Faculty Bibliography

BACKGROUND: Neurocognitive deficits are recognized as a cardinal feature of schizophrenia, but the determinants of these deficits remain unknown. Recent reports have suggested that a functional polymorphism, Val(158)Met in exon III of the catechol-O-methyltransferase gene, shares approximately 4% variance with performance on the Wisconsin Card Sorting Test. These findings led to suggestions that the catechol-O-methyltransferase polymorphism may exert its effects by modulating prefrontal dopamine function, but few other neurocognitive measures have been examined, leaving open questions about phenotypic specificity. METHODS: We examined the effects of the catechol-O-methyltransferase Val(158)Met polymorphism in 58 individuals with chronic schizophrenia who completed a battery of 15 neurocognitive tests, which were reduced to four reliable neurocognitive domain scores. We examined the effects of genotype on these four domains and on global neurocognitive ability. RESULTS: The Met allele was associated with better performance in the Processing Speed and Attention domain, but not with other domain scores measuring executive and visuoperceptual functions, declarative verbal learning and memory, simple motor ability, or global neurocognitive function. Genotype shared approximately 11% of variance with Processing Speed and Attention scores, and approximately 2% of variance with Wisconsin Card Sorting Test scores. CONCLUSIONS: The findings provide independent support for the hypothesis that the catechol-O-methyltransferase Val(158)Met polymorphism influences neurocognitive function in schizophrenia, and suggest that the functional effects may be expressed on measures of Processing Speed and Attention. This information may prompt reconsideration of the 'prefrontal dopamine' hypothesis and invites examination of a broader range of effects in efforts to refine the neurocognitive phenotype that is most relevant to variation in catechol-O-methyltransferase expression

OBJECTIVE: Newer antipsychotic drugs have shown promise in ameliorating neurocognitive deficits in patients with schizophrenia, but few studies have compared newer antipsychotic drugs with both clozapine and conventional agents, particularly in patients who have had suboptimal response to prior treatments. METHOD: The authors examined the effects of clozapine, olanzapine, risperidone, and haloperidol on 16 measures of neurocognitive functioning in a double-blind, 14-week trial involving 101 patients. A global score was computed along with scores in four neurocognitive domains: memory, attention, motor function, and general executive and perceptual organization. RESULTS: Global neurocognitive function improved with olanzapine and risperidone treatment, and these improvements were superior to those seen with haloperidol. Patients treated with olanzapine exhibited improvement in the general and attention domains but not more than that observed with other treatments. Patients treated with risperidone exhibited improvement in memory that was superior to that of both clozapine and haloperidol. Clozapine yielded improvement in motor function but not more than in other groups. Average effect sizes for change were in the small to medium range. More than half of the patients treated with olanzapine and risperidone experienced 'clinically significant' improvement (changes in score of at least one-half standard deviation relative to baseline). These findings did not appear to be mediated by changes in symptoms, side effects, or blood levels of medications. CONCLUSIONS: Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs, and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects

The goals of this study were to examine the relationship between community violence and inpatient assaults and to identify neurological and neuropsychological deficits underlying violent behavior. Thirty-three inpatients with a history of community violence were compared with 69 patients who did not have such a history. Inpatient assaults were recorded for 4 weeks; a neurological/neuropsychological battery was then administered. Patients without community violence were more likely to show transient or no violence while in the hospital. Patients with community violence performed more poorly on the Wisconsin Card Sorting Test and on psychomotor tasks, impairments that are consistent with frontal lobe dysfunction. Inpatient assaults were not associated with these neuropsychological impairments. They were related, however, to impairment on frontal motor programming tasks and a history of community violence

CSF levels of 5-hydroxyindolacetic acid (5-HIAA), the serotonin metabolite, were assayed in 10 violent and 10 matched nonviolent patients with schizophrenia. Mean group levels of 5-HIAA in cerebrospinal fluid were found to be nearly identical. Possible explanations, including effects of medications, are discussed

Antidepressants or stimulants are commonly used to treat attention deficit disorder (ADD). We report the results of an open-label trial of the recently marketed antidepressant venlafaxine in 16 adult patients with ADD. Patients were treated with venlafaxine (25 to 225 mg/day) for 8 weeks. Four patients discontinued treatment within the first week because of sedation, agitation, or nausea. In the remaining 12 patients, venlafaxine treatment decreased ADD ratings by almost half

OBJECTIVE: High doses of neuroleptic medication are still administered to many patients, although many studies have shown the effectiveness of low-dose strategies. The purposes of the study were to determine whether and in what ways high-dose patients differed from patients on regular dosages and whether the higher dosages were more effective. METHODS: In a case-control study at two large state hospitals, 38 high-dose patients were compared with 29 regular-dose patients. RESULTS: The high-dose patients had a persistent course of illness, with severe chronic symptoms resulting in hospitalizations of much longer duration than those of the regular-dose patients. The high-dose patients evidenced more regressed functioning and were more violent. To control these behaviors, clinicians increased neuroleptic dosages. CONCLUSIONS: The high-dose patients represented a subgroup of chronic regressed and violent patients. Clinicians prescribed high dosages and continued to use them despite a lack of clear evidence that such treatment is effective