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Longitudinal studies of cognition and functional outcome in schizophrenia: Implications for MATRICS
Abstract
It is generally accepted that cognitive deficits in schizophrenia are related to functional outcome. However, support for longitudinal relationships between cognition and functional outcome has not been as well documented. The current paper presents a review of 18 recently published longitudinal studies (minimum 6-month follow up) of the relationships between cognition and community outcome in schizophrenia. Results from these studies reveal considerable support for longitudinal associations between cognition and community outcome in schizophrenia. These studies demonstrate that cognitive assessment predict later functional outcome and provide a rationale for psychopharmacological interventions for cognitive deficits in schizophrenia. Although the relationships between cognition and community outcome are well-supported, it is clear that community functioning is also affected by a host of factors apart from cognition that are usually not considered in clinical trial studies (e.g., psychosocial rehabilitation and educational/vocational opportunities). In the second part of the paper, we consider intervening steps between cognitive performance measures and community outcome. These steps are apt to have important implications for clinical trials of cognition-enhancing agents in schizophrenia.
... Several studies have found that interventions targeting negative symptoms, i. e., cognitive remediation therapy and social skills training, can positively affect cognitive abilities [20,21]. Furthermore, clinical focus on negative symptoms to enhance cognitive function in schizophrenia is of major importance since cognitive impairments are also strongly linked to functional outcomes, such as employment and social interaction [22]. Thus, by better management of negative symptoms, clinicians may open a pathway to enhance the overall real-world performance and functional recovery of patients with schizophrenia [22,23]. ...
... Furthermore, clinical focus on negative symptoms to enhance cognitive function in schizophrenia is of major importance since cognitive impairments are also strongly linked to functional outcomes, such as employment and social interaction [22]. Thus, by better management of negative symptoms, clinicians may open a pathway to enhance the overall real-world performance and functional recovery of patients with schizophrenia [22,23]. ...
... While the verbal memory, processing speed, reasoning, and vigilance domains were dominated by age and IQ as the most relevant factors, the working memory and neurocognitive summary domains seem to be attributable to a highly multifaceted interplay of influencing factors. Our findings confirm a strong connection between negative symptoms and impaired cognitive function, as discussed in previous studies [19,22,23]. Personalized treatment plans might benefit from a focus on better management of negative symptoms to enhance real-world performance and functional recovery in schizophrenia patients. ...
Introduction: The complex nature of neurocognitive impairment in schizophrenia has been discussed in light of the mixed effects of antipsychotic drugs, psychotic symptoms, dopamine D2 receptor blockade, and intelligence quotient (IQ). These factors have not been thoroughly examined before.
Methods: This study conducted a comprehensive re-analysis of the CATIE data using machine learning techniques, in particular Conditional Inference Tree (CTREE) analysis, to investigate associations between neurocognitive functions and moderating factors such as estimated trough dopamine D2 receptor blockade with risperidone, olanzapine, or ziprasidone, Positive and Negative Syndrome Scale (PANSS), and baseline IQ in 573 patients with schizophrenia.
Results: The study reveals that IQ, age, and education consistently emerge as significant predictors across all neurocognitive domains. Furthermore, higher severity of PANSS-negative symptoms was associated with lower cognitive performance scores in several domains. CTREE analysis, in combination with a genetic algorithm approach, has been identified as particularly insightful for illustrating complex interactions between variables. Lower neurocognitive function was associated with factors such as age>52 years, IQ<94/95,<12/13 education years, and more pronounced negative symptoms (score<26).
Conclusions: These findings emphasize the multifaceted nature of neurocognitive functioning in patients with schizophrenia, with the PANSS-negative score being an important predictor. This gives rise to a role in addressing negative symptoms as a therapeutic objective for enhancing cognitive impairments in these patients. Further research must examine nonlinear relationships among various moderating factors identified in this work, especially the role of D2 occupancy.
... Negative symptoms and cognitive deficits that are present throughout life to a various extent in a high percentage of schizophrenia patients are usually key predictors of functional outcomes [16][17][18][19][20][21][22][23][24][25][26] . ...
... The expression of emotions is presented as blunted affect and alogia and mainly affects active relationships. Emotional experience, including avolition, anhedonia and asociality, mirrors a lack of motivation to attend activities and social interaction and is linked to poorer functional outcomes [19][20][21][22][23][24][25]42 . ...
... In our study, cognitive deficit also influenced psychosocial functioning with medium predictive value; however, after taking into account negative symptoms (experience and expression deficits), the predictive influence of cognitive impairment was substantially lower. Some studies demonstrated in contradiction with our results a higher impact of cognitive impairment on function outcome than psychotic symptoms (negative and positive) 23,25 . In our sample, the worst findings in cognitive performance were in social cognition, speed of processing and attention/vigilance domains. ...
Schizophrenia has a profound influence on the real-life functioning of patients. There are several factors inherent to the disease course affecting the level of psychosocial functioning. Our study focused on the impact of cognitive deficit and severity of negative symptoms (i.e., the experiential domain (avolition, asociality, and anhedonia) and the expressive domain (blunted affect and alogia)) to explore psychosocial functioning in schizophrenia. Schizophrenia patients ( n = 211) were tested for the presence of cognitive impairment using the NIMH-MATRICS: Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Cattery (MCCB; MATRICS Consensus Cognitive Battery) and the extent of negative symptoms using the PANSS (PANSS; Positive and Negative Syndrome Scale—selected items). The level of psychosocial functioning was measured with the Personal and Social Performance Scale (PSP). The path analysis using three regression models was used to analyse variables influencing psychosocial functioning (PSP). One of these models analyzed influence of cognitive functioning (MCCB) and negative schizophrenia symptoms (PANSS selected items reflecting expressive and experiential deficits) as predictors and NART/CRT and disease length as confounders. R ² was 0.54. The direct effect of the MCCB ( β = 0.09) on the PSP was suppressed by the strong effect of the negative symptoms ( β = −0.64). The presence of cognitive deficits and negative symptoms in our sample of schizophrenia patients significantly influences the level of their psychosocial functioning, a key factor in remission and recovery.
... It was established that the cognitive deficit (which is entirely deducible) is the cause of the catastrophic psychosocial outcome of schizophrenia. Throughout the disease, a reduction in IQ from the norm of 100 to [70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85] has been reported [20][21][22]. Cognitive symptoms are also the primary tool for adaptation to the dynamically changing reality. ...
... When comparing patients with resistance and those with a treatment effect, we found a significant difference in all measures, which was most pronounced in terms of fixation. Our observations confirm the results of other authors on the presence of differences between patients with and without deficits, and that deficits in memory and attention are associated with a poor prognosis [81,82]. The data from the literature show that the cognitive deficit is observed even before the onset of psychosis [83,84] and remains stable for a certain period [41,42,45], and after ten years a deterioration can be observed, usually associated with other factors such as BMI metabolic disorders as well as those involving other organs and systems [46]. ...
Unlabelled:
Schizophrenia is traditionally associated with the presence of psychotic symptoms. In addition to these, cognitive symptoms precede them and are present during the entire course of the schizophrenia process. The present study aims to establish the relationship between working memory (short-term memory and attention), the features of the clinical picture, and the course of the schizophrenic process, gender distribution and resistance to treatment.
Methods:
In total, 105 patients with schizophrenia were observed. Of these, 66 were women and 39 men. Clinical status was assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), Dimensional Obsessive-Compulsive Symptom Scale (DOCS), scale for dissociative experiences (DES) and Hamilton Depression Rating Scale (HAM-D)-cognitive functions using the Luria 10-word test with fixation assessment, reproduction and attention analysis. The clinical evaluation of resistance to the treatment showed that 45 patients were resistant to the ongoing medical treatment and the remaining 60 had an effect from the therapy.
Results:
Our study showed that, in most patients, we found disorders of working memory and attention. In 69.82% of the patients, we found problems with fixation; in 38.1%, problems with reproduction; and in 62.86%, attention disorders. Conducting a regression analysis showed that memory and attention disorders were mainly related to the highly disorganized symptoms scale, the duration of the schizophrenic process and the dissociation scale. It was found that there was a weaker but significant association between the age of onset of schizophrenia and negative symptoms. In the patients with resistant schizophrenia, much greater violations of the studied parameters working memory and attention were found compared to the patients with an effect from the treatment.
Conclusion:
Impairments in working memory and attention are severely affected in the majority of patients with schizophrenia. Their involvement is most significant in patients with resistance to therapy. Factors associated with the highest degree of memory and attention impairment were disorganized symptoms, duration of schizophrenia, dissociative symptoms and, to a lesser extent, onset of illness. This analysis gives us the right to consider that the early and systematic analysis of cognition is a reliable marker for tracking both clinical dynamics and the effect of treatment.
... Cognitive impairment is at the core of schizophrenia psychopathology as demonstrated by a very large body of literature indicating deficits in several domains such as Working Memory (WM), attention, executive function, episodic memory, and social cognition (Antonucci et al., 2020;Barch and Ceaser, 2012;Kahn and Keefe, 2013;McCutcheon et al., 2020;Weinberger and Harrison, 2011). Cognitive deficits impact realworld functioning in patients with schizophrenia contributing to longterm disability and increasing the disease burden (Bowie et al., 2006;Cowman et al., 2021;Green et al., 2004;Mucci et al., 2021). Even though different cognitive remediation strategies have been proposed with some currently used in clinical practice (Galderisi et al., 2010;Velligan et al., 2000), the effect on functional outcome is low-tomoderate (Allott et al., 2020;McGurk et al., 2007;Vita et al., 2021;Wykes et al., 2011) and no specific pharmacological treatment is available to modulate cognitive deficits. ...
... MNI coordinates (x, y, z) are in mm. models (Bang and Brown, 2009;Esclassan et al., 2009) and experimental medicine studies in humans (Green et al., 2004;Koller et al., 2003) indicating that antagonism at muscarinic receptors impairs WM processing. Here we did not find an effect of ACB on reaction time during the N-Back. ...
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.
... Significant cognitive impairments are present in an overwhelming majority of individuals diagnosed with schizophrenia and other psychotic spectrum disorders (Harvey et al., 2022), and have been shown to predict both progress in psychosocial rehabilitation (Kurtz et al., 2011) as well as overall functioning (Green et al., 2004). As such, cognitive impairments represent an important treatment target. ...
While cognitive remediation therapy (CRT) and compensatory strategy training both have large literature bases supporting their efficacy on both proximal and distal outcomes, the research base on stand-alone cognitive training (CT) is smaller and less consistent, with little information about factors associated with better outcomes. In this study, we examined the efficacy of CT on training task, cognitive, symptom, and functional ability measures as well as the impact of motivational interviewing (MI), motivation level, and session attendance on treatment outcomes. Adults with psychotic spectrum disorders (n = 114) were randomized to MI or a sham control interview (CI), followed by 4 months of computerized CT. In whole sample analyses, participants improved on training tasks, cognitive performance, and psychiatric symptoms, but self-reported cognition, self-reported depression, and functional ability did not change. Compared to CI, MI was associated with greater reductions in self-reported depressive symptoms. Motivation level and session attendance did not significantly influence outcomes. Findings support the efficacy of CT on several key outcomes, and its simplicity may be advantageous in uptake in community clinics with limited staffing. The lack of functional gains underscores the need to incorporate treatment ingredients that promote generalization and real-world implementation of learned skills. We also speculate that engagement during course of training may be a better predictor of training success than baseline task-specific motivation.
... One of the most disabling symptoms of schizophrenia is the impairment of cognitive function [1][2][3]. This should receive full attention in treatment since cognitive function is associated with functional outcomes [4]. Improving cognitive function is an important treatment goal. ...
Background: Cognitive impairment is a core symptom of schizophrenia and is associated with functional outcomes. Improving cognitive function is an important treatment goal. Studies have reported beneficial cognitive effects of the second-generation antipsychotic (SGA) ziprasidone. Reducing the dose of first-generation antipsychotics (FGA) might also improve cognitive function. This study compared the cognitive effects in long-stay patients who were randomized to groups who underwent FGA dose reduction or switched to ziprasidone. Methods: High-dose FGA was reduced to an equivalent of 5 mg of haloperidol in 10 patients (FGA-DR-condition), and 13 patients switched to ziprasidone 80 mg b.i.d. (ZIPRA condition). Five domains of cognitive function were assessed before dose reduction or switching (T0) and after 1 year (T1). This study was approved by the ethics committee of the Open Ankh (CCMO number 338) and registered at the Netherlands Trial Register (code 5864). Results: Non-significant deterioration was seen in all cognitive domains studied in the FGA-DR condition, whereas there was a non-significant improvement in all cognitive domains in the ZIPRA condition. The most robust difference between conditions, in favor of ziprasidone, was in executive function. Conclusions: In patients with severe chronic schizophrenia, ziprasidone had a non-significant and very modest beneficial effect on cognitive function compared with FGA dose reduction. Larger trials are needed to further investigate this effect.
... Despite some studies failing to identify substantial variations between BDNF levels of patients with SCZ and those of healthy controls (Huang and Lee, 2006;Shimizu et al., 2003), several meta-analyses have shown that SCZ patients display reduced levels of BDNF (Fernandes, 2015;Green et al., 2011;Rodrigues-Amorim et al., 2018). BDNF levels have been associated with symptom severity in SCZ, with several studies indicating an association between lower BDNF levels and higher severity of depressive and negative symptoms (Fang et al., 2019;Isayeva et al., 2022;Manchia et al., 2022;Wysokiński, 2016), as well as impaired cognitive function (Ahmed et al., 2015;Carlino et al., 2011;Green et al., 2004;Isayeva et al., 2022;Zhang et al., 2012). The Val66Met (rs6265) polymorphism within the BDNF gene, produces valine (Val) to methionine (Met) substitution at codon 66, and is the most commonly studied polymorphism within the BDNF gene. ...
... The deficits are relatively stable during the illness, and nearly all cognitive deficits are comparable in magnitude across first episode psychosis (FEP) individuals and chronic schizophrenia [2], though recent studies show evidence for selective cognitive declines over time [7,8]. Cognitive deficits are associated with difficulties in social functioning and a worse prognosis, [9][10][11] and are more predictive of social functioning than psychotic symptoms [12][13][14] Whereas established non-pharmacological interventions for FEP patients usually include family interventions, psychoeducation, cognitive-behavioral therapy, and vocational interventions [15], cognitive impairments in early intervention services are generally undetected and undertreated. This is so despite the fact that attending to neurocognitive deficits through appropriate treatments has proved effective in improving social functioning [16]. ...
Neurocognitive deficits are a core feature of psychotic disorders, but it is unclear whether they affect all individuals uniformly. The aim of this systematic review and meta-analysis was to synthesize the evidence on the magnitude, progression, and variability of neurocognitive functioning in individuals with first-episode psychosis (FEP). A multistep literature search was conducted in several databases up to November 1, 2022. Original studies reporting on neurocognitive functioning in FEP were included. The researchers extracted the data and clustered the neurocognitive tasks according to the seven Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) domains and six additional domains. Random-effect model meta-analyses, assessment of publication biases and study quality, and meta-regressions were conducted. The primary effect size reported was Hedges g of (1) neurocognitive functioning in individuals at FEP measuring differences with healthy control (HC) individuals or (2) evolution of neurocognitive impairment across study follow-up intervals. Of 30,384 studies screened, 54 were included, comprising 3,925 FEP individuals and 1,285 HC individuals. Variability analyses indicated greater variability in FEP compared to HC at baseline and follow-up. We found better neurocognitive performance in the HC group at baseline and follow-up but no differences in longitudinal neurocognitive changes between groups. Across the 13 domains, individuals with FEP showed improvement from baseline in all studied domains, except for visual memory. Metaregressions showed some differences in several of the studied domains. The findings suggest that individuals with FEP have marked cognitive impairment, but there is greater variability in cognitive functioning in patients than in HC. This suggests that subgroups of individuals suffer severe disease-related cognitive impairments, whereas others may be much less affected. While these impairments seem stable in the medium term, certain indicators may suggest potential further decline in the long term for a specific subgroup of individuals, although more research is needed to clarify this. Overall, this study highlights the need for tailored neurocognitive interventions for individuals with FEP based on their specific deficits and progression.
... In addition, we recently reported an association between the severity of treatment resistance and longitudinal cognitive decline among patients with schizophrenia, with ultra-treatmentresistant subjects showing an overall cognitive deterioration over time compared to both first-line responders and clozapine responders [52]. If cognitive deficits represent major determinants of functional outcome and quality of life [1,25], targeting cognitive impairment becomes even more crucial in TRS patients in order to minimize cognitive and functional deterioration. ...
Treatment-Resistant Schizophrenia (TRS) represents a main clinical issue, associated with worse psychopathological outcomes, a more disrupted neurobiological substrate, and poorer neurocognitive performance across several domains, especially in verbal abilities. If cognitive impairment is a major determinant of patients’ functional outcomes and quality of life, targeting cognitive dysfunction becomes even more crucial in TRS patients in order to minimize cognitive and functional deterioration. However, although Cognitive Remediation Therapy (CRT) represents the best available tool to treat cognitive dysfunction in schizophrenia, specific evidence of its efficacy in TRS is lacking. Based on these premises, our study aimed at investigating possible differences in CRT outcomes in a sample of 150 patients with schizophrenia, stratified according to antipsychotic response (TRS vs. non-TRS). Subjects were assessed for neurocognition through Brief Assessment of Cognition in Schizophrenia (BACS) and the Wisconsin Card Sorting Test (WCST) at baseline and after CRT. As expected, we observed greater baseline impairment among TRS patients in BACS-Verbal Memory and WCST-Executive Functions. Repeated measures ANCOVAs showed significant within-group pre-/post-CRT differences in the above-mentioned domains, both among non-TRS and TRS subjects. However, after CRT, no differences were observed between groups. This is the first study to indicate that CRT represents a highly valuable resource for TRS patients, since it may be able to fill the cognitive gap between treatment response groups. Our finding further highlights the importance of early implementation of CRT in addition to pharmacotherapy to reduce the cognitive and functional burden associated with the disease, especially for TRS patients.
... This can lead to significant economic burdens for both the patient and their family, as unemployment and loss of income are common consequences of the illness [36][37][38] . Several factors, including cognitive function, psychiatric symptoms, and social functioning, contribute to employment in patients with schizophrenia 29,39,40 . It is important to recognize that employment plays a crucial role in the lives of patients with schizophrenia. ...
Schizophrenia is a psychiatric disorder that is associated with various social dysfunctions, including shorter work hours. To measure the degree to which psychiatrists adhere to guidelines for pharmacological therapy of schizophrenia, we recently developed the individual fitness score (IFS) for adherence among psychiatrists in each patient. However, it remains unclear whether better adherence among psychiatrists is associated with higher patients’ social functional outcomes, such as work hours. In this study, we examined the relationship between adherence to guidelines among psychiatrists and work hours in patients with schizophrenia. To evaluate the association between adherence to guidelines for pharmacological therapy among psychiatrists for treating schizophrenia and work hours, we used the IFS and social activity assessment, respectively, in 286 patients with schizophrenia. The correlation between IFS values and work hours was investigated in the patients. The adherence among psychiatrists to guidelines was significantly and positively correlated with work hours in patients with schizophrenia ( rho = 0.18, p = 2.15 × 10 ⁻ ³ ). When we divided the patients into treatment-resistant schizophrenia (TRS) and nontreatment-resistant schizophrenia (non-TRS) groups, most patients with TRS ( n = 40) had shorter work hours (0–15 h/week). Even after excluding patients with TRS, the positive correlation between adherence to guidelines among psychiatrists and work hours in patients with non-TRS ( n = 246) was still significant ( rho = 0.19, p = 3.32 × 10 ⁻ ³ ). We found that work hours were longer in patients who received the guideline-recommended pharmacotherapy. Our findings suggest that widespread education and training for psychiatrists may be necessary to improve functional outcomes in patients with schizophrenia.
... From a clinical perspective, schizophrenia is usually manifested with a gradual and slow onset, very rarely abruptly within a few days or weeks and mostly in early adolescence or at young age, but may also occur later in life, and is more common in females. The clinical presentation is focused on the subjective and objective syndromes, symptoms or signs of schizophrenia, i.e. the manifestation of the disorder is heterogeneous and is best described by the so-called pentagonal model of symptoms that includes positive, negative, cognitive, affective, and aggressive-hostile symptoms [4,5]. The positive or psychotic symptoms in schizophrenia refer to painful ideas -delusions, illogical speech and hallucinations, and the negative symptoms include: decreased motivation, lethargy, numbness of emotional expression and poorer speech [6]. ...
Objective: The aim of the study was to introduce the relationship between positive and negative symptoms, cognitive deficit and antipsychotic treatment in acute schizophrenic patients. Methods: The study included 21 acute schizophrenic patients who were selected from the Psychiatric Hospital in Skopje, and were diagnosed according to the ICD-10. All patients were receiving antipsychotic medication treatment at the time of testing and during the time they were clinically stable. At the beginning of the treatment all subjects received higher dose of neuroleptics, and before they left the hospital they were given lower drug doses. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of positive and negative symptoms respectively. The Schizophrenia Cognition Rating Scale (SCoRS) was used to assess the cognitive function before and after the neuroleptic treatment. Statistical analysis of the results obtained in the research was conducted with SPSS 20.0 for Windows package program. The results were analyzed by applying Wilcoxon Signed Ranks Test and Pearson correlation coefficient. Results: The results indicated that the acute schizophrenic patients had higher global rating score in the SCoRS assessment (M=53.667, SD=8.345) in the first weeks after psychosis onset. After 6-8 weeks treatment with antipsychotic medications, they had lower global rating score in the SCoRS assessment (M=41.952, SD=6.951). There was a positive relationship between the total SCoRS score and the dose of neuroleptics (Z=-3.925, sig.=0.000, p<.001). The high degree of positive and negative symptoms was a strong predictor of higher cognitive deficits in schizophrenic patients. The positive relationship was observed between the high dose of therapy, PANSS-Positive and ScoRS level (r=.552, p<.01) and PANSS-Negative and ScoRS level (r=.607, p<.01). In addition, there was a positive relationship between the low dose of therapy, PANSS-Positive and ScoRS level (r=.342, p<.05) and PANSS-Negative and ScoRS level (r=.432, p<.01). Conclusions: During our work, we found that the regular and continued use of antipsychotic medications in schizophrenic disorders and good cooperation with the patients during the therapy could be important for better cognitive function of the person.
... Therefore, developing adjunctive cognition-enhancing treatments is a high priority for the population with psychotic disorders. Improving cognitive function indicates disease regression, helps patients resume their social lives earlier, and reduces the burden on family and society [3]. ...
Cognitive impairment is a core feature of schizophrenia, which is aggravated by antipsychotics-induced metabolic disturbance and lacks effective pharmacologic treatments in clinical practice. Our previous study demonstrated the efficiency of metformin in alleviating metabolic disturbance following antipsychotic administration. Here we report that metformin could ameliorate cognitive impairment and improve functional connectivity (FC) in prefrontal regions. This is an open-labeled, evaluator-blinded study. Clinically stable patients with schizophrenia were randomly assigned to receive antipsychotics plus metformin (N = 48) or antipsychotics alone (N = 24) for 24 weeks. The improvement in cognition was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Its association with metabolic measurements, and voxel-wise whole-brain FC with dorsolateral prefrontal cortex (DLPFC) subregions as seeds were evaluated. When compared to the antipsychotics alone group, the addition of metformin resulted in significantly greater improvements in the MCCB composite score, speed of processing, working memory, verbal learning, and visual learning. A significant time × group interaction effect of increased FC between DLPFC and the anterior cingulate cortex (ACC)/middle cingulate cortex (MCC), and between DLPFC subregions were observed after metformin treatment, which was positively correlated with MCCB cognitive performance. Furthermore, the FC between left DLPFC A9/46d to right ACC/MCC significantly mediated metformin-induced speed of processing improvement; the FC between left A46 to right ACC significantly mediated metformin-induced verbal learning improvement. Collectively, these findings demonstrate that metformin can improve cognitive impairments in schizophrenia patients and is partly related to the FC changes in the DLPFC. Trial Registration: The trial was registered with ClinicalTrials.gov (NCT03271866). The full trial protocol is provided in Supplementary Material.
... For instance, large trials with antipsychotics indicate no or minimal positive effects on different cognitive domains (47) including attention (69) in clinically similar samples of schizophrenic patients compared to our study. Therefore, the bene cial effect of APVG on sustained attention with the accompanied increase of HC-PFC network is noteworthy with regard to possible intervention strategies in schizophrenia since cognitive de cits and particularly attentional de cits(70) are a core aspect of the disease and have a major impact on the patient's functional outcome (25). ...
Recent research shows that videogame training enhances neuronal plasticity and cognitive improvements in healthy individuals. As patients with schizophrenia exhibit reduced neuronal plasticity linked to cognitive deficits and symptoms, we investigated whether videogame-related cognitive improvements and plasticity changes extend to this population. In a training study, patients with schizophrenia and healthy controls were randomly assigned to 3D or 2D platformer videogame training or E-book reading (active control) for 8 weeks, 30 minutes daily. After training, both videogame groups showed significant increases in sustained attention compared to the control group, correlated with increased functional connectivity in a hippocampal-prefrontal network. Notably, patients trained with videogames mostly improved in negative symptoms, general psychopathology, and perceived mental health recovery. Videogames, incorporating initiative, goal setting and gratification, offer a training approach closer to real life than current psychiatric treatments. Our results provide initial evidence that they may represent a possible adjunct therapeutic intervention for complex mental disorders.
... • La presencia de un déficit cognitivo franco (Liddle, 2000;Green, Kern & Heaton, 2004;Kessler et al., 2009). ...
En este trabajo se propone una reflexión en torno a qué se entiende por rehabilitaciónpsicosocial de las personas que sufren un trastorno mental severo y recurrente, cuál es susentido, su porqué, qué caracteriza a sus legítimas praxis y si a día de hoy la rehabilitaciónpsicosocial tiene vigencia. Para ello se analizan los conceptos de deterioro psicosocial yFilosofía de la Rehabilitación, así como su alcance e importancia para la práctica profesional. Sedetallan nueve principios en los que la Filosofía de la Rehabilitación se puede resumir. Talesprincipios siempre deberían marcar y guiar todo el trabajo rehabilitador. Se esgrimenargumentos para sustentar que, inherente a los procesos de rehabilitación psicosocial, sedistingue una serie de componentes estructurales que otorgan sentido e identidad a larehabilitación, y otros componentes, coyunturales, que, no siendo ni esenciales ni vertebrales,cobran importancia y sentido en el ámbito de lo circunstancial y lo situacional. Así mismo, seaportan criterios para determinar cuándo es pertinente aplicar programas estructurados,sistemáticos y activos de rehabilitación psicosocial y bajo que premisas no estaría indicadohacerlo. Se termina concluyendo que, sólo se rehabilita psicosocialmente cuando se promuevenconductas similares a las que la sociedad reconoce como propias y se fomenta hábitos queidentifican a la persona como integrante de su comunidad de referencia. A día de hoy, si no sere-habilita la rehabilitación psicosocial, se corre el riesgo de que, al menos las personas contrastorno mental severo y deterioro psicosocial más grave, queden desplazadas de unaatención comunitaria y rehabilitadora a una atención ocupacional e “institucionalizadora”.
... There is clear evidence that cognitive impairments are present at different stages of SCZ, from prodrome to multi-episode stage, and more severe in chronic patients 2 . Longitudinal studies (at least 6-month follow-up) have reported significant associations between cognition and community outcomes in SCZ 3 . Antipsychotic drugs are the main treatment for SCZ and are effective in alleviating positive symptoms, however, they have a minimal effect on cognitive deficits and their treatment remains unsatisfactory 4,5 . ...
High frequency (HF)-rTMS has been shown to improve cognitive functions in patients with schizophrenia (SCZ). This study aimed to investigate whether COX-2 rs5275 variants were associated with cognitive improvements following rTMS treatment in patients with SCZ. Forty-eight hospitalized patients with SCZ were assigned to the neuronavigation HF-rTMS group and 28 patients to the sham group over left DLPFC for 1 month. Cognitive function was evaluated using the repeatable battery for the assessment of neuropsychological status (RBANS) at weeks 0 and 4. COX-2 rs5275 polymorphism was genotyped by a technician. At baseline, C allele carriers showed better cognitive performance relative to patients with TT homozygote. Additionally, C allele carriers had greater improvement in memory from the follow-up to baseline following rTMS stimulation, while patients with the TT genotype showed no significant improvement in memory index. More importantly, we found that COX-2 rs5275 was correlated with the response to rTMS after controlling for the covariates. This study data indicate that COX-2 rs5275 was associated with improvements in immediate memory after HF-rTMS treatment in patients with SCZ. rTMS shows an effect on memory only in C allele carriers, but not in those with the TT genotype.
... Specifically, deficits in cognitive processing can hamper adhering to working life or education. 42,43 Note, however, that in addition to cognitive impairments, low functional outcome could also result from factors such as medication 43 and substance abuse. 44 Overall, our findings imply that neuroimaging-based ML models trained to distinguish SCH from controls adopt a pattern that weights cognitive abnormalities, potentially leading to false positives in other diagnostic groups with cognitive impairments. ...
Background and hypothesis
Neuroimaging-based machine learning (ML) algorithms have the potential to aid the clinical diagnosis of schizophrenia. However, literature on the effect of prevalent comorbidities such as substance use disorder (SUD) and antisocial personality (ASPD) on these models’ performance has remained unexplored. We investigated whether the presence of SUD or ASPD affects the performance of neuroimaging-based ML models trained to discern patients with schizophrenia (SCH) from controls.
Study design
We trained an ML model on structural MRI data from public datasets to distinguish between SCH and controls (SCH = 347, controls = 341). We then investigated the model’s performance in two independent samples of individuals undergoing forensic psychiatric examination: sample 1 was used for sensitivity analysis to discern ASPD (N = 52) from SCH (N = 66), and sample 2 was used for specificity analysis to discern ASPD (N = 26) from controls (N = 25). Both samples included individuals with SUD.
Study results
In sample 1, 94.4% of SCH with comorbid ASPD and SUD were classified as SCH, followed by patients with SCH + SUD (78.8% classified as SCH) and patients with SCH (60.0% classified as SCH). The model failed to discern SCH without comorbidities from ASPD + SUD (AUC = 0.562, 95%CI = 0.400–0.723). In sample 2, the model’s specificity to predict controls was 84.0%. In both samples, about half of the ASPD + SUD were misclassified as SCH. Data-driven functional characterization revealed associations between the classification as SCH and cognition-related brain regions.
Conclusion
Altogether, ASPD and SUD appear to have effects on ML prediction performance, which potentially results from converging cognition-related brain abnormalities between SCH, ASPD, and SUD.
... In chronic PSDs, prior research demonstrates that neurocognitive impairment is related to poor social and functional outcomes (Bowie et al., 2010;Green et al., 2004;Sheffield et al., 2018). Some research shows that negative symptoms mediate the relationship between neurocognition and psychosocial outcomes (Lin et al., 2013;Ventura et al., 2009). ...
Social impairment is a core deficit in psychotic spectrum disorders (PSDs). Prior work shows that language abnormalities can predict psychosis onset and are related to social outcomes in PSDs. Few studies have investigated nuanced relationships between language/verbal abilities and social functioning in the early psychosis spectrum, including at-risk (schizotypy) and first episode of psychosis (FEP) individuals. This study aimed to examine the relationship to between language/verbal performance and performance-based and examiner-rated social functioning. We also aimed to replicate prior models that demonstrate neurocognition is related to social functioning through negative symptoms and social cognition. Low schizotypy (n = 42), high schizotypy (n = 44), and FEP (n = 15) participants completed a battery of language/verbal, social cognition, and social functioning measures. Regression analyses revealed that Proverb Test performance was uniquely and significantly associated with performance-based but not examiner-rated social functioning. Other language/verbal measures were not significantly related to social functioning. In mediational analyses, language/verbal performance was indirectly related to social functioning through negative traits, and also through social cognition. Findings extend support for negative symptom and social cognitive intervention in the early psychosis spectrum, and uniquely suggest that executively-mediated language skills may be an additional target to improve social functioning.
... La désinstitutionalisation et l'amélioration des traitements pharmacologiques ont placé le handicap psychique et la réhabilitation au premier plan des prises en charge actuelles. De nombreuses recherches ont établi que le fonctionnement social et l'insertion dans la communauté sont essentiellement prédits par le fonctionnement cognitif ( Green et al., 2004 ;Prouteau et al., 2005 ), aujourd'hui reconnu par de nombreux psychiatres comme une cible de traitement pertinente chez les personnes ayant une schizophrénie. Cependant, les synthèses actuelles montrent qu'une part non négligeable du handicap psychique demeure inexpliquée par les troubles cognitifs ou les symptômes, et que d'autres facteurs, notamment subjectifs, pourraient compléter le modèle ( Koren & Harvey, 2006 ). ...
... Uniquely, veterans with SMI have more than twice the rate of suicide and death ideation compared to nonveterans with SMI (Jahn et al., 2018) and have higher suicide rates compared to veteran and U.S. populations without SMI (Aslan et al., 2020). Moreover, those with SMI are frequently disengaged from care (Dixon et al., 2016), have cognitive impairments (Green, 1996;Green et al., 2004;Stergiopoulos et al., 2015;Twamley et al., 2002;Velligan et al., 1997), and have limited social supports (Chronister et al., 2015;Corrigan et al., 2004;Hendryx et al., 2009;Kilbourne et al., 2007), which may impact recovery. ...
Veterans Health Administration’s (VHA) Psychosocial Rehabilitation and Recovery Centers (PRRCs) provide recovery-oriented care to veterans with serious mental illness (SMI). As part of program evaluation, PRRC providers regularly assess recovery-oriented outcomes. Given the high rates of suicidal thoughts and behaviors among veterans with SMI, understanding such outcomes in relation to suicide risk is crucial. Among veterans entering a PRRC (N = 4,731), the present study aimed to (a) report suicidal ideation frequency in the past 2 weeks across demographics and psychiatric diagnoses, (b) explore rates of current functional impairment, internalized stigma, and well-being, and (c) examine differences in suicidal ideation frequency and functional impairment, internalized stigma, and well-being. Measurements before treatment were utilized. Younger (ρ = −0.08, p < .001), married (z = −5.23, p < .001) veterans, those not identifying as Black or African American (z = −4.80, p < .001), not diagnosed with schizophrenia (z = −6.97, p < .001), diagnosed with depressive disorders (z = −8.79, p < .001), anxiety disorders (z = −5.01, p < .001), posttraumatic stress disorder (PTSD; z = −7.69, p < .001), or personality disorders (z = −7.12, p < .001) were significantly more likely to endorse suicidal ideation. Veterans in this cohort had higher than average functional impairment (M = 18.05, SD = 9.85), mild internalized stigma (M = 2.36, SD = 0.51), and lower than average well-being (M = 18.96, SD = 3.93). The more often a veteran reported thinking about suicide in the past 2 weeks, the more likely the veteran viewed themselves to be more functionally impaired (p < .001), reported higher levels of internalized stigma (p < .001), and reported lower levels of well-being (p < .001). Findings and limitations, particularly the suicidal ideation frequency measurement, are discussed to contextualize suggestions to integrate recovery-oriented practices and suicide prevention care.
... First, the effects of CR on real-world functional outcomes may be mediated by gains in neuro-cognitive functioning (Fiszdon et al., 2008;Reeder et al., 2017;Wykes et al., 2007). Multiple studies have illustrated a relationship between neurocognition and functioning outcomes (Fett et al., 2011;Green et al., 2004;Halverson et al., 2019). The association between neurocognition and functioning outcomes appears especially strong for functioning in work (Dickinson et al., 2007;Gold et al., 2002). ...
Background: Most cognitive remediation (CR) programs are based on multiple scientific learning principles. The role of those learning principles in the beneficial effects of CR is poorly understood. A better understanding of such underlying mechanisms is important to further tailor the intervention and to learn about optimal contexts.
Method: An explorative secondary analysis was conducted of data from a randomized controlled trial (RCT) comparing the effects of Individual Placement and Support (IPS) with and without CR. The present study evaluated how CR learning principles of “massed practice,” “errorless learning,” “strategy use” and “therapist contribution” (therapist fidelity) were associated with cognitive and vocational outcomes within 26 participants in this RCT who were treatment exposed.
Results: Cognitive gains after CR were positively associated with “massed practice” and “errorless learning.” Negative associations were found with “strategy use” and “therapist fidelity.” No direct relationship was found between CR principles and vocational outcomes.
Conclusions: Results tentatively suggest that CR is most effective and efficient with a good balance between sufficient intensity, of more than 200 tasks, and a limited duration of the training up to 20 h, using tasks that remain both challenging and rewarding, being applied in a context that facilitates real-life practice.
Background One central characteristic of schizophrenia is cognitive dysfunction, which typically has modest to severe effects on a variety of cognitive areas. Evidence suggests that cognitive impairment may occur far sooner than the clinical symptoms. The connection between cognitive deficiencies and functional outcome indicators has attracted increasing attention in recent years. Cognitive deficits are widely known to affect overall functioning, In India, few studies have been conducted to determine the profile of cognitive abnormalities in individuals in the chronic phase of schizophrenia as well as those in remission. Research from developing nations is crucial because schizophrenia prevalence in these nations is thought to be lower than that in industrialized nations. The aim of this study will be to assess the prevalence of cognitive dysfunction in individuals with schizophrenia and examine the relationship between cognitive dysfunction with psychopathology and quality of life in individuals with schizophrenia. Protocol This will be a cross sectional hospital-based study. After ethical clearance, all patients in the Psychiatry Department meeting the criteria of Schizophrenia, according to the ICD-10, will be part of the study. The expected number of participants is 228. All participants within the age group of 18 to 65 years who are clinically diagnosed to have schizophrenia using ICD-10 and who are able to give written informed consent will be included in the study. The patient’s sociodemographic data will be collected in Outpatient or inpatient basis and then the following questionnaires will be applied to them: i) Socio-demographic Proforma; ii) The Positive and Negative Syndrome Scale (PANSS); iii) The World Health Organization Quality of Life-BREF scale (WHOQOL-BREF); and iv) Addenbrooke’s cognitive examination III (ACE). Once the aforementioned questionnaires are completed, the prevalence of cognitive dysfunction in patients with schizophrenia will be assessed, and its relationship with psychopathology and quality of life will be studied.
Aim
Baseline cognitive functions of patients predicted the efficacy of cognitive remediation therapy (CRT), but results are mixed. Eye movement is a more objective and advanced assessment of cognitive functions than neuropsychological testing. We aimed to investigate the applicability of eye movements in predicting cognitive improvement after patients with schizophrenia were treated with CRT.
Methods
We recruited 79 patients with schizophrenia to complete 8 weeks of CRT and assessed their cognitive improvement outcomes. Eye movements were assessed by prosaccades, antisaccades, and free-viewing tasks at baseline, and neuropsychological tests in four cognitive domains were assessed before and after treatment to calculate treatment outcomes. Predictors of demographic information, clinical characteristics, and eye movement measures at baseline on cognitive improvement outcomes were analyzed using logistic regression analysis. We further compared the predictive performance between eye movement measurements and neuropsychological test regarding the effect of CRT on cognitive improvement, and explored factors that could be affect the treatment outcomes in different cognitive domains.
Results
As operationally defined, 33 patients showed improved in cognition (improved group) and 46 patients did not (non-improved group) after CRT. Patients with schizophrenia being employed, lower directional error rate in antisaccade task, and lower the gap effect (i.e., the difference in saccadic latency between the gap condition and overlap condition) in prosaccade task at baseline predicted cognitive improvement in CRT. However, performance in the free-viewing task not associated with cognitive improvement in patients in CRT. Our results show that eye-movement prediction model predicted the effect of CRT on cognitive improvement in patients with schizophrenia better than neuropsychological prediction model in CRT. In addition, baseline eye-movements, cognitive reserve, antipsychotic medication dose, anticholinergic cognitive burden change, and number of training sessions were associated with improvements in four cognitive domains.
Conclusion
Eye movements as a non-invasiveness, objective, and sensitive method of evaluating cognitive function, and combined saccadic measurements in pro- and anti-saccades tasks could be more beneficial than free-viewing task in predicting the effect of CRT on cognitive improvement in patients with schizophrenia.
Although it is well established that individuals living with psychosis are at increased risk for suicidal ideation, attempts, and death by suicide, several gaps in the literature need to be addressed to advance research and improve clinical practice. This Call-to-Action highlights three major gaps in our understanding of the intersection of psychosis and suicide as determined by expert consensus. The three gaps include research methods, suicide risk screening and assessment tools used with persons with psychosis, and psychosocial interventions and therapies. Specific action steps to address these gaps are outlined to inform research and practice, and thus, improve care and prognoses among persons with psychosis at risk for suicide.
Early detection of psychotic-spectrum disorders among adolescents and young adults is crucial, as the initial years after psychotic symptom onset encompass a critical period in which psychosocial and pharmacological interventions are most effective. Moreover, clinicians and researchers in recent decades have thoroughly characterized psychosis-risk syndromes, in which youth are experiencing early warning signs indicative of heightened risk for developing a psychotic disorder. These insights have created opportunities for intervention even earlier in the illness course, ideally culminating in the prevention or mitigation of psychosis onset. However, identification and diagnosis of early signs of psychosis can be complex, as clinical presentations are heterogeneous, and psychotic symptoms exist on a continuum. When a young person presents to a clinic, it may be unclear whether they are experiencing common, mild psychotic-like symptoms, early warning signs of psychosis, overt psychotic symptoms, or symptoms better accounted for by a non-psychotic disorder. Therefore, the purpose of this review is to provide a framework for clinicians, including those who treat non-psychotic disorders and those in primary care settings, for guiding identification and diagnosis of early psychosis within the presenting clinic or via referral to a specialty clinic. We first provide descriptions and examples of first-episode psychosis (FEP) and psychosis-risk syndromes, as well as assessment tools used to diagnose these conditions. Next, we provide guidance as to the differential diagnosis of conditions which have phenotypic overlap with psychotic disorders, while considering the possibility of co-occurring symptoms in which case transdiagnostic treatments are encouraged. Finally, we conclude with an overview of early detection screening and outreach campaigns, which should be further optimized to reduce the duration of untreated psychosis among youth.
Cognitive impairments in schizophrenia are pivotal clinical issues that need to be solved urgently. However, the mechanism remains unknown. It has been suggested that cognitive impairments in schizophrenia are associated with connectome damage, and are especially relevant to the disrupted hub nodes in the frontal and parietal lobes. Activating the dorsolateral prefrontal cortex (DLPFC) via repetitive transcranial magnetic stimulation (rTMS) could result in improved cognition. Based on several previous magnetic resonance imaging (MRI) studies on schizophrenia, we found that the first-episode patients showed connectome damage, as well as abnormal activation and connectivity of the DLPFC and inferior parietal lobule (IPL). Accordingly, we proposed that DLPFC-IPL pathway destruction might mediate connectome damage of cognitive impairments in schizophrenia. In the meantime, with the help of multimodal MRI and noninvasive neuromodulation tool, we may not only validate the hypothesis, but also find IPL as the potential intervention target for cognitive impairments in schizophrenia.
Purpose
This clinical focus article aims to provide a comprehensive overview of schizophrenia and understanding of communication disorders resulting from its psychopathology. Schizophrenia is a spectrum disorder with varying levels of symptom expression. It is characterized by positive and negative symptoms that can cause communication disorders of different severity levels. Communication difficulties manifest as a range of symptoms such as alogia, disorganized speech, and impaired social communication. These challenges may result in receptive and expressive language deficits that lead to misunderstandings, reduced social interactions, and difficulties expressing thoughts and emotions effectively. The purpose of this clinical focus article is to explore the role of the speech-language pathologist (SLP) in assessing and treating communication disorders presented in schizophrenia.
Conclusions
In order to understand the role of the SLP in assessing and treating communication disorders in schizophrenia, it is imperative to understand the overall course, etiology, assessment, and treatment consideration of this condition. SLPs can provide services in the areas of social skills training and community-based intervention contexts.
Functional neuroimaging emerged with great promise and has provided fundamental insights into the neurobiology of schizophrenia. However, it has faced challenges and criticisms, most notably a lack of clinical translation. This paper provides a comprehensive review and critical summary of the literature on functional neuroimaging, in particular functional magnetic resonance imaging (fMRI), in schizophrenia. We begin by reviewing research on fMRI biomarkers in schizophrenia and the clinical high risk phase through a historical lens, moving from case‐control regional brain activation to global connectivity and advanced analytical approaches, and more recent machine learning algorithms to identify predictive neuroimaging features. Findings from fMRI studies of negative symptoms as well as of neurocognitive and social cognitive deficits are then reviewed. Functional neural markers of these symptoms and deficits may represent promising treatment targets in schizophrenia. Next, we summarize fMRI research related to antipsychotic medication, psychotherapy and psychosocial interventions, and neurostimulation, including treatment response and resistance, therapeutic mechanisms, and treatment targeting. We also review the utility of fMRI and data‐driven approaches to dissect the heterogeneity of schizophrenia, moving beyond case‐control comparisons, as well as methodological considerations and advances, including consortia and precision fMRI. Lastly, limitations and future directions of research in the field are discussed. Our comprehensive review suggests that, in order for fMRI to be clinically useful in the care of patients with schizophrenia, research should address potentially actionable clinical decisions that are routine in schizophrenia treatment, such as which antipsychotic should be prescribed or whether a given patient is likely to have persistent functional impairment. The potential clinical utility of fMRI is influenced by and must be weighed against cost and accessibility factors. Future evaluations of the utility of fMRI in prognostic and treatment response studies may consider including a health economics analysis.
Impairment in attention, memory, processing speed and executive functions have been described in patients with schizophrenia. Such impairments can be observed in early stages of the disease and in chronic patients; discrepancy in findings regarding the cognitive deficits at different stages of the illness keeps the debate about schizophrenia as a neurodegenerative condition which courses with continuous deterioration, or if deficits remain stable, as the neurodevelopmental hypothesis suggests.
The launch (2018) and approval (2019) of the 11th Revision of the ICD (ICD-11) by the World Health Organization (WHO) provided a major opportunity to bring the ICD classification of Mental, Behavioural, or Neurodevelopmental Disorders (MBND) into line with current empirical evidence and clinical practice. It is expected to enhance the global applicability and clinical utility of ICD improving evidence-based interventions.
This chapter represents an overview of essential and associated features required to diagnose schizophrenia or other primary psychotic disorders, to examine diagnostic boundaries from normality to pathology, and provide differential diagnosis with other disorders together with common comorbidities. Additionally, the key changes and advantages of ICD-11 classification of mental disorders compared to ICD-10 and DSM-5 are provided.
Background and hypothesis:
Individuals at familial risk for developing schizophrenia (FRSZ) or bipolar disorder (FRBD) have shared and unique genetic risks. Few studies have compared neural activation between these two groups. Therefore, the present meta-analysis investigated functional brain similarities and differences between FRSZ and FRBD individuals.
Study design:
A systematic literature review was conducted of articles that compared FRSZ or FRBD individuals to healthy controls (31 FRSZ and 22 FRBD). Seed-based d mapping was used to conduct the meta-analysis. Analyses included comparisons of FRSZ to controls, FRBD to controls, and both relative groups to each other.
Study results:
Using a highly conservative family-wise error rate correction, there were no significant findings. Using a less conservative threshold, FRSZ compared to controls had lower activation in the left precuneus (Puncorrected = .02) across all studies and in the left middle frontal gyrus (Puncorrected = .03) in nonsocial cognition studies. FRBD compared to controls had lower activation in the left superior parietal gyrus (Puncorrected = .03) and right angular gyrus (Puncorrected = .03) in nonsocial cognition studies, and higher activation in the left superior frontal gyrus (Puncorrected = .01) in social tasks. Differences between FRSZ and FRBD were not significant.
Conclusions:
There were few robust differences between FRSZ or FRBD compared to controls. This suggests only weak support for neural activation differences between individuals at genetic risk for schizophrenia or bipolar disorder and controls. The tentative findings observed were in different brain regions for FRSZ and FRBD, with no strong evidence for shared effects between schizophrenia and bipolar genetic risk on neural activation.
We investigated the feasibility and effectiveness of an Action-Based Cognitive Remediation group within an outpatient early psychosis program. Sixteen participants completed the group including pre-post measures to assess quantitative outcomes of improvement. Eight participants completed individual, semistructured, qualitative interviews at 3–6 months post-intervention to assess feasibility and acceptability. The group was well tolerated. Significant improvements were observed in general cognition and functional capacity, which extended to psychiatric symptoms and illness stigma. Participants identified themes related to improved cognition and self-esteem, as well as generalizing skills to everyday activities. Action-Based Cognitive Remediation is a feasible and efficacious intervention for early psychosis.
Aim:
Action-based cognitive remediation (ABCR) is a group cognitive remediation treatment that aims to improve neurocognitive impairments experienced in patients with severe mental illness. Developed in research settings, ABCR is not yet widely available in community settings. As such, this study examines the feasibility of implementing ABCR in community clinics in an early psychosis network.
Methods:
Eighty-five allied health professionals who work within an early psychosis intervention network were trained in the provision of ABCR. They were surveyed 6-months after training to gather information regarding their experience implementing ABCR within their clinical settings (e.g., barriers, perceived helpfulness of the treatment, modifications made to the manualized treatment). Access to ongoing training supports (e.g., treatment manual, asynchronous digital communication, conference calls) was also assessed.
Results:
Fifty-one clinicians responded to the survey. Staff time, manager support, and equipment were rated as organizational barriers. Geographic location, other responsibilities, and motivation were rated as patient barriers. Over half of the sample modified the overall dose of ABCR to offer fewer sessions and/or shorter duration of sessions than the manualized approach. Clinicians that reduced the dose of ABCR reported significantly higher barriers with manager support than staff who delivered ABCR as manualized but did not report worse patient outcomes. We found asynchronous learning opportunities (i.e., manual, online discussion forum) were perceived as the most accessible and helpful methods of ongoing training support.
Conclusions:
The results provide preliminary information about barriers to implementing time-intensive cognitive treatments into clinical settings and may inform future training practices to increase successful implementation of cognitive remediation treatments.
Objectives : This study aimed to investigate the effects of the Neuropsychological Educational Approach to Cognitive Remediation (NEAR) in improving cognitive function and its sustainability in patients with schizophrenia or schizoaffective disorders.
Methods : The z-scores of the Brief Assessment of Cognition in Schizophrenia (BACS) of patients who had experienced NEAR during psychiatric day care in the past were compared using results at the baseline, post-NEAR, and a follow-up evaluation. To investigate changes in cognitive function over time, a correlation analysis was conducted between the number of days from post-NEAR to follow-up and the degree of change in z-scores. Living conditions were compared between the group with maintained z-scores and the group with declined z-scores.
Results : 34 patients (22 men) participated. Repeated-measures analysis of variance showed that participants had significantly higher z-scores at the post-NEAR stage than at the baseline (p＜.01). The follow-up evaluation showed a slow decline in z-scores. Participants in the group that had declined z-scores tended to be younger and had a longer follow-up period. Of them, 52.94％ were admitted to a psychiatric hospital during the followup period.
Conclusion : The increase in z-scores post-NEAR suggests that NEAR is effective in improving cognitive function. Decline in cognitive function during the follow-up period was slight and gradual over subsequent years. In the case of participants whose z-scores had decreased, it is likely that unstable disease conditions had affected the decline in their cognitive function because over half of them were hospitalised during the follow-up period.
The study aimed to investigate the cognitive processing of prospective memory (PM) in patients with schizophrenia spectrum disorders (SSDs) by using an eye-tracking paradigm. In addition, the facilitating effects of prosocial intention (the desire to help others) on PM in SSDs were also examined. In phase 1, 26 patients (group1) and 25 healthy controls (HCs) were compared in an eye-tracking PM paradigm in terms of the PM accuracy and eye-tracking indices. In phase 2, 21 more patients (group2) were recruited, and a prosocial intention was introduced in the eye-tracking PM paradigm. Their PM accuracy and eye-tracking indices were compared with those in group1. The PM cue monitoring was indicated by the total fixation counts and fixation time on distractor words. In phase 1, group1 showed lower PM accuracy, fewer fixation counts and less fixation time on distractor words than HCs. In phase 2, group2 (with prosocial intention) performed significantly better than group1 (with typical instruction) on both PM accuracy and fixation time on distractor words. In both groups of SSDs, the PM accuracy was significantly correlated with both the fixation counts and the fixation time of distractor words. After controlling for the cue monitoring indices, the difference in PM accuracy remained significant between group1 and HCs but disappeared between group1 and group2. The cue monitoring deficit contributes to the PM impairment in SSDs. The facilitating effect of prosocial intention disappears after the control of cue monitoring, also indicating its critical role in PM.
Schizophrenia is a neuropsychiatric condition that is associated with impaired attentional processing and performance. Failure to support increasing attentional load may result, in part, from inhibitory failure in attention-relevant cortical regions, and available antipsychotics often fail to address this issue. Orexin/hypocretin receptors are found throughout the brain and are expressed on neurons relevant to both attention and schizophrenia, highlighting them as a potential target to treat schizophrenia-associated attentional dysfunction. In the present experiment, rats (N = 14) trained in a visual sustained attention task that required discrimination of trials which presented a visual signal from trials during which no signal was presented. Once trained, rats were then co-administered the psychotomimetic N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801: 0 or 0.1mg/kg, intraperitoneal injections) and the dual orexin receptor antagonist filorexant (MK-6096: 0, 0.1, or 1mM, intracerebroventricular infusions) prior to task performance across six sessions. Dizocilpine impaired overall accuracy during signal trials, slowed reaction times for correctly-responded trials, and increased the number of omitted trials throughout the task. Dizocilpine-induced increases in signal trial deficits, correct response latencies, and errors of omission were reduced following infusions of the 0.1mM, but not 1mM, dose of filorexant. As such, orexin receptor blockade may improve attentional deficits in a state of NMDA receptor hypofunction.
Objective:
Cerebral blood flow (CBF) plays a critical role in the maintenance of neuronal integrity, and CBF alterations have been linked to deleterious white matter changes. Several studies report CBF and white matter structural alterations individually. However, whether and how these pathological changes relate to each other remains elusive. By using our cohort of individuals with early-stage schizophrenia, we investigated the relationship between CBF and white matter structure.
Method:
We studied 51 early-stage schizophrenia patients and age- and sex-matched healthy controls. We investigated the relationship among tissue structure (assessed with diffusion weighted imaging), perfusion (accessed by pseudo-continuous arterial labeling imaging), and neuropsychological indices (focusing on processing speed). We focused on the corpus callosum, due to its major role in associative functions and directness on revealing the architecture of a major white matter bundle. We performed mediation analysis to identify the possible mechanism underlay the relationship among cognition and white matter integrity and perfusion.
Results:
The CBF and the fractional anisotropy (FA) were inversely correlated in the corpus callosum of early-stage schizophrenia patients. While CBF negatively correlated with processing speed, FA correlated positively with this cognitive measure. These results were not observed in controls. Mediation analysis revealed that the effect of FA on processing speed was mediated via the CBF.
Conclusions:
We provide evidence of a relationship between brain perfusion and white matter integrity in the corpus callosum in early-stage schizophrenia. These findings may shed the light on underlying metabolic support for structural changes with cognitive impact in schizophrenia.
There is enormous literature citing the importance of workplace spirituality. This article focuses on the concept of spirituality and to understand its role in workplace using narrative review methodology. A few definitions of spirituality and workplace spirituality are examined and common features in those definitions are identified. Existing literature on why spirituality at workplace is vital is reviewed. The arguments against and for the workplace spirituality are expressed. The core purpose of the paper is to understand the concept of spirituality and how it manifests at the workspace, whether it should be nurtured or discouraged with respect to its impact on the employee and the organisation (consequentialist framework) or because of the individuals search for meaning, purpose, transcendence and divinity (spiritual-philosophical framework).The result indicate that spiritual-philosophical framework should be the primary reason for organisations to promote workplace spirituality. The reasons for, and implications of the same are discussed.
N-methyl-d-aspartate glutamate receptor (NMDAR) hypofunction is implicated in the impaired neuroplasticity and cognitive impairments associated with schizophrenia (CIAS). We hypothesized that enhancing NMDAR function by inhibiting the glycine transporter-1 (GLYT1) would improve neuroplasticity and thereby augment benefits of non-pharmacological cognitive training (CT) strategies. This study examined whether co-administration of a GLYT1 inhibitor and computerized CT would have synergistic effects on CIAS. Stable outpatients with schizophrenia participated in this double-blind, placebo-controlled, within-subject, crossover augmentation study. Participants received placebo or GLYT1 inhibitor (PF-03463275) for two 5-week periods separated by 2 weeks of washout. PF-03463275 doses (40 or 60 mg twice daily) were selected to produce high GLYT1 occupancy. To limit pharmacodynamic variability, only cytochrome P450 2D6 extensive metabolizers were included. Medication adherence was confirmed daily. Participants received 4 weeks of CT in each treatment period. Cognitive performance (MATRICS Consensus Cognitive Battery) and psychotic symptoms (Positive and Negative Syndrome Scale) were assessed in each period. 71 participants were randomized. PF-03463275 in combination with CT was feasible, safe, and well-tolerated at the doses prescribed but did not produce greater improvement in CIAS compared to CT alone. PF-03463275 was not associated with improved CT learning parameters. Participation in CT was associated with improvement in MCCB scores.
A total of 172 individuals diagnosed with a schizophrenia spectrum disorder were followed for 36 months in 3 distinct models of community-based care. Functional outcome data gathered every 6 months were combined with service implementation data to test hypotheses concerning the impact of service characteristics on prospective client outcomes. The results using hierarchical linear modeling supported associations between the intensity, specificity, and longitudinality of services and improved client outcomes. Specifically, more intense services were associated with higher levels or rates of improvement on all indices of clinical and psychosocial functioning. The specificity results suggested that services needed to be targeted to specific areas of functioning in order for improvement to occur. The effect of longitudinality was contingent on the outcome domain examined.
Social functioning as an outcome variable in family interventions with schizophrenic patients has been a relatively neglected area. The requirements of a scale of social functioning to measure the efficacy of family interventions include: the measurement of skill/behaviour relevant to the impairments and the demography of this group; the ability to yield considerable information with an economy of clinical time; and the establishment of 'comparative' need through comparison between subscales and with appropriate reference groups. Results from three samples show that the Social Functioning Scale is reliable, valid, sensitive and responsive to change.
We review limitations of representative measures of function and disability associated with schizophrenia and specify requirements of a suitable measure for service evaluation: It should reliably and validly assess constructs relevant to survival, function, and adaptation in the community. Additionally, it should be brief, comprise specific and jargon-free items assessing distinct behaviors, and therefore be capable of completion by family members and community housing managers as well as by professional staff. The initial development of such a measure, the 39-item Life Skills Profile (LSP), with its five scales, is described. We report data to suggest that it is likely to be a measure of considerable utility both in research studies and in defining and assessing clinical services.
We examined social problem solving in schizophrenia. Twenty-seven schizophrenic patients in an acute hospital, 19 patients with bipolar disease, and 17 demographically matched nonpatient controls were tested on an empirically developed problem-solving battery that assessed the ability to generate solutions to problems, the ability to evaluate the effectiveness of solutions, and the ability to implement solutions in a role-playing format. Schizophrenic Ss were impaired on all 3 problem-solving domains compared with the nonpatient controls, but bipolar Ss were equally impaired. Several alternative explanations for these findings were considered. The most compelling hypothesis is that the deficits resulted from different factors: cognitive impairment for schizophrenic Ss and acute illness for bipolar Ss. However, longitudinal studies are required to determine whether problem-solving deficits in schizophrenic patients persist during periods of remission. Implications for rehabilitation strategies are discussed.
There has been a growing trend in medicine to evaluate the impact of illness on functional abilities. Such studies typically rely on the patient's or caregiver's report. The goal of this study was to assess directly the functional capacity of psychiatric patients, especially older ones.
The subjects were 55 outpatients with schizophrenia and 72 normal persons ranging in age from 45 to 86 years. The subjects were administered the Direct Assessment of Functional Status Scale, which assess behaviour during simulated daily activity tasks in the areas of time orientation, communication, transportation, finance, shopping, grooming, and eating.
The patients with schizophrenia had significantly greater disability than the normal subjects according to total scale scores as well as the communication, transportation, finance, and shopping subscale scores. Global cognitive status was the best predictor of total scale score.
The Direct Assessment of Functional Status Scale is a promising instrument for functional assessment in outpatients with schizophrenia.
The search is on for meaningful psychopharmacological and cognitive/behavioral interventions for neurocognitive deficits in schizophrenia. Findings in this area are emerging rapidly, and in the absence of integrating frameworks, they are destined to emerge chaotically. Clear guidelines for testing neurocognitive interventions and interpreting results are critical at this early stage. In this article, we present three models of increasing complexity that attempt to elucidate the role of neurocognitive deficits in schizophrenia in relation to treatment and outcome. Through discussion of the models, we will consider methodological issues and interpretive challenges facing this line of investigation, including direct versus indirect neurocognitive effects of antipsychotic medications, selection of particular neurocognitive constructs for intervention, the importance of construct validity in interpreting cognitive/behavioral studies, and the expected durability of treatment effects. With a growing confidence that some neurocognitive deficits in schizophrenia can be modified, questions that seemed irrelevant only a few years ago are now fundamental. The field will need to reconsider what constitutes a successful intervention, what the relevant outcomes are, and how to define treatment efficacy.
Cognitive impairments may be an important contributor to disability in schizophrenia and may limit the rate of improvement
in work rehabilitation. Thirty-three outpatients with schizophrenia or schizoaffective disorder who participated in a 6-month
work rehabilitation program were assessed for symptom severity and administered neuropsychological testing at intake. Their
work performance was evaluated biweekly using the Work Behavior Inventory. On each of five domains of work performance, 76
to 91 percent of subjects reached proficiency or improved significantly over 26 weeks. Individual differences in rate of improvement
were robustly predicted by neuropsychological variables: Work Habits, r2 = 0.79; Personal Presentation, r2 =0.73; Cooperativeness, r2 = Work Quality, r2 =0.56; Social Skills, r2 =0.27; Total, r2 =0.44. Neuropsychological measures had differential relationships to work domains. Individual differences in improvement
were not predicted by symptom measures. These findings link cognitive impairment to disability and suggest that remediating
or accommodating such deficits may be necessary for successful rehabilitation.
Instruments to assess everyday functioning have utilized self-report, proxy report, clinician ratings, or direct observation
of performance. Each of these methods has strengths and weaknesses. In this article we argue for the inclusion of performance-based
measures of functional capacity in studies of severely mentally ill persons and describe a new measure, the UCSD Performance-Based
Skills Assessment (UPSA). We administered the UPSA to 50 middle-aged and older outpatients with schizophrenia or schizoaffective
disorder, and 20 normal comparison subjects. Participants' performance in five domains of functioning (Household Chores; Communication;
Finance; Transportation; and Planning Recreational Activities) was assessed in standardized role-play situations. Administration
of the UPSA required an average of 30 minutes to complete. Interrater reliability of ratings was excellent. Patients' performance
was significantly more impaired than that of normal subjects. Among patients', the UPSA performance correlated significantly
with severity of negative symptoms and of cognitive impairment but not with that of positive or depressive symptoms. The UPSA
scores correlated highly with those on another performance-based measure. We believe that UPSA would be useful for assessing
everyday functioning in severely mentally ill adults.
There is clear evidence that cognitive performance is a correlate of functional outcome among patients with schizophrenia. However, few studies have specifically examined the cognitive correlates of competitive employment performance or the longer-term outcomes of vocational rehabilitation. The objective of the present study was to examine the cognitive predictors of vocational functioning in the context of a controlled clinical trial by comparing two approaches to vocational rehabilitation.
A broad neuropsychological battery was administered to 150 patients upon entry into the vocational rehabilitation trial. Vocational performance was assessed over a 24-month follow-up interval.
There were no differences in baseline cognitive performance between the 40 patients who obtained competitive employment and the 110 patients who remained unemployed over the follow-up interval. In contrast, multiple cognitive measures were significantly correlated with the total number of hours that patients were employed. The cognition-job tenure relationship appears to be fairly general, involving measures of IQ, attention, working memory, and problem solving.
Cognitive performance was a significant predictor of job tenure but not job attainment in the context of a clinical trial of two vocational rehabilitation approaches. It appears that many persistently unemployed patients are capable of obtaining competitive employment with effective vocational services. Longer-term employment success, however, may be related to multiple aspects of baseline cognitive performance.
Impairment in basic self-care skills is common in patients with schizophrenia and is even more severe in elderly patients with a chronic course of institutional care. While cognitive impairment has proven to be a major predictor of overall functional deficit in schizophrenia, other potential factors, such as medical comorbidity, need to be considered.
Geriatric institutionalized schizophrenic patients (N=124) were assessed three times over 4 years to determine levels of positive and negative symptoms, impairment in activities of daily living, impairment in cognitive functioning, and medical problems. Path analysis was used to determine which variables best predicted changes in self-care functions.
Functional status, negative symptoms, cognitive functions, and health status all significantly worsened during the follow-up. The path analyses showed that change in health status did not predict change in activities of daily living after the analysis accounted for negative symptoms and cognitive functions.
The results highlight the relative importance of cognitive impairments in the functional impairments of older schizophrenic patients with increased medical burden.
HIV-1 infection can be associated with neuropsychological (NP) deficits ranging from subtle to severe. The purpose of this study was to evaluate the functional, or "real-world" impact of HIV-associated NP impairment in a group of 267 HIV-infected participants. All participants received comprehensive NP, neuromedical, and standardized functional evaluations that included laboratory measures of shopping, cooking, financial management, medication management and vocational abilities. Compared to NP-normal participants, those with NP impairment performed significantly worse on all laboratory measures of everyday functioning. Multivariate analyses revealed that the NP ability domains of Abstraction/Executive Function, Learning, Attention/Working Memory and Verbal abilities most strongly and consistently predicted failures on the functional battery. Both NP impairment and impairment on the functional battery were significantly associated with subjective experiences of cognitive difficulties, as well as unemployment and increased dependence in activities of daily living; multivariate prediction models that also considered depressed mood and biological measures of disease progression revealed that impairment on the functional battery and depression were the only unique predictors of all three indicators of "real-world" functioning. The current results add to growing evidence concerning the clinical significance of HIV-associated NP impairment. Objective, laboratory based functional measures, such as those used here, may compliment NP testing in future studies directed at understanding the impact on life quality of central nervous system disorders and their treatments. Finally, there is a need for additional research investigating the apparently independent effect of depression on level of everyday functioning in HIV infected persons.
Several, although not all, studies suggest that prolonged duration of untreated illness (DUI) predicts poor outcome in psychotic disorders such as schizophrenia. It is unclear whether this association can be explained by factors such as baseline deficits or poor premorbid adjustment. First episode psychotic patients were evaluated at 1 and 2 years following baseline evaluations. Predictive measures showing significant correlations with outcome were entered in multiple regression analyses with Strauss-Carpenter scale (SC) and Global Assessment of Functioning scale (GAF) outcome scores as dependent variables. Illness duration computed from the onset of the prodrome (DUI-pro), used both as a dichotomous and as a continuous measure, highly significantly predicted both GAF and SC scores at 2 years. On the other hand, baseline functioning significantly predicted the 1-year but not the 2-year outcome. When Premorbid Adjustment Scale (PAS) scores were additionally entered into the analyses in a smaller subset, the relation between DUI-pro and the 2-year outcome scores remained significant. Significant associations were also seen between outcome and baseline neuropsychological deficits involving attention and memory. Further research is needed to examine whether prolonged untreated illness is simply associated with poor outcome or plays a causal role in relation to outcome. The latter, if true, would strongly support therapeutic intervention efforts in the prodromal and early psychotic phases of schizophrenia.
Research is described that addresses the nature and consequences of neuropsychological (NP) impairment associated with HIV infection. Results suggest increasing rates of NP impairment at each successive stage of infection (asymptomatic, mildly symptomatic, AIDS). NP deficits are related to independent evidence of abnormal brain structure and function, and are not explained by medical or psychiatric confounds. The NP impairment is “spotty” across infected persons, but is most frequently observed on tests of attention/speed of information processing and learning efficiency. Clinical and research assessments of HIV infected persons should especially focus on putative “subcortical” abilities, but maximum sensitivity requires coverage of multiple ability domains. NP impairment in this population also is associated with increased unemployment, complaints of job performance difficulties, and worse performance on standardized work samples. Interference with vocational functioning and general life quality may reflect considerable clinical importance of even subtle brain involvement in HIV infection.
A resource allocation model was developed to assist in planning services for the severely mentally ill. Given program objectives and resource constraints, the model employs linear programming methods to find optimal strategies for assigning clients to services. It can also forecast client movement and resource consumption. To field test the model it was applied to a Community Support Program in a predominately rural state. Model results suggest the need for targeting resources to specific client subpopulations.
During the past few years there has been increased interest in assessing the quality of life of the chronically mentally ill to assist in planning and evaluating programs for these patients. New initiatives to integrate and expand psychiatric, medical, and social services for the chronically mentally ill make such broad-based service evaluations all the more relevant. This paper describes the development and psychometric evaluation of a structured, 45-minute Quality of Life Interview for the chronically mentally ill. Based upon studies with nearly 500 chronically mentally ill patients, the interview has satisfactory reliability and validity. After a description of the interview, the author discusses several issues regarding the status of QOL assessments in this population, the potential relevance of such assessments to program development and evaluation, their potential applications in clinical practice, and persistent problems in interpreting and applying the results of QOL evaluations.
This paper describes the standard version of the MRC Social Performance Schedule, which covers 21 behaviour areas such as hygiene, initiating conversations, etc. and was designed to be used with long-stay populations, within a hospital or the community. Data on the schedule's consistency over raters, informants, time, and situation showed that the reliability was reasonable over all four areas. The schedule is recommended as a standard instrument to describe the behavioural difficulties of patients likely to be dependent on psychiatric services for some time. Recent data are provided on the levels of problem behaviours found within both long-stay hospitals and community settings, together with references for more detailed behaviour profiles of such groups.
The renewed interest in the care and treatment of chronic psychiatric patients has led to an awareness of the need for improved assessment methods for this group. This article describes the development of REHAB, a behavior rating scale for use with people with chronic psychiatric disability, which has been carefully designed with respect to content, format, and ease of use. The article also draws together the various factor-analytic, reliability, validity, and sensitivity-to-change studies that provide the basic psychometric evidence for the scale's value. REHAB is presented as an integrated package of materials with special attention paid to training of raters and simplicity of interpretation. It has been used for a variety of different assessment purposes, in both research and clinical settings.
There is growing interest in deficit symptoms in studies of the course and treatment response of schizophrenia. However, existing clinical assessment instruments focus primarily on productive symptoms. The authors describe the Quality of Life Scale (QLS), a 21-item scale based on a semistructured interview designed to assess deficit symptoms and thereby fill an important gap in the range of instruments now available. Data regarding reliability and training in the use of the QLS are presented. A factor analysis of the items yields results compatible with the conceptual model on which the scale is based. The factor analysis was also performed separately by sex and was fundamentally similar for men and women.
Discusses the role of testing in (a) delineating the behavioral consequences of brain lesions and (b) predicting the likely impact of such ability deficits on everyday functioning. The available studies that relate neuropsychological test scores to aspects of self-care and independent living, academic achievement, and vocational functioning are reviewed. Results are generally positive, but the clinical value of these studies is limited by the fact that most used only intelligence or screening tests with S groups that were not very representative of the patient population referred for neuropsychological testing. Methodological considerations for future research are discussed, in addition to the potential advantages of clinical over actuarial prediction in this area. To illustrate this type of clinical interpretation and suggest hypotheses for future research, it is described how results on comprehensive neuropsychological testing can be considered in relation to questions about patients' everyday functioning. (50 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The authors describe the development, reliability testing, and validation of a 17-item instrument that measures the level of functioning of chronically mentally ill persons living in the community. The Multnomah Community Ability Scale is designed to be completed by case managers. The instrument provides a measure of the consumer's severity of disability which can, in turn, be used to: (a) describe an agency's "case mix" of clients; (b) measure consumer progress; (c) assign clients to different levels of service; and (d) assist payors in determining reimbursement. The Multnomah Community Ability Scale is aimed specifically at persons with chronic mental illness, is sensitive to differences among individuals within this special population, and is quick and easy to complete. The scale's reliability and validity have been examined in detail. Inter-rater and test-retest reliability are good. Criterion variables such as length of psychiatric hospitalization and clinicians' global ratings correlated highly with scale scores. Finally, the instrument predicts subsequent state and local hospital admissions.
The quality of life in persons with severe and persistent mental illness is often poor. Most treatment programmes have the goal of increasing quality of life. Unfortunately, existing methods to assess quality of life are cumbersome and oriented towards research rather than clinical settings. This study describes preliminary steps in the development, testing and application of a new patient focused index for measuring quality of life in persons with severe mental illness. The Quality of Life Index for Mental Health (QLI-MH) differs from existing instruments in that it is based on an easy to use, self-administered questionnaire that assesses nine separate domains that together encompass quality of life. Each domain can be individually weighted depending on its relative importance to the patient. Different parts of the instrument solicit information from the patient, the primary clinician, and, when available, the family. The instrument and its scoring system address limitations of previous approaches to quality of life measurement.
It has been well established that schizophrenic patients have neurocognitive deficits, but it is not known how these deficits influence the daily lives of patients. The goal of this review was to determine which, if any, neurocognitive deficits restrict the functioning of schizophrenic patients in the outside world.
The author reviewed studies that have evaluated neurocognitive measures as predictors and correlates of functional outcome for schizophrenic patients. The review included 1) studies that have prospectively evaluated specific aspects of neurocognition and community (e.g., social and vocational) functioning (six studies), 2) all known studies of neurocognitive correlates of social problem solving (five studies), and 3) all known studies of neurocognitive correlates and predictors of psychosocial skill acquisition (six studies).
Despite wide variation among studies in the selection of neurocognitive measures, some consistencies emerged. The most consistent finding was that verbal memory was associated with all types of functional outcome. Vigilance was related to social problem solving and skill acquisition. Card sorting predicted community functioning but not social problem solving. Negative symptoms were associated with social problem solving but not skill acquisition. Notably, psychotic symptoms were not significantly associated with outcome measures in any of the studies reviewed.
Verbal memory and vigilance appear to be necessary for adequate functional outcome. Deficiencies in these areas may prevent patients from attaining optimal adaptation and hence act as "neurocognitive rate-limiting factors." On the basis of this review of the literature, a series of hypotheses are offered for follow-up studies.
A total of 172 individuals diagnosed with a schizophrenia spectrum disorder were followed for 36 months in 3 distinct models of community-based care. Functional outcome data gathered every 6 months were combined with service implementation data to test hypotheses concerning the impact of service characteristics on prospective client outcomes. The results using hierarchical linear modeling supported associations between the intensity, specificity, and longitudinality of services and improved client outcomes. Specifically, more intense services were associated with higher levels or rates of improvement on all indices of clinical and psychosocial functioning. The specificity results suggested that services needed to be targeted to specific areas of functioning in order for improvement to occur. The effect of longitudinality was contingent on the outcome domain examined.
It has been suggested that level of cognitive functioning as assessed by formal neurocognitive tests may be as important as, or even more important than, symptoms in predicting level of community functioning for patients with schizophrenia. The results of past prospective studies, when carefully examined, do not consistently support this hypothesis. In the current study, the authors used symptom and neurocognitive data to predict subsequent level of functioning in the community.
Neurocognitive and symptom data collected as part of an earlier study were used to predict the community functioning of 50 patients with a diagnosis of schizophrenia. Using the Life Skills Profile, staff of a community mental health program assessed community functioning while blind to the earlier symptom ratings and neurocognitive performance.
Symptoms were more predictive of community functioning than were neurocognitive measures. Disorganization symptoms were generally more predictive of community functioning than was either psychomotor poverty or reality distortion.
The results of this study and of previous longitudinal studies suggest the importance of using symptom levels after optimal treatment, rather than symptoms during acute episodes, as predictors of community functioning. They also indicate the need to evaluate the effects of treatment on disorganization as a separable dimension of symptoms.
This cross-sectional study examined the relationships between neurocognitive and social functioning in a sample of 80 outpatients
with DSM-III-R schizophrenia. The neurocogrntive battery included measures of verbal ability, verbal memory, visual memory, executive functioning,
visual-spatial organization, vigilance, and early information processing. Positive and negative symptoms were assessed with
the Positive and Negative Syndrome Scale. A range of social behaviors were assessed using the Social Functioning Scale (SFS),
the Quality of Life Scale (QLS), and a video-based test, the Assessment of Interpersonal Problem-Solving Skills (AIPSS). Social
functioning as assessed by the SFS was unrelated to neurocognitive functioning. Poor cognitive flexibility was associated
with low scores on the QLS and the AIPSS. Verbal ability and verbal memory were also significantly associated with the AIPSS.
Visual-spatial ability and vigilance were associated with the sending skills subscale of the ALPSS. In this study, which used
a wide range of neurocognitive tests and measures of community functioning and social problem solving, results support earlier
research that suggests an association between certain aspects of neurocognitive functioning and social functioning.
Neurocognitive deficits have been associated with the social functioning impairments of patients with schizophrenia. More information is needed about how cognitive status and other variables predict social functioning over defined periods of time. In this study, 72 relatively stable outpatients with schizophrenia were compared between baseline and a 2-year follow-up on measures of social functioning. Patients were also assessed with a battery of neurocognitive tests and the Positive and Negative Syndrome Scale. Results were compared by univariate and multivariate analyses. A total of four out of seven subscales of the Social Functioning Scale (SFS) and the total SFS score did not show a significant change over the 2-year period. On the three SFS subscales that did show a significant change, residual change scores were correlated with better neurocognitive performance at baseline, younger age, and shorter illness duration. For the Multnomah Community Ability Scale, 48.9% of the total score at follow-up was predicted by initial negative symptoms and scores on the Aphasia Screening Test. These results document the independent contribution of demographic variables, negative symptoms, and neurocognitive deficits to the social functioning impairments of individuals with schizophrenia.
There has been a surge of interest in the functional consequences of neurocognitive deficits in schizophrenia. The published literature in this area has doubled in the last few years. In this paper, we will attempt to confirm the conclusions from a previous review that certain neurocognitive domains (secondary verbal memory, immediate memory, executive functioning as measured by card sorting, and vigilance) are associated with functional outcome. In addition to surveying the number of replicated findings and tallying box scores of results, we will approach the review of the studies in a more thorough and empirical manner by applying a meta-analysis. Lastly, we will discuss what we see as a key limitation of this literature, specifically, the relatively narrow selection of predictor measures. This limitation has constrained identification of mediating variables that may explain the mechanisms for these relationships.
In our previous study we demonstrated that, in 80 schizophrenia subjects, verbal ability, verbal memory and executive functioning were significantly associated with social problem solving. The objective of this present study was to assess the longitudinal stability of the relationship between social and neurocognitive functioning in schizophrenia. This 2.5 year longitudinal cohort study re-assessed community functioning, social problem solving and symptoms in 65 of the 80 original subjects to determine the predictive ability of neurocognitive functioning. Neurocognition was not re-assessed at this follow-up. Positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale. Social functioning was assessed using the Social Functioning Scale, the Quality of Life Scale, and the Assessment of Interpersonal Problem-Solving Skills (AIPSS). Verbal ability, verbal memory and vigilance were significant predictors of social problem solving as assessed by the AIPSS. Results suggest that the association between neurocognition and social functioning remains consistent over time.
We examined whether specific neurocognitive deficits predicted specific domains of community outcome in 40 schizophrenic patients. Neuropsychological assessments were conducted before hospital discharge, and measures of functional outcome were obtained 1 to 3.5 years later. A priori hypotheses were generated based upon a recent review by Green (Green MF [1996] What are the functional consequences of neurocognitive deficits in schizophrenia? American Journal of Psychiatry, 153(3):321-330). As hypothesized, verbal memory predicted all measures of community outcome, vigilance predicted social outcomes, and executive functioning predicted work and activities of daily living (ADLs). However, in addition to the predicted relationships, many other associations were found between neuropsychological test scores and adaptive function. Furthermore, both cognitive and functional measures were intercorrelated. If deficits in adaptive functioning are neurocognitively multi-determined, utilizing compensatory strategies to bypass multiple areas of cognitive impairment may be more efficient than cognitive remediation in improving community outcomes.
Quantifying the functional consequences of illness in terms of quality of life can enhance our understanding of both mental and physical disorders. However, little is known about the quality of life among older inpatients vs. outpatients with schizophrenia. We present the results of health-related quality of life assessments in 54 middle-aged and elderly long-term inpatients with schizophrenia and a demographically matched outpatient sample. Assessments were performed using the Quality of Well-Being (QWB) scale, along with standard measures of psychopathology and global cognitive impairment. Compared with outpatients, the inpatients had a significantly lower health-related quality of life, as measured by the QWB. In the inpatient and outpatient groups, higher levels of positive symptoms were associated with lower health-related quality of life. Health-related quality of life remained fairly stable among the inpatients who remained hospitalized over 6 months. In both inpatients and outpatients, baseline cognitive status and psychopathology predicted QWB scores at the 6-month follow-up. These findings further support the use of the QWB in severely mentally ill populations; implications for improving health-related quality of life among older patients with schizophrenia are discussed.
Neurocognitive deficits are believed to be important predictors of functional outcome in chronic psychotic disorders, but few supporting studies have utilized prospective designs and adequate control. The aim of this study was to estimate the relative influence of symptoms and neurocognitive deficits on the development of social behavior skills in a cohort of individuals with schizophrenia or schizoaffective disorder recovering from acute symptom exacerbations. Forty-six individuals were recruited upon discharge from an inpatient unit and completed assessments of symptoms, neurocognitive function, and social behavior at 3-month intervals for 1 year. Correlational analyses and random regression models were used to model social behavioral capacities longitudinally. Social behavior improved modestly (10% improvements in ratings) over the follow-up period for the group as a whole. Disorganized and negative symptoms, as well as neurocognitive deficits in short-term and working memory predicted changes in social behavior over time. Individuals with better working memory function showed significantly greater abilities to recover social behavior skills, whereas those with working memory deficits showed no functional improvement over time. Both symptoms and neurocognitive deficits are important determinants of functional outcome in schizophrenia. It is proposed that clinicians should consider neurocognitive thresholds for treatment response when developing rehabilitation plans.
The differential strength of correlation between symptoms, cognition and other patient characteristics with community functioning in first-episode psychosis has not been fully investigated.
In a sample of 66 first-episode psychosis patients demographic variables, ratings of pre-morbid adjustment, positive and negative symptoms, duration of untreated psychosis (DUP) and assessment of cognitive functions at baseline, and symptoms, cognitive functions and adherence to medication 1 year, were correlated with scores on social relations and activities of daily living (ADL) (outcome) at 1 year. Hierarchical regression analysis was used to confirm the independent contribution of baseline and concurrent variables to functional outcome at 1 year.
Scores on functioning related to social relations and ADL were both significantly correlated with pre-morbid adjustment, all dimensions of residual positive and negative symptoms and adherence to medication at 1 year. Scores on social relations were also modestly correlated with DUP and several cognitive measures at baseline and 1 year (verbal IQ, attention, visual memory, word fluency and working memory). Hierarchical regression confirmed independent contribution of pre-morbid adjustment, total residual symptoms and adherence to medication at 1 year for both dimensions of outcome, and psychomotor poverty and working memory for social relations.
In addition to pre-morbid adjustment potentially malleable variables such as level of residual (but not acute) symptoms, adherence to medication and cognitive deficits are likely to influence outcome on aspects of community functioning in individuals treated for first episode of psychosis.
The present study examined the predictive validity of neuropsychological measures to functional outcome in 26 schizophrenic patients 15-plus year post-testing. Outcome measures included score on the Resource Associated Functional Level Scale (RAFLS), number of state hospital admissions, and total duration of state hospital inpatient stay. Results of several stepwise multiple regressions revealed that verbal memory significantly predicted RAFLS score, accounting for nearly half of the variance. Trails B significantly predicted duration of state hospital inpatient status. Discussion focused on the utility of these measures for clinicians and system planners.
Studies have shown that cognitive functioning may limit the rate, tenure, and type of work performed by people with schizophrenia. The present study tested the hypothesis that cognitive abilities needed for initial improvement in work performance would differ from those needed in later vocational development. Ninety-six outpatients with schizophrenia or schizoaffective disorder who participated in a work rehabilitation program were administered neuropsychological testing at intake. Their work performance was evaluated biweekly for 26 weeks. Cognitive test variables were entered into regressions predicting the slope of individual performance curves from weeks 1 to 13 and 13 to 26. Neuropsychological variables accounted for 28% of the variance in slope during the initial period. The strongest predictor was a Continuous Performance Task variable that measures inattentiveness. Other important variables were measures of idiosyncratic thinking, cognitive flexibility, and verbal memory. Neuropsychological variables accounted for 19% of the variance in the slope during the final period. The strongest predictor was verbal learning, while measures of cognitive impulsivity and psychomotor functioning were also significant contributors. There was no relationship between work performance and symptoms for weeks 1 to 13 or 13 to 26. These findings suggest that while attention is more important for initial success, verbal memory becomes more important for sustained improvement. Remediating or accommodating such deficits in a time-sensitive fashion may be a necessary feature for successful rehabilitation.
Neuropsychological (NP) studies in schizophrenia often require data reduction to avoid statistical type I error from multiple comparisons. Typically, this involves grouping measures into domains defined by experts a priori based on delineations validated in brain-injured but not schizophrenia samples (e.g. attention, executive functioning, memory, language visuospatial, motor). Component measures are arbitrarily selected and validity may not generalize to different samples or within the same sample over time. One solution to these problems is illustrated using neurocognitive subdomains based on recent schizophrenia literature, and validated with data from a longitudinal study (156 subjects) involving repeated NP testing (baseline--within 6 months of hospital discharge--and 6 and 18 months later). A priori subdomains were grouped and submitted to principal component analysis (PCA) at each time point. Longitudinal stability of the resulting factors was tested by computing congruency coefficients. Six stable factors were extracted having good construct, divergent and predictive validity. Five neuropsychological measures frequently studied in schizophrenia were not correlated with these factors, suggesting that they should be maintained as independent neurocognitive subdomains. Distinct factors for executive functioning, verbal memory and motor functions could not be validated; this raises concerns about conclusions of previous studies regarding the pattern, severity and correlates of specific neurocognitive functions in schizophrenia.
The natural history of neurocognitive impairments in schizophrenia is unclear. We aimed to characterise this in an epidemiological first-episode cohort and relate it to long-term outcome. All but 1 of 112 first-episode psychosis cases ascertained from a geographical catchment area were traced at 10-12 years. Neurocognitive and multi-dimensional outcome assessments were made at interview in 49 cases with schizophrenia and related disorders. Twenty-four of these had completed the same neurocognitive battery at index admission. Comparisons with normative data showed impaired executive function in a proportion of the first episode (FE) sample at baseline. Significant deterioration was seen over the follow-up period in three of nine sub-tests: object assembly, picture completion and memory for designs. Neurocognitive impairments at outcome, but not baseline, correlated with clinical outcome. Poor outcome was associated with a decline in performance on visuo-spatial tasks and a failure to improve on frontal-temporal tasks during the follow-up period. Executive deficits may be present in the FE, but do not progress over 10-12 years. Visuo-spatial function is spared in the FE but may deteriorate over time. Changes in both these patterned deficits are predictive of clinical outcome.
Cognitive dysfunction in schizophrenia has well-known functional consequences. The ability to learn (learning potential) may be an important mediator. This study examines the relationship between learning and functional status in schizophrenia patients before and after participation in a rehabilitation program. We reasoned that learning is a broad construct, encompassing controlled, effortful as well as automatic (learning by doing) mechanisms, called explicit and implicit learning, respectively. Both types of learning ability are important in daily life. The study included 44 medicated schizophrenia patients and 79 healthy controls. We included measures of implicit and explicit learning as well as measures of the cognitive domains for which significant relationships with functional outcome have been established: immediate and secondary verbal memory, card sorting and vigilance. Learning potential and the patient's 'learner status' were also assessed. The results show that learning, as assessed by measures of explicit and implicit learning and learning potential, was not associated with social functioning or rehabilitation outcome. The highest correlations between cognitive functioning and social functioning were found for more or less 'static' performance measures when they were assessed for a second time with or without instructions on how to do the test. Optimized cognitive performance (i.e. performance after instruction or training) seems to be a better predictor of complex domains of functioning than naive or everyday performance.
The present study examined the predictive validity of neuropsychological measures to quality of life (QOL) indicators in 30 outpatients with severe and persistent mental illness (SPMI), an average of 15 years post-testing. Outcome measures included subscale scores on the Brief Quality of Life Inventory (BQOLI). Results of several stepwise multiple regressions revealed that memory was predictive of income, satisfaction with daily activities, and general health. Executive functioning was predictive of contact with family and financial support. Motor skills were predictive of satisfaction with family contact, and working memory was predictive of victimization and satisfaction with social contacts. Discussion focused on neurocognition as a predictor of QOL, clinical implications, and the potential for improving QOL through cognitive interventions.
To stimulate the development of new drugs for the cognitive deficits of schizophrenia, the National Institute of Mental Health (NIMH) established the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. This article presents an overview of decisions from the first MATRICS consensus conference. The goals of the meeting were to 1) identify the cognitive domains that should be represented in a consensus cognitive battery and 2) prioritize key criteria for selection of tests for the battery. Seven cognitive domains were selected based on a review of the literature and input from experts: working memory, attention/vigilance, verbal learning and memory, visual learning and memory, reasoning and problem solving, speed of processing, and social cognition. Based on discussions at this meeting, five criteria were considered essential for test selection: good test-retest reliability, high utility as a repeated measure, relationship to functional outcome, potential response to pharmacologic agents, and practicality/tolerability. The results from this meeting constitute the initial steps for reaching a consensus cognitive battery for clinical trials in schizophrenia.
The NIMH-Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative requires, among other things, the establishment of a reliable, valid, and consensus-derived method of assessing cognition. The derived battery will provide a standardized way to assess the effects of cognition-enhancing agents across clinical trials. To this end, the first of six consensus-oriented conferences was held April 2003. The goals were twofold: (a) To select which cognitive constructs to measure in a consensus battery, and (b) to select which criteria to use in evaluating tests for inclusion in the battery. Based on consultation with experts on the RAND Panel Method, 74 experts were invited to participate in a pre-meeting survey to provide information relevant to decisions on the cognitive battery. The survey included sections on reliability, validity, test administration, norms and interpretation of tests, cognitive domains and their integration, battery duration, and overall importance of test qualities. For selection of cognitive targets, the results showed that experts ranked executive functions, attention/vigilance, memory processes, and problem-solving ability highest. For test qualities, the experts ranked test-retest reliability, good coverage of key individual cognitive constructs, and comparable alternate forms highest. This article presents the results of the pre-conference survey that was the first step in the RAND process towards development of the NIMH-MATRICS consensus battery to assess cognition in schizophrenia.
The impairments in social and vocational outcome that are common in schizophrenia are strongly related to the severity of impaired neurocognition. This observation led to the initiation of The NIMH's Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative, which supports the development of pharmacological agents to improve cognition in schizophrenia. MATRICS addresses barriers to drug development through a number of activities, including the development of a consensus battery for measuring cognition in schizophrenia; the development of a consensus regarding the most promising molecular targets that should be the focus of drug development; the use of a joint meeting with representatives from the industry, academia, NIMH, and the U.S. Food and Drug Administration (FDA) to clarify guidelines for the design of clinical trials for cognition enhancing agents; and finally, to assist NIMH in developing its research agenda in this area.
Follow-up studies have found that a substantial number of patients with schizophrenia achieve full recovery (i.e., sustained improvement in both symptoms and social/vocational functioning) when examined decades after an index admission. This study addressed recovery during the crucial early course of the illness.
Subjects in their first episode of schizophrenia or schizoaffective disorder (N=118) were assessed at baseline and then treated according to a medication algorithm. Full recovery required concurrent remission of positive and negative symptoms and adequate social/vocational functioning (fulfillment of age-appropriate role expectations, performance of daily living tasks without supervision, and engagement in social interactions).
After 5 years, 47.2% (95% CI=36.0%-58.4%) of the subjects achieved symptom remission, and 25.5% (95% CI=16.1%-34.7%) had adequate social functioning for 2 years or more. Only 13.7% (95% CI=6.4%-20.9%) of subjects met full recovery criteria for 2 years or longer. Better cognitive functioning at stabilization was associated with full recovery, adequate social/vocational functioning, and symptom remission. Shorter duration of psychosis before study entry predicted both full recovery and symptom remission. More cerebral asymmetry was associated with full recovery and adequate social/vocational functioning; a schizoaffective diagnosis predicted symptom remission.
Although some patients with first-episode schizophrenia can achieve sustained symptomatic and functional recovery, the overall rate of recovery during the early years of the illness is low.
An integrative approach to quality of life assessment: the general health policy model Quality of Life in Clinical Studies
- R M Kaplan
- J P Anderson
Kaplan, R.M., Anderson, J.P., 1990. An integrative approach to quality of life assessment: the general health policy model. In: Spilker, B. (Ed.), Quality of Life in Clinical Studies. Raven Press, New York, pp. 131 – 149.
Social Adjustment Scale II Publication ADM 79-328
- N R Schooler
- G E Hogarty
- M M Weissman
Schooler, N.R., Hogarty, G.E., Weissman, M.M., 1979. Social Adjustment Scale II. In: Hargreaves, W.P., Attkisson, C.C., Sorenson, J.E. (Eds.), Resource Materials for Community Health Program Evaluations, (2nd ed.). Publication ADM 79-328. US Department of Health, Education, and Welfare, Rockville, MD, pp. 290 – 302.
A community ability scale for chronically mentally ill consumers. Part 1: reliability and validity
- Barker