Real-world Functioning In Schizophrenia Research Articles

Effect of anticholinergic burden on brain activity during Working Memory and real-world functioning in patients with schizophrenia.

Cognitive impairment has been associated with poor real-world functioning in patients with Schizophrenia. Previous studies have shown that pharmacological treatment with anticholinergic properties may contribute to cognitive impairment in Schizophrenia. We investigated the effect of the anticholinergic burden (ACB) on brain activity, cognition, and real-world functioning in Schizophrenia. We hypothesized that greater ACB would be associated with altered brain activity along with poorer cognitive performance and lower real-world functioning. A sample of 100 patients with a diagnosis of schizophrenia or schizoaffective disorder was recruited in the naturalistic multicenter study of the Italian Network for Research on Psychoses (NIRP) across 7 centres. For each participant, ACB was evaluated using the Anticholinergic Cognitive Burden scale. The association of ACB with brain function was assessed using BOLD fMRI during the N-Back Working Memory (WM) task in a nested cohort (N=31). Real-world functioning was assessed using the Specific Level of Functioning (SLOF) scale. Patients with high ACB scores (≥3) showed lower brain activity in the WM frontoparietal network (TFCE corrected alpha <0.05) and poorer cognitive performance (p=0.05) than patients with low ACB scores (<3). Both effects were unaffected by demographic characteristics, clinical severity, and antipsychotic dosage. Moreover, patients with high ACB showed poorer real-world functioning than patients with lower ACB (p=0.03). Our results suggest that ACB in Schizophrenia is associated with impaired WM and abnormal underlying brain function along with reduced real-world functioning. Clinical practice should consider the potential adverse cognitive effects of ACB in the treatment decision-making process.

Cognitive deficits, clinical variables, and white matter microstructure in schizophrenia: a multisite harmonization study.

Cognitive deficits are among the best predictors of real-world functioning in schizophrenia. However, our understanding of how cognitive deficits relate to neuropathology and clinical presentation over the disease lifespan is limited. Here, we combine multi-site, harmonized cognitive, imaging, demographic, and clinical data from over 900 individuals to characterize a) cognitive deficits across the schizophrenia lifespan and b) the association between cognitive deficits, clinical presentation, and white matter (WM) microstructure. Multimodal harmonization was accomplished using T-scores for cognitive data, previously reported standardization methods for demographic and clinical data, and an established harmonization method for imaging data. We applied t-tests and correlation analysis to describe cognitive deficits in individuals with schizophrenia. We then calculated whole-brain WM fractional anisotropy (FA) and utilized regression-mediation analyses to model the association between diagnosis, FA, and cognitive deficits. We observed pronounced cognitive deficits in individuals with schizophrenia (p < 0.006), associated with more positive symptoms and medication dosage. Regression-mediation analyses showed that WM microstructure mediated the association between schizophrenia and language/processing speed/working memory/non-verbal memory. In addition, processing speed mediated the influence of diagnosis and WM microstructure on the other cognitive domains. Our study highlights the critical role of cognitive deficits in schizophrenia. We further show that WM is crucial when trying to understand the role of cognitive deficits, given that it explains the association between schizophrenia and cognitive deficits (directly and via processing speed).

Psychometric properties of the BIRT Motivation Questionnaire (BMQ), a self-measure of avolition in individuals with schizophrenia

AimsAvolition defined as a lack of interest or engagement in goal-directed behavior plays a key role in everyday functioning in schizophrenia and is considered as one of the main contributors to the burden of disease. The aim of this study was to 1) validate the self-report BIRT Motivation Questionnaire (BMQ-S) seldom used before in schizophrenia 2) examine the degree of agreement between the BMQ-S and its informant-report version 3) to assess its ability to predict real-world outcome at 12 month follow-up. MethodsOne hundred and twenty-two (51.9% inpatients) adults with a diagnosis of schizophrenia were included. Exploratory Factor analysis was performed on the BMQ-S to identify the underlying structure. Real life functioning was measured with the Global Assessment of Functioning scale (GAF). Convergent validity was assessed with the Scale for Assessment of Negative Symptom (SANS) and the Lille Apathy Rating Scale (LARS). ResultsThe main psychometric properties of the BMQ-S (internal consistency, test-retest reliability) were satisfactory. Exploratory factorial analysis revealed a 4-factor model which explained 76% of the overall variance. The BMQ-S correlated significantly with the LARS and the SANS avolition subscore suggesting adequate convergent validity. The correlation between the BMQ-S and the clinician-report version was 0.48. The global score and in particular the Initiation/disorganisation dimension was a significant predictor of global functioning at 12-months even when adjusted for age, chlorpromazine intake and depression. ConclusionOur findings indicate that the BMQ-S has satisfactory psychometric properties and that schizophrenia patients can reliably assess their lack of motivation. Self-evaluation of avolition should be considered in the overall prediction of real-world functioning in schizophrenia.

Predicting Real-World Functioning in Schizophrenia: The Relative Contributions of Neurocognition, Functional Capacity, and Negative Symptoms

Neurocognition and functional capacity are commonly reported predictors of real-world functioning in schizophrenia. However, the additional impact of negative symptoms, specifically its subdomains, i.e., diminished expression (DE) and avolition-apathy (AA), on real-world functioning remains unclear. The current study assessed 58 individuals with schizophrenia. Neurocognition was assessed with the Brief Assessment of Cognition in Schizophrenia, functional capacity with the UCSD Performance-based Skills Assessment (UPSA-B), and negative symptoms with the Negative Symptom Assessment-16. Real-world functioning was assessed with the Multnomah Community Ability Scale (MCAS) with employment status as an additional objective outcome. Hierarchical regressions and sequential logistic regressions were used to examine the associations between the variables of interest. The results show that global negative symptoms contribute substantial additional variance in predicting MCAS and employment status above and beyond the variance accounted for by neurocognition and functional capacity. In addition, both AA and DE predict the MCAS after controlling for cognition and functional capacity. Only AA accounts for additional variance in employment status beyond that by UPSA-B. In summary, negative symptoms contribute substantial additional variance in predicting both real-world functioning and employment outcomes after accounting for neurocognition and functional capacity. Our findings emphasize both DE and AA as important treatment targets in functional recovery for people with schizophrenia.

Is Utena's Brief Objective Measures (UBOM) useful in real‐world behavioral assessment of functioning? Validity and utility testing in patients with schizophrenia

Utena's Brief Objective Measures (UBOM) was developed to assess psychophysiological functions proximal to real-world functioning in individuals with psychiatric disorders, including schizophrenia (SCZ), to facilitate shared decision-making. However, the validity of UBOM has not been fully examined. We conducted a cross-sectional observational study to evaluate the validity of each of the three tests in UBOM: UBOM-Pulse, UBOM-Ruler, and UBOM-Random. We investigated associations: (i) between UBOM and existing cognitive- and autonomic-function tests; and (ii) between UBOM and daily social functioning. The participants included SCZ individuals and healthy controls. We evaluated the cognitive and autonomic function using UBOM, the heart rate variability test, the simple reaction time test, and the Brief Assessment of Cognition in Schizophrenia, Japanese version. We also assessed the daily social functioning using the WHO Disability Assessment Schedule 2.0 and the modified Global Assessment of Functioning, Japanese version. Thirty-one SCZ individuals and 35 healthy control individuals participated in this study. In the SCZ group, UBOM-Ruler was significantly associated with the Cognition and Getting Along domains of WHO Disability Assessment Schedule 2.0. UBOM-Random was significantly associated with the Brief Assessment of Cognition in Schizophrenia's Working Memory, Verbal Fluency and Attention domains, and the modified Global Assessment of Functioning in the SCZ group. The validity of the current version of UBOM is imperfect and further improvements will be necessary to attain the originally intended goal of developing a brief assessment tool for real-world functioning in SCZ.

What Do People With Schizophrenia Do All Day? Ecological Momentary Assessment of Real-World Functioning in Schizophrenia

Schizophrenia is a major cause of disability worldwide. As new treatments for functioning are tested, the need grows to demonstrate real-world functioning gains. Ecological momentary assessment (EMA) may provide a more ecologically valid measure of functioning. In this study, smartphone-based EMA was used to signal participants with schizophrenia (N = 100) and controls (N = 71) 7 times a day for 7 days to respond to brief questionnaires about social interactions and functioning behaviors. Excellent adherence was found, with both groups completing an average of 85% of surveys and only 3% of participants with schizophrenia excluded for poor adherence. Four-week test-retest reliability was high (r = .83 for total productive behaviors). Relative to controls, participants with schizophrenia reported significantly less total productive activity (d = 1.2), fewer social interactions (d = 0.3), more nonproductive behaviors (d = 1.0; watching TV, resting), and more time at home (d = 0.8). Within the schizophrenia group, participants living independently showed better functioning on EMA relative to participants in supported housing (d = 0.8) and participants engaged in vocational activities showed better functioning than individuals not engaged in vocational activities (d = 0.55). Modest correlations were found between EMA and an in-lab self-report measure of functioning activities performed in the community, but not between EMA and measures of functional capacity or potential. This study demonstrated the feasibility, sensitivity reliability, and validity of EMA methods to assess functioning in schizophrenia. EMA provides a much-needed measure of what individuals with schizophrenia are actually doing in real-world contexts. These results also suggest that there may be important disjunctions between indices of abilities and actual real-world functioning.

Disorganization and real-world functioning in schizophrenia: Results from the multicenter study of the Italian Network for Research on Psychoses

BackgroundA general consensus has not yet been reached regarding the role of disorganization symptoms in real-world functioning in schizophrenia. MethodsWe used structural equations modeling (SEM) to analyze the direct and indirect associations between disorganization and real-world functioning assessed through the Specific Levels of Functioning Scale (SLOF) in 880 subjects with schizophrenia. ResultsWe found that: 1) conceptual disorganization was directly and strongly connected with SLOF daily activities; difficulty in abstract thinking was associated with moderate strength to all SLOF domains, and poor attention was connected with SLOF work skills; 2) grandiosity was only related with poor work skills, and delusions were associated with poor functioning in all SLOF domains; interpersonal relationships were weakly indirectly influenced by hallucinatory behavior, delusions and unusual thought contents through the mediation of social cognition (SC); 3) among the negative symptoms, avolition had only direct links with SLOF work skills and SLOF activities; anhedonia had direct links with SLOF work skills and SLOF interpersonal and indirect link with SLOF work skills through functional capacity (FC); asociality with SLOF interpersonal; blunted affect had direct links with SLOF activities and indirect links with SLOF interpersonal relationships mediated by SC. Lastly, alogia had only indirect links mediated by SC, FC, and neurocognition (NC). ConclusionsOverall conceptual disorganization is the symptom that contributed more (both directly and indirectly) to the activities of community living in real-world. Thus, it should be considered as a treatment target in intervention programs for patients with schizophrenia.

S240. DETERMINANT FACTORS OF REAL-WORLD FUNCTIONING IN SCHIZOPHRENIA

BackgroundNegative, cognitive and depressive symptoms, as well as physical comorbidities, have a great impact on the real-world functioning in patients with schizophrenia (SZ) (1, 2, 3). However, not all the studies have employed accurate psychometric instruments to assess these symptoms, nor have all these factors been studied simultaneously.The aim of the current study is to analyze the determinants of functionality in SZ measured by the Personal and Social Performance (PSP) scale, and considering not exclusively psychopathological and cognitive variables, but also aspects related to physical health and inflammation.MethodsSample: 73 outpatients with SZ, duration of illness ≤10 years, under stable maintenance treatment [mean age (31.7 ± 6.5), males (61.6%)].Clinical variables: PANSS, CGI-Severity, Clinical Assessment Interview of Negative Symptoms (CAINS) -Motivation/Pleasure (MAP) & Expression (EXP) domains-, Brief Negative Symptom Scale (BNSS), Calgary Depression Scale (CDS), MATRICS Consensus Cognitive Battery (MCCB), PSP.Biological variables: Glucose, cholesterol, LDL, HDL, triglycerides, TSH, prolactin, insulin, uric acid, alkaline phosphatase (APh), C-reactive protein (CRP), TNF-α, interleukin(IL)-6, IL-2, IL-1β, IL-1RA, homocysteine, HT (% hemolysis), lipid peroxidation (LPO), catalase.Pearson correlations were performed to select variables significantly related to PSP scores which were later included in stepwise multiple linear regression analyses. Age, sex, education, smoking, alcohol use, BMI, antipsychotic equivalent doses and other confounding factors were considered.ResultsFinal model for PSP total score (R2=0.778, F=45.564, p<0.001) identified that CGI-Severity (β= -0.279), PANSS-NM (negative Marder Factor) (β = -0.218), Asociality subscale of BNSS (β= -0.383) and IL-2 (β= -0.269) were significant predictors.Predicting variables included in regression models for specific PSP domains:- Self-care (R2=0.661, F=22.947, p<0.001): PANSS-NM (β=0.458), Avolition subscale of BNSS (β=0.248), IL-2 (β=0.221), APh (β=0.201).- Useful activities (R2=0.563, F=42.473, p<0.001): CGI-S (β=0.245), Avolition (β=0.557).- Social relationships (R2=0.731, F=56.998, p<0.001): Asociality (β=0.578), PANSS-GP (β=0.276), CAINS-EXP (β=0.178).- Aggresive behaviour (R2=0.335, F=16.892, p<0.001): PANSS-P (β=0.408), CDS (β=0.273).Discussion1.Negative symptoms are the most important determinants of a deficit in the real-world functioning in SZ, especially “asociality.”2.“Apathy” has a negative impact on self-care and useful activities domains.3.Proinflammatory cytokine IL-2 marks poor functionality.

Laboratory to Life: Linking Brain Responses to Problems of Real World Functioning in Schizophrenia

Laboratory to Life: Linking Brain Responses to Problems of Real World Functioning in Schizophrenia

Negative symptoms and everyday functioning in schizophrenia: A cross-sectional study in a real world-setting

Negative symptoms have been suggested to have a greater impact on real-world functioning in schizophrenia than other symptoms. We aimed to examine the relationship of specific negative symptoms components (“expressive deficits” – DE – which include alogia and blunted affect, and “avolition” – AA – which includes amotivation, anhedonia, and asociality), with separate domains of real-world outcomes (the Personal and Social Performance Scale – PSP – and selected items of the Heinrichs Quality of Life Scale – QLS – that did not overlap with negative symptoms) and two functional milestones (recent employment and marriage). Regression analyses were performed to identify the determinants of QLS and PSP scores and of the two milestones, in 92 consecutive outpatients with stable schizophrenia. AA was the strongest predictor of QLS interpersonal relations and social network (IRSN), PSP total score and the first three PSP domains. The variance explained ranged from 36% for PSP self care to 54% for the PSP personal and social relationships. Moreover, higher scores in AA were significant predictors of the single status. DE does not appear to have an impact at real-world functional performance. Taken together, our analysis indicates a relatively specific set of relationships between the AA subdomain and aspects of real-world functioning in schizophrenia. These findings, if confirmed, could have important implications for research, diagnostics and treatment: in fact our results would suggest that AA and DE should be analyzed as separate and distinct domains to be rated and treated individually.

Real-world functioning in schizophrenia: pathways between neurocognition, social cognition, and functional competence

Real-world functioning in schizophrenia: pathways between neurocognition, social cognition, and functional competence

Direct and mediated effects of cognitive function with multidimensional outcome measures in schizophrenia: The role of functional capacity

Although cognitive ability is a known predictor of real-world functioning in schizophrenia, there has been an expanded interest in understanding the mechanisms by which it explains real-world functioning in this population. We examined the extent to which functional capacity (i.e., skills necessary to live independently) mediated the relationship between cognitive ability and both observer and self-reported real-world functioning in 138 outpatients with schizophrenia. Functional capacity significantly mediated the relations between cognitive ability and observer-rated real-world functioning, but not self-reported real-world functioning, with small to medium effect sizes observed for all outcomes. The role of cognitive ability in observer versus self-reported real-world functioning may be explained by different mechanisms.

Cognitive Remediation in Schizophrenia: Current Status and Future Perspectives

Objectives. This study is aimed to review the current scientific literature on cognitive remediation in schizophrenia. In particular, the main structured protocols of cognitive remediation developed for schizophrenia are presented and the main results reported in recent meta-analyses are summarized. Possible benefits of cognitive remediation in the early course of schizophrenia and in subjects at risk for psychosis are also discussed. Methods. Electronic search of the relevant studies which appeared in the PubMed database until April 2013 has been performed and all the meta-analyses and review articles on cognitive remediation in schizophrenia have been also taken into account. Results. Numerous intervention programs have been designed, applied, and evaluated, with the objective of improving cognition and social functioning in schizophrenia. Several quantitative reviews have established that cognitive remediation is effective in reducing cognitive deficits and in improving functional outcome of the disorder. Furthermore, the studies available support the usefulness of cognitive remediation when applied in the early course of schizophrenia and even in subjects at risk of the disease. Conclusions. Cognitive remediation is a promising approach to improve real-world functioning in schizophrenia and should be considered a key strategy for early intervention in the psychoses.

A path model investigation of neurocognition, theory of mind, social competence, negative symptoms and real-world functioning in schizophrenia

Problems in real-world functioning are pervasive in schizophrenia and much recent effort has been devoted to uncovering factors which contribute to poor functioning. The goal of this study was to examine the role of four such factors: social cognition (theory of mind), neurocognition, negative symptoms, and functional capacity (social competence). 178 individuals with schizophrenia or schizoaffective disorder completed measures of theory of mind, neurocognition, negative symptoms, social competence, and self-reported functioning. Path models sought to determine the relationships among these variables. Theory of mind as indexed by the Hinting Task partially mediated the relationship between neurocognition and social competence, and negative symptoms and social competence demonstrated significant direct paths with self-reported functioning. Study results suggest theory of mind serves as an important mediator in addition to previously investigated social cognitive domains of emotional and social perception. The current study also highlights the need to determine variables which mediate the relationship between functional capacity and real-world functioning.

Further support for the role of dysfunctional attitudes in models of real-world functioning in schizophrenia

According to A.T. Beck and colleagues’ cognitive formulation of poor functioning in schizophrenia, maladaptive cognitive appraisals play a key role in the expression and persistence of negative symptoms and associated real-world functioning deficits. They provided initial support for this model by showing that dysfunctional attitudes are elevated in schizophrenia and account for significant variance in negative symptoms and subjective quality of life. The current study used structural equation modeling to further evaluate the contribution of dysfunctional attitudes to outcome in schizophrenia. One hundred eleven outpatients and 67 healthy controls completed a Dysfunctional Attitudes Scale, and patients completed a competence measure of functional capacity, clinical ratings of negative symptoms, and interview-based ratings of real-world functioning. Patients reported higher defeatist performance beliefs than controls and these were significantly related to lower functional capacity, higher negative symptoms, and worse community functioning. Consistent with Beck and colleagues’ formulation, modeling analyses indicated a significant indirect pathway from functional capacity → dysfunctional attitudes → negative symptoms → real-world functioning. These findings support the value of dysfunctional attitudes for understanding the determinants of outcome in schizophrenia and suggest that therapeutic interventions targeting these attitudes may facilitate functional recovery.

Neurocognitive and symptom correlates of daily problem-solving skills in schizophrenia

Functional outcome for individuals with schizophrenia has been associated with cognitive impairment. Deficits in attention, memory, speed of information processing and problem-solving skills affect independent functioning, vocational performance, and interpersonal functioning. This study investigated the relationship between neurocognitive functioning, clinical symptoms and daily problem-solving skills in seriously and persistently ill persons. Thirty-eight inpatients and outpatients were administered a neurocognitive battery for attention, working memory, processing speed, perceptual organization, and executive functioning; and semi-structured clinical interviews using the BPRS and SANS. Estimates of daily problem-solving skills were obtained using the relevant factor subscale from the Independent Living Scales (ILS-PB). Daily problem-solving skills were significantly correlated with negative symptoms, processing speed, verbal memory, and working memory scores. A regression model using an enter method suggests that working memory and negative symptoms are significant predictors of daily problem-solving skills and account for 73.2% of the variance. Further analyses demonstrate that daily problem-solving skills and negative symptoms were significantly different for inpatients and outpatients and significantly correlated with community status. The findings suggest the ILS-PB has utility as a proxy measure for assessing real-world functioning in schizophrenia.

C.17.04 Comparison of lithium and valproate in the treatment of mania: predictive factors and tolerance issues

Negative symptoms have been suggested to have a greater impact on real-world functioning in schizophrenia than other symptoms. We aimed to examine the relationship of specific negative symptoms components (“expressive deficits” – DE – which include alogia and blunted affect, and “avolition” – AA – which includes amotivation, anhedonia, and asociality), with separate domains of real-world outcomes (the Personal and Social Performance Scale – PSP – and selected items of the Heinrichs Quality of Life Scale – QLS – that did not overlap with negative symptoms) and two functional milestones (recent employment and marriage). Regression analyses were performed to identify the determinants of QLS and PSP scores and of the two milestones, in 92 consecutive outpatients with stable schizophrenia. AA was the strongest predictor of QLS interpersonal relations and social network (IRSN), PSP total score and the first three PSP domains. The variance explained ranged from 36% for PSP self care to 54% for the PSP personal and social relationships. Moreover, higher scores in AA were significant predictors of the single status. DE does not appear to have an impact at real-world functional performance. Taken together, our analysis indicates a relatively specific set of relationships between the AA subdomain and aspects of real-world functioning in schizophrenia. These findings, if confirmed, could have important implications for research, diagnostics and treatment: in fact our results would suggest that AA and DE should be analyzed as separate and distinct domains to be rated and treated individually.