrenia. This relationship was not identified in affective psychoses. Examination of other medications, doses, and clinical measures did not account for these findings. Patients with schizophrenia may have increased cognitive susceptibility to anticholinergic medications and the aggregate effects of one’s medication regimen may be important to consider in clinical practice.

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Section: Introductionsupporting

confidence: 72%

Cognitive burden of anticholinergic medications in psychotic disorders

Eum

Hill

Rubin

et al. 2017

Schizophrenia Research

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“…In fact, cluster analysis studies have reported within‐group heterogeneity in the cognitive performance of individuals with BD, suggesting the existence of subgroups based on performance. While some authors divide them into similar to the HC range and selective cognitive impairment (representing almost one‐third of the sample), 66,67 others divide the impaired group into selective cognitive impairment (modest deficits on only a subset of domains) and global severe impairment (deficit across most of the cognitive domains) 68‐71 …”

Section: Discussionmentioning

confidence: 99%

Functioning in euthymic patients with bipolar disorder: A systematic review and meta‐analysis using the Functioning Assessment Short Test

2020

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Objectives Systematically review the prevalence of functional impairment (FI) in euthymic patients with bipolar disorder (BD), as assessed only with the Functioning Assessment Short Test (FAST), explore the prevalence of this impairment among all the domains, identify the most compromised of them and the clinical variables associated with low functioning in this population. Methods Meta‐analyses were performed, searching for relevant papers published from 2007 to 2019 in Medline, Embase, Cochrane, PsycINFO databases and via hand‐searching, without language restrictions. 1128 studies were initially identified, 13 of which were ultimately chosen based on the eligibility criteria. A two‐step meta‐analysis was performed using the mean difference with a 95% confidence interval for continuous variables and proportion estimation with a fixed‐effects model for categorical variables. Results In the first step, all FAST domains showed worse FI in patients than in healthy controls, with significant differences between groups. In the second step, the prevalence of FI domains were as follows: global, 58.6%; occupational, 65.6%; cognitive, 49.2%; autonomy, 42.6%; interpersonal relationships, 42.1%; leisure, 29.2%; and financial issues, 28.8%. Residual depressive symptoms were the most frequently cited variable associated with FI. Conclusions This study reinforces the relevant functional impact of BD in this population and suggests that the occupational domain may be the most impaired. Greater efforts should be directed toward targeting functioning in patient care, as it constitutes the most meaningful endpoint of response to treatment, especially with occupational and cognitive rehabilitation, thus allowing patients to overcome the course of illness and carry fulfilling lives.

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“…Cluster analysis is a statistical technique that identifies subgroups in wider multidimensional or heterogeneous data, which application to multifaceted diseases, such as major depression, could help dissect disease heterogeneity, advancing diagnostic criteria, and improving treatment plans 34 – 36 .…”

Section: Introductionmentioning

confidence: 99%

Deconstructing major depressive episodes across unipolar and bipolar depression by severity and duration: a cross-diagnostic cluster analysis on a large, international, observational study

et al. 2020

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A cross-diagnostic, post-hoc analysis of the BRIDGE-II-MIX study was performed to investigate how unipolar and bipolar patients suffering from an acute major depressive episode (MDE) cluster according to severity and duration. Duration of index episode, Clinical Global Impression-Bipolar Version-Depression (CGI-BP-D) and Global Assessment of Functioning (GAF) were used as clustering variables. MANOVA and post-hoc ANOVAs examined between-group differences in clustering variables. A stepwise backward regression model explored the relationship with the 56 clinical-demographic variables available. Agglomerative hierarchical clustering with two clusters was shown as the best fit and separated the study population (n = 2314) into 65.73% (Cluster 1 (C1)) and 34.26% (Cluster 2 (C2)). MANOVA showed a significant main effect for cluster group (p < 0.001) but ANOVA revealed that significant betweengroup differences were restricted to CGI-BP-D (p < 0.001) and GAF (p < 0.001), showing greater severity in C2. Psychotic features and a minimum of three DSM-5 criteria for mixed features (DSM-5-3C) had the strongest association with C2, that with greater disease burden, while non-mixed depression in bipolar disorder (BD) type II had negative association. Mixed affect defined as DSM-5-3C associates with greater acute severity and overall impairment, independently of the diagnosis of bipolar or unipolar depression. In this study a pure, non-mixed depression in BD type II significantly associates with lesser burden of clinical and functional severity. The lack of association for less restrictive, researchedbased definitions of mixed features underlines DSM-5-3C specificity. If confirmed in further prospective studies, these findings would warrant major revisions of treatment algorithms for both unipolar and bipolar depression.

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Deconstructing Bipolar Disorder and Schizophrenia: A cross-diagnostic cluster analysis of cognitive phenotypes

Cited by 54 publications

References 60 publications

Cognitive burden of anticholinergic medications in psychotic disorders

Cognitive burden of anticholinergic medications in psychotic disorders

Functioning in euthymic patients with bipolar disorder: A systematic review and meta‐analysis using the Functioning Assessment Short Test

Deconstructing major depressive episodes across unipolar and bipolar depression by severity and duration: a cross-diagnostic cluster analysis on a large, international, observational study

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