Robert W. Buchanan

The Schizophrenia Patient Outcomes Research Team (PORT): Updated Treatment Recommendations 2009

The Schizophrenia Patient Outcomes Research Team (PORT) project has played a significant role in the development and dissemination of evidence-based practices for schizophrenia. In contrast to other clinical guidelines, the Schizophrenia PORT Treatment Recommendations, initially published in 1998 and first revised in 2003, are based primarily on empirical data. Over the last 5 years, research on psychopharmacologic and psychosocial treatments for schizophrenia has continued to evolve, warranting an update of the PORT recommendations. In consultation with expert advisors, 2 Evidence Review Groups (ERGs) identified 41 treatment areas for review and conducted electronic literature searches to identify all clinical studies published since the last PORT literature review. The ERGs also reviewed studies preceding 2002 in areas not covered by previous PORT reviews, including smoking cessation, substance abuse, and weight loss. The ERGs reviewed over 600 studies and synthesized the research evidence, producing recommendations for those treatments for which the evidence was sufficiently strong to merit recommendation status. For those treatments lacking empirical support, the ERGs produced parallel summary statements. An Expert Panel consisting of 39 schizophrenia researchers, clinicians, and consumers attended a conference in November 2008 in which consensus was reached on the state of the evidence for each of the treatment areas reviewed. The methods and outcomes of the update process are presented here and resulted in recommendations for 16 psychopharmacologic and 8 psychosocial treatments for schizophrenia. Another 13 psychopharmacologic and 4 psychosocial treatments had insufficient evidence to support a recommendation, representing significant unmet needs in important treatment domains.

The schedule for the deficit syndrome: An instrument for research in schizophrenia

The Schedule for the Deficit Syndrome (SDS) is an instrument for categorizing schizophrenic patients into those with and those without the deficit syndrome. In a study of 40 schizophrenic patients diagnosed by DSM-III criteria, raters using the SDS demonstrated good interrater reliability for this categorization, as well as for individual negative symptoms and a rating of global severity.

The neurological evaluation scale (NES): A structured instrument for the assessment of neurological signs in schizophrenia

The significance of neurological signs in schizophrenia is poorly understood. In part, this may reflect the marked variability in the methods of ascertainment in previous studies. The Neurological Evaluation Scale (NES) is designed to standardize the assessment of neurological impairment in schizophrenia. The battery consists of 26 items. Data on the interrater reliability for total score, functional areas of interest, and individual items are presented. Preliminary validity data demonstrate the ability of the battery to discriminate patients with schizophrenia from nonpsychiatric controls.

Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study

Abstract Objective: To quantify the association between olanzapine and diabetes. Design: Population based nested case-control study. Setting: United Kingdom based General Practice Research Database comprising 3.5 million patients followed between 1987 and 2000. Participants: 19 637 patients who had been diagnosed as having and treated for schizophrenia. 451 incident cases of diabetes were matched with 2696 controls. Main outcome measures: Diagnosis and treatment of diabetes. Results: Patients taking olanzapine had a significantly increased risk of developing diabetes than non-users of antipsychotics (odds ratio 5.8, 95% confidence interval 2.0 to 16.7) and those taking conventional antipsychotics (4.2, 1.5 to 12.2). Patients taking risperidone had a non-significant increased risk of developing diabetes than non-users of antipsychotics (2.2, 0.9 to 5.2) and those taking conventional antipsychotics (1.6, 0.7 to 3.8). Conclusion: Olanzapine is associated with a clinically important and significant increased risk of diabetes.

Significance and meaning of neurological signs in schizophrenia.

The authors review studies of abnormal signs on clinical neurological examination of schizophrenic patients. In spite of a number of methodologic limitations, the cumulative evidence strongly argues that there are more neurological signs in schizophrenic patients than in nonpsychiatric control subjects. Although less consistent, there is considerable evidence of more neurological signs in schizophrenic patients than in patients with affective disorders or with mixed, nonpsychotic disorders. The existing literature suggests several preliminary hypotheses with respect to neuroanatomical localization of neurological signs, subtyping of schizophrenia, and utility of studies of relatives at high risk and family history studies. Directions for future research in these areas are described.

The comparative efficacy and long-term effect of clozapine treatment on neuropsychological test performance

Previous studies have suggested that clozapine may improve neuropsychological test performance. The current study was designed to examine the comparative efficacy and the long-term effect of clozapine (versus haloperidol), on neuropsychological test performance. Neuropsychological measures of executive/attention, visuospatial, and memory function were administered to schizophrenic patients at baseline, at the end of a 10-week double-blind study, and after 1 year of open clozapine treatment. Symptoms and function ratings were obtained at the same time points. The 10-week double-blind study revealed significant group-by-time interactions for two measures: Categorical Fluency and WAIS-R Block Design. At the end of 1 year of open treatment there were significant improvements in Verbal Fluency, Mooney Faces Closure, and WAIS-R Block Design performance, and trend improvements in Stroop Color-Word Interference, Category Fluency, and WMS-R Logical Memory performance. Improvements in neuropsychological performance were unrelated to symptom changes. Change in selected neuropsychological measures were significantly correlated with improvement in quality of life. The results suggest that long-term clozapine treatment may have beneficial effects on a broad range of cognitive functions.

Domains of psychopathology: an approach to the reduction of heterogeneity in schizophrenia.

The manifest clinical heterogeneity of schizophrenia, combined with the failure, to date, to demonstrate the existence of a unitary disease process, has led to the conceptualization of schizophrenia as a pathophysiologically heterogeneous disorder. Various approaches have been developed to define homogeneous subgroups of schizophrenic patients. An alternative approach to the use of multiple criteria for defining putative disease entities is the use of specific sign and symptom complexes, or domains of psychopathology, for reducing heterogeneity. There is now considerable evidence supporting the separation of schizophrenic symptoms into three domains: hallucinations and delusions, thought disorder, and deficit symptoms. The conceptual evolution and validating evidence for this approach are reviewed, and an illustration of how the domains of psychopathology are applied in schizophrenia research is presented.

Deconstructing negative symptoms of schizophrenia: Avolition–apathy and diminished expression clusters predict clinical presentation and functional outcome

BACKGROUND Previous studies indicate that negative symptoms reflect a separable domain of pathology from other symptoms of schizophrenia. However, it is currently unclear whether negative symptoms themselves are multi-faceted, and whether sub-groups of patients who display unique negative symptom profiles can be identified. METHODS A data-driven approach was used to examine the heterogeneity of negative symptom presentations in two samples: Study 1 included 199 individuals with schizophrenia assessed with a standard measure of negative symptoms and Study 2 included 169 individuals meeting criteria for deficit schizophrenia (i.e., primary and enduring negative symptoms) assessed with a specialized measure of deficit symptoms. Cluster analysis was used to determine whether different groups of patients with distinct negative symptoms profiles could be identified. RESULTS Across both studies, we found evidence for two distinctive negative symptom sub-groups: one group with predominantly Avolition-Apathy (AA) symptoms and another with a predominantly Diminished Expression (DE) profile. Follow-up discriminant function analyses confirmed the validity of these groups. AA and DE negative symptom sub-groups significantly differed on clinically relevant external validators, including measures of functional outcome, premorbid adjustment, clinical course, disorganized symptoms, social cognition, sex, and ethnicity. CONCLUSIONS These results suggest that distinct subgroups of patients with elevated AA or DE can be identified within the broader diagnosis of schizophrenia and that these subgroups show clinically meaningful differences in presentation. Additionally, AA tends to be associated with poorer outcomes than DE, suggesting that it may be a more severe aspect of psychopathology.

Evoked gamma band synchronization and the liability for schizophrenia.

OBJECTIVE Electroencephalographic (EEG) synchronization in the gamma band is thought to represent a neuronal mechanism by which the brain integrates information processed in different cortical areas to build a coherent internal representation. Previous studies have reported abnormal gamma range ( approximately 40 Hz) synchronization in schizophrenic patients. We tested a group of first-degree relatives of schizophrenic probands who have schizophrenia spectrum personality symptoms, and a group of schizophrenic patients, to examine whether individuals with increased liability for schizophrenia have reduced gamma synchronization. METHOD A steady-state auditory evoked potential paradigm was used to evaluate the brains capacity to sustain 20, 30, and 40 Hz EEG synchronization in 11 relatives, 24 schizophrenic patients (11 on conventional, 13 on new generation antipsychotic medications), and 17 normal controls. RESULTS Relatives with schizophrenic spectrum personality symptoms had reduced power at 40 Hz synchronization compared to normal controls (p=0.022). Previous findings of reduced steady-state gamma band synchronization in schizophrenic patients were not directly replicated in this study. Patients as a group did not significantly differ from controls, but patients taking new generation antipsychotics had significantly enhanced 40 Hz synchronization compared to patients taking conventional antipsychotics (p<0.001). There were no group differences in 20 or 30 Hz synchronization. CONCLUSIONS Gamma band synchronization was found to be reduced in first-degree relatives with schizophrenia spectrum personality symptoms. Patients on new generation antipsychotic medications may exhibit enhanced gamma band synchronization.

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.