Dane Wingerson

The MOS 36-Item Short Form Health Survey: reliability, validity, and preliminary findings in schizophrenic outpatients.

OBJECTIVES The authors test the reliability and validity of the Medical Outcomes Study Short Form 36-Item Health Survey (SF-36) as a written, self-administered survey in outpatients with chronic schizophrenia. METHODS Thirty-six schizophrenic outpatients completed a written and oral form of the SF-36. A psychiatrist rated the patients using the Brief Psychiatric Rating Scale to determine severity of psychopathology. Cognitive functioning and academic achievement were also assessed. Internal consistency, test-retest reliability, concurrent and discriminative validity of the oral and written versions were determined. RESULTS The SF-36 in both forms was shown to have good internal consistency, stability, and concurrent validity. The mental health SF-36 subscales had poor discriminant validity, compared with the physical functioning scale that demonstrated good discriminant validity. CONCLUSIONS The validity of using the written form of the SF-36 on a sample of patients with chronic mental illness was demonstrated. The SF-36 appears to be an appropriate outcome measure for changes in physical and role functioning in consumers of outpatient mental health programs.

Relationships between Neuropsychological and Oculomotor Measures in Schizophrenia Patients and Normal Controls

Establishing the relationship between oculomotor and neuropsychological impairments might facilitate a more coherent description of schizophrenia-associated neurocognitive deficits. Therefore, we assessed several aspects of neuropsychological and oculomotor function in 25 medicated schizophrenia patients and 24 age-matched controls. Neuropsychological tasks included the Wisconsin Cart Sort Test (WCST), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test, and finger tapping speed. Oculomotor functions assessed included smooth pursuit, initiation of smooth pursuit, predictive pursuit, fixation, visually guided saccades, remembered saccades, and antisaccades. Among the schizophrenia patients, predictive pursuit performance correlated significantly with finger tapping (dominant hand), TMT (both parts), and one WCST measure (categories completed). The only other significant correlation among the schizophrenia patients was between antisaccade performance and part A of the TMT. Perseverative errors during the WCST and antisaccade performance were the only measures significantly correlated among the normals. Closely related neurocognitive deficits may be responsible for impairments in TMT, WCST, predictive pursuit, and antisaccade performance in schizophrenia.

Personality traits and early discontinuation from clinical trials in anxious patients.

Patients who discontinue early from clinical trials frequently give ambiguous or no reasons for leaving the study. Using Clonigers Tridimensional Personality Questionnaire, we examined the potential role of personality traits in early discontinuation in patients with panic disorder and generalized anxiety disorder. Early dropouts and completers were comparable at baseline on demographic and clinical variables but differed significantly on the Tridimensional Personality Questionnaire. For panic disorder and generalized anxiety disorder patients combined, early dropouts scored higher on total novelty seeking, as well as on the novelty-seeking traits of both disorderliness/dislike of regimentation and impulsiveness. There was no significant interaction between dropout status and diagnosis for this finding, indicating it applied equally to both groups. This study suggests that personality traits involving novelty seeking may contribute to early discontinuation from clinical trials, independent of side effects, lack of efficacy, or at baseline, significantly worse symptoms of anxiety.

Assertive Community Treatment for Patients with Chronic and Severe Mental Illness Who Abuse Drugs

The Assertive Community Treatment model of mental health service delivery has been extensively studied and has undergone various modifications over the past twenty years. This article describes a modified ACT Team approach to the treatment of individuals who suffer from severe comorbid mental illness and substance abuse. Demographics of patients who are chosen to receive these intensive services, service utilization patterns, and elements of team treatment are discussed. Comparisons with less severely ill dual diagnosis patients who receive more traditional case management services are reviewed.

Effect of benzodiazepines on plasma levels of homovanillic acid in anxious patients and control subjects

The effects of four logarithmically increasing doses of intravenous diazepam or placebo on plasma homovanillic acid (HVA) were determined in benzodiazepine-naive patients with panic disorder (PD) or generalized anxiety disorder (GAD), and in healthy controls. Plasma HVA was measured at baseline and 3 min after the first and fourth doses of diazepam/placebo. Mean baseline plasma HVA levels were significantly lower in PD patients compared with GAD patients and controls. Although plasma HVA levels decreased significantly with time in all groups, there was no diazepam effect. This study suggests that low dopaminergic activity may occur in a subset of anxious patients (PD), and that diazepam does not significantly affect dopaminergic activity as measured by plasma HVA in humans.

Oral physostigmine in alzheimer's disease: Effects on norepinephrine and vasopressin in cerebrospinal fluid and plasma

Physostigmine is a cholinesterase inhibitor which enhances central and peripheral cholinergic activity. In this study, we explored in persons with Alzheimers disease (AD) the effects of an acute dose of physostigmine in patients receiving chronic physostigmine treatment on the activity of the cholinergically regulated noradrenergic and arginine vasopressin (AVP) systems. Specifically, we estimated the effects of sustained release oral physostigmine on central and peripheral noradrenergic and AVP systems by measuring norepinephrine (NE) and AVP in cerebrospinal fluid (CSF) and plasma. Lumbar punctures were performed in both physostigmine and no drug treatment conditions. In some subjects the effects of physostigmine on the plasma AVP response to the osmolar stimulus of a hypertonic saline infusion also were measured. NE concentrations in both CSF and plasma were significantly lower in the physostigmine than in the no drug condition. AVP concentrations did not differ between conditions in either compartment, nor did physostigmine affect the AVP response to hypertonic saline. Physostigmine appears to decrease both central and peripheral noradrenergic activity in AD.

Lack of cholinergic regulation of vasopressin and norepinephrine responses to hypertonic saline in humans

In vitro studies in hypothalamic-pituitary explants in the rat have suggested cholinergic mediation of arginine vasopressin (AVP) osmoregulation. In this study we attempted to demonstrate, in humans, cholinergic mediation of AVP osmoregulation. Specifically, we tested the hypothesis that the plasma AVP response to an osmolar stimulus would be attenuated by pharmacologic blockade of central nervous system muscarinic or nicotinic receptors in humans. We also evaluated the effects of cholinergic blockade on the norepinephrine (NE) response to an osmolar stimulus. Young normal males underwent hypertonic saline infusion following administration of the centrally active muscarinic antagonist scopolamine or the centrally active nicotinic antagonist mecamylamine. Neither mecamylamine nor scopolamine affected the AVP response to hypertonic saline infusion. Mecamylamine reduced NE concentrations in a dose-dependent manner, but did not affect the slope of the NE increase during hypertonic saline infusion. In a second experiment, we evaluated the effects of scopolamine and mecamylamine on the AVP and NE responses to physostigmine, a cholinesterase inhibitor which stimulates AVP release into plasma through a non-osmolar central nervous system cholinergic mechanism. Scopolamine eliminated the AVP response to physostigmine. Mecamylamine reduced NE concentrations both before and after scopolamine administration but did not affect the slope of the AVP response. These results fail to support cholinergic regulation of the AVP response to osmolar stimulation in humans.

Plasma arginine vasopressin response to hypertonic saline infusion in Alzheimer disease.

Summary In this study, we tested the hypothesis that the plasma arginine vasopressin (AVP) response to osmotic stimulation induced by hypertonic saline infusion is blunted in the early and middle stages of Alzheimer disease (AD). Because animal data support stimulatory cholinergic mediation of AVP osmoregulation at a brain level, the AVP response in AD might provide clinically useful information about the status of brain cholinergic systems. Seventeen AD outpatients and eight normal older subjects underwent both a 90-min hypertonic saline infusion and a 90-min control (normal saline) infusion. Substantial increases in plasma osmolality during hypertonic saline infusion were accompanied by substantial and linear increases in plasma AVP in both groups. However, there were no significant differences in AVP responses between AD and normal older subjects. These results do not support the utility of plasma AVP response to hypertonic saline in the assessment of brain cholinergic status in AD.