Faculty Bibliography

The anterior cingulate cortex (ACC) is a key component of a network that directs both spatial attention and saccadic eye movements, which are tightly linked. Diffusion tensor imaging (DTI) has demonstrated reduced microstructural integrity of the anterior cingulum bundle as indexed by fractional anisotropy (FA) in schizophrenia, but the functional significance of these abnormalities is unclear. Using DTI, we examined the white matter underlying anterior cingulate cortex in schizophrenia to determine whether reduced FA is associated with prolonged latencies of volitional saccades. Seventeen chronic, medicated schizophrenia outpatients and nineteen healthy controls had high-resolution DTI scans. FA maps were registered to structural scans and mapped across participants using a surface-based coordinate system. Cingulate white matter was divided into rostral and dorsal anterior regions and a posterior region. Patients showed reduced FA in cingulate white matter of the right hemisphere. Reduced FA in the white matter underlying anterior cingulate cortex, frontal eye field, and posterior parietal cortex of the right hemisphere was associated with longer saccadic latencies in schizophrenia, though given the relatively small sample size, these relations warrant replication. These findings demonstrate that in schizophrenia, increased latency of volitional saccades is associated with reduced microstructural integrity of the white matter underlying key cortical components of a right-hemisphere dominant network for visuospatial attention and ocular motor control. Moreover, they suggest that anterior cingulate white matter abnormalities contribute to slower performance of volitional saccades and to inter-individual variability of saccadic latency in chronic, medicated schizophrenia

OBJECTIVE: The present study was to characterize relationships among sexual functioning, schizophrenia symptoms and quality of life measures. In addition, sexual functioning was compared among patients treated with different antipsychotic agents. METHODS: Outpatient subjects were assessed using the Positive and Negative Symptom Scale (PANSS), the Changes in Sexual Functioning Questionnaire (CSFQ) and the Hamilton Rating Scale for Depression (HAMD). Quality of life was assessed using two different instruments: observer-rated Heinrich's Quality of Life Scale (QLS) and self-rated The Behavior and Symptom Identification Scale (BASIS). RESULTS: One hundred twenty-four patients with schizophrenia or schizoaffective disorder were enrolled in the study. Eight-six patients (69%) completed at least part of the CSFQ assessment, which generated at least one valid subscale score. High rates of sexual impairment were found in both male and female patients (65%-94% across different subscales). For males, higher scores on the PANSS-positive subscale were associated with a lower frequency of sexual activity (p=0.04). For females, higher scores on the PANSS-positive subscale and PANSS-general psychopathology subscale were significantly associated with more difficulty in both sexual arousal and orgasm (p's<0.05). For both males and females, there were no significant relationships between any CSFQ subscale measures and the quality of life measures (p's>0.05). No significant differences were found among three antipsychotic treatment groups (clozapine, olanzapine or typical agents) on any CSFQ subscale measures or quality of life measures after controlling for PANSS total scores (p's>0.05). CONCLUSIONS: Effective treatment strategies still need to be developed to address sexual dysfunction and quality of life in patients with schizophrenia

It has been hypothesized that impaired task-switching underlies some of the behavioural deficits in schizophrenia. However, task-switching involves many cognitive operations. In this study our goal was to isolate the effects on latency and accuracy that can be attributed to specific task-switch processes, by studying the inter-trial effects in blocks of randomly mixed prosaccades and antisaccades. By varying the preparatory interval between an instructional cue and the target, we assessed the costs of both (1) an active reconfiguration process that was triggered by the cue, and (2) passive carry-over effects persisting from the prior trial. We tested 15 schizophrenic subjects and 14 matched controls. A very short preparatory interval increased error rates and saccadic latencies in both groups, but more so in schizophrenia, suggesting difficulty in rapidly activating saccadic goals. However, the contrast between repeated and switched trials showed that the costs of task switching in schizophrenia were not significantly different from the controls, at either short or long preparatory intervals, for both antisaccades and prosaccades. These results confirm prior observations that passive carry-over effects are normal in schizophrenia, and show that active reconfiguration is also normal in this disorder. Thus problems with executive control in schizophrenia may not affect specific task-switching operations

OBJECTIVE: We conducted a retrospective epidemiologic study assessing the incidence of new-onset diabetes mellitus presenting as diabetic ketoacidosis in patients with schizophrenic disorders (ICD-9 295.0-295.9; referred to as 'schizophrenia patients' hereafter) treated with atypical antipsychotic agents. METHOD: The identification of patients and the review of records were achieved by using an electronic database linking administrative and clinical laboratory data between January 1, 1995, and December 31, 2001. The main outcome measure was the incidence of diabetic ketoacidosis or hyperosmolar hyperglycemic syndrome per 10,000 patient years in patients with new-onset or existing diabetes mellitus. We also determined the incidence of diabetic ketoacidosis associated with the use of atypical antipsychotics and calculated the mean hemoglobin A1c (HbA1c) level for all patients. RESULTS: During the 7-year period, 18.4% of schizophrenia patients were diagnosed with diabetes mellitus, compared with 6.6% in the general hospital population (p < .001). After chart review, 23 schizophrenia patients were identified with diabetic ketoacidosis: 11 had diabetes presenting as diabetic ketoacidosis, 8 had diabetic ketoacidosis with known diabetes mellitus, 2 had new-onset diabetes mellitus-hyperosmolar hyperglycemic syndrome, and 2 had hyperosmolar hyperglycemic syndrome with known diabetes mellitus. The incidence of diabetes presenting as diabetic ketoacidosis in schizophrenia patients was more than 10-fold higher than that reported in the general population: 14.93 per 10,000 patient years in schizophrenia patients versus 1.4 per 10,000 patient years in the general population (p < .000001) and versus the 1.98 per 10,000 patient years in the general hospital population (p < .000001). The incidence of diabetic ketoacidosis for each of atypical antipsychotic drugs over the 7-year period was as follows: clozapine, 2.2%; olanzapine, 0.8%; and risperidone, 0.2% (no incidence with ziprasidone or quetiapine). Of the 11 patients with diabetes presenting as diabetic ketoacidosis, the mean HbA1c level at admission was 13.3% +/- 1.9% (10.4%-16.9%). CONCLUSIONS: The incidence of diabetes mellitus presenting as diabetic ketoacidosis in schizophrenia patients is higher than in the general hospital population and differs across atypical antipsychotic agents. Elevated HgbA1c levels observed suggests that patients had undiagnosed diabetes mellitus for at least several weeks before the diabetic ketoacidosis episode

BACKGROUND: The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been associated with both overall schizophrenia risk and severity of negative symptoms. This study examined whether schizophrenia patients homozygous for the risk allele (T/T) exhibit greater impairment in executive function, and determined the extent to which MTHFR's effects on negative symptoms underlie this relationship. METHODS: 200 outpatients with chronic schizophrenia were evaluated with the Verbal Fluency Test (VFT), Wisconsin Card Sort Test (WCST), and California Verbal Learning Test (CVLT). Performance was stratified by MTHFR C667T genotype. Path analysis determined the extent to which MTHFR effects on negative symptoms mediated the relationship between genotype and cognitive measures. RESULTS: T/T subjects exhibited significantly greater deficits on the VFT and had more difficulty achieving the first category on the WCST. Genotype groups did not differ in CVLT performance. C677T effects on negative symptoms contributed to, but did not fully account for, genotype effects on VFT. Negative symptoms did not mediate WCST performance. CONCLUSIONS: MTHFR C677T genotype contributes to certain executive function deficits in schizophrenia. These deficits remained significant when taking into account mediating effects of negative symptoms. Although the intermediate mechanisms for C677T effects remain uncertain, these results suggest that MTHFR-related cognitive impairment and negative symptoms reflect differing neural substrates

RATIONALE: Risperidone augmentation of clozapine in refractory schizophrenia has theoretical but only inconsistent support from clinical trials. OBJECTIVES: To examine if adding risperidone to stable yet symptomatic schizophrenia outpatients on optimized clozapine monotherapy improves psychopathology. METHODS: We conducted a double-blind placebo-controlled parallel-group trial of a fixed dose of 4 mg/day risperidone added for 6 weeks in 24 outpatients with schizophrenia. RESULTS: Subjects who received risperidone showed a non-significant decrease in PANSS total score. The PANSS disorganized thought subscale improved significantly (beta=-3.3079, p=0.047). CONCLUSIONS: Our trial does not support the routine addition of risperidone to clozapine in refractory schizophrenia patients. However, much larger trials are needed to conclusively settle the question of added efficacy from this combination

Catatonia may be monosymptomatic at presentation, with stupor or coma as the cardinal and only manifestation. A case of catatonic coma with profound bradycardia is presented to help clinicians recognize this entity and include catatonia in the differential diagnosis of coma as a rare etiology after other more common causes of coma have been excluded. Cases of catatonic coma are nevertheless important to identify because treatment with intravenous benzodiazepines is simple and highly effective. The authors argue that the descriptive term 'catatonic coma' is preferable over terms implying psychogenesis, such as 'psychogenic' or 'hysterical' coma; for catatonia, the authors have a specific treatment, in the form of benzodiazepines; for 'psychogenesis,' there is none

The present study examined the hypothesis that elevated serum levels of C-reactive protein (CRP) would be associated with more severe clinical symptoms in patients with schizophrenia. Twenty-six inpatients with schizophrenia or schizoaffective disorder were enrolled. Serum levels of CRP were measured, and each patient was assessed with the Positive and Negative Syndrome Scale (PANSS). Subjects with CRP levels above the normal range (CRP>0.50 mg/dl, elevated CRP group, N=5) scored significantly higher than those with CRP levels in the normal range (CRP<or=0.50 mg/dl, normal CRP group, N=21) on the PANSS total score, negative symptom subscale score and general psychopathology subscale score. There was no significant difference between the two groups on the PANSS positive symptom subscale score. An inflammatory process, as reflected by elevated serum levels of CRP, might be associated with more severe psychopathology in a subgroup of patients with schizophrenia

OBJECTIVE: We studied a sample of schizophrenia out-patients to test the hypotheses that serum homocysteine concentrations would correlate positively with measures of glucose metabolism. METHOD: Subjects underwent a nutritional assessment and fasting plasma, serum insulin and homocysteine tests. RESULTS: Males had a significantly higher homocysteine levels than females (7.69 +/- 1.42 microM vs. 6.63 +/- 1.40 microM; P = 0.02). Comparing subjects with normal fasting glucose (NFG) (glucose < 100 mg/dl) and impaired fasting glucose (IFG) (> or = 100 mg/dl) subjects with IFG (mean 8.2 +/- 1.5 microM) had significantly higher homocysteine levels than those with NFG (mean 7.2 +/- 1.4 microM, P = 0.03). IFG was also associated with greater mean values for a Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) (P = 0.002) and diastolic blood pressure (P = 0.045). CONCLUSION: The group with IFG had higher fasting serum homocysteine concentrations than those with NFG which supports a connection to an important cardiovascular risk factor.