Remission in schizophrenia: the relationship to baseline symptoms and changes in symptom domains during a one-year study.

The concepts of partial recovery and remission have become increasingly important for the evaluation of the effectiveness of schizophrenia therapeutics. The relationship of baseline symptoms and changes in symptoms to remission of psychosis was evaluated. Fifty-six outpatients with residual schizophrenia completed a double-blind trial of olanzapine versus haloperidol and were then enrolled into a one-year open-label trial of olanzapine. Out of these 56 subjects, 13 (23%) met remission criteria at the beginning of the open-label treatment and were excluded. During the one-year study, 7/43 (16%) subjects met remission criteria. These subjects had significantly lower baseline ratings for tardive dyskinesia (TD) than subjects who did not achieve remission (1.8 +/- 1.5 vs. 4.2 +/- 4.6, P = 0.03). As expected, remitted subjects had significantly greater improvements in Brief Psychiatric Rating Scale total scores, positive subscale scores and scale for the Assessment of Negative Symptoms total scores. Remitted subjects also experienced a significantly greater improvement in depressive symptoms (P = 0.001), activation (P = 0.005), and Clinical Global Impressions scores (P < 0.001), as well as greater improvements in extrapyramidal symptoms (P = 0.007) and TD (P < 0.001). These results suggest that the relationship of depressive symptoms and improved side effects to the construct of remission in schizophrenia may deserve special attention. Future studies should aim to relate remission criteria to functional outcomes, cognition, and other important symptom domains.

A program for treating olanzapine-related weight gain.

This study evaluated the effectiveness of a Weight Watchers program for patients with schizophrenia who had olanzapine-related weight gain and ascertained whether the severity of patients' psychiatric symptoms was correlated with the patients' success in losing weight. Seven men and four women who had been treated with olanzapine and who had gained at least 7 percent of their pretreatment body weight attended Weight Watchers meetings and were offered supervised exercise sessions. The patients' weight, body mass index, and psychiatric symptoms were assessed and were compared with those of a matched comparison group who did not attend the Weight Watchers program. Only the men experienced significant weight loss. No correlation was found between weight loss and exercise or change in psychiatric symptoms.

A five-year followup study of deficit and nondeficit schizophrenia.

Previous studies have suggested that deficit schizophrenia is a stable subtype of schizophrenia, and that patients with the deficit schizophrenia have different course of illness from other people with schizophrenia. We tested the ability of the deficit/nondeficit categorization to predict clinical features at five years' followup in a group of chronically ill outpatients. Outpatients categorized into deficit (N = 46) and nondeficit (N = 174) schizophrenia were assessed at an average of five years after the categorization was made. Raters making the followup assessments were blind to the initial categorization. At followup, the deficit patients had poorer quality of life, poorer social and occupational function, and more severe negative symptoms. Despite these differences, deficit patients were less distressed (as measured by depressive mood, anxiety, and guilt), and they did not have more severe hallucinations, delusions, thought disorder. These differences could not be attributed to demographic differences. The group differences in quality of life and level of psychosocial function remained significant after accounting for the severity of baseline negative symptoms. These findings confirm that patients with the deficit schizophrenia have a set of relatively stable clinical features that are associated with poor outcome.

Effects of sustained-release bupropion and supportive group therapy on cigarette consumption in patients with schizophrenia.

OBJECTIVE: The study examined the efficacy, tolerability, and safety of supportive group psychotherapy and adjunctive sustained-release bupropion for nicotine addiction in patients with schizophrenia. METHOD: Eight patients participated in a 14-week open-label trial. End expired breath carbon monoxide level, symptom levels, neuropsychological performance, and suppression of the P50 event-related potential were measured before and after the 14-week trial. RESULTS: Patients showed a decrease in carbon monoxide levels that was not associated with any worsening in symptom, neuropsychological, or P50 suppression measures. CONCLUSIONS: Use of sustained-release bupropion in combination with supportive group therapy may help patients with schizophrenia decrease their cigarette consumption.

A separate disease within the syndrome of schizophrenia.

If schizophrenia is a clinical syndrome rather than a single disease, the identification of specific diseases within the syndrome would facilitate the advance of knowledge and the development of more specific treatments. We propose that deficit psychopathology (ie, enduring, idiopathic negative symptoms) defines a group of patients with a disease different from schizophrenia without deficit features, as the deficit and nondeficit groups differ in their signs and symptoms, course, biological correlates, treatment response, and etiologic factors. These differences cannot be attributed to more severe positive psychotic symptoms or a greater duration of illness in the deficit group. The alternative interpretation that patients with deficit schizophrenia are at the severe end of a single disease continuum is not supported by risk factor and biological features data, but there is a need for independent replication of these findings. We suggest a series of studies designed to falsify one of these hypotheses, ie, multiple diseases vs a single disease.

Short form of the WAIS-III for use with patients with schizophrenia.

The recent publication of the Wechsler Adult Intelligence Scale (WAIS-III), the most widely used standard test of intelligence, requires the development of a new short form for use with patients with schizophrenia for many clinical and research purposes. We used regression analyses of complete WAIS-III data on 41 outpatients with schizophrenia and 41 education-, and age-matched healthy subjects to determine the best combination of subtests to use as a short form. Excluding three subtests that are time-consuming to administer, and requiring that the solution includes one subtest from each of the four WAIS index scores, the combination that most fully accounted for the variance in full-scale IQ (FSIQ) for both participants with schizophrenia (R(2)=0.90) and healthy controls (R(2)=0.86) included the information, block design, arithmetic, and digit symbol subtests. When the restrictions regarding which subtests could enter were relaxed, the best four-subtest solution included information, block design, comprehension, and similarities. Although the latter explained 95% of the variance in FSIQ for schizophrenia participants and 90% of the variance for healthy controls, it consistently overestimated FSIQ for the schizophrenia group. We recommend the four-factor short form for use in future research and clinical practice in which a quick, accurate IQ estimate is desired.

Effects of contextual processing on visual conditional associative learning in schizophrenia.

BACKGROUND: We adapted visual conditional associative learning paradigms to assess the contextual processing deficit model of schizophrenic cognitive impairment proposed by J.D. Cohen and D. Servan-Schreiber in 1992. In this task subjects learn the associations between four sets of stimuli through the use of feedback. We administered two experimental conditional associative learning conditions: in one, the eight stimuli used to make four pairs were all different; in the other, the pairs were made from different combinations of four identical stimuli, requiring the use of contextual information to mediate correct performance. Two additional associative learning tasks were administered where subjects generated the stimulus pairings or observed the experimenter form the pairs, eliminating the need to learn from feedback. METHODS: We tested 37 patients with schizophrenia and 20 healthy control subjects in each conditional associative learning task condition. RESULTS: Patients demonstrated significant impairments on all four conditional associative learning tasks. The demand to process contextual information did not differentially impact patient performance. Patients were better able to learn associations if they generated or observed the pairings rather than utilized feedback to guide learning. CONCLUSIONS: Patients with schizophrenia demonstrate pronounced deficits in the ability to utilize feedback to guide learning. We found no evidence of an additional deficit in processing of contextual information.

Mazindol treatment of negative symptoms.

Hypodopaminergic and hyponoradrenergic pathophysiology may be a basis for primary and/or secondary negative symptoms in schizophrenia. The hypothesis that enhanced neurotransmission in these systems would be therapeutic for negative symptoms was tested by comparing mazindol and placebo in a double-blind, cross-over design trial. Outcome following mazindol supplementation was comparable to placebo supplementation (F(1,30) = 0.9; p = .57). Results for deficit and non-deficit schizophrenia subjects were similar, and were not affected by whether concurrent the antipsychotic drug treatment was clozapine, fluphenazine, or haloperidol. The efficacy hypothesis was not supported for either primary or secondary negative symptoms.

Schizophrenia research: a progress report, summarizing proceedings of the 1999 International Congress on Schizophrenia Research.

The Seventh International Congress on Schizophrenia Research was held in Santa Fe, New Mexico, in April 1999. This was the largest Congress meeting to date, with almost 1,000 presentations that covered all aspects of schizophrenia research. This article provides an account of the Congress proceedings. Several research areas received extensive coverage, including early detection of illness through the use of cognitive and behavioral precursors of schizophrenia and the etiology and treatment of childhood-onset and first episode schizophrenia. The etiopathophysiological hypothesis of schizophrenia as a disorder of neural dysconnectivity was promoted across cognitive, neurochemical, neuroimaging, and postmortem domains. The importance of cognition as a major outcome measure and the impact of new antipsychotics on the treatment and conceptualization of schizophrenia were also major topics. Overall, the conference was noteworthy for the convergence of findings across research domains.

Neurological signs and the heterogeneity of schizophrenia.

OBJECTIVE: More than 20 studies of schizophrenia have found a three-factor model of symptom complexes or syndromes consisting of hallucinations/delusions, disorganization of thought and behavior, and negative symptoms. Several lines of evidence suggest that these syndromes relate to neurobiological differences. We examined the relationship of these three syndromes to neurological signs. METHOD: The relationships among the subscales of the Neurological Evaluation Scale and hallucinations/delusions, disorganization, and the deficit syndrome were examined in 83 clinically stable outpatients with schizophrenia. Patients with the deficit syndrome have enduring, idiopathic (or primary) negative symptoms. RESULTS: Each of the three syndromes had a distinctive pattern of relationships to neurological signs. Disorganization was significantly related to the total score on the Neurological Evaluation Scale, to sensory integration, and to the sequencing of complex motor acts. The deficit syndrome was significantly related to sensory integration only. Neither hallucinations/delusions nor a continuous measure of negative symptoms derived from the Brief Psychiatric Rating Scale (that measured both primary and secondary negative symptoms, as well as enduring and transient symptoms) was related to any of the Neurological Evaluation Scale subscales or total score. Drug treatment was not related to neurological impairment. CONCLUSIONS: The results further support the neurobiological significance of the three clinical syndromes of schizophrenia. Ratings on a scale measuring negative symptoms appear to be less sensitive to neurobiological correlates than is the categorization of the presence or absence of the deficit syndrome.

Assessing the efficacy of treatments for the deficit syndrome of schizophrenia.

The primary, enduring negative symptoms found in some patients with schizophrenia have become the focus of clinical treatment trials, but there has been no consensus on the best methods for approaching this area. In future trials, a number of issues need to be considered, including analytic strategies, the limitations in instruments used to measure negative symptoms, and study design. An appropriate design for establishing the efficacy of treatments for the deficit syndrome is proposed.

Repeatable battery for the assessment of neuropsychological status as a screening test in schizophrenia I: sensitivity, reliability, and validity.

OBJECTIVE: Cognitive impairment is an important feature of schizophrenia and is correlated with functional outcome. However, psychiatry lacks a screening instrument that can reliably assess the types of cognitive impairment often seen in schizophrenia. The authors assessed the sensitivity, convergent validity, and reliability of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) as well as the relationship of the RBANS to symptoms and employment status. This newly published test takes 25 minutes to administer and was standardized on a U.S.-Census-matched adult population. The test provides a total score and five index scores, each with a mean value of 100 (SD = 15). METHOD: RBANS data were obtained from 129 patients with schizophrenia in the outpatient and inpatient programs of the Maryland Psychiatric Research Center. RBANS data were correlated with WAIS-III and Wechsler Memory Scale, 3rd ed. performance in 38 patients. Reliability data for alternate forms of the RBANS were obtained from 53 patients; symptom ratings were obtained from 48 patients; and employment status was examined in 77 patients. RESULTS: The patients with schizophrenia demonstrated marked impairment on the RBANS (their mean total score was 71.4). The patients' index scores suggested that they had relatively less impairment of language and visual functions than of memory and attention. The RBANS demonstrated high correlations with full-scale IQ and memory measures. The total score demonstrated good reliability. RBANS performance minimally correlated with Brief Psychiatric Rating Scale ratings but was strongly related to employment outcome. CONCLUSIONS: The RBANS appears to be a useful cognitive screening instrument in schizophrenia. The instrument may be a useful prognostic indicator and offers a means of assessing cognitive status.

Prediction of neuropsychological performance by neurological signs in schizophrenia.

OBJECTIVE: The major purposes of this study were 1) to examine whether neurological signs predict cognitive performance in both schizophrenic patients and healthy subjects and 2) to determine the ability of neurological signs and neuropsychological tests to discriminate schizophrenic patients from healthy subjects. METHOD: Eighty-five patients with a DSM-III-R diagnosis of schizophrenia and 36 normal comparison subjects were included in the study. All subjects were administered a comprehensive neuropsychological test battery, and neurological signs were assessed with the Neurological Evaluation Scale. Stepwise regression analyses were used to predict neuropsychological test performance from the subscale scores on the Neurological Evaluation Scale. Forward stepwise linear discriminant function analyses were used to examine the discriminative ability of neurological subscale scores, neuropsychological test scores, and the two combined. RESULTS: Scores on the Neurological Evaluation Scale predicted the neuropsychological test performance of both patients and comparison subjects. The sensory integration subscale score was the most frequent predictor of neuropsychological test performance. In contrast, the "others" subscale, which includes frontal release signs, abnormalities in eye movements, and short-term memory, was the most highly discriminating subscale, correctly classifying 78.5% of the total study group. The best predictors from the neuropsychological battery (category fluency and Trail Making Test, part A, time test) correctly classified 81.8%. When both sets of variables were used, the Neurological Evaluation Scale "others" subscale entered the discriminant function first. CONCLUSIONS: Neurological signs are reliably related to measures of neuropsychological performance and also reliably discriminate between patients and healthy subjects. However, some neurological signs may be more sensitive to the presence of schizophrenia, while others may be more predictive of neuropsychological performance.

Deficit psychopathology and a paradigm shift in schizophrenia research.

Despite recognition that schizophrenia must have syndrome status in the absence of proof of a single etiopathophysiologic process, a century of work has been based on designs that conceptualize schizophrenia as a single disease entity. Reducing heterogeneity at several levels of functioning is desirable. In this article we summarize progress using deficit syndrome psychopathology to address heterogeneity. The deficit syndrome has proven to be reliable, with construct validity, as well as predictive validity with biological, treatment, and course variables. We propose a shift in schizophrenia research away from the syndrome level toward study designs that identify more homogeneous entities. Doing so will increase the statistical power of study designs by reducing false positive cases.

Cognitive rehabilitation for schizophrenia: problems, prospects, and strategies.

Increasing awareness of the importance of neurocognitive impairments in schizophrenia has fostered considerable interest in the prospects for cognitive rehabilitation. Nevertheless, optimism has outpaced progress. We first review recent literature on the central assumptions that underlie cognitive rehabilitation, including the hypothesis that cognitive deficits play a central role in social disability and other problems schizophrenia patients experience in daily living, and that these impairments must be rectified if we are to achieve effective rehabilitation. We next discuss developments in knowledge about the neurobiology of schizophrenia that bear on the potential for cognitive rehabilitation and the selection of appropriate targets for intervention. Third, we propose a new research strategy for investigating cognitive functioning in schizophrenia and for examining the relationship of cognitive deficits to role functioning in the community: examining patients who have good vocational outcomes in order to identify strengths or compensatory factors that compensate for core deficits. We present new data that lend support to our proposed approach. We next discuss putative limits to cognitive rehabilitation based on data documenting cognitive deficits in healthy siblings and parents. Finally, we briefly describe an interim rehabilitation strategy that minimizes the load on cognitive processes rather than attempting to improve cognitive functioning.

Gender differences in temporal lobe structures of patients with schizophrenia: a volumetric MRI study.

OBJECTIVE: The temporal lobe and associated structures have been previously implicated in the neuroanatomy of schizophrenia. This study was designed to assess the potential influence of gender on the morphology of temporal lobe structures, including the superior temporal gyrus and the amygdala/hippocampal complex, in patients with schizophrenia and to examine whether schizophrenic patients differ morphologically in these structures from comparison subjects. METHOD: Magnetic resonance imaging was used to measure the volume of temporal lobe structures, including the superior temporal gyrus, the amygdala/hippocampal complex, and the temporal lobe (excluding the volumes of the superior temporal gyrus and amygdala/hippocampal complex), and two comparison areas--the prefrontal cortex and caudate--in 36 male and 23 female patients with schizophrenia and 19 male and 18 female comparison subjects. RESULTS: There was a significant main effect of diagnosis in the superior temporal gyrus and the amygdala/hippocampal complex, with smaller volumes in patients than in comparison subjects. There was a significant gender-by-diagnosis-by-hemisphere interaction for temporal lobe volume. Temporal lobe volume on the left was significantly smaller in male patients than in male comparison subjects. Female patients and female comparison subjects demonstrated no significant difference in temporal lobe volume. There were no statistically significant gender interactions for the superior temporal gyrus, the amygdala/hippocampal complex, or the comparison regions. CONCLUSIONS: These findings suggest that there may be a unique interaction between gender and the pathophysiologic processes that lead to altered temporal lobe volume in patients with schizophrenia.

Stability of the diagnosis of deficit syndrome in schizophrenia.

OBJECTIVE: Primary, enduring negative symptoms have been distinguished from negative symptoms more generally and are used to define the deficit syndrome of schizophrenia. Although the validity of the deficit syndrome has been demonstrated by using brain imaging, neuropsychological, illness outcome, and developmental history data, the stability of this diagnostic category has not been tested prospectively by using direct patient assessments. METHOD: Forty-three outpatients with schizophrenia and schizoaffective disorder were categorized into deficit and nondeficit groups an average of 3.8 years after having been previously categorized. RESULTS: There was 83% agreement between initial and blind follow-up designations of deficit status and 88% agreement on the nondeficit categorization. CONCLUSIONS: These results provide evidence for the long-term stability of the deficit syndrome in patients with schizophrenia and the reliability of the deficit/nondeficit categorization when diagnosed by those with appropriate training. Furthermore, they validate the method of categorizing deficit patients by using cross-sectional and retrospective data.