Faculty Bibliography

We investigated the influence of the direction of preceding saccadic trials on the latency of current prosaccades and antisaccades, in healthy subjects and patients with schizophrenia. When prosaccades and antisaccades were performed in separate, single-task blocks, we found that only prosaccades were delayed if the saccade in the prior trial was in the same direction, consistent with the expected directional effect from an 'inhibition of return'-like alternation advantage. However, both types of saccades were executed more quickly when the saccade in the penultimate trial was in the same direction, consistent with previous demonstrations of directional plasticity in monkeys. In blocks of randomly mixed prosaccades and antisaccades, the directional effects in healthy subjects were greatest when a prosaccade was preceded by an antisaccade, consistent with a summation of effects of alternation advantage (from the prior stimulus) and directional plasticity (from the prior saccade). Schizophrenic patients showed an additional phenomenon, a directionally specific inhibition of upcoming saccades by preceding antisaccades. These results suggest that saccades in humans are modulated by inter-trial effects attributable to both an 'inhibition of return'-like alternation advantage and directional plasticity

Persons diagnosed with schizophrenia have higher morbidity and mortality rates from cardiovascular disease, yet often have limited access to appropriate primary care screening or treatment. Metabolic disorders such as diabetes, hyperlipidemia and hypertension are highly prevalent in populations with schizophrenia, exceeding 50% in some studies; however, there have been few published studies on treatment rates among schizophrenia patients screened for these disorders. METHODS: Using the baseline data from subjects (N=1460) recruited into the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study, we examined the point prevalence of diabetes, hyperlipidemia and hypertension treatment at the time of enrollment for the entire cohort and those with fasting laboratory values obtained 8 or more hours since last meal. RESULTS: Rates of non-treatment ranged from 30.2% for diabetes, to 62.4% for hypertension, and 88.0% for dyslipidemia. Nonwhite men were more likely to be treated for DM and dyslipidemia than nonwhite women. CONCLUSIONS: These data indicate the high likelihood that metabolic disorders are untreated in patients with schizophrenia, with particularly high rates of non-treatment for hypertension and dyslipidemia. Nonwhite women may be especially vulnerable to undertreatment of dyslipidemia and diabetes compared to nonwhite men. The findings here support the need for increased attention to basic monitoring and treatment of cardiovascular risk factors in this vulnerable and often underserved psychiatric population

OBJECTIVE: Recent studies have suggested a beneficial role of insulin on brain function and psychological well-being. This study was undertaken to examine whether fasting serum insulin levels are associated with the psychopathology profile in a cross-sectional sample of acutely ill non-diabetic inpatients with schizophrenia. METHODS: Subjects were recruited from a county hospital. Each subject underwent a psychopathology assessment with the Positive and Negative Syndrome Scale (PANSS). A fasting blood sample was taken to measure serum insulin, plasma glucose and lipids. RESULTS: Twenty-six subjects (7 females, 19 males) were included in the study. Pearson correlation analysis showed significant inverse relationships between serum insulin level and PANSS-Total, Positive Symptom subscale, and General Psychopathology subscale scores (r=-0.41, p=0.037; r=-0.49, p=0.010; r=-0.45, p=0.023, respectively). However, there was no significant relationship between serum insulin level and PANSS-Negative Symptom subscale score (r=-0.13, p=0.53). Partial correlation analysis showed that the inverse relationships between serum insulin levels and PANSS-Total, Positive Symptom subscale, and General Psychopathology subscale scores became even stronger after controlling for potential confounding variables including age, gender, race, family history of mental illness, age of illness onset and body-mass index (BMI). CONCLUSIONS: Higher fasting serum insulin levels are associated with a better psychopathology profile in acutely ill non-diabetic inpatients with schizophrenia. It is speculated that insulin might improve clinical symptoms of schizophrenia by interacting with dopamine and other neurotransmitter systems

OBJECTIVE: The appropriateness and effectiveness of the outpatient medical management of cardiac risk factors for patients with diabetes who had a diagnosis of schizophrenia or a related psychotic syndrome were examined. METHODS: In a cross-sectional analysis of 4,236 patients with diabetes, ICD-9 billing codes were used to identify 214 patients with schizophrenia or a schizophrenia-related syndrome. Measures of treatment appropriateness and effectiveness for the management of cardiac risk factors (control of blood sugar, blood pressure, and lipids) were assessed for this group and compared with measures from patients with diabetes but no severe mental illness (N = 3,594). Odds ratios were adjusted for between-group differences in gender, race, age, and clinic setting. RESULTS: There were no statistically significant between-group differences on any of the five measures of treatment appropriateness, indicating that patients with schizophrenia received a similar regimen of medical treatment for cardiac factors. However, two of the seven measures of treatment effectiveness indicated significant deficiencies, with fewer patients with schizophrenia meeting the clinical quality benchmarks for cholesterol and low-density lipoprotein control. This disparity may have been caused by factors other than the measured treatment appropriateness variables, including the prescription of older lipid-lowering agents and a higher rate of missed appointments in the group with schizophrenia. CONCLUSIONS: Effective lipid control may be more difficult to attain for at least some patients with schizophrenia. Given that population's high rates of cardiovascular mortality, additional research to clarify the barriers to effective lipid management is essential

An impairment in the build-up and use of context has been proposed as a core feature of schizophrenia. The current study tested the hypothesis that schizophrenia patients show impairments in building up context within sentences because of abnormalities in combining semantic with syntactic information. Schizophrenia patients and healthy controls read and made acceptability judgments about sentences containing verbs that were semantically associated with individual preceding words but that violated either the meaning (animacy/semantic constraints) or the syntactic structure (morphosyntactic constraints) of their preceding contexts. To override these semantic associations and determine that such sentences are unacceptable, participants must integrate semantic with syntactic information. These sentences were compared with congruous and pragmatically/semantically violated sentences that imposed fewer semantic-syntactic integration demands. At sentence-final words and decisions, patients showed smaller reaction time differences than controls to animacy/semantically violated or morphosyntactically violated sentences relative to pragmatically/semantically violated or nonviolated sentences. The relative insensitivity to these violations in patients with schizophrenia may arise from impairments in combining semantic and syntactic information to build up sentence context.

OBJECTIVE: Clozapine and olanzapine treatment has been associated with insulin resistance in non-obese schizophrenia patients. Much less is known regarding other agents such as quetiapine. The objective of this study was to compare matched olanzapine- and quetiapine-treated schizophrenia patients and normal controls on measures of glucose metabolism. METHOD: A cross-sectional comparison of quetiapine-treated and olanzapine-treated non-obese (body mass index < 30.0 kg/m2) schizophrenia subjects (DSM-IV) with matched normal controls using a frequently sampled intravenous glucose tolerance test and nutritional assessment was conducted from April 2002 to October 2004. Data from 24 subjects were included in the analysis (7 quetiapine, 8 olanzapine, 9 normal controls). RESULTS: There was a significant difference among groups for fasting baseline plasma glucose concentrations (p = .02), with olanzapine greater than normal controls (p = .01). The insulin sensitivity index (SI) differed significantly among groups (p = .039); olanzapine subjects exhibited significant insulin resistance compared to normal controls (p = .01), but there was no significant difference for quetiapine versus olanzapine (p = .1) or quetiapine versus normal controls (p = .40). SI inversely correlated with quetiapine dose (p = .0001) and waist circumference (p = .03) in quetiapine-treated subjects. Insulin resistance calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) also differed significantly among groups (p = .03). The olanzapine group had a higher HOMA-IR level than normal controls (p = .01). There was a significant difference in glucose effectiveness (SG) among the groups (p = .049). SG was lower in the olanzapine group than in the quetiapine group (p = .03) and in the olanzapine group compared to normal controls (p = .049). CONCLUSIONS: Our findings are consistent with our previous report that nonobese olanzapine-treated subjects showed insulin resistance, measured by both HOMA-IR and SI, and reduction in SG. Studies that include larger samples, unmedicated patients, and varying durations of antipsychotic exposure are necessary to confirm these results

Event-related potentials to critical verbs were measured as patients with schizophrenia and healthy controls read sentences word by word. Relative to their preceding context, critical verbs were (a) congruous, (b) incongruous and semantically unrelated to individual preceding words (pragmatic-semantic violations), (c) incongruous but semantically related to individual preceding words (animacy-semantic violations), or (d) syntactically anomalous. The N400 was modulated normally in patients, suggesting that semantic integration between individual words within sentences was normal in schizophrenia. The amplitude of the P600 to both syntactic and animacy-semantic violations was reduced in patients relative to controls. The authors suggest that, in schizophrenia, an abnormality in combining semantic and syntactic information online to build up propositional meaning leaves sentence processing to be primarily driven by semantic relationships between individual words.

BACKGROUND: The increasing prevalence of overweight and obesity has become a priority public health issue in the United States. Forty to 62% of people with schizophrenia are obese or overweight (1, 2). High morbidity and mortality in schizophrenia may be attributed to an unhealthy lifestyle such as poor diet, lack of exercise, smoking, and substance abuse (3). Obesity is associated with greater risk of developing hypertension, type 2 diabetes, coronary heart disease, stroke, death, and reduced quality of life compared with that found in the general population (4, 5). We performed a cross-sectional study evaluating the dietary intake of patients with schizophrenia or schizoaffective disorder treated with atypical antipsychotic agents. METHODS: Dietary intake of 88 patients from an urban community mental health clinic was measured using a four-day dietary record. Nutritional variables included total energy intake, fat, protein, carbohydrate, cholesterol, fiber, sucrose, folate, calcium, sodium, zinc, alcohol and caffeine. Data were compared to the general population using data matched for age, gender, and ethnicity from the National Health and Nutrition Examination Survey (NHANES), 1999-2000. RESULTS: The Body Mass Index (BMI) of the schizophrenia group (M = 31.3, SD = 12.67) was significantly greater than the NHANES group (M = 28.3, SD = 6.62) (p = .001). The schizophrenia group consumed significantly fewer calories, carbohydrate, protein, total fat, saturated fat, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), fiber, folate, sodium and alcohol and significantly more caffeine than the NHANES group. CONCLUSIONS: The findings may suggest that obesity in schizophrenia patients is not solely related to food consumption, but perhaps other effects including medication side effects and reduced physical activity. Education and interventions for the schizophrenia population should focus more on overall lifestyle factors such as physical activity and healthy food choices

INTRODUCTION: Delusions may arise from abnormalities in emotional perception. In this study, we tested the hypothesis that delusional schizophrenia patients are more likely than non-delusional schizophrenia patients and healthy participants to assign affective meanings to neutral stimuli. METHODS: Unpleasant, pleasant, and neutral words were randomly presented to three subject groups--patients with schizophrenia with prominent delusions, patients with schizophrenia without delusions, and healthy participants. Participants performed three tasks: one in which they decided whether a letter string was a word or a non-word (lexical decision) and two affective classification tasks in which they judged whether words were 1) neutral or unpleasant, or 2) neutral or pleasant. RESULTS: While there were no significant between-group differences in lexical decision performance, patients with delusions showed selective performance deficits in both affective classification tasks. First, delusional patients were significantly more likely than non-delusional patients and healthy participants to classify words as unpleasant. Second, delusional patients took significantly longer than both other groups to correctly classify neutral words in both affective classification tasks. CONCLUSIONS: Taken together, these findings suggest that delusions are associated with the explicit misattribution of salience to neutral stimuli

Smaller medial temporal lobe volume is a frequent finding in studies of patients with schizophrenia, but the relative contributions of the hippocampus and three surrounding cortical regions (entorhinal cortex, perirhinal cortex, and parahippocampal cortex) are poorly understood. We tested the hypothesis that the volumes of medial temporal lobe regions are selectively changed in schizophrenia. We studied 19 male patients with schizophrenia and 19 age-matched male control subjects. Hippocampal and cortical volumes were estimated using a three-dimensional morphometric protocol for the analysis of high-resolution structural magnetic resonance images, and repeated measures ANOVA was used to test for region-specific differences. Patients had smaller overall medial temporal lobe volumes compared to controls. The volume difference was not specific for either region or hemisphere. The finding of smaller medial temporal lobe volumes in the absence of regional specificity has important implications for studying the functional role of the hippocampus and surrounding cortical regions in schizophrenia.