Toxoplasma gondii and other risk factors for schizophrenia: an update.

The failure to find genes of major effect in schizophrenia has refocused attention on nongenetic, including infectious factors. In a previous study, antibodies to Toxoplasma gondii were found to be elevated in 23 studies of schizophrenia (OR 2.73; 95% CI 2.10-3.60). The current study replicates this finding with 15 additional studies (OR 2.71; 95% CI 1.93-3.80) and compares this with other identified schizophrenia risk factors. The highest risk factors are having an affected mother (relative risks [RR] 9.31; 95% CI 7.24-11.96), father (RR 7.20; 95% CI 5.10-10.16), or sibling (RR 6.99; 95% CI 5.38-9.08) or being the offspring of immigrants from selected countries (RR 4.5; 95% CI 1.5-13.1). Intermediate risk factors, in addition to infection with T. gondii, include being an immigrant from and to selected countries (RR 2.7; 95% CI 2.3-3.2), being born in (RR 2.24; 95% CI 1.92-2.61) or raised in (RR 2.75; 95% CI 2.31-3.28) an urban area, cannabis use (OR 2.10-2.93; 95% CI 1.08-6.13), having minor physical anomalies (OR 2.23; 95% CI 1.42-3.58), or having a father 55 or older (OR 2.21-5.92; 95% CI 1.46-17.02). Low-risk factors include a history of traumatic brain injury (OR 1.65; 95% CI 1.17-2.32), sex abuse in childhood (OR 1.46; 95% CI 0.84-2.52), obstetrical complications (OR 1.29-1.38; 95% CI 1.00-1.84), having a father 45 or older (OR 1.21-1.66; 95% CI 1.09-2.01), specific genetic polymorphisms (OR 1.09-1.24; 95% CI 1.06-1.45), birth seasonality (OR 1.07-1.95; 95% CI 1.05-2.91), maternal exposure to influenza (RR 1.05; 95% CI 0.98-1.12), or prenatal stress (RR 0.98-1.00; 95% CI 0.85-1.16).

Development and psychometric evaluation of a clinical global impression for schizoaffective disorder scale.

OBJECTIVE: The Clinical Global Impression for Schizoaffective Disorder scale is a new rating scale adapted from the Clinical Global Impression scale for use in patients with schizoaffective disorder. The psychometric characteristics of the Clinical Global Impression for Schizoaffective Disorder are described. DESIGN: Content validity was assessed using an investigator questionnaire. Inter-rater reliability was determined with 12 sets of videotaped interviews rated independently by two trained individuals. Test-retest reliability was assessed using 30 randomly selected raters from clinical trials who evaluated the same videos on separate occasions two weeks apart. Convergent and divergent validity and effect size were evaluated by comparing scores between the Clinical Global Impression for Schizoaffective Disorder and the Positive and Negative Syndrome Scale, 21-item Hamilton Rating Scale for Depression, and Young Mania Rating Scale scales using pooled patient data from two clinical trials. Clinical Global Impression for Schizoaffective Disorder scores were then linked to corresponding Positive and Negative Syndrome Scale scores. RESULTS: Content validity was strong. Inter-rater agreement was good to excellent for most scales and subscales (intra-class correlation coefficient ≥ 0.50). Test-retest showed good reproducibility, with intraclass correlation coefficients ranging from 0.444 to 0.898. Spearman correlations between Clinical Global Impression for Schizoaffective Disorder domains and corresponding symptom scales were 0.60 or greater, and effect sizes for Clinical Global Impression for Schizoaffective Disorder overall and domain scores were similar to Positive and Negative Syndrome Scale Young Mania Rating Scale, and 21-item Hamilton Rating Scale for Depression scores. Raters anticipated that the scale might be less effective in distinguishing negative from depressive symptoms, and, in fact, the results here may reflect that clinical reality. CONCLUSION: Multiple lines of evidence support the reliability and validity of the Clinical Global Impression for Schizoaffective Disorder for studies in schizoaffective disorder.

Training for assessment of negative symptoms of schizophrenia across languages and cultures: comparison of the NSA-16 with the PANSS Negative Subscale and Negative Symptom factor.

BACKGROUND: The 16-item Negative Symptom Assessment scale (NSA-16) has been validated in English-speaking raters. We analyzed the level of agreement achieved among raters of different nationalities using the NSA-16 and the Positive and Negative Syndrome Scale (PANSS) negative subscale and Marder negative factor. METHODS: Raters participating in two international trials were trained in the use of each instrument through lectures and feedback on their ratings of at least one videotaped interview of a schizophrenic patient. Overall and regional (North America, Western Europe, Eastern Europe, South/Central America, and Australia and South Africa combined) kappa values were calculated and mean total scores were compared (1-way analysis of variance) by region for each instrument. In addition, within-scales variance was calculated by item to help identify negative symptoms that were particularly challenging to obtain agreement on across cultures. RESULTS: In the combined group of international raters, the kappa values for ratings of the NSA-16, PANSS negative subscale, and Marder negative factors were 0.89, 0.84, and 0.82, respectively. Kappa values calculated by geographic region ranged from 0.87 to 0.94 for the NSA-16 compared with 0.82 to 0.86 for the PANSS negative subscale and 0.79 to 0.87 for the PANSS Marder negative factor. CONCLUSIONS: Despite cultural and linguistic differences among raters, standardizing measurement of negative symptoms in international clinical trials is possible using available rating scales: NSA-16, PANSS negative subscale, and Marder negative subscale. Agreement among raters was at least as high using the NSA-16 as using the PANSS instruments.

Pharmacotherapy of schizophrenic patients: preponderance of off-label drug use.

Multiple drug class combinations are often prescribed for the treatment of schizophrenia, although antipsychotic monotherapy reflects FDA labeling and scientific justification for combinations is highly variable. This study was performed to gain current data regarding drug treatment of schizophrenia as practiced in the community and to assess the frequencies of off-label drug class combinations. 200 DSM IV-diagnosed schizophrenic patients recruited from community treatment sources participated in this cross-sectional study of community based schizophrenic patients. Drug class categories include First and Second Generation Antipsychotic drugs (FGA and SGA, respectively), mood stabilizers, antidepressants and anti-anxiety drugs. 25.5% of patients received antipsychotic monotherapy; 70% of patients received an antipsychotic and another drug class. A total of 42.5% of patients received more than one antipsychotic drug. The most common drug class combination was antipsychotic and a mood stabilizer. Stepwise linear discriminant function analysis identified the diagnosis of schizoaffective schizophrenia, history of having physically hurt someone and high scores on the General Portion of the PANSS rating scale predicted the combined use of an antipsychotic drug and a mood stabilizer. "Real world" pharmacotherapy of schizophrenia has developed its own established practice that is predominantly off-label and may have outstripped current data support. The economic implications for public sector payers are substantial as well as for the revenue of the pharmaceutical industry, whose promotion of off-label drug use is an increasingly problematic. These data are consistent with the recognition of the therapeutic limitations of both first and second generation antipsychotic drugs.

A cross-sectional evaluation of perimenopausal depression.

OBJECTIVE: Overall, the clinical spectrum of depression during the perimenopause is not well characterized. This cross-sectional study examined the following: (1) clinical characteristics of women who presented to the National Institute of Mental Health midlife mood disorders clinic (between March 1990 and January 2004) with peri-menopausal major and minor depressions and (2) the impact on these characteristics of either a prior episode of depression or the presence of hot flushes. METHOD: Historical variables, reproductive status, symptom ratings, and plasma hormone measures were examined in 116 women between the ages of 40 and 55 years who met research criteria for perimenopause-related depression (a current episode of major or minor depression according to the Structured Clinical Interview for DSM-IV or Primary Care Evaluation of Mental Disorders supplemented with a past history form). RESULTS: Clinical characteristics did not differ in those women with first-onset (39%) versus recurrent depressions or in those with (57%) and without hot flushes. Depressive episodes clustered in the later stages of the menopause transition and the first year postmenopause. Seven women (6%) reported a past postpartum major depression, and 55% of women reported a history of premenstrual dysphoria (PMD). CONCLUSIONS: We found no evidence that either hot flushes or a previous episode of depression conveys a distinct clinical profile in these women. The clustering of onsets of depression suggests the hormone events that characterize the late menopause transition may be relevant to the onset of this form of depression. Finally, although we observed a high rate of PMD, neither postpartum depression nor PMD are consistent accompaniments of perimenopausal depression.

The Ab-Adductometer: a new device for measuring the muscle strength and function of the thumb.

The purpose of this study was to present normative values for thumb abduction and adduction and also to present measures of reliability of the measuring system arising from the use of the Ab-Adductometer. With the Ab-Adductometer, we obtained abductor and adductor measurements of intrinsic muscle strength of the healthy hand thumb in 600 volunteers. Handgrip strength values were obtained with the Jamar dynamometer. Age and male-female specific reference ranges for the Ab-Adductometer and the Jamar dynamometer are presented. This study, with a very large number of volunteer subjects, 600, presents reference ranges for pure palmar adduction and abduction of the thumb. The results indicate that the Ab-Adductometer is a clinically useful device for the purpose of quantitatively measuring thumb adduction and abduction strength at various starting angles of thumb abduction relative to the plane of the palm. The device may be especially helpful in the evaluation of compressive neuropathies of the median or ulnar nerves such as carpal tunnel syndrome or cubital tunnel syndrome as well as for primary disease of the peripheral nerves that affect intrinsic muscles and for thumb function in proximal conditions such as tetraplegia and brachial plexopathy.

Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis.

Recent studies have linked infectious agents to schizophrenia. The largest number of studies has involved the analysis of Toxoplasma gondii; these studies were subjected to a meta-analysis. Published articles and abstracts were identified by searches of MEDLINE, Ovid, and Google Scholar; by a search of Chinese publications; through letters to researchers; and by visiting China. Published and unpublished controlled studies that used serological methods for measuring T. gondii antibodies to assess inpatients and/or outpatients diagnosed with schizophrenia were selected for analysis, and source documents were translated as needed. Forty-two studies carried out in 17 countries over 5 decades were identified; 23 of these (6 unpublished) met selection criteria. The combined odds ratio (OR) was 2.73 (95% confidence interval, 2.10 to 3.60; chi-square with 1 df 263; P < .000001). Seven studies that included only patients with first-episode schizophrenia (OR 2.54) did not differ significantly from 16 studies that included patients in all clinical phases (OR 2.79). The results suggest that individuals with schizophrenia have an increased prevalence of antibodies to T. gondii. This association is consistent with other epidemiological studies as well as with animal studies. Although the OR of 2.73 is modest, it exceeds that for genetic or other environmental factors identified to date and suggests that Toxoplasma is in some way associated with a large number of cases of schizophrenia. If an etiological association can be proven, it would have implications for the design of measures for the prevention and treatment of this disease.

First psychiatric hospitalizations in the US military: the National Collaborative Study of Early Psychosis and Suicide (NCSEPS).

BACKGROUND: Military samples provide an excellent context to systematically ascertain hospitalization for severe psychiatric disorders. The National Collaborative Study of Early Psychosis and Suicide (NCSEPS), a collaborative study of psychiatric disorders in the US Armed Forces, estimated rates of first hospitalization in the military for three psychiatric disorders: bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia. METHOD: First hospitalizations for BD, MDD and schizophrenia were ascertained from military records for active duty personnel between 1992 and 1996. Rates were estimated as dynamic incidence (using all military personnel on active duty at the midpoint of each year as the denominator) and cohort incidence (using all military personnel aged 18-25 entering active duty between 1992 and 1996 to estimate person-years at risk). RESULTS: For all three disorders, 8723 hospitalizations were observed in 8,120,136 person-years for a rate of 10.7/10,000 [95% confidence interval (CI) 10.5-11.0]. The rate for BD was 2.0 (95% CI 1.9-2.1), for MDD, 7.2 (95% CI 7.0-7.3), and for schizophrenia, 1.6 (95% CI 1.5-1.7). Rates for BD and MDD were greater in females than in males [for BD, rate ratio (RR) 2.0, 95% CI 1.7-2.2; for MDD, RR 2.9, 95% CI 2.7-3.1], but no sex difference was found for schizophrenia. Blacks had lower rates than whites of BD (RR 0.8, 95% CI 0.7-0.9) and MDD (RR 0.8, 95% CI 0.8-0.9), but a higher rate of schizophrenia (RR 1.5, 95% CI 1.3-1.7). CONCLUSIONS: This study underscores the human and financial burden that psychiatric disorders place on the US Armed Forces.

The ipsilateral silent period in boys with attention-deficit/hyperactivity disorder.

OBJECTIVE: Characterize maturation of transcallosal inhibition (ipsilateral silent period [iSP]) in attention deficit/hyperactivity disorder (ADHD) using transcranial magnetic stimulation (TMS). BACKGROUND: Maturation of the iSP is related to acquisition of fine motor skills in typically developing children suggesting that dexterous fine motor skills depend upon mature interhemispheric interactions. Since neuromotor maturation is abnormal in boys with ADHD we hypothesized that iSP maturation in these children would be abnormal. We studied iSP maturation in 12 boys with ADHD and 12 age-matched, typically developing boys, 7-13 years of age. METHODS: Surface electromyographic activity was recorded from right first dorsal interosseus (FDI). During background activation, focal TMS was delivered at maximal stimulator output over the ipsilateral motor cortex. RESULTS: Maturation of finger speed in boys with ADHD was significantly slower than that in the control group. The iSP latency decreased with age in the control group but not in the ADHD group. CONCLUSIONS: These findings suggest the presence of a complex relationship between abnormalities of certain interhemispheric interactions (as represented by iSP latency) and delayed maturation of neuromotor skills in boys with ADHD. SIGNIFICANCE: These data provide preliminary physiologic evidence supporting delayed or abnormal development of interhemispheric interactions in boys with ADHD.

Neurochemical markers for schizophrenia, bipolar disorder, and major depression in postmortem brains.

BACKGROUND: Previous studies of postmortem neurochemical markers in severe psychiatric disorders have been carried out on different brain collections, making it difficult to compare results. METHODS: One hundred RNA, protein, and other neurochemical markers were assessed in a single set of 60 postmortem brains (15 each with schizophrenia, bipolar disorder, major depression without psychosis, and unaffected control subjects) in relation to seven neurochemical systems. Quantitative measures of continuous variables for prefrontal, hippocampus, anterior cingulate, superior temporal cortex, or a combination of these were analyzed from published and unpublished studies by 56 research groups. RESULTS: Before correcting for multiple comparisons, 23% of markers (23/100) were abnormal in one or more regions, with most indicating decreased expression. The largest percentage were associated with the developmental/synaptic (10/22) and gamma-aminobutyric acid (GABA; 3/7) systems. Bipolar disorder (20) and schizophrenia (19) had the most abnormalities, with a 65% overlap. When all brain areas were considered together and corrected for multiple comparisons, reelin, parvalbumin, and GAD67 were the most abnormal. CONCLUSIONS: Confirming other studies, the GABA and developmental/synaptic neurochemical systems are promising areas for research on schizophrenia and bipolar disorder. Research should include tissue from both diseases, and additional brain areas should be assessed.

Cerebrospinal fluid beta-amyloid1-42 and tau in control subjects at risk for Alzheimer's disease: the effect of APOE epsilon4 allele.

BACKGROUND: Cerebrospinal fluid (CSF) measures of beta-amyloid(1-42) and tau are linked with the known neuropathology of Alzheimer's disease (AD). Numerous lines of evidence have also suggested that individuals with at least one APOE epsilon4 allele on chromosome 19 are at increased risk of developing AD. We tested these CSF markers in groups of subjects with AD and healthy older control subjects, using the absence or presence of the APOE epsilon4 allele as a predictive variable in the search for possible prognostic biomarkers of AD. METHODS: We assessed the levels of beta-amyloid(1-42) and total tau in the CSF of 292 subjects (142 control subjects and 150 subjects with mild-to-moderate AD), who were research participants at the National Institute of Mental Health. The group of control subjects was enriched with a high percentage of subjects with a positive family history of AD. All subjects underwent extensive global cognitive testing. RESULTS: When divided according to the absence or presence of the APOE epsilon4 allele, the control subjects with at least one epsilon4 allele had significantly lower CSF beta-amyloid(1-42) but not tau levels than control subjects without an APOE epsilon4 allele (p < .01). As expected, the AD patients had lower levels of CSF beta-amyloid(1-42) and higher CSF tau levels than the normal control group (p < .01). CONCLUSIONS: The association of APOE epsilon4 allele and lower, more AD-like levels of CSF beta-amyloid(1-42) in older control subjects is consistent with previous studies showing possible neuroimaging and cognitive abnormalities with epsilon4 carriers and suggests that CSF beta-amyloid(1-42) decreases might represent an early biomarker of AD. Longitudinal follow-up is of course required to verify whether this biomarker is indeed predictive of clinical conversion to AD.

Seasonal variation in mood in African American college students in the Washington, D.C., metropolitan area.

OBJECTIVE: The authors attempted to estimate the occurrence, frequency, and pattern (winter versus summer) of seasonal affective disorder in African American college students. They hypothesized that winter seasonal affective disorder would be more prevalent than summer seasonal affective disorder. METHOD: Undergraduate and graduate college students who identified themselves as African Americans living in the Washington, D.C., metropolitan area were invited to participate in the study. The Seasonal Pattern Assessment Questionnaire was used to calculate a global seasonality score and to estimate the frequency of seasonal affective disorder and subsyndromal seasonal affective disorder. The frequency of the summer versus winter pattern of seasonality of seasonal affective disorder was compared by using multinomial probability distribution tests. The effects of gender and the awareness of seasonal affective disorder were evaluated with a two-way analysis of variance. RESULTS: Of 646 students who were invited to participate, 597 returned the questionnaires, and 537 (83.1%) fully completed them. Winter seasonal affective disorder was significantly more prevalent than summer seasonal affective disorder. The mean global seasonality score was 8.3 (SD=5.3). The majority of the subjects (80%) were not aware of the existence of seasonal affective disorder. CONCLUSIONS: The authors found that the frequency, magnitude, and pattern of seasonality of mood in African American students were similar to those previously reported in the general population at similar latitude, but that awareness of the existence of seasonal affective disorder, a condition with safe and effective treatment options, was lower.

Effect size of symptom status in withdrawal of typical antipsychotics and subsequent clozapine treatment in patients with treatment-resistant schizophrenia.

OBJECTIVE: In light of the efficacy of newer antipsychotic agents and the possibility that drug withdrawal may negatively affect subsequent drug response, concern has arisen that the use of placebo in schizophrenia research may be unethical. This study examines the effect size of symptom exacerbation during drug washout with placebo and the effects of drug washout on the efficacy of subsequent drug treatment. METHOD: Fifty patients with treatment-resistant schizophrenia hospitalized on a research unit participated in a double-blind longitudinal study of the effects of drug washout after chronic treatment with a typical antipsychotic and before prospective treatment with clozapine. Brief Psychiatric Rating Scale (BPRS) scores were analyzed to examine drug effects and effect sizes for baseline treatment with a typical antipsychotic (>6 months treatment), drug washout with placebo (mean=34 days), early treatment with clozapine (mean=42 days, mean dose=345.0 mg/day), and optimal clozapine treatment (mean=83 days, mean dose=450.5 mg/day). RESULTS: Patients' BPRS total, positive, and negative symptom scores significantly increased during placebo washout, compared with baseline treatment, and significantly decreased with administration of clozapine, compared with placebo washout and baseline treatment. However, 30% of patients showed some symptom improvement during placebo washout. The effect sizes for the BPRS total score were 0.63 for baseline treatment versus placebo washout, 1.10 for optimal clozapine treatment versus placebo washout, and 0.82 for optimal clozapine treatment versus baseline treatment. CONCLUSIONS: Symptom exacerbation induced by drug withdrawal in patients with treatment-resistant schizophrenia did not impede subsequent responsiveness to clozapine. The effect size for clozapine, compared with typical antipsychotics, suggests that the drug-washout longitudinal design is useful for establishing a drug-free baseline and for investigating drug response, while requiring relatively few subjects.

Decreased beta-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease.

CONTEXT: Alzheimer disease (AD) is characterized by pathological results at autopsy of amyloid plaques and tau-associated neurofibrillary tangles, but the clinical diagnosis of AD is determined on the basis of medical history, cognitive symptoms, and exclusionary criteria. The search for antemortem biomarkers is intense and has focused on cerebrospinal fluid (CSF) beta-amyloid1-42 and tau proteins. OBJECTIVES: To compare CSF beta-amyloid and tau levels in a new population of AD patients and controls. To perform a meta-analysis of studies of CSF beta-amyloid and tau levels in AD patients and controls. DESIGN: Cross-sectional study of the comparison of baseline CSF beta-amyloid1-42 and tau levels in AD patients and controls. Meta-analysis involved 17 studies of CSF beta-amyloid and 34 studies of CSF tau. SETTING: Clinical research unit of the National Institute of Mental Health, Bethesda, Md. PATIENTS: The Geriatric Psychiatry Branch evaluated AD patients as inpatients at the National Institutes of Health Clinical Center between May 1985 and January 2001. A total of 203 patients participated in this study (131 with AD and 72 controls). None had other serious illnesses, and 31 of 131 AD cases had AD confirmed at autopsy. Meta-analysis provided an additional 3133 AD patients and 1481 controls. MAIN OUTCOME MEASURES: Levels of CSF beta-amyloid1-42 were measured by a sandwich enzyme-linked immunoabsorbent assay with a polyclonal capture antibody and a monoclonal detection antibody. Levels of CSF tau were measured with a standard commercial immunoassay. RESULTS: Levels of CSF beta-amyloid1-42 were significantly lower in the AD patients vs controls (mean [SD], 183 [121] pg/mL vs 491 [245] pg/mL; P<.001). Levels of CSF tau were significantly higher in AD patients (mean [SD], 587 [365] pg/mL vs 244 [156] pg/mL; P<.001). The cutpoints of 444 pg/mL for CSF beta-amyloid1-42 and 195 pg/mL for CSF tau gave a sensitivity and specificity of 92% and 89%, respectively, to distinguish AD patients from controls, which is comparable with rates with clinical diagnosis. Meta-analyses of studies comparing CSF beta-amyloid and tau levels in AD participants and controls confirmed an overall difference between levels in these 2 groups. CONCLUSIONS: Alzheimer disease is associated with a significant decrease in CSF beta-amyloid1-42 levels along with an increase in CSF tau levels. These findings suggest that the 2 measures are biological markers of AD pathophysiology. While these CSF measures may have a potential clinical utility as biomarkers of disease, the preliminary and retrospective nature of the findings, the absence of assay standardization, and the lack of comparison patient populations must be addressed in future studies testing the usefulness of these CSF measures for predictive, diagnostic, or treatment evaluation purposes.

Patients with seasonal affective disorder have lower odor detection thresholds than control subjects.

BACKGROUND: Behavioral changes in patients with seasonal affective disorder resemble seasonal changes in photoperiodic animals. Because the olfactory system has a modulatory role in seasonal photoperiodic responses in certain species, we hypothesized that olfactory function may differ between patients with seasonal affective disorder and healthy control subjects. METHODS: Fourteen patients who had winter seasonal affective disorder and 16 healthy volunteers were studied once in winter and once in the subsequent summer. We administered a phenyl ethyl alcohol detection threshold test to each side of the nose in a counterbalanced order, with the nostril contralateral to the tested site occluded. Patient and control data were compared using a 4-way repeated measure analysis of covariance (with group and gender as between-subjects factors, season and side-of-the-nose as within-subjects factors, and age as a covariate). RESULTS: The patients exhibited lower thresholds than did the controls (F(1,25) = 9.2; P =.006). There was no main effect of season. CONCLUSION: In humans, marked seasonal behavioral rhythms with recurrent winter depression may be associated with a more acute sense of smell.

Test-retest stability of the Repeatable Battery for the Assessment of Neuropsychological Status in schizophrenia.

OBJECTIVE: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was designed as a cognitive screening test, providing both a total scale score and five specific cognitive ability index scores. This study examined the test-retest stability of the RBANS in individual patients with schizophrenia relative to a healthy comparison group. METHOD: A total of 181 patients with schizophrenia or schizoaffective disorder were recruited from three clinical settings. Healthy comparison subjects were recruited as part of the RBANS standardization. Participants were administered one form of the RBANS on one occasion and another form at a later date, with intervals ranging from 1 to 134 days. RESULTS: Intraclass correlation coefficients for the RBANS total scale were 0.84 for the patients with schizophrenia and 0.77 for the healthy comparison subjects. Confidence intervals and percentile data for the total scale change scores were similar for both groups. CONCLUSIONS: The RBANS demonstrated reasonable intraclass correlation coefficient test-retest reliability for both schizophrenia patients and healthy comparison subjects. Confidence intervals are comparable to those previously published for the WAIS-R and Wechsler Memory Scale-Revised, suggesting that retest measurement error is not dramatically increased in the RBANS, despite the brevity of the test. These data may serve as an informative guide for using the RBANS to evaluate neuropsychological change on the level of the individual subject.

Simulation study of a panel of reliability indicators applied to paired measurements.

Reliability is a subject of continuing discussion in biomedial specialty areas, including physical anthropology and nutritional epidemiology. The purpose of this study was to explore techniques of detecting differences between two evaluators or methods. A field study in which anthropometric dimensions would be taken by two independent evaluators on each participant in a study group was simulated. A panel of reliability indicators was applied across a broad range of parameters using simulation, and then the panel was applied to field anthropometric data. The panel consisted of the intraclass correlation coefficient (ICC), paired t-test, a simultaneous test of evaluator means and variances, technical error of measurement, mean absolute difference, and mean difference. The simultaneous test for equal evaluator means and variances uses regression to model paired differences versus paired sums. The simulation demonstrated general properties of the reliability indicators across many conditions of population variance, measurer bias, and measurer error variance. High values of ICC often exist in cases in which the measurers are different. The simultaneous test is thus a powerful method for detecting measurer differences, especially when combined with the paired t-test. However, a single reliability indicator that is sufficient to determine all measurer inconsistencies was not identified. The field study and the simulation permitted the development of a logical approach to determining the source and magnitude of measurer differences using the panel of reliability indicators. © 1994 Wiley-Liss, Inc.