Source monitoring impairments in schizophrenia: characterisation and associations with positive and negative symptomatology

This article describes a consistent pattern of the associations between source monitoring failure and clinical symptomatology in schizophrenia. The associations with positive symptoms in this sample have been reported previously, but not the associations with negative symptoms. Forty patients with schizophrenia were administered several memory tasks including free recall of lists of words, recognition and source memory. Various memory errors assumed to stem from source monitoring failure were derived. They include intrusions and recall of words from previous lists in free recall, false recognitions, and confusion with regard to the source of the stimuli. We studied the associations of these memory errors with positive symptoms and with a broad range of negative symptoms. All the memory errors were positively associated with at least one positive symptom. On the other hand, these errors were inversely associated with certain negative symptoms reflecting lack of emotion or lack of social interactions. Thus positive and negative symptomatology appear to have opposite links to the source monitoring errors observed in patients with schizophrenia. Cognitive mechanisms leading to different types of source monitoring errors and possibly to the formation of positive symptoms are discussed.     

Verbal memory, negative symptomatology and prediction of psychosocial functioning in schizophrenia

Negative symptomatology and neurocognitive variables have been considered good predictors of functional outcome in schizophrenia. Specifically, secondary verbal memory has been proposed to be one of the main predictors of psychosocial functioning. In this study, negative symptoms and memory performance were analyzed for associations with psychosocial function. Linear regression methods were used to analyze the value of verbal memory and negative symptomatology as predictors of everyday life skills in a sample of 29 DSM-IV schizophrenia outpatients with predominant negative symptoms. We also took into account the role of gender in the analyses. Secondary verbal memory was found to explain 40% of the variance in psychosocial functioning, independently of gender, whereas the negative symptoms predicted 26%. When both variables were combined, the explained variance was about 49%. These results support the hypothesis that cognitive variables are better predictors than symptomatology. Finally, secondary verbal memory is a good predictor of psychosocial functioning in chronic schizophrenia with predominant negative symptomatology.     

White matter alterations in schizophrenic patients with pronounced negative symptomatology and with positive family history for schizophrenia

BACKGROUND: In recent years, in vivo and post-mortem studies detected structural brain changes in schizophrenia. The aim of our analysis was to investigate potential changes of white matter in schizophrenic patients compared to controls, and the relationship to clinical characteristics. METHODS: Fifty male, right-handed schizophrenic patients who met DSM-IV criteria for schizophrenia were recruited. Fifty right-handed, age- and sex-matched subjects without a psychiatric disorder were enrolled as controls. Volumes of white matter in several brain regions were measured by 1.5 T MRI using a volumetry and segmentation software (BRAINS). Regions of interest including frontal, temporal, parietal, occipital and subcortical areas were determined using Talairach spaces. RESULTS: No significant differences in white matter volumes of total brain tissue and regions of interest were detected between patients and controls. A significant reduction of white matter in parietal cortex of right hemisphere was found in a subgroup of patients with pronounced negative symptoms. Furthermore, patients with first-grade relatives suffering from schizophrenia showed a reduction of subcortical white matter in the right hemisphere. CONCLUSIONS: Our results indicate that subgroups of schizophrenic patients show alterations of white matter in distinct brain regions, including the right parietal lobe.     

精神分裂症患者的记忆功能障碍与精神症状和疗效的关系

目的　探讨精神分裂症记忆功能与精神症状和疗效的关系。方法　对 88例精神分裂症患者分别给予奎的平、舒必利、维思通治疗。采用PANSS量表评定精神症状 ,修订韦氏成人记忆量表 (WMS -RC)测查记忆功能(治疗前用甲式 ,治疗后用乙式 )分别于治疗前、治疗后第 6周末各评一次 ,并采用Pearson相关分析和多元逐步回归进行分析。结果　治疗前记忆商数与阴性症状、一般病理性症状、PANSS总分呈显著负相关 ,与阳性症状无相关性 ;多元逐步回归分析显示治疗前记忆商数与阴性症状关系最密切 ;治疗后记忆商数增加值与阴性症状的减分值呈显著正相关 (r=0 337,P <0 0 1,88例 ) ;治疗前记忆商数与治疗第 6周末的阴性症状减分值、一般病理性症状减分值呈显著负相关 (r =- 0 2 6 5 ,P <0 0 5 ;r =- 0 2 35 ,P <0 0 5 ,88例 )。结论　本研究支持精神分裂症记忆损害与阴性症状存在相似的病理机制假说。     

Verbal memory errors and symptoms in schizophrenia.

OBJECTIVE: To extend and test hypotheses linking positive and negative symptoms to selective aspects of verbal memory in schizophrenia. BACKGROUND: Verbal memory includes the ability to discriminate and prevent the intrusion of irrelevant information into recall and recognition. This ability has been proposed as a cognitive process that differentially mediates positive and negative symptoms. METHOD: Four error discrimination and 1 general recall memory index from the California Verbal Learning Test as well as general ability (IQ) and sex were used as predictors of symptom ratings in 55 schizophrenia patients within a regression framework. RESULTS: Intrusion errors during free recall contributed significantly to the prediction equation for negative symptoms (Brief Psychiatric Rating Scale). In contrast, positive symptoms and general psychopathology were not predicted by any of the discrimination indices. However, general recall memory (California Verbal Learning Test total words trials 1-5) contributed significantly to the prediction of general psychopathology and marginally to the prediction of negative symptoms. CONCLUSIONS: Impaired recall memory predicts levels of nonspecific psychopathology in schizophrenia. Negative symptoms associate with low intrusion error rates, but there is no evidence of an association between elevated errors and positive symptoms.     

Assessment of negative and positive symptoms in schizophrenia

Reliable, convenient rating scales to assess negative and positive symptoms in schizophrenia are necessary to evaluate further the theoretical and clinical importance of this division of symptoms and signs. The authors describe the application of the Rasch model, a probabilistic, item-independent, and sample-independent test construction procedure to the development of scales for both types of symptoms. The scales for negative and positive symptoms, which are based separately on the Schedule for Affective Disorders and Schizophrenia-Current (SADS-C) and the Nurses' Observation Scale for Inpatient Evaluation (NOSIE), demonstrated excellent reliability and temporal stability (i.e., yielded a rank order of patients that remained stable over time). The pattern of interscale correlations supports the view that positive symptoms, cognitive-affective negative symptoms, and social withdrawal are independent of one another.     

Morphology of the orbitofrontal cortex in first-episode schizophrenia: relationship with negative symptomatology

Different studies have documented OFC abnormalities in schizophrenia, but it is unclear if they are present at disease onset or are a consequence of disease process and/or drug exposure. The evaluation of first-episode, drug-naïve subjects allows us to clarify this issue. Magnetic resonance imaging was performed on 43 first-episode, antipsychotic-naïve schizophrenia patients and 53 healthy comparison subjects matched for age, gender, race, and handedness. Gray matter OFC volumes were measured blind to the diagnoses. As compared to controls, patients had greater volumes in left total OFC (p = 0.048) and left lateral OFC (p = 0.037). Severity of negative symptoms (anhedonia, flattened affect, and alogia) positively correlated with both the left lateral (Spearman's, rho = 0.37, p = 0.019; rho = 0.317, p = 0.041; r = 0.307, p = 0.048, respectively) and the left total OFC (Spearman's, rho = 0.384, p = 0.014; rho = 0.349, p = 0.023; rho = 0.309, p = 0.047, respectively). The present results suggest that first-episode, antipsychotic-naïve schizophrenia subjects exhibit increased OFC volumes that correlate with negative symptoms severity. The OFC, through extensive and complex interconnections with several brain structures with putative role in pathophysiology of schizophrenia including amygdala, hippocampus, thalamus, DLPFC, and superior temporal lobe, may mediate schizophrenia symptoms such as blunting of emotional affect and impaired social functioning. Although the specific neuropathological mechanisms underlying structural abnormalities of the OFC remain unclear, increased OFC volumes might be related to deviations in neuronal migration and/or pruning. Future follow-up studies examining high-risk individuals who subsequently develop schizophrenia at different stages of disease could be especially instructive.     

Dexamethasone suppression test in positive and negative schizophrenia

Fifty-four inpatients with a DSM-III diagnosis of schizophrenia were studied. Patients were divided into positive and negative subtypes of schizophrenia according to Andreasen's criteria. Blood samples were obtained from all patients for 2 consecutive days to determine plasma cortisol concentrations before and after a single administration (1 mg, p.o.) of dexamethasone at 11 p.m. The results revealed a significant increase in plasma cortisol levels in schizophrenic patients, with 40% of the patients being nonsuppressors on the dexamethasone suppression test. A higher percentage (62.5%) of patients with the negative form of schizophrenia were nonsuppressors.     

精神分裂症记忆与阳性、阴性症状的研究

目的探讨精神分裂症患者记忆特点及与阳性、阴性症状的关系。方法采用修正的加工分离记忆实验程序测试精神分裂症患者记忆变化情况,用PANSS评定精神分裂症患者阳性、阴性症状分。结果精神分裂症外显记忆与对照组比较明显受损(P0.05),其文字概念和图像概念实验类型驱动的内隐记忆成绩与对照组比较也受损(P0.05);阳性症状为主的患者外显记忆成绩均高于阴性症状为主的患者组(P0.05);阳性症状为主的患者内隐记忆成绩与以阴性症状为主的患者组之间的差异无统计学意义(P0.05);阳性症状与外显记忆无显著相关关系(P0.05),阴性症状与外显记忆呈显著负相关关系(P0.01);阳性症状、阴性症状与内隐记忆均无显著相关关系(P0.05)。结论精神分裂症外显记忆严重受损,而内隐记忆不同程度的受损;外显记忆与阳性症状无相关性,与阴性症状有显著相关;内隐记忆与阳性、阴性症状均无明显相关性。     

Neuroleptic responsivity of negative and positive symptoms in schizophrenia

The authors prospectively examined the effects of double-blind, placebo-controlled neuroleptic withdrawal and administration on ratings of negative and positive symptoms in 19 young patients with chronic schizophrenia. Negative symptoms were significantly reduced by neuroleptic treatment, and negative and positive symptoms demonstrated similar patterns of reduction and exacerbation during neuroleptic treatment and withdrawal, respectively. The changes in negative and positive symptoms induced by neuroleptic treatment and withdrawal were not significantly correlated, however. The negative and positive symptom profiles of individual patients were significantly altered by neuroleptic treatment, indicating limitations to the cross-sectional classification of patients on the basis of predominance of one or the other symptom group. The authors discuss implications for the neurobiological underpinnings of negative and positive symptoms.     

P50 inhibitory gating deficit is correlated with the negative symptomatology of schizophrenia

Abnormal sensory gating in schizophrenia has frequently been reported. The strength of central inhibitory pathways was measured using the P50 component of the auditory evoked potential in a conditioning-testing paradigm. The relationships between a relative decrease in P50 amplitude to repeated auditory stimuli and clinical symptoms remain controversial. Using the Positive and Negative Syndrome Scale, we studied the P50 auditory conditioning-testing paradigm in 81 schizophrenic subjects, categorized into subgroups with and without prominent negative symptoms, in comparison with 88 control subjects. We found increased ratios of testing stimuli to conditioning stimuli in both schizophrenic subgroups relative to findings in the control group. In addition, we found significantly increased mean latencies of the P50 responses to conditioning (C) and testing (T) stimuli and significantly increased T/C ratios in the subgroup with negative symptoms compared with the subgroup with non-negative symptoms.     

Cognitive functioning and positive and negative symptoms in schizophrenia

The present study examined schizophrenics' performance on a variety of cognitive measures in order to explore the relationship between schizophrenic symptoms and cognitive performance. The Wechsler Adult Intelligence Scale and a battery of neuropsychological tests, developed at the Montreal Neurological Institute, were administered to 38 acutely ill, hospitalized schizophrenics. Patients were diagnosed using DSM III criteria. Negative symptoms were assessed with the SANS and positive symptoms with the SAPS. Both the cognitive tests and the symptom rating scales were re-administered to this sample at a 6 month follow-up period. Analyses revealed that, at both time periods cognitive deficits were more likely to be associated with high negative symptom ratings than with positive symptoms. Only certain tests showed significant improvement at the follow-up period. Furthermore, improved cognitive functioning was related to an improvement in positive, but not negative, symptoms.     

Gender-specific associations of depression with positive and negative symptoms in acute schizophrenia

This clinical study analyzed gender-specific relationships of depression with other psychopathological and clinical variables in hospitalized patients with schizophrenia. During clinical routine treatment 119 inpatients with acute schizophrenia (DSM-IV) were investigated with the Calgary Depression Rating Scale for Schizophrenia (CDSS), the Clinical Global Impressions (CGI), and the Positive and Negative Syndrome Scale (PANSS). Depression scores of 77 male and 42 female patients (mean age 31.6+/-10.3 years) were related to background variables and to positive and negative symptom scores. Mean CDSS (5.8+/-5.6) and PANSS scores (total 76.9+/-22.1, positive symptoms 17.6+/-7.6, negative symptoms 20.5+/-7.8) were not significantly different between males and females. In females, depression was independently associated with higher negative symptom scores (P<0.01) and younger age (P<0.05) whereas in males positive symptoms (P<0.05) and short hospitalization (P<0.05) were the main factors associated with depression. The study revealed gender-specific differences in the relationship of depression with negative and positive symptoms.     

Social burden of positive and negative schizophrenia.

Sixty patients diagnosed as 'positive' or 'negative' schizophrenics were studied to evaluate social burden experienced by a key relative. The study had a prospective design and the patients were followed for a period of six months. At the time of initial assessments, in the 'positive schizophrenia' group, no significant correlation between ratings on psychopathology and social burden was observed, although at the end of the period of follow-up significant reductions in ratings on psychopathology and social burden as well as significant correlation between severity of psychopathology and burden of care were noted. In the 'negative schizophrenia' group, the severity of psychopathology and social burden were significantly correlated, but at the end of six months no significant change either in severity of psychopathology or social burden emerged.     

Assessing positive and negative symptoms in outpatients with schizophrenia and mood disorders

The Positive and Negative Syndrome Scale (PANSS) was developed to assess symptomatology in inpatients with schizophrenia. We examined its reliability and validity among outpatients with schizophrenia (N = 75) and mood disorders (N = 61). Because the hypothesized three-scale structure of the PANSS has not been supported by existing research, we also examined its factor structure. Interrater reliability for individual items and the positive and negative scales was demonstrated. Evidence supported the internal consistency of each scale in the overall sample and the schizophrenia group but was mixed among those with mood disorders. PANSS scores were higher in the schizophrenia group. These scores, in turn, were lower than those generally reported among inpatients with schizophrenia, providing known-groups validity evidence. Four of five factors were similar to those reported among inpatients with schizophrenia. Together, these results support the use of the PANSS among outpatients and reinforce existing support for assessing positive and negative symptoms in mood disorders.     

Prefrontal dysconnectivity links to working memory deficit in first-episode schizophrenia

Working memory (WM) deficit is a core feature of schizophrenia and is characterized by abnormal functional integration in the prefrontal cortex, including the dorsolateral prefrontal cortex (dLPFC), dorsal anterior cingulate cortex (dACC), and ventrolateral prefrontal cortex (vLPFC). However, the specific mechanism by which the abnormal neuronal circuits that involve these brain regions contribute to this deficit is still unclear. Therefore, this study focused on these regions and sought to answer which abnormal causal relationships in these regions can be linked to impaired WM in schizophrenia. We used spectral dynamic causal modeling to estimate directed (effective) connectivity between these regions based on resting-state functional magnetic resonance imaging data from healthy control (HC) subjects and patients with first-episode schizophrenia (FES). By comparing these effective connections in the controls and patients, we found that the effective connectivity from the dACC to the dLPFC and from the right dLPFC to the left vLPFC was weaker in the FES group than in the HC group. Furthermore, these effective connections displayed a positive correlation with WM performance in the HCs. However, in the FES patients, the effective connectivity from the dACC to the dLPFC was not correlated with WM performance, and the effective connectivity from the right dLPFC to the left vLPFC was negatively correlated with WM performance. These results could be explained by an aberrant top-down mechanism of WM processing and provide new evidence for the dysconnectivity hypothesis of schizophrenia.     

Cognitive impairment in schizophrenia: specific relations to ventricular size and negative symptomatology

A number of studies of schizophrenia have demonstrated associations between cognitive impairment and both cerebral ventricle size and negative symptomatology. The nature of these associations, however, have been obscured by interstudy differences in the assessment of cognitive functioning and by the lack of function-related specificity in measures of structural brain abnormality. In this study, 28 SCID-diagnosed chronic schizophrenic inpatients were administered a brief comprehensive battery of neuropsychological tests, a computed tomography (CT) scan, and were rated for positive and negative symptomatology. Enlarged ventricle-to-brain ratio (VBR) of the anterior portion of the lateral ventricles, the frontal horns, was found to be related to deficits in general intellectual level, conceptual thinking, immediate verbal memory, and psychomotor speed. VBR of the more usually studied bodies of the lateral ventricles was associated only with deficits in verbal memory and motor speed. VBRs were unrelated to both positive and negative symptom measures in this sample. Results suggest that more widespread impairment of schizophrenics' cognitive functioning may be related to structural abnormality within the frontal lobes, complementing recent findings linking structural and metabolic abnormalities of this area of the brain to the disease itself.     

Olfactory acuity in the positive and negative syndromes of schizophrenia

The olfactory thresholds of 46 schizophrenic subjects were measured. This group yielded 11 patients with a stringently defined positive syndrome and 12 with a negative syndrome when rated with the Positive and Negative Syndrome Scale. The negative group had a significantly (p less than 0.01) higher olfactory threshold than the positive group although neither of the groups differed significantly from a control group. Implications of this finding are discussed.     

Lifelong course of positive and negative symptoms in chronically institutionalized patients with schizophrenia

BACKGROUND: Despite widespread policies of deinstitutionalization, a substantial number of patients with schizophrenia require continuous custodial care. The hospital records of such patients provide contemporaneous documentation of symptoms throughout the illness, permitting a longitudinal study of the course of symptoms. We sought to describe this course, and to determine the influences of sex, age of onset, and treatment on its evolution. METHODS: Using the modified Diagnostic Evaluation After Death, we performed standardized chart reviews of 99 chronic inpatients who remained in state institutions through the 1960's and 1970's and subsequently died in those institutions. Data were available from the onset of illness until death. RESULTS: We found significant decreases in positive symptoms and increases in negative symptoms over the course of the illness. Symptom patterns were analyzed by repeated measures ANOVA. Onset before age 25 was associated with greater numbers of negative symptoms at a given age (p = 0.05). Female sex was associated with greater numbers of positive symptoms (p=0.04). The widespread introduction of neuroleptic drugs in the mid-1950's did not affect the trends in symptom patterns. CONCLUSIONS: The lifetime course of schizophrenia in chronically institutionalized individuals is characterized by a decrease in positive symptoms and an increase in negative symptoms. Schizophrenia with earlier onset is associated with greater numbers of negative symptoms throughout life. In this sample of patients, chronically hospitalized until death, neuroleptic drugs failed to effect a persistent decrease in positive symptoms.