Working memory correlates of three symptom clusters in schizophrenia

This study was designed to examine whether discrete working memory deficits underlie positive, negative and disorganised symptoms of schizophrenia. Symptom dimension ratings were assigned to 52 outpatients with schizophrenia (ICD-10 criteria), using items drawn from the Positive and Negative Syndrome Scale (PANSS). Linear regression and correlational analyses were conducted to examine whether symptom dimension scores were related to performance on several tests of working memory function. Severity of negative symptoms correlated with reduced production of words during a verbal fluency task, impaired ability to hold letter and number sequences on-line and manipulate them simultaneously, reduced performance during a dual task, and compromised visuospatial working memory under distraction-free conditions. Severity of disorganisation symptoms correlated with impaired visuospatial working memory under conditions of distraction, failure of inhibition during a verbal fluency task, perseverative responding on a test of set-shifting ability, and impaired ability to judge the veracity of simple declarative statements. Severity of positive symptoms was uncorrelated with performance on any of the measures examined. The present study provides evidence that the positive, negative and disorganised symptom dimensions of the PANSS constitute independent clusters, associated with unique patterns of working memory impairment.     

Social cognition and symptom dimensions

This study used the Picture Arrangement subtest of the Wechsler Adult Intelligence Scale to assess social cognitive functioning of psychotic patients diagnosed with bipolar, schizophrenia, or schizoaffective disorder. All participants were rated on positive and negative symptom rating scales, from which three symptom dimensions were obtained. Symptom dimensions were not significantly related to ratings of symptom severity or mental status examination scores. Disorganized symptoms were correlated with a wide range of impairments on nearly all subscale measures of social cognition. Negative symptoms were correlated with lower ratings of capacity for emotional investment, complexity of representations, and integration of episodes. Psychoticism was associated with negative affect tone. Diagnostic categories were not related to social cognitive impairments independent of estimates of premorbid level of cognitive function. Evidence of syndromal differences suggests that heterogeneity of variance in studies of functioning of schizophrenic patients can be reduced by inclusion of symptom dimensions.     

Depressive factors and their relationships with other symptom domains in schizophrenia, schizoaffective disorder, and psychotic depression

Relationships among different symptom domains were investigated in patients with acute exacerbation of schizophrenia with depressive symptoms, psychotic depression, or schizoaffective disorder, depressive subtype. Scores for depression and depressive factors were correlated with positive, negative, and extrapyramidal symptoms within diagnostic categories. No between-group differences in the relationship of different symptom domains could be found, and no substantial relationship between depression and positive symptoms could be revealed in any diagnostic subgroup. Only the retardation factor of depression showed a significant overlap with negative symptoms; depressive core symptoms did not. Core symptoms of depression were independent from other symptoms in all investigated diagnostic groups. Depression seems to represent a heterogeneous symptom domain with unique relationships of components to positive and negative symptoms across nosological borders. A more differentiated assessment, analysis, and treatment of depressive symptoms is therefore recommended for patients with combined depressive and psychotic symptoms.     

首发精神分裂症患者症状群因子分析研究

目的　探讨首发精神分裂症患者治疗前存在的独立症状群及其治疗后的变化。方法　对首发精神分裂症患者 ,在治疗前后分别评定简明精神病评定量表、阴性症状评定量表、汉密尔顿抑郁量表和测查 7种认知功能 ,然后进行因子分析。结果　首发精神分裂症患者的认知症状、阴性症状、情感症状在治疗前、后完全独立 ,无明显变化 ;而阳性症状的独立性在治疗前、后则不稳定 ,因子负荷分别在执行功能、情感症状因子上。结论　在首发精神分裂症患者中情感症状、认知症状是独立存在的 ,与治疗干预、阴性症状及阳性症状关系不肯定 ,应重视对两者的评估和治疗。     

Effortful cognitive resource allocation and negative symptom severity in chronic schizophrenia

BACKGROUND: The relationship between negative symptoms, early visual information-processing deficits, and effortful processing resource allocation was investigated. METHODS: Older patients with chronic schizophrenia (n = 58) and healthy controls (n = 71) participated. Pupillary responses were recorded during performance of the span of apprehension task (blocks of 3- and 10-letter arrays) as an index of resource allocation or mental effort during the task. RESULTS: Patients and controls showed larger pupillary responses in higher relative to lower processing loads both during array processing and just prior to array onset (preparation). Both groups, therefore, invested more cognitive effort preparing for and then processing larger arrays. A subgroup of patients with abnormally small pupillary responses and impaired performance showed greater negative symptom severity relative to a subgroup of patients with normal pupillary responses. Smaller pupillary responses in the patients were also significantly correlated with greater negative symptom severity, independent of positive symptom severity. Patients with reduced effortful resource allocation, therefore, exhibited greater negative symptomatology. A subgroup of patients with normal pupillary responses still showed impaired detection accuracy relative to controls, suggesting that reduced cognitive effort or resource allocation problems cannot account for impairments in early visual information processing in this subgroup. CONCLUSIONS: The study illustrates important relationships between cognitive effort and performance that can impact conclusions about the nature of cognitive impairments and associations between negative symptoms and neurocognition in schizophrenia.     

Ego-pathology and common symptom factors in schizophrenia

The phenomenological construct of ego-pathology in schizophrenia has been widely referred to in psychopathological textbooks but was systematically assessed in very few empirical studies. This study investigated the association between ego-pathology (Ego-Pathology Inventory) and common symptom factors (Positive and Negative Symptom Scale) in paranoid schizophrenia patients within 3 days after admission and after 2 weeks of treatment. The predictive value of ego-pathology for short-term treatment outcome was also assessed. A factor analysis of all subscale scores revealed a four-factor solution: positive symptoms, negative symptoms, and two distinct ego-pathology factors, i.e., general and identity. Although the ego-pathology subscale "activity" loaded on the positive symptom factor, the other four subscales formed the two ego-pathology factors with no high loadings on other factors. High scores on ego-demarcation at admission predicted poor treatment outcome after 2 weeks. The findings suggest that ego-pathology might be used to capture additional and clinically meaningful symptom dimensions in schizophrenia.     

The dimensional symptom structure of schizophrenia and its association with temperament and character

Recent studies suggest that personality may influence symptom expression and social functioning in schizophrenia. This study investigated the relationships between personality and symptom dimensions in schizophrenia patients. Fifty-two schizophrenia patients and 25 five healthy subjects were assessed using the Temperament and Character Inventory (TCI). The patients were also assessed for positive and negative symptoms using SAPS and SANS and scored according to Andreasen's (1995: Andreasen, N.C., Arndt, S., Alliger, R., Miller, D., Flaum, M. 1995. Symptoms of schizophrenia. Methods, meanings, and mechanisms. Arch. Gen. Psychiatry, 52, 341-351) classical three dimensional model and by the five dimensional model of Toomey et al. (1997: Toomey, R., Kremen, W.S., Simpson J.C., Samson, J.A., Seidman, L.J., Lyons, M.J., Faraone, S.V., Tsuang, M.T. 1997. Revisiting the factor structure for positive and negative symptoms: evidence from a large heterogeneous group of psychiatric patients. Am. J. Psychiatry, 154, 371-377). Comparisons between patients and controls revealed significant differences on various TCI scores consistent with a global disorganization of personality in schizophrenia involving both basic neurophysiological and potentially genetically determined traits (i.e. temperament) and developmental aspects of personality (i.e. character). Correlation analysis showed distinct associations between symptoms and personality dimensions. The results suggest that the negative and disorganized dimensions of schizophrenia are related temperamental factors, whereas the psychotic symptoms are more related to characterological abnormalities. The observed patterns of associations also underline the heterogeneity of the classical negative and positive dimensions of schizophrenia.     

Gender differences in the relationship of homelessness to symptom severity, substance abuse, and neuroleptic noncompliance in schizophrenia

This study examined gender differences in the relationship of homelessness in schizophrenia to symptom severity, risk behaviors, and prognostic features. Four hundred subjects with schizophrenia were studied: 100 homeless men, 100 homeless women, 100 never homeless men, and 100 never homeless women. Assessments included derivation of five symptom factors by using the Positive and Negative Syndrome Scale (PANSS). Homelessness for the entire sample was associated with greater severity of positive, activation, and autistic preoccupation symptoms, younger age at first hospitalization, and substance abuse (SA). For men only, homelessness was associated with neuroleptic noncompliance (NN). When NN and SA were statistically controlled, symptom severity was not different between the homeless and never homeless. Women, independent of residential status, had more severe negative, activation, and autistic preoccupation symptoms that were not associated with prognostic features or risk behaviors. For both men and women, SA was associated with homelessness, but independent of residence, SA was less severe in women. Additionally, SA was less severe in homeless women than never homeless men. Thus, symptom severity in homeless individuals with schizophrenia appears as an interaction of symptom profiles and risk behaviors that are gender specific. Although cross-sectional analyses cannot distinguish cause from effect, these findings suggest gender-specific routes to homelessness among indigent urban adults with schizophrenia.     

The relationship between symptom severity and regional cortical and grey matter volumes in schizophrenia

Objective

To investigate the relationship between symptom severity and cortical and grey matter volumes in schizophrenia.

Method

Fifty-three outpatients with schizophrenia were assessed by the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. Symptoms were grouped into five factors (negative, relational, inattention, disorganization, and reality distortion). Cortical and lobar grey matter volumes within all regions of the brain were obtained from magnetic resonance images using two independent software tools. The relationships between brain volumes and symptom factors were analyzed by partial correlations controlling for age, gender, dose and type of antipsychotic medication, and intracranial volume.

Results

Negative symptoms were generally associated with larger cortical volumes in all regions of the brain, and the relational and inattention factors were associated with larger frontal grey matter volumes. The reality distortion factor was associated with smaller cortical volumes throughout the brain and with smaller frontal and temporal grey matter volumes.

Conclusion

Differential contribution of positive and negative symptoms to variation in cortical and grey matter volumes indicates separate neurobiological mechanisms underlying the two major symptom domains in schizophrenia.     

Relationship between symptom dimensions and neurocognitive functioning in schizophrenia: a meta-analysis of WCST and CPT studies. Wisconsin Card Sorting Test. Continuous Performance Test

Cognitive deficits have been hypothesized to be differentially related to the negative, positive and disorganization dimensions of schizophrenia symptoms. In this article, we quantitatively review the published literature on the relationships between symptom dimensions in schizophrenia and performance on the two most widely applied tests of executive functioning and sustained attention, the Wisconsin Card Sorting Test (WCST) and the Continuous Performance Test (CPT). Meta-analyses were conducted on studies that reported correlational data for the relations between performance on these tests and scales of positive and negative symptoms. The more recent distinction between disorganization and reality distortion was also taken into account. The results showed statistically significant relationships of negative symptoms with worse performance on the WCST and the CPT. Disorganization symptoms showed a significant positive correlation with perseverations on the WCST, but not with CPT performance. In contrast, reality distortion symptoms and general scores for all positive symptoms did not correlate with either measure. Although some correlations were statistically significant, the observed associations between psychiatric symptoms and cognitive performance were typically weak, suggesting relative independence of these disease processes.     

Assessment of symptom exacerbations in a longitudinal study of children with Tourette's syndrome or obsessive-compulsive disorder

OBJECTIVES: The severity of tic and obsessive-compulsive (OC) symptoms varies over time. Consequently, how do we, as clinicians, know when a change in symptom severity occurs that falls outside of the normal range of fluctuation? The goal of this study was to describe the level of symptom severity fluctuation over time and to establish an objective, prospective, and quantitative method for identifying symptom exacerbations in children with Tourette's syndrome, obsessive-compulsive disorder (OCD), or both. A second major aim was to assess whether fluctuations in tic and OC symptom severity covaried with one another. METHOD: Monthly consecutive Yale Global Tic Severity Scale and Children's Yale-Brown Obsessive Compulsive Scale scores were prospectively obtained in 64 children diagnosed with Tourette's syndrome and/or OCD for periods ranging from 3 to 39 months. Exacerbation thresholds were estimated by using state-of-the-art bootstrap methods. These thresholds were then independently evaluated by asking two expert clinicians to identify, retrospectively, clinically significant exacerbations based on a review of all available clinical and research records. RESULTS: The severity of tic and OC symptoms displayed a high degree of intrasubject variability. Exacerbation thresholds, which incorporated the change score from the previous month and the current symptom score, provided the best agreement with those of expert clinicians. When both tic and OC symptoms were present, they showed a significant degree of covariation. CONCLUSIONS: Evidence-based treatments are coming of age. The use of valid, clinician-rated severity scales will likely become a standard part of clinical practice. Bootstrapping methods may provide a quantitative and convenient way to obtain clinically valid thresholds to assess tic and OC symptom exacerbations. This method has the potential to be applied to other symptom domains where exacerbation thresholds are needed.     

Assessment of enduring deficit and negative symptom subtypes in schizophrenia.

The clinical importance of subtypes based on enduring deficit or negative symptoms was examined in a group of schizophrenic patients who were assessed twice over a 1-year period. Subgroups of patients with high levels of enduring negative or deficit symptoms, based on the Scale for the Assessment of Negative Symptoms and the Quality of Life Scale, had a poorer prognosis and were consistently worse in social adjustment, quality of life, and thought disorder over the year than were patients with less severe negative symptoms. Subtypes based on Andreasen's negative schizophrenia classification and on enduring thought disorder were only weakly related to other symptoms and social adjustment. Social-skill deficits were weakly related to the enduring negative symptom subtype and Andreasen's negative schizophrenia. The results suggest that enduring negative and deficit symptoms may be associated with a poor outcome in schizophrenia, including more severe positive symptoms, lower levels of social adjustment, and a poorer quality of life.     

Symptom dimensions in the course of childhood-onset schizophrenia

The symptom dimensions of childhood-onset schizophrenia (COS) are described by focussing on the clinical features of 44 patients at onset of illness during the first episode and at follow-up investigation 42 years after onset. All subjects were re-diagnosed according to DSM IV. The symptomatology was evaluated with the Positive and Negative Symptom Scale (PANSS) at onset and at follow-up. Two principal component factor analyses with varimax-rotation were applied to the complete items set of the PANSS. The frequencies of positive, negative, and global symptoms were compared longitudinally in an ANOVA-repeated measures design. The factor analysis revealed 5 orthogonal symptom dimensions (factors) at onset of psychosis: Cognition, social withdrawal, antisocial behaviour, excitement, and reality distortion. At follow-up a five-factor solution was found, too, but different dimensions emerged: a positive, negative, excitement, cognitive, and anxiety/depression component which fits to the 5-factor model of White et al. (1997). The first psychotic episode of EOS is accompanied with more unspecific symptoms such as social withdrawal and antisocial behavior. In the later stages of (COS) the structure of symptom dimensions changes to that known from adult-onset schizophrenia (AOS). The results indicate that COS and AOS are comparable nosological entities and that more than 3 dimensions are required to describe the relevant clinical symptom structure. Positive and global symptoms decreased significantly during the course of illness. The frequencies of negative symptoms did not change which demonstrates their disabling impact.     

Symptom dimensions in the course of childhood-onset schizophrenia

The symptom dimensions of childhood-onset schizophrenia (COS) are described by focussing on the clinical features of 44 patients at onset of illness during the first episode and at follow-up investigation 42 years after onset. All subjects were re-diagnosed according to DSM IV. The symptomatology was evaluated with the Positive and Negative Symptom Scale (PANSS) at onset and at follow-up. Two prinicpal component factor analyses with varimax-rotation were applied to the complete items set of the PANSS. The frequencies of positive, negative, and global symptoms were compared longitudinally in an ANOVA-repeated measures design. The factor analysis revealed 5 orthogonal symptom dimensions (factors) at onset of psychosis: Cognition, social withdrawal, antisocial behaviour, excitement, and reality distortion. At follow-up a five-factor solution was found, too, but different dimensions emerged: a positive, negative, excitement, cognitive, and anxiety/depression component which fits to the 5-factor model of White et al. (1997). The first psychotic episode of EOS is accompanied with more unspecific symptoms such as social withdrawal and antisocial behavior. In the later stages of (COS) the structure of symptom dimensions changes to that known from adult-onset schizophrenia (AOS). The results indicate that COS and AOS are comparable nosological entities and that more than 3 dimensions are required to describe the relevant clinical symptom structure. Positive and global symptoms decreased significantly during the course of illness. The frequencies of negative symptoms did not change which demonstrates their disabling impact.     

Insomnia as a predictor for symptom worsening following antipsychotic withdrawal in schizophrenia

Sleep disturbances have been associated with schizophrenia, and are an especially prominent feature during the prodrome preceding psychotic relapse. In this study, we examined the changes in sleep quality following withdrawal of antipsychotic treatment, as well as the predictive value of sleep disturbances on symptom exacerbation. One hundred twenty-two patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder underwent a 3-week medication wash-out prior to neuroimaging studies. Sleep quality was rated using items on the Hamilton Rating Scale for Depression (HAM-D), while symptom severity was measured using the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS). Sleep quality deteriorated progressively following antipsychotic discontinuation. Total insomnia score prior to antipsychotic withdrawal had a significant effect on the severity of psychotic symptoms at the last weekly assessment, while baseline terminal insomnia had a significant effect on disorganized symptoms at the end of the medication-free period. These findings were independent of baseline symptom severity. Our findings suggest that schizophrenia patients with sleep disturbances are at a greater risk for worsening of positive symptoms after antipsychotic discontinuation. The implications of these findings in research and clinical settings are discussed.     

Relationship between psychopathology and cognitive functioning in schizophrenia

The purpose of this study was to delineate the relationship between positive, negative, cognitive, depressive, and excitement symptom dimensions of schizophrenia and cognitive functioning. Fifty-eight patients with schizophrenia (DSM-IV criteria) were assessed using the Positive and Negative Syndrome Scale (PANSS) and a battery of neuropsychological tests (executive function/abstraction, verbal and spatial working memory, verbal and nonverbal memory/learning, attention, visuospatial ability, and psychomotor speed). The cognitive symptom dimension correlated with executive functions, attention, verbal memory, and spatial ability. Severity of the negative symptom dimension was related to impairment in the structure of the semantic knowledge system, verbal memory, and auditory attention. In contrast, severity of the positive symptom dimension correlated only with impairment in the structure of the semantic knowledge system, and psychomotor speed. Finally, severity of the depressive and excitement symptom dimension was not associated with cognition. Correlations between symptom dimensions and cognitive measures were at best modest. Severity of cognitive and negative symptoms was mainly correlated with deficits on executive functions, semantic memory, and verbal memory, while positive symptoms only with semantic memory. These correlations were modest, suggesting that psychopathology and cognitive deficits in schizophrenia are caused, at least partially, by distinct pathophysiological processes.     

Depression in patients with schizophrenia during an acute psychotic episode.

There is disagreement about whether depressive symptoms in schizophrenia are part of the basic disease process, or whether they represent adverse effects of treatment with antipsychotic medications. In a sample of initially antipsychotic drug-free acutely hospitalized patients with schizophrenia (N = 104), we measured change in depressive symptoms after 4 weeks of treatment. We also examined the relationship of changes in depressive symptoms to changes in positive and negative schizophrenic symptoms. Depressive symptoms improved after 4 weeks of antipsychotic medication treatment, and their improvement corresponded with improvement in both positive and negative schizophrenic symptoms. These results suggest that depressive symptoms in schizophrenia are related to the disease process itself, at least during acute exacerbations of schizophrenia. Depressive symptoms may be responsive to antipsychotic medications directly or as a secondary response to improvement in positive and negative symptoms.     

Evaluation and interpretation of symptom structures in patients with schizophrenia

Seventy Japanese DSM-III-R schizophrenic patients were assessed for 30 clinical symptoms using the Positive and Negative Syndrome Scale (PANSS) of Kay et al. Principal component analysis was applied to the full item set of this scale and disclosed 5 orthogonal independent symptom groups: negative, hostile/excited, thought-disordered, delusional/hallucinatory and depressive components. Our results provided further support of the contention that more than 2 (i.e., positive and negative) dimensions are required to account for structures of the schizophrenic symptoms.     

CAG repeat length in the hKCa3 gene and symptom dimensions in schizophrenia.

BACKGROUND: Long CAG repeats in the hKCa3 potassium channel gene have been associated with schizophrenia. We sought evidence for associations between this polymorphism and aspects of the schizophrenia phenotype. METHODS: Associations were investigated between CAG repeat length and gender, age of illness onset, and psychotic symptom dimensions in 203 unrelated individuals with DSM-IIIR schizophrenia. RESULTS: No association was found between CAG repeat length and gender or age of onset. Long CAG repeats were associated with higher negative symptom dimension scores. CONCLUSIONS: This study provides preliminary evidence that genetic liability to negative symptoms in schizophrenia may be partly mediated through the hKCa3 gene.     

Functional connectivity between hemispheres and schizophrenic symptoms: a longitudinal study of interhemispheric EEG coherence in patients with acute exacerbations of schizophrenia.

To clarify whether interhemispheric electroencephalogram (EEG) coherence reflecting functional connectivity between the two cerebral hemispheres can change in a symptom-dependent manner in schizophrenia, we measured resting EEG and symptom severity twice at an average interval of 32.7 days during the course of treatment in 15 patients hospitalized for acute exacerbations of schizophrenia. Symptom severity was estimated quantitatively by means of the Brief Psychiatric Rating Scale (BPRS). Correlation analysis showed that increases in the beta-band coherence for frontal electrode pairs during the treatment were associated with improvement in the total score and the score on the positive subscale of BPRS. This result suggests that functional disconnection between the left and right frontal lobes may be related to the generation of psychotic symptoms and can normalize following antipsychotic treatment.