Remediation of cognitive deficits in schizophrenia

Studies have suggested that schizophrenia is characterized by an impairment in the dorsolateral prefrontal cortex that prevents learning of some elementary information processing tasks. To test this hypothesis, the authors administered the Wisconsin Card Sorting Test to 16 schizophrenic inpatients with standard instructions and either contingent or noncontingent reinforcement. Performance was markedly impaired under each condition. A second cohort (N = 12) was tested after receiving instructions plus rehearsal and feedback. These subjects' performance was comparable to nonpatient norms and was maintained on a subsequent day. The results indicate that deficits in performance on the Wisconsin Card Sorting Test are remediable, whether or not they are due to neurological impairment.     

Depression and cognitive deficits in geriatric schizophrenia

Objective

Past reports have found patients with comorbid depression and schizophrenia spectrum disorders exhibit greater deficits in memory and attention compared to schizophrenia spectrum disorder patients without depressive symptoms. However, in contrast to younger schizophrenia patients, the few past studies using cognitive screens to examine the relationship between depression and cognition in inpatient geriatric schizophrenia have found that depressive symptomatology was associated with relatively enhanced cognitive performance. In the current study we examined the relationship between depressive symptoms and cognitive deficits in geriatric schizophrenia spectrum disorder patients (n = 71; mean age = 63.7) on an acute psychiatric inpatient service.

Method

Patients completed a battery of cognitive tests assessing memory, attention and global cognition. Symptom severity was assessed via the PANSS and Calgary Depression Scale for Schizophrenia.

Results

Results revealed that geriatric patients' depression severity predicted enhancement of their attentional and verbal memory performance. Patients' global cognitive functioning and adaptive functioning were not associated with their depression severity.

Conclusion

Contrary to patterns typically seen in younger patients and non-patient groups, increasing depression severity is associated with enhancement of memory and attention in geriatric schizophrenia spectrum disorder patients. Also, diverging from younger samples, depression severity was unassociated with patients adaptive and global cognitive functioning.     

精神分裂症认知功能障碍的研究进展

认知功能障碍严重影响精神分裂症患者的社会功能和生活质量,这一核心症状稳定、持久地存在于精神分裂症的不同病程中.研究认知功能障碍的特征有助于疾病机制的探索,加深对疾病发展进程的理解并提供有针对性的干预策略.现就精神分裂症认知功能障碍的特征及机制展开综述.     

Methods for treating cognitive deficits in schizophrenia

Studies from the molecular to clinical level suggest that cognitive dysfunction is central in characterizing schizophrenia. Accordingly, there have been increased efforts to search for effective treatments of these broad and debilitating cognitive deficits. Three general strategies for treating cognitive dysfunction in schizophrenia have emerged in the literature. The second-generation (atypical) antipsychotic medications have received much attention but their procognitive effects tend to be modest. Augmentation strategies, driven from basic science or translational research, have often been promising in small uncontrolled trials; however, few agents have fared well in rigorously designed trials. Behavioral interventions have demonstrated positive effects that generalize to other symptom domains and persist after the intervention, but tend to be costly and labor intensive. Thus, although there have been some exciting advances in treating cognitive dysfunction, the gains to date are modest and the search for treatment methods continues.     

Correlates of cognitive deficits in first episode schizophrenia

OBJECTIVE: The presence of cognitive dysfunction in schizophrenia has been well documented, but questions remain about whether there are relationships between this dysfunction and clinical symptomatology. If present, such relationships should be most clearly observable in patients with first episode schizophrenia; that is, before the effects of chronic illness, institutionalization, or treatment might confound them. METHOD: 307 schizophrenia subjects in their first episode of illness were recruited to participate in a clinical trial comparing the long-term efficacy of haloperidol and risperidone. The psychopathology, cognitive functioning, early treatment history, and duration of untreated psychosis of these subjects were assessed prior to their assignment to randomized, double-blind treatment. Approximately two-thirds of the subjects were receiving antipsychotic treatment at the time of assessment; however, the duration of treatment was limited to 12 weeks or less. RESULTS: The severity of negative symptoms at the time of assessment was associated with deficits in memory, verbal fluency, psychomotor speed and executive function. Positive symptoms were not associated with cognitive deficits. Also, the duration of untreated illness (DUI) prior to assessment was not significantly associated with cognitive impairment. CONCLUSIONS: The results of this study of first episode schizophrenia patients suggest that a relationship exists between negative symptoms and cognitive dysfunction. However, that relationship accounts for only a minor portion of the variance (i.e., 10-15%) in the severity of cognitive dysfunction after controlling for a number of potentially confounding factors. This finding provides support for the theory that the neurobiological processes that give rise to symptomatology and cognitive dysfunction in schizophrenia are partially overlapping.     

Predicting drug efficacy for cognitive deficits in schizophrenia

The purpose of this article is to discuss the prediction of cognitive enhancement in schizophrenia from preclinical data. Despite increasing focus on the significance of cognitive impairment in schizophrenia, the progress of novel treatments has been slow. Hyman and Fenton's identification of a "translational gap" between preclinical and clinical science underscores the need to revise preclinical, clinical, and regulatory practice. A review of the clinical literature identifies evidence for some cognitive benefits with current antipsychotics. The magnitude of these effects may, in some cases, be too small to be functionally relevant, and many studies are methodologically flawed, but the data might nevertheless allow translational links to be identified between clinical and preclinical studies. The literature is reviewed to determine if the cognitive signal reported in clinical studies is detectable in preclinical studies. The effects of antipsychotics on prepulse-inhibition deficits in animals is robust and demonstrates a reversal of drug-induced and developmentally induced deficits, although predictive links to the clinic are not well established. The preclinical literature on antipsychotic effects on attention, learning and memory, and recognition and executive function shows, with rare exceptions, impaired learning or task performance, rather than improvement. In general, therefore, preclinical studies have not detected the small pro-cognitive signal evident in the clinical literature. A number of factors may account for this. Effective closure of the translation gap for cognitive deficits in schizophrenia will require the design of a coherent preclinical strategy, and some of the potential elements of such a strategy are outlined and discussed.     

General and specific cognitive deficits in schizophrenia.

BACKGROUND: It is controversial whether the cognitive deficit in schizophrenia is better characterized as generalized or as reflecting relatively independent deficits in different cognitive domains. The issue has implications for assessment practice, intervention design, and the exploration of schizophrenia genetics. METHODS: We used a specialized structural equation modeling approach, single common factor analysis, to explore the relative importance of generalized versus independent cognitive deficits in schizophrenia. Eighteen subtest scores from the Wechsler Adult Intelligence Scale-III and the Wechsler Memory Scale-III were included in the analysis. We analyzed these data for 97 schizophrenia or schizoaffective disorder outpatients and 87 healthy control subjects. RESULTS: Approximately two thirds of the overall effect of a schizophrenia diagnosis on cognitive performance was mediated through a single common factor. The Wechsler subtest scores showed almost uniformly strong relationships with this factor. The independent associations of group status with the subtest scores were smaller in magnitude and only selectively significant. CONCLUSIONS: The relatively greater magnitude of illness effects mediated through the common factor in this analysis, compared with the specific, independent effects, suggests that a generalized cognitive deficit is a core feature of schizophrenia.     

Treating cognitive dysfunction in patients with schizophrenia

Cognitive dysfunction is a common, chronically disabling component of schizophrenia. It has been proposed that many of the symptoms of schizophrenia can be understood as a result of disruption of fundamental cognitive processes. This paper reviews treatment strategies aimed at improving cognitive function in patients with schizophrenia. Nonpharmacologic interventions include instruction in the performance of tasks such as the Wisconsin Card Sorting Test. Mixed results have been achieved, but it appears that instruction methods involving reinforcement of information held in working memory are more successful. Computer-aided remediation has also been used with variable success. Novel antipsychotic drugs appear to have an advantage over conventional antipsychotic drugs in terms of their effect on cognitive function. The development of more precisely tailored methods of remedial teaching, along with optimal pharmacologic treatment, may lead to more effective treatment of cognitive dysfunction in patients with schizophrenia.     

Treatment of cognitive dysfunctions and behavioral deficits in schizophrenia.

Integrated Psychological Therapy (IPT) is a structured intervention program that prescribes steps to remediate cognitive and behavioral dysfunctions that are characteristic of the psychopathology of schizophrenia. Evaluative studies of IPT indicated that the program improved schizophrenic patients' elementary cognitive processes such as attention, abstraction, and concept formation but that patients' performance was still below the normal range. The clinical utility of IPT will depend on studies that document the hierarchical generalization of improvements from the cognitive to the social and symptomatic levels of functioning.     

Toward a prefrontal microcircuit model for cognitive deficits in schizophrenia

I present here a biophysically-based model of cortical microcircuits capable of both internal representation (memory storage) and dynamical processing (decision and action selection). The model is illustrated through computer simulations that account for neurophysiological and behavioral data from studies using nonhuman primates. This computational theory proposes that an interplay between slow reverberating excitation and competitive synaptic inhibition enables a cortical area, such as the prefrontal cortex, to subserve cognitive functions. It is argued that quantitatively accurate microcircuit models can potentially provide a framework for a systematic approach to pharmacological treatment of schizophrenia and other mental disorders.     

Functional network connectivity impairments and core cognitive deficits in schizophrenia

Cognitive deficits contribute to functional disability in patients with schizophrenia and may be related to altered functional networks that serve cognition. We evaluated the integrity of major functional networks and assessed their role in supporting two cognitive functions affected in schizophrenia: processing speed (PS) and working memory (WM). Resting‐state functional magnetic resonance imaging (rsfMRI) data, N = 261 patients and 327 controls, were aggregated from three independent cohorts and evaluated using Enhancing NeuroImaging Genetics through Meta Analysis rsfMRI analysis pipeline. Meta‐ and mega‐analyses were used to evaluate patient‐control differences in functional connectivity (FC) measures. Canonical correlation analysis was used to study the association between cognitive deficits and FC measures. Patients showed consistent patterns of cognitive and resting‐state FC (rsFC) deficits across three cohorts. Patient‐control differences in rsFC calculated using seed‐based and dual‐regression approaches were consistent (Cohen's d: 0.31 ± 0.09 and 0.29 ± 0.08, p < 10^?4). RsFC measures explained 12–17% of the individual variations in PS and WM in the full sample and in patients and controls separately, with the strongest correlations found in salience, auditory, somatosensory, and default‐mode networks. The pattern of association between rsFC (within‐network) and PS (r = .45, p = .07) and WM (r = .36, p = .16), and rsFC (between‐network) and PS (r = .52, p = 8.4 × 10^?3) and WM (r = .47, p = .02), derived from multiple networks was related to effect size of patient‐control differences in the functional networks. No association was detected between rsFC and current medication dose or psychosis ratings. Patients demonstrated significant reduction in several FC networks that may partially underlie some of the core neurocognitive deficits in schizophrenia. The strength of connectivity‐cognition relationships in different networks was strongly associated with network's vulnerability to schizophrenia.     

Association of symptomatology and cognitive deficits to functional capacity in schizophrenia

PURPOSE: This study aimed to evaluate the association of positive and negative symptoms, as well as of neurocognition to functional status in patients with schizophrenia. Participants were 309 veterans with DSM-IV-diagnosed schizophrenia or schizoaffective disorder who were enrolled in a 12-month double-blind clinical trial and randomized to receive either 5 to 20 mg/d of oral olanzapine or haloperidol. Patients were assessed at study entry and at 3, 6 and 12-months on the PANSS and measures of verbal memory, verbal fluency, fine motor coordination, visual sequencing/set shifting, and conceptual reasoning. Functional status was evaluated by the Heinrichs-Carpenter Quality of Life Scale (QLS) and by days of employment in the past 30. Hierarchical regression models examined the association of functional status with symptomatology and three neurocognitive factors (motor skills, memory and card sorting), controlling for demographics and visit number. A mixed effects model was used to adjust for repeated observations from the same subjects. RESULTS: The PANSS explained 16% additional variance in QLS total score after accounting for demographics and visit number (p<.001), while the neurocognitive factors explained only 4% additional variance beyond the effect of symptoms. When neurocognition was entered before symptoms, it explained an additional 8% of the variance on the QLS total score, while the PANSS explained an additional 12% over and above neurocognition. CONCLUSIONS: These findings suggest that symptoms may pose an equal or greater impediment to functional capacity independent of neurocognition, at least in younger non-institutionalized people with schizophrenia.     

Gender differences in cognitive deficits in schizophrenia with and without diabetes

This study investigated gender differences in cognition in schizophrenia with and without diabetes. Cognition was assessed in 263 individuals with schizophrenia with age range (40–68): 67 males and 34 females with schizophrenia with diabetes; and 125 males and 37 females with schizophrenia without diabetes according to the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Fasting glucose, hemoglobin A1c (HbA1c) and lipid levels were measured. Results showed that male individuals performed worse on most cognitive tasks, especially attention, in schizophrenia with than without diabetes. This result was not observed in female individuals. Also, individuals of both genders showed higher fasting glucose and HbA1c in schizophrenia with than without diabetes. In schizophrenia with diabetes, males had significantly worse cognition than females in all cognitive domains. Higher HbA1c, lower high-density lipoprotein, and an earlier age of onset of schizophrenia were found in males compared with female individuals. HbA1c was negatively associated with attention and the RBANS total score for males but not for females. In schizophrenia without diabetes, males showed worse performance in immediate and delayed memory than females. This study support cognition was worse for males with schizophrenia irrespective of whether they have diabetes. However, diabetes exemplified the gender differences, especially in attention.     

Self-rated and performance-based empathy in schizophrenia: The impact of cognitive deficits

People may be much less empathic than they think they are. It is not clear whether patients with schizophrenia who have impaired empathic abilities also exhibit diminished ability to accurately appraise their own such skills. The present study aimed to examine: (a) the accuracy of self-appraisal of empathy and (b) the impact of specific cognitive functions on both self-rated and performance-based empathy in schizophrenia patients and healthy volunteers. Self-reported empathy and performance-based empathy were assessed in 52 chronic patients with schizophrenia and 45 matched healthy participants with the empathy quotient and the empathy score in the Faux Pas test, respectively. Neuropsychological functioning and symptom severity were also assessed. No significant correlations between self-reported and performance-based empathy scores were found in patients, whereas these correlations were significant and positive in the control group, with the exception of Faux Pas recognition. Cognitive deficits, specifically in processing speed and theory of mind, negatively affected performance-based but not self-rated empathy in schizophrenia. Patients with less negative and more positive symptoms and lower set shifting ability reported higher empathic abilities. Self-reported empathy and empathic abilities do not show a simple relationship. Our findings highlight a double deficit related to empathic responding in schizophrenia: diminished performance associated with cognitive deficits and inaccurate self-appraisal of empathic abilities.