Olanzapine: efficacy in treating the positive and negative symptoms of schizophrenia

In the second of this series of updates on recent advances in medication, RICHARD GRAY summarises trials into the novel antipsychotic olanzapine, which has been shown to compare well to haloperidol, and is now widely used for treating schizophrenia and related psychoses.     

Models of positive and negative symptoms in schizophrenia: An empirical evaluation of latent structures.

The present investigation empirically evaluated three competing models of the relations between positive and negative symptoms in schizophrenia, namely the I. I. Gottesman et al (see record 2005-09771-003), N. C. Andreasen and S. Olsen's (see record 1982-30452-001), and T. J. Crow's (see record 1981-28160-001) severity-liability model unidimensional bipolar model, independent dual-process model. Using positive and negative symptom ratings based on 220 schizophrenic subjects, the results of a LISREL VI confirmatory factor analysis revealed that Crow's model of positive and negative symptoms provided the best fit to the observed data among the 3 models. The severity-liability model provided a modest fit to observed data, and Andreasen's model fit the data poorly. Results support the validity of the positive and negative symptom distinction in schizophrenia and as providing substantive empirical support for Crow's independent dual-process model. The methodological advantages of confirmatory factor analysis in the specification and evaluation of theoretical models in experimental and developmental psychopathology are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Two factors of experienced deficits in schizophrenia and their relationships with positive, negative, and depressive symptoms

Benign prostatic hyperplasia (BPH) is the most common benign tumor in men and is responsible for urinary symptoms in the majority of men older than 50 years of age. Although transurethral resection of the prostate (TURP) is the gold standard, its complications have impacted upon its utility. As a consequence, new pharmacologic and minimally invasive approaches to the management of BPH have been developed. One minimally invasive approach that employs interstitial laser coagulation by the Indigo 830e LaserOptic system heats the prostate to the point of irreversible necrosis while preserving the urethral lining, potentially resulting in fewer complications. To test the efficacy of this device we evaluated the interim results obtained in 25 patients treated for BPH. Parameters evaluated included the AUA symptom score, uroflowometry, post-void residual, and prostate size. Following treatment, patients were discharged home and the catheter was removed within 3-7 days. Patients were assessed at 1 month and at subsequent 3-month intervals following the procedure using a questionnaire, AUA symptom score, and uroflowometry. The results of the paired t-tests demonstrated a significant increase in the maximal and average flow rates from baseline. The mean baseline maximal flow rate was 8.3 ml/s and increased to 10, 12.7, 14.1, and 12.0 ml/s at 1, 3, 6, and 9 months, respectively, and the mean baseline average flow rate was 4.4 ml/s and increased to 5.3, 6.0, 6.6, and 6.2 ml/s at 1, 3, 6, and 9 months, respectively. The AUA symptom scores decreased from 20.2 to 9.8 at 9 months. There was no intraoperative complication. Six patients developed transient retention. No patient developed bladder neck contractures, urinary incontinence, impotence, or urinary tract infections. One patient developed retrograde ejaculation and one patient required retreatment by TURP. Hence, improvements in symptom scores and voiding parameters suggest that the laser interstitial coagulation prostatectomy is safe and effective for the treatment of BPH.     

Anhedonia, positive and negative affect, and social functioning in schizophrenia

This study examines the relationship between anhedonia and the trait dimensions of positive affect (PA) and negative affect (NA) in schizophrenia. The relationship between poor social functioning in schizophrenia and these individual differences in affectivity is also examined. Schizophrenia outpatients (n = 37) and normal controls (n = 15) were assessed at a baseline evaluation and again approximately 90 days later. Consistent with the hypothesized decrease in hedonic capacity in schizophrenia, patients reported significantly greater physical and social anhedonia and less PA than controls. However, the schizophrenia group also reported significantly greater NA and social anxiety than did controls. In support of the dispositional view of these individual differences in affectivity, trait measures demonstrated test-retest reliability, and group differences between the schizophrenia group and controls were stable over the 90-day followup period. Within the schizophrenia group, physical and social anhedonia were comparably negatively correlated with trait PA; however, social but not physical anhedonia was significantly positively correlated with NA and social anxiety. Poor social functioning in the schizophrenia group was associated with greater physical and social anhedonia and greater NA and social anxiety. Alternatively, greater trait PA was related to better social functioning. These findings indicate that schizophrenia is characterized by both low PA and elevated NA and that these affective characteristics are a stable feature of the illness. The results also suggest important links between affect and social functioning in schizophrenia.     

Failure of positive but not negative emotional valence to enhance memory in schizophrenia.

Abnormalities in the integration of emotion and cognition have long been considered hallmark characteristics of schizophrenia. Study authors used a well-established emotional memory model from the neuroscience literature to assess the facilitative impact of emotional valence of information on long-term memory consolidation in schizophrenia. Participants with schizophrenia (n=33) indicated somewhat higher levels of emotional intensity in response to emotional images than did healthy (n=28) participants. However, when recognition memory was tested 24 hr later, schizophrenia participants did not show enhancement of memory for positive images as was found in healthy participants. Their memory enhancement for negative images did not differ from that of healthy participants. Correlations between self-reported physical and social anhedonia were significantly inversely correlated with intensity ratings of positive stimuli during the encoding phase for healthy participants but were negligible for schizophrenia participants. These results suggest a failure to adequately integrate positive emotional experience in memory consolidation processes in schizophrenia participants, despite appropriate initial response to positive stimuli, which may contribute to symptoms such as anhedonia by reducing the long-term impact of positive experiences in motivating hedonic behavior in day-to-day life. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropsychological correlates of ADHD symptoms in preschoolers.

The authors examined the neuropsychological status of 22 preschoolers at risk for attention-deficit/hyperactivity disorder (ADHD) and 50 matched control children, using measures of nonverbal working memory, perceptual and motor inhibition, and memory for relative time. All tasks included paired control conditions, which allowed for the isolation of discrete executive function constructs. Group differences were evident on several measures of neuropsychological functioning; however, after accounting for nonexecutive abilities, no deficits could be attributed to specific functions targeted by the tasks. Performance on executive measures was not related to objective indices of activity level or ratings of ADHD symptoms. Yet, the fact that at-risk preschoolers were highly symptomatic casts doubt on whether executive function deficits and/or frontostriatal networks contribute etiologically to early behavioral manifestations of ADHD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropsychological differences among subtypes of schizophrenia.

Administered the WAIS, the Halstead-Reitan Neuropsychological Test Battery, associated test procedures, and complete neurological evaluations to 140 schizophrenic inpatients. These Ss were subdivided according to 3 criteria: paranoid vs nonparanoid, neurologically normal vs abnormal, and long-term vs short-term institutionalization. Comparisons between groups were made using 3 stepwise discriminant analyses. Although all of these analyses yielded percentages of correct classification that exceeded chance, the greatest accuracy by far was obtained for the long-term vs short-term institutionalization subdivision. Individual tests contributing the most discriminatory power varied from comparison to comparison, with a complex problem-solving test being the best discriminator in the long-term vs short-term comparison and a simple motor test the best discriminator in the other comparisons. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of positive and negative thinking on performance in an achievement situation.

To induce different types of thinking, 151 undergraduates were given either positive or negative self-referent statements about competence in either an achievement or a social interaction situation and were asked to recall an experience in which they had had the thoughts conveyed by these statements. They then completed an anagrams task that was described as a measure of intelligence and verbal ability. Before doing the anagrams, half the Ss in each condition predicted how well they might perform, whereas the other half performed the task without generating predictions. Negative thinkers tended to perform better than positive thinkers when either (a) Ss' thoughts were achievement-related and they did not predict their performance on the anagrams task before engaging in it, or (b) Ss' thoughts pertained to social relations and they did predict their performance on the anagrams task. In no case did positive thinking lead to significantly better performance than negative thinking. Results suggest that the effects of positive and negative thinking were mediated by the influence of these different types of thinking on the motivation to perform well on the achievement task. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The performance of psychopathic individuals under conditions of positive and negative partial reinforcement.

Previous theorizing had distinguished a group of primary psychopaths (PP) from neurotic psychopaths (NP) on the basis of weakness of conscience and disregard for social law (PP) vs. a strong conscience with need to get caught and be punished (NP). The present study is an attempt to distinguish NPs from PPs with regard to their ability to profit from experience (in this instance to profit from differential reinforcement schedules in a learning situation). NPs were seen to be not too different from a control group of normals. However, PPs manifested rigidity of thinking under certain conditions of reinforcement (reward vs. punishment, immediate vs. delayed), and their performance deteriorated the greater the time between stimulus and response. The study, moreover, pointed up the lack of homogeneity in groups grossly defined as "psychopath." From Psyc Abstracts 36:04:4JJ53P. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Motivation and performance in schizophrenia.

Schizophrenic patients and normals learned a series of motor responses to successively presented visual stimuli; the schizophrenics and normals were each divided into 2 groups, Shock and Rapport, matched on an initial test, Pattern I. The shock groups were each tested on two subsequent tasks, Patterns II and III. "The results showed a differential facilitative effect of the shock stimulation for the schizophrenic patients on Pattern III but not on Pattern II. The schizophrenic rapport group declined in efficiency from Pattern II to III, a result not seen in the shock group of patients or in either normal group. These findings were interpreted in terms of an inferred process of motivational dissipation during performance in schizophrenia." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia

PURPOSE: To assess the effectiveness and safety of self-expanding metallic stents as a primary palliative treatment for inoperable malignant colorectal strictures. METHODS: Under radiological guidance 20 self-expanding metallic Wallstents were implanted in 16 consecutive patients with colorectal stenoses caused by malignant neoplasms, when surgical treatment of the condition had been ruled out. The patients were followed up clinically for 1-44 months, until death or termination of this study. RESULTS: The stents were successfully implanted in all cases and resolved the clinical obstruction in all the patients except one, who underwent subsequent colostomy. During follow-up of the remaining 15 patients, clinical complications arising from the procedure were pain (two patients), minor rectal bleeding (one patient), and severe rectal bleeding (one patient) (26%). There were three cases of stent migration and three cases of stent occlusion, and reintervention by us was necessary in 20% of cases (3/15). The mean life span following the procedure was 130 days, and none of the patients exhibited clinical symptoms of obstruction at the time of death (12 patients) or termination of the study (3 patients). CONCLUSION: Deployment of metallic stents under radiologic guidance is an effective alternative as a primary palliative measure in malignant colorectal obstruction, though the possible clinical complications and need for repeat intervention during follow-up should be taken into account.     

On the role of positive and negative affectivity in job performance: A meta-analytic investigation.

Although interest regarding the role of dispositional affect in job behaviors has surged in recent years, the true magnitude of affectivity's influence remains unknown. To address this issue, the authors conducted a qualitative and quantitative review of the relationships between positive and negative affectivity (PA and NA, respectively) and various performance dimensions. A series of meta-analyses based on 57 primary studies indicated that PA and NA predicted task performance in the hypothesized directions and that the relationships were strongest for subjectively rated versus objectively rated performance. In addition, PA was related to organizational citizenship behaviors but not withdrawal behaviors, and NA was related to organizational citizenship behaviors, withdrawal behaviors, counterproductive work behaviors, and occupational injury. Mediational analyses revealed that affect operated through different mechanisms in influencing the various performance dimensions. Regression analyses documented that PA and NA uniquely predicted task performance but that extraversion and neuroticism did not, when the four were considered simultaneously. Discussion focuses on the theoretical and practical implications of these findings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A neuropsychological study of prefrontal lobe function in the positive and negative subtypes of schizophrenia

The symptoms of schizophrenia are frequently divided into positive and negative subtypes. It has been suggested that the negative symptoms are similar to those seen with prefrontal lobe cortical dysfunction. Several neuropsychological investigations of that hypothesis have been carried out, but none have directly compared a negative symptom group with a positive symptom group on the same test battery. In the present study, the Positive and Negative Syndrome Scale (PANSS; Kay, Fiszbein, & Opler, 1987) was used to distinguish two groups of 20 patients with schizophrenia with predominant positive or negative symptoms. A battery of 7 neuropsychological tests considered capable of isolating prefrontal lobe dysfunction was administered. A significant group difference was noted on 6 of the tests; the negative symptom group performed much worse than the positive symptom group. The results of this study support the hypothesis that a relationship exists between the negative symptoms of schizophrenia and prefrontal lobe dysfunction.     

Validity of specific subscales of the positive and negative symptom scales in older schizophrenia outpatients

The principal natural food colorants used in modern food manufacture are anthocyanins, betalains, carotenoids, chlorophylls, riboflavin and caramel. Carotenoids (carotenes and xanthophylls) occur naturally in some foods such as carrots, red tomatoes, butter, cheese, paprika, palm oil, corn kernels, marigold petals, annatto, and red salmon. Carotenoids (alpha- or beta-carotene and xanthophylls) are excellent antioxidants and inhibit some types of cancers. In the present study, we used the Salmonella typhimurium tester strain YG1024 in the plate-incorporation test to examine the antimutagenicity of xanthophylls extracted from Aztec Marigold (Tagetes erecta) on 1-nitropyrene (1-NP) mutagenicity. Further, we investigated the effect of lutein on DNA-repair system of tester strain YG1024, using a preincubation test. The possible mechanism of lutein on 1-NP mutagenicity was studied by comparing the absorption spectrum of lutein, 1-NP and lutein plus 1-NP. In a dose-response curve of 1-NP, the mutagenic potency was 4317 revertants/nmol, and the dose of 0.06 microgram of 1-NP/plate was chosen for the antimutagenicity studies. Lutein and xanthophylls from Aztec Marigold (pigments for poultry and human use) inhibited mutagenicity of 1-NP in a dose-dependent manner. Lutein and the pigments were not toxic to the bacteria at the concentrations tested (0.002, 0.02, 0.2, 2.0 and 10 micrograms/plate). The percentages of inhibition of 1-NP mutagenicity were 72%, 92% and 66.2% for lutein (10 micrograms/plate), pigment for poultry use (10 micrograms/plate) and pigment for human use (2 micrograms/plate), respectively. Lutein had no effect on the DNA-repair system of strain YG1024. A new peak was detected at 429 nm when lutein was added at 1-NP, and it was stable throughout the incubation time. The results suggest that the major mechanisms of lutein against 1-NP mutagenicity is the potential formation of a complex between lutein and 1-NP, which could limit the bioavailability of 1-NP.     

Neuropsychological disturbance in schizophrenia: A diffusion tensor imaging study.

Patients with schizophrenia and healthy control subjects underwent both neuropsychological evaluation and magnetic resonance diffusion tensor imaging, during which the cingulum bundle (CB) and the uncinate fasciculus (UF) were defined with fiber tractography and their integrity was quantified. On the basis of prior findings, it was hypothesized that neuropsychological disturbance in schizophrenia may be characterized, in part, by 2 dissociable functional neuroanatomical relationships: (a) executive functioning-CB integrity and (b) episodic memory-UF integrity. In support of the hypothesis, hierarchical regression results indicated that reduced white matter of the CB and the UF differentially and specifically predicted deficits in executive functioning and memory, respectively. Neuropsychological correlates of the CB also extended to lower generalized intelligence, as well as to reduced visual memory that may be related to failures of contextual monitoring of to-be-remembered scenes. Reduced white matter of the CB and the UF may each make distinct contributions to neuropsychological disturbance in schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Integration of positive and negative affectivity and cognitive content-specificity: Improved discrimination of anxious and depressive symptoms.

In a sample of 159 psychiatric outpatient adults, negative affectivity (NA) was significantly correlated with a broad range of anxiety and depressive symptoms and was not useful for the differentiation of anxiety from depression. Low positive affectivity (PA) was significantly related only to depressive symptoms. Whereas depressive cognitions demonstrated discriminant capability, anxiety cognitions (in isolation) demonstrated nonspecificity. A combination of NA and anxious cognitions significantly predicted anxiety symptoms, better than did cognitions or affect alone. NA, depressive cognitions, and low PA significantly predicted depressive symptoms. Results support the integration of affective and cognitive models for the discrimination of anxious from depressive symptoms and have implications for measure development. Modifications in the cognitive content-specificity theory of anxiety states are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropsychological impairment in patients with schizophrenia and evidence of hyponatremia and polydipsia.

Patients with schizophrenia and water imbalance may represent a subset of patients with distinct pathophysiological abnormalities and susceptibility to cognitive impairment. Specifically, patients with polydipsia and hyponatremia have been shown to have smaller anterior hippocampal volumes, which are also associated with various impairments in neuroendocrine function. To determine whether abnormalities in patients with water imbalance extend to the cognitive realm, the present study evaluated neuropsychological functioning in three groups of patients with schizophrenia: polydipsic hyponatremic, polydipsic normonatremic, and nonpolydipsic normonatremic. Participants were administered cognitive tests assessing intelligence, attention, learning/memory (verbal, nonverbal, emotional), and facial discrimination. Hyponatremic patients showed poorer overall neuropsychological functioning relative to all other patients, and polydipsic normonatremic patients performed intermediate to the other two groups. Results indicate that patients with schizophrenia and polydipsia, and particularly those with hyponatremia, show prominent cognitive deficits relative to patients without water imbalance. The clinical, neuroendocrine, and cognitive abnormalities in these patients may arise from pathology within the anterior hippocampus and associated prefrontal/limbic brain regions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropsychological differences among empirically derived clinical subtypes of schizophrenia.

Neuropsychological profile differences between empirically derived clinical subtypes of schizophrenia were examined. Two hundred five patients and 209 demographically matched controls were administered a neuropsychological battery examining 8 domains. Subtypes included negative, disorganized, paranoid, Schneiderian, and mild. All subtypes displayed a neuropsychological profile of generalized impairment with greater deficits in learning, memory, and attention. Results were suggestive of diffuse cognitive dysfunction in schizophrenia with more severe deficits in learning and memory relative to executive skills. This pattern of greater learning and memory impairment was pronounced for disorganized patients. In contrast, paranoid patients outperformed disorganized and negative patients in several domains. These findings reflect bilateral frontal–temporal dysfunction, particularly in disorganized and negative patients. Subtype differences highlight the importance of conceptualizing schizophrenia as a multifocal disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropsychological impairments in schizophrenia: Integration of performance-based and brain imaging findings.

[Correction Notice: An erratum for this article was reported in Vol 134(3) of Psychological Bulletin (see record 2008-04614-006). In the article "Neuropsychological Impairments in Schizophrenia: Integration of Performance-Based and Brain Imaging Findings," by Abraham Reichenberg and Philip D. Harvey (Psychological Bulletin, 2007, Vol. 133, No. 5, pp. 833-858), on page 837, right column, first paragraph; in Table 1 (p. 835); and in Table 2 (p. 843), the word perseverations was misspelled as preservations. In addition, on page 846, left column, third paragraph, the last word in the sentence was incorrect. The correct word should be hyperactivation.] Until recently, the dominant view was that schizophrenia patients have limited, if any, neuropsychological impairments, and those that are observed are only secondary to the florid symptoms of the disorder. This view has dramatically changed. This review integrates recent evidence demonstrating the severity and profile of neuropsychological impairments in schizophrenia. We present quantitative evaluation of the literature demonstrating that the most severe impairments are apparent in episodic memory and executive control processes, evident on a background of a generalized cognitive deficit. The neuropsychological impairments potentially represent genetic liability to the disorder, as similar, yet milder, impairments are evident in schizophrenia patients even before the onset of psychotic symptoms, as well as in the nonpsychotic relatives of schizophrenia patients. Corresponding cognitive neuroimaging literature on executive functions, episodic memory, and working memory in schizophrenia documenting abnormalities in frontal and medial temporal lobes is summarized, and current models integrating neuropsychological and neuroimaging data are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)