Can specific deficits in executive functioning explain the negative symptoms of schizophrenia? A review

The relationship between clinical symptoms and neurocognitive impairment has been a growing interest in the field of schizophrenia research. We review the empirical evidence for whether some schizophrenia symptoms can be viewed as expressions of disordered executive functioning. A specific focus of our review is Frith's (1992) neurocognitive theory of negative symptoms, and whether this theory is supported by studies of executive functioning in schizophrenia. The current trend towards viewing executive functioning in terms of fractionable cognitive processes is discussed. Difficulties with traditional clinical measures (e.g. the Wisconsin Card Sorting Test; WCST) in separating these processes are highlighted. Neurocognitive studies of schizophrenia are then reviewed in terms of this fractionated view of executive processes. We conclude that a more specific approach to executive functioning deficits in schizophrenia using more selective measures is needed before stronger conclusions can be drawn about their relationship to clinical symptoms.     

Neuropsychological functioning as a moderator of the relationship between psychosocial functioning and the subjective experience of self and life in schizophrenia

Psychosocial interventions and models of quality of life in schizophrenia are based on the notion that increases in psychosocial functioning will be related to improvements in subjective experience outcomes such as self-esteem and satisfaction with life. However, studies have repeatedly failed to demonstrate a direct relationship between psychosocial functioning and subjective experience in schizophrenia. This study of 40 individuals diagnosed with schizophrenia examined whether neurocognitive measures of executive functioning moderated the relationship between psychosocial functioning and subjective experience. Subjective experience was represented by measures of satisfaction with life and self-esteem. The Global Assessment Scale measured psychosocial functioning, and the Wisconsin Card Sorting Test measured executive functioning. Multiple regression and correlation analyses indicated that executive functioning was a strong moderator. Specifically, individuals with schizophrenia with impaired executive functioning displayed a positive and statistically significant association between psychosocial functioning and both measures of subjective experience (r = 0.55 and 0.61). However, among schizophrenia patients with intact executive performance, psychosocial functioning was negatively associated with self-esteem and satisfaction with life (r = -0.24 and -0.46). And the findings were internally replicated using two other neuropsychological measures relevant to executive functioning. These findings indicate that executive functioning plays a major role in moderating the relationship between subjective experience and psychosocial functioning in schizophrenia. Implications for biosocial models, psychosocial interventions, and models of quality of life in schizophrenia are discussed.     

Neurocognition and suicidal behaviour in an Irish population with major psychotic disorders

OBJECTIVES: Although neurocognitive deficits are seen as core to schizophrenia the association between suicidality and neurocognition has received little attention. Our aim was to examine the relationship between neurocognitive variables and suicidal behaviour in patients with schizophrenia and schizoaffective disorder. METHODS: Seventy-eight patients with DSM-IV diagnoses of schizophrenia or schizoaffective disorder were categorised as either having attempted suicide or not having attempted suicide based on clinical interview and chart review. Attempters and non-attempters were compared on an extensive neuropsychological battery examining pre-morbid and current general cognitive functioning, episodic memory, and executive functioning. RESULTS: Suicide attempters tended to out perform non-attempters across all areas of executive functioning, and showed significantly better performances on measures of attention and verbal fluency. After controlling for relevant clinical and demographic variables, the differences between attempters and non-attempters remained significant for measures of attention (F = 4.97, p = 0.03) and verbal fluency (F = 4.28, p = 0.04). CONCLUSION: This study adds to existing data that suicide attempters with schizophrenia or schizoaffective disorder may have higher cognitive functioning than non-attempters. In particular, the preservation of higher executive function may influence the ability to initiate and plan suicidal behaviour.     

Do specific neurocognitive deficits predict specific domains of community function in schizophrenia?

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.     

Insight in schizophrenia: its relationship to measures of executive functions.

Lack of awareness of specific symptoms among persons with schizophrenia has not been adequately studied in the context of neuropsychological function. The purpose of this study is to investigate whether poor insight as measured by the Scale to Assess Unawareness of Mental Disorder is empirically related to performance measures having a known association with executive functions in a group of individuals with chronic schizophrenia. The results showed that unawareness and misattribution of negative symptoms are significantly associated with deficits in some aspects of executive functioning even after a test of general intelligence had been partialed from the analyses. We conclude that unawareness of negative symptoms is associated with executive functioning in individuals with chronic schizophrenia. Unawareness of other symptoms (i.e., positive symptoms) may reflect dysfunction in other types of neuropsychological processes, or it may reflect motivation to deceive oneself or others.     

Théorie de l’esprit : un médiateur entre symptômes et fonctionnement dans la schizophrénie ?

This literature review aimed to summarize the scientific knowledge concerning the links between psychosocial functioning and social cognition. Social cognition, and particularly Theory of Mind, is strongly disturbed in patients with schizophrenia. There were strong arguments that psychosocial functioning was more strongly associated with Theory of Mind than with neurocognition (defined as nonsocial information processing in contrast to social cognition). The functional capacity mediated this influence. Moreover, longitudinal studies suggested a unidirectional causal pathway with primary neurocognitive disorders leading to secondary deficits in social cognition, which in turn led to disturbances in psychosocial functioning. Studies using structural equation modelling showed that positive, negative and disorganization symptoms were associated with disturbances in psychosocial functioning. Regarding negative symptoms and disorganization, the influences were mediated by social cognition. The influence of positive symptoms on psychosocial functioning was independent of social cognition. This literature review suggests that social cognitive remediation in patients with should improve the psychosocial functioning in patients with schizophrenia.     

Basic neuropsychological dimensions in schizophrenia

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 relative influences of symptoms, insight, and neurocognition on social adjustment in schizophrenia and schizoaffective disorder

Impaired insight and neurocognitive deficits are commonly seen in schizophrenia. No study to date, however, has documented the relative influences of insight deficits, neurocognitive functioning, and psychotic symptoms on overall social adjustment in this population. This was done in a cohort of individuals recovering from acute exacerbations. Forty-six individuals with schizophrenia or schizoaffective disorder were recruited upon discharge from an inpatient unit. Symptom levels, neurocognitive functioning (information processing, memory, and executive functioning), and symptom awareness were documented, and social adjustment was assessed in three domains: treatment compliance, social behavior, and subjective quality of life. Cross-sectional data from initial assessments are reported. Sequential linear regression analyses identified differential associations between illness characteristics and outcome domains. Treatment compliance was most influenced by insight; social behavior deficits were associated with thought disorder and neurocognitive (working memory and visuo-spatial) impairments; and quality of life was associated with mood disturbances. Outcome is multidimensional in schizophrenia, and there are differential patterns of associations between illness characteristics and domains of social adjustment. Studies such as this can guide clinicians in determining the most appropriate treatments for specific individuals and should also guide researchers in efforts to clarify the processes that underlie treatment response and recovery in schizophrenia.     

Neurocognitive Predictors of Objective and Subjective Quality of Life in Individuals With Schizophrenia: A Meta-Analytic Investigation

Quality of life (QOL) has been recognized as a crucial domain of outcome in schizophrenia treatment, and yet its determinants are not well understood. Recent meta-analyses suggest that symptoms have only a modest relationship to QOL (Eack SM, Newhill CE. Psychiatric symptoms and quality of life in schizophrenia: a meta-analysis. Schizophr Bull. 2007;33:1225–1237). Individuals with schizophrenia show 1–2 SD deficits on measures of elementary neurocognition, and links between these deficits and objective measures of community functioning (eg, employment and independent living) are well established. While objective measures of community functioning and measures of QOL would appear to be closely related, studies investigating the ability of neurocognitive variables to predict QOL in individuals with schizophrenia have yielded conflicting results. One potential explanation for opposing findings in the schizophrenia literature is the interchangeable use of objective and subjective indices of QOL. This study used quantitative methods of meta-analysis to clarify the relationship between neurocognitive determinants of objective QOL (ie, observable, clinician-rated) and subjective QOL (ie, patient satisfaction) separately in individuals with schizophrenia. A total of 20 studies (10 objective and 10 subjective) consisting of 1615 clients were aggregated from relevant databases. Weighted effect size analysis revealed that there were small–moderate relationships (d ≤ 0.55) between crystallized verbal ability, working memory verbal list learning, processing speed, and executive function and objective indices of QOL. In contrast, results revealed either nonsignificant or inverse relationships for the vast majority of neurocognitive measures and measures of subjective QOL. Moderating variables and implications for future research and treatment development are discussed.     

Neurocognition as a stable endophenotype in bipolar disorder and schizophrenia

Linkage and association studies have paid increasing attention to neurocognition as a putative endophenotype. However, there exists little documentation of its trait stability in schizophrenia or bipolar disorder. Our aim was to determine the longitudinal stability of neurocognitive performance in bipolar versus schizophrenia probands. We administered a neurocognitive battery at two time points, approximately 5 years apart, in 16 schizophrenia and 16 bipolar disorder age-matched subjects. There were no significant changes over time on variables including education, estimated IQ, depression, psychosis, global functioning, or medication status. Schizophrenia subjects showed significant deterioration in one measure of executive functioning but no significant changes in seven of eight other domains. Bipolar patients showed stability over time in attentional measures but greater variability in other domains. These preliminary findings suggest that neurocognitive domains appear longitudinally stable across broad domains in schizophrenia. In contrast, stable functioning may be more limited to attentional domains in bipolar disorder.     

Spatial working memory deficits in schizophrenia: relationship with tardive dyskinesia and negative symptoms

OBJECTIVE: This study examined the interrelationship between negative symptoms, orofacial tardive dyskinesia, and specific neurocognitive processes, particularly those involved in memory and executive function, in patients with schizophrenia. METHOD: A set of computerized neurocognitive tasks, the Cambridge Neuropsychological Test Automated Battery, was used to assess executive and memory function in 54 hospitalized patients with chronic schizophrenia. Analysis of covariance was used to examine differences between groups with or without the topographical syndromes of orofacial tardive dyskinesia and between groups with high or low negative symptom scores. Principal-components and path analyses were used to examine further the influence of negative symptoms and orofacial tardive dyskinesia on performance on tests of memory and executive function. RESULTS: Both orofacial tardive dyskinesia and negative symptoms were significantly and independently associated with deficits on measures of spatial working memory span derived from principal-components analysis, but only orofacial tardive dyskinesia was associated with deficits on measures of spatial working memory strategy. Both were also associated with impairment on the delayed-matching-to-sample task, a test of memory. These associations were not explained by deficits in global intellectual function. Path analysis suggested that the relationships between the clinical symptoms and performance on the delayed-matching-to-sample task were mediated entirely through their relationship with the spatial working memory measures. CONCLUSIONS: In schizophrenia, orofacial tardive dyskinesia and evident negative symptoms are relatively independent markers of compromise of the cerebral systems that mediate spatial working memory. Candidate neural circuits include the frontal-striatal-thalamic systems, particularly those involving the dorsolateral prefrontal cortex.     

Neurocognitive functioning and suicidality in schizophrenia spectrum disorders

Objective

The aim of this study was to investigate whether suicide attempters had higher IQ, better executive functioning, or were more impulsive as measured by neuropsychological tests than non-attempters in a group of patients with schizophrenia spectrum disorders.

Method

One hundred seventy-four patients with schizophrenia spectrum disorders were assessed with a clinical interview for diagnosis, suicidality, symptoms and function, and underwent an extensive neurocognitive test battery.

Results

There were no statistically significant differences in any neurocognitive domains between lifetime suicide attempters and non-attempters, or between patients with different rates of suicide attempts. Currently suicidal patients were significantly more impulsive (had poorer inhibitory control) than currently non-suicidal patients, but this difference was mediated by positive psychotic symptoms.

Conclusion

The findings indicate that among patients with schizophrenia spectrum disorders, there are no significant differences in IQ or neurocognitive functioning between suicide attempters and non-attempters.     

Symptoms and cognition as predictors of community functioning: a prospective analysis

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.     

Is theory of mind in schizophrenia more strongly associated with clinical and social functioning than with neurocognitive deficits?

This paper examines the correlations between 'Theory of Mind' (ToM) and neurocognitive performance, together with clinical and social functioning, in out-patients with schizophrenic disorders. It was hypothesised that, since the ability to make inferences about the environment and about other peoples' mental states is a key ingredient of social competence, the assessment of ToM would correlate more strongly with current social functioning than with more traditional neurocognitive measures. 'Independent raters' assessed Theory of Mind, neurocognitive and clinical variables as well as community functioning in 44 subjects with schizophrenia. The neuropsychological measures were more closely associated with community functioning than with psychiatric symptoms. These associations remained evident when the effects of intelligence were controlled. Patients with a higher level of competence in making social inferences had better overall community functioning than those who showed less ability in this aspect of social cognition. In a regression model, the capacity to comprehend other people's mental states (ToM-2) was among the best predictors of global social functioning, together with recent onset of illness, good verbal fluency and low levels of negative and positive symptoms. These results are consistent with other recent findings. ToM measures of social cognition may be a useful addition to neuropsychological assessment when developing programmes for reducing clinical impairments and improving the community functioning of subjects with schizophrenic disorders. Further studies are needed to verify the value of these measures as predictors of the successful application of specific psychosocial rehabilitation strategies.     

Association of obsessions and compulsions in schizophrenia with neurocognition and negative symptoms

It is unclear whether obsessions and compulsions in schizophrenia spectrum disorders are associated with a unique pattern of symptoms and deficits. Accordingly, the present study compared symptom levels and neurocognitive function of participants with schizophrenia or schizoaffective disorder with (n=11) and without (n=52) significant obsessive-compulsive symptoms. Analyses of variance revealed that the obsessive-compulsive group performed more poorly on measures of executive function and vigilance and had higher levels of negative and emotional discomfort symptoms. Unexpectedly, the obsessive-compulsive group also demonstrated superior performance on a measure of visual memory. The implications of these clinical correlates of obsessive-compulsive phenomena in schizophrenia spectrum disorders are discussed.     

Neurocognitive and social functioning in schizophrenia: a 2.5 year follow-up study

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.     

The role of cognition in vocational functioning in schizophrenia

Schizophrenia is associated with long-term unemployment. Cognitive dysfunction, rather than clinical symptoms, may be the most important factor in the ability to work for patients with this disorder. To evaluate the relationship of clinical symptoms and cognitive functioning to work status, thirty patients with schizophrenia, who were participants in a vocational rehabilitation program, were evaluated with a comprehensive neuropsychological battery and assessment of psychopathology. Subjects were classified as being in stable full-time, part-time or unemployed work status for at least a year. Univariate analysis indicated that patients who were working full-time were significantly better educated, more likely to be treatment-resistant, more likely to be treated with an atypical antipsychotic medication, had more positive symptoms, and were engaged in work tasks which were more cognitively complex than the part-time employed and unemployed work groups. An ANCOVA controlling for education demonstrated that the full-time employed group performed significantly better than the unemployed group on measures of executive functioning, working memory and vigilance; and significantly better than the part-time group on measures of vigilance and executive functioning. Although negative symptoms did not significantly relate to work status in the univariate analysis, a multiple regression indicated that negative symptoms, level of education, and executive functioning differentiated the work groups. These results suggest that poor premorbid function, negative symptoms and cognitive dysfunction are significantly associated with unemployment in schizophrenia.     

Predictors of metabolic monitoring among schizophrenia patients with a new episode of second-generation antipsychotic use in the Veterans Health Administration

Background

The underlying nature of negative symptoms in psychosis is poorly understood. Investigation of the relationship between the different negative subsymptoms and neurocognition is one approach to understand more of the underlying nature. Apathy, one of the subsymptoms, is also a common symptom in other brain disorders. Its association with neurocognition, in particular executive functioning, is well documented in other brain disorders, but only studied in one former study of chronic patients with schizophrenia. This study investigates the association between apathy and neurocognitive functioning in patients with first episode psychosis (FEP), with the hypothesis that apathy is more associated with tests representing executive function than tests representing other neurocognitive domains.

Methods

Seventy-one FEP patients were assessed with an extensive neuropsychological test battery. Level of apathy was assessed with the abridged Apathy Evaluation Scale (AES-C-Apathy).

Results

AES-C-Apathy was only significantly associated with tests from the executive domain [Semantic fluency (r =.37, p <.01), Phonetic fluency (r =.25, p <.05)] and working memory [Letter Number Span (r =.26; p =<.05)]; the first two representing the initiation part of executive function. Confounding variables such as co-occuring depression, positive symptoms or use of antipsychotic medication did not significantly influence the results.

Conclusion

We replicated in FEP patients the relationship between apathy and executive functioning reported in another study for chronic patients with schizophrenia. We also found apathy in FEP to have the same relationship to executive functioning, as assessed with the Verbal fluency tests, as that reported in patients with other brain disorders, pointing to a common underlying nature of this symptom across disorders.     

Deficits in neurocognition, theory of mind, and social functioning in patients with schizophrenic disorders: are they related?

In schizophrenic disorders, impairments in social functioning, neurocognition, and theory of mind (ToM) are frequently reported but little is known about the relationships between them. The aim of this study is twofold: (a) to compare neurocognition, social-functioning, and ToM in patients and controls and (b) to investigate whether impairments in these domains are related to psychiatric symptoms. Participants were 16 outpatients with schizophrenic disorders (DSM-IV), and 16 healthy controls. We administered neuropsychological tests, ToM, social functioning, and psychopathology measures. Patients and controls differed on most neurocognitive variables (memory, attention, executive functions). We also found significant differences in 1 ToM factor and 2 social measures. The latter were the only 2 related to manic-hostility and negative symptoms subscores of Brief Psychiatric Rating Scale. Our findings suggest that there is no direct relation between neurocognitive impairments and social dysfunctions.