Faculty Bibliography

The goal of this study was to investigate the characteristics of schizophrenic patients with a history of childhood attention deficit hyperactivity disorder (ADHD). The study was performed on 37 adolescent patients meeting the DSM-III-R criteria for schizophrenia and ADHD and 40 controls with schizophrenia only. Schizophrenic patients who were diagnosed in childhood as suffering from ADHD had more prominent developmental disturbances in infancy, more insidious course of schizophrenia, failed to respond to neuroleptics and had poorer outcome as compared to patients with schizophrenia only. The results of this study indicate that schizophrenia subsequent to childhood ADHD has a poor prognosis as compared to schizophrenia only

Oral metachlorophenylpiperazine (m-CPP) as a direct-acting postsynaptic serotonergic agonist was used to study serotonergic dysfunction in treatment-refractory chronic schizophrenia based on the hypothesis that some patients may show central serotonergic hypersensitivity. Seventeen DSM-III-R chronic schizophrenic patients with a history of neuroleptic nonresponse underwent double-blind challenge with oral m-CPP (0.25 mg/kg body weight) and placebo after medication washout: m-CPP significantly elevated both prolactin and cortisol levels as compared to placebo. There was a significant relationship between change in cortisol level and change in psychopathology under m-CPP; a blunted cortisol response was associated with a decrease in total psychopathology, while an increase in cortisol response related to an increase in psychopathology. Similarly, decrease in severity of the activation factor and the hostility factor was associated with a smaller cortisol response in the m-CPP condition. These results point to heterogeneity in central serotonergic sensitivity within the context of different subpopulations of serotonergic receptors

Data on extrapyramidal symptoms (EPS) from both arms of the North American multicenter comparative study of risperidone, placebo, and haloperidol were analyzed. The subjects were 523 patients with chronic schizophrenia who, after a 1-week washout period, received placebo, risperidone (2, 6, 10, or 16 mg/day), or haloperidol (20 mg/day) for 8 weeks; the trial was completed by 253 patients. Severity of EPS was assessed by means of the Extrapyramidal Symptom Rating Scale (ESRS). Mean changes (increases) in ESRS scores from baseline to worst score were significantly lower in each risperidone group than the haloperidol group on the total ESRS (parkinsonism + dystonia + dyskinesia), total parkinsonism, hypokinetic symptoms, and on the questionnaire (p < 0.001). On several of the subscales (dyskinesia, buccolinguomasticatory, and Clinical Global Impression severity of dyskinesia), mean change scores were significantly lower in some of the risperidone groups than in the placebo group (p < 0.05). At the clinically most effective risperidone dose (6 mg/day), the mean ESRS change score was not significantly different from that of the placebo group. A significant linear relationship was noted between mean change scores and increasing risperidone dose on 4 of the 12 ESRS subscales; nevertheless, even at 16 mg/day of risperidone, mean change scores were lower than in the haloperidol group. A linear relationship between increasing risperidone dose and use of antiparkinsonian medications was also apparent. Acute dystonic reactions occurred both in patients receiving risperidone and haloperidol. Patients with severe baseline EPS were at higher risk of EPS during the study than patients with low or moderate baseline EPS. It is concluded that low doses of risperidone cause few or no EPS and recommendations for initiation of risperidone treatment are made

The authors investigated the syndromal and cognitive profiles of 25 DSM-III-R older schizophrenic inpatients with continuous acute psychotic symptoms and compared them with 20 younger schizophrenic patients by means of a multidimensional assessment battery. Subjects were medically well and without neurological comorbidity and were comparable in length of current hospitalization and medication regimens. There were no significant differences between the two groups on various symptom rating scores or on neurological variables. The older group's mean scores for various cognitive measures did not reach the value for senile dementia. They also scored significantly better on a memory test and on formal cognitive functions. These findings support the notion of a stable encephalopathy, rather than a dementia-like process, underlying the course of the illness. Authors discussed limitations and implications of these findings

The Positive and Negative Syndrome Scale (PANSS) is widely used as a method for the assessment of symptoms of schizophrenia but the most complete model of how symptoms are structured has not been determined. Using the methods of confirmatory factor analysis with a large sample of 1,233 of schizophrenic subjects this study examined the goodness of fit of 20 previously proposed models. None of these proposed models met criteria for adequate fit to the empirical data. The sample was then stratified and half of the data was used to calibrate a new model. The model was validated in the second half of the data. The new pentagonal model uses 25 of the 30 items of the PANSS in 5 factors: positive, negative, dysphoric mood, activation, and and autistic preoccupation. Patients who varied widely in age, severity, and chronicity of illness did not differ in their overall symptom structure. The results of this study also implicated some problems in the validity of the PANSS as currently configured when used to assess symptoms of schizophrenia

Reviews 12 studies (1976-1996) on the relationship between clozapine plasma levels and clinical response in patients with treatment-resistant schizophrenia according to methodologic criteria described in the article. The range of clozapine plasma levels appears to be wide e.g., ranging from 200 ng/mL to 450 ng/mL. The target plasma level for the vast majority of patients might be around 250 ng/mL, while higher plasma levels would be accompanied by increasing sedation and other side effects. This finding may mean clinically that patients who have not responded at a plasma level of 250 ng/mL after 6 wks of treatment should be raised to above 420 ng/mL. This strategy will result in increased responsiveness of some patients. Variability in the ratio of plasma level per dose has been great from study to study. The range of oral doses used, which yielded plasma levels associated with clinical response was between 250 mg and 650 mg. This range may represent an estimated optimal mean dose for a vast majority of patients at 6 wks, but individual patient variables need to be considered in determining the final dose.