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M Waldo

Publications and source records attributed to M Waldo.

35 records · Page 2Linked to original sources
PubMed1992

Auditory sensory gating and catecholamine metabolism in schizophrenic and normal subjects.

Diminished neuronal response to repeated sensory input is a sensory-gating phenomenon that has been found to be deficient in schizophrenic patients. For example, schizophrenic patients fail to decrease the amplitude of the P50 wave of the auditory evoked potential to the second of paired click stimuli. In some studies, however, normal subjects have also failed to decrease their P50 responses. The aim of this study was to determine if accommodation to the recording situation over time would affect the gating of the P50 response. The gating of the P50 wave is measured as the ratio of the amplitude of the second response to the amplitude of the first. Three successive auditory evoked potentials were compiled, each from trains of 32 pairs of stimuli. Twelve normal subjects and 12 schizophrenic patients were studied. Unconjugated catecholamine metabolites were measured from venous samples drawn before and after the electrophysiological recording. Between the first and third trials, the normal subjects significantly increased their gating of P50. This increase in gating of P50 was related to decreased levels of the noradrenergic metabolite 3-methoxy-4-hydroxyphenylglycol. No similar phenomenon was observed in the schizophrenic patients, a number of whom had a further decrease in P50 gating over the three trials. Transient failure to observe gating of P50 in normal subjects may be related to increased state-dependent noradrenergic activity, which is known to disrupt sensory gating. This mechanism does not seem to account for the more persistent failure of sensory gating in schizophrenia.

Acoustic Stimulation↗
PubMed1990

Sensory gating deficits in psychiatric inpatients: relation to catecholamine metabolites in different diagnostic groups.

Acutely ill psychiatric inpatients were examined for a deficit in sensory gating, measured as failure to suppress the P50 wave of the auditory-evoked response to the second of paired stimuli. Previously, we had found that in mania, this sensory gating deficit is correlated with increased plasma-free levels of the noradrenergic metabolite 3-methoxy, 4-hydroxyphenylglycol (pMHPG), whereas in schizophrenia, there is no correlation with catecholamine metabolism. To assess the generalizability of these findings, we examined inpatients with a broader range of diagnoses, including those with multiple DSM III-R Axis I, II, and III diagnoses. The patients were grouped into three diagnostic spectra for analysis: schizophrenic, manic, and depressive. In the schizophrenic patients, there was no relationship between pMHPG or other catecholamine metabolites and the sensory gating deficit. In manic patients, however, a positive correlation between pMHPG level and the sensory gating deficit was again observed. This relationship did not extend to the depressive patients, who uniquely showed sensory gating deficits that correlated negatively with the severity of their illness. The data suggest that sensory gating deficits are common to these three diagnostic spectra, but the deficits in each group have different relationships to catecholamine metabolism and symptom severity that may reflect differences in the underlying neuronal pathophysiology of these illnesses.

Adult↗
PubMed1989

Unconjugated methoxylated catecholamine metabolites in human saliva. Quantitation methodology and comparison with plasma levels.

A newly developed method for the simultaneous extraction and quantitation of the unconjugated levels of the catecholamine metabolites vanilmandelic acid (VMA), 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and homovanillic acid (HVA) in plasma by high performance liquid chromatography with electrochemical detection was modified and applied to studies of human saliva. The assay had a mean coefficient of variation under 3% for each of the metabolites. Levels of plasma VMA, MHPG and HVA were measured in 28 normal subjects and compared to their saliva levels, obtained before and after stimulation by mastication. Significant correlations were found between plasma and saliva MHPG and HVA, but there was no correlation between plasma and saliva VMA. Salivary MHPG and HVA can be reproducibly assayed and may be useful tools for indications of changes in central and peripheral catecholamine metabolism.

Catecholamines↗
PubMed1988

Reproducibility of the measurement of plasma noradrenergic and dopaminergic metabolites in normal subjects.

The object of this study was to determine the reproducibility of the measurement of plasma catecholamine metabolites in normal control subjects and to assess the influence of factors such as time of day, diet, activity, blood pressure, and mood on the variance of these measures. Plasma free homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and vanillylmandelic acid (VMA) were simultaneously measured by high performance liquid chromatography with electrochemical detection. Samples were collected from 15 doctors and nurses at 8 a.m. and at noon on 2 separate days. After the fasting 8 a.m. sample, the subjects ate a regular hospital breakfast. Activity in their usual tasks on an inpatient psychiatric unit was monitored electronically by an activity meter. Levels of each metabolite were not significantly different between days at the respective assay times and were highly correlated for individuals. MHPG showed a significant increase from morning to noon, while HVA showed a significant decrease. Activity, dietary intake of tyrosine and tyramine, blood pressure, pulse, scores on the Profile of Mood States, age, and sex were not related to plasma levels. The results demonstrate that measures of dopamine and norepinephrine metabolites have significant reliability in normal subjects in a setting used for research studies with psychiatric patients.

Adult↗
PubMed1987

Neurophysiological assessment of sensory gating in psychiatric inpatients: comparison between schizophrenia and other diagnoses.

Gating of auditory sensory responsiveness was examined in 75 psychiatric inpatients using a conditioning-testing paradigm with the P50 wave of the auditory evoked response, in which pairs of stimuli are presented to the subject. In previous studies, most schizophrenics did not decrement the second response to the extent seen in normals. Acutely ill patients, who were representative of patients admitted to a public university teaching service and a proprietary hospital, were used to examine the extent to which diminished sensory gating is found in diagnoses other than schizophrenia. About half of these patients showed diminished sensory gating that correlated with measures of severity of illness. The data, taken together with that from other studies using this paradigm, suggest that diminished sensory gating, like several other psychophysiological abnormalities, is a trait deficit in schizophrenia, but a state deficit in many other mental illnesses.

Adjustment Disorders↗
PubMed1987

Neurobiological studies of sensory gating in schizophrenia.

The sensory disturbance in schizophrenia is often described as an inability to filter out extraneous noise from meaningful sensory inputs. The neurobiological basis of this inability to filter has been examined using auditory evoked potentials, which are computerized averages of the brain's electrical response to sound. The sounds are presented in pairs to test the ability of the brain to inhibit, or gate, its response to a repeated stimulus. Schizophrenic patients lack the ability to gate the neuronal response shown by a particular wave, the P50 wave. The measurement of this deficit in human subjects and the exploration of its neurobiology in animals has produced evidence about several issues in the pathophysiology of schizophrenia: (1) the role of dopamine in improvement of sensory function in schizophrenic patients treated with neuroleptic drugs, (2) the interaction between familial or genetic deficits in sensory functioning in schizophrenic patients and possible abnormalities in dopamine metabolism, and (3) a mechanism by which noradrenergic hyperactivity in mania and other psychiatric illnesses might mimic some pathophysiological deficits in schizophrenia.

Antipsychotic Agents↗
PubMed1985

Long-term amitriptyline in chronic depression.

Medication was discontinued under a placebo-controlled, double-blind, six-month protocol with 17 chronically depressed patients who had been taking an average daily dose of 138 mg amitriptyline (AMI) for an average of 3.7 years. Only one of nine patients became depressed on active medication, while of the 15 patients receiving a placebo trial, 11 had a depressive recurrence at an average time of 9.3 weeks. These 11 were subsequently restarted on AMI, and responded similarly to the way in which acutely depressed patients respond, although the patients showed either a need for less AMI or decreased symptoms, compared to entry. Tolerance did not develop to anticholinergic side-effects during long-term medication. Twelve of the 15 patients on placebo showed a withdrawal reaction during the first few weeks of tapered AMI discontinuation which could be distinguished from recurrence of depression. This study suggests that the majority of patients on long-term antidepressant will suffer a recurrence of depressive symptoms when the medication is discontinued.

Amitriptyline↗
PubMed1984

Deficits in sensory gating in schizophrenic patients and their relatives. Evidence obtained with auditory evoked responses.

A deficit in inhibitory gating of auditory evoked responses was examined in 15 schizophrenic patients, their first-degree relatives, and normal subjects, using a conditioning-testing paradigm with the P50 wave of the auditory evoked response. This paradigm demonstrates inhibition by presenting paired stimuli to the subject; the P50 wave evoked by the second stimulus is reduced because of inhibitory mechanisms activated during the response to the first stimulus. In normal subjects, the mean amplitude of the second P50 response was reduced to less than 20%. In the schizophrenics, the mean amplitude of the second response was more than 85% of the first, a result that replicates our previous finding of a deficit in inhibition in schizophrenia. Approximately half the first-degree relatives, generally including at least one parent, had a similar deficit. Presence of this deficit in the parents was associated with a family history of schizophrenia. Family members with this deficit also had significantly higher scores on several scales of the Minnesota Multiphasic Personality Inventory than did family members without the deficit. Despite the deficit in inhibition, other characteristics of the P50 wave were normal in the relatives, in contrast to unmedicated schizophrenics, who showed additional abnormalities in wave latency and amplitude.

Acoustic Stimulation↗
PubMed1984

Vocational adjustment patterns of alcohol and drug misusers following treatment.

Vocational adjustment following treatment was studied in 77 men patients (39 alcohol and 38 drug misusers) of a residential treatment program for substance misuse. Significantly more patients were employed at discharge from treatment, and at 1, 3 and 6 months postdischarge than at 1 month pretreatment. Patients employed at discharge experienced a significant decrease in employment level at 1, 3 and 6 months postdischarge. Patients who participated in outpatient treatment following discharge had significantly higher levels of employment at 3 months following discharge. Since there is a significant general decrease in employment level during the first 3 months postdischarge, it is suggested that counselors be aware of this as a vocational crisis period. The third through sixth months postdischarge are more stable. The first 3 months are especially important for younger drug misusers with legal problems. Alcoholics may sometimes need added incentive from vocational counselors because they tend to have fewer legal problems than drug misusers and therefore less outside pressure to gain employment.

Adaptation, Psychological↗
PubMedDate not supplied

Genetic influences on the effects of alcohol on auditory evoked potentials.

Effects of alcohol on auditory evoked potentials were examined in 77 subjects without a history of alcohol abuse. Subjects were monozygotic twins, dizygotic twins, siblings, and adoptees, all same-sexed and reared together. Alcohol was administered to achieve 0.1 g/dl blood levels. Ten additional control subjects received placebo doses. The amplitude of the P50 wave of the auditory evoked response was reproducibly diminished in alcohol-treated subjects compared to controls. Evoked potentials were recorded in a conditioning-testing paradigm, which uses paired stimuli. The second or test response is decremented compared to the first or conditioning response. The paradigm thus examines gating of response to sensory stimulation. In addition to the alcohol-induced decrease of the P50 amplitude in the conditioning response already noted, the ratio of the P50 test response amplitude to the conditioning response amplitude increased after alcohol. This change, reflective of decreased sensory gating, was variable between subjects, but showed high test-retest reliability. These effects of alcohol on P50 amplitude and its decrement in the conditioning-testing paradigm were used to examine possible genetic influences on sensitivity to alcohol. The latter parameter showed significantly higher correlations in monozygotic twins than in siblings or adoptees; dizygotic twins had intermediate values. The results suggest that alcohol's effects on suppression of P50 in the conditioning-testing paradigm may be genetically influenced.

Adoption↗
PubMedDate not supplied

Elementary neuronal dysfunctions in schizophrenia.

This paper describes an elementary deficit in sensory processing in people with schizophrenia. If paired sounds are presented to normal subjects, the response to the first sound, as measured by the P50 wave of the auditory-evoked potential, is much greater than the response to the second sound. The diminished response to the second sound is an example of a sensory gating mechanism that enables people to regulate their vigilance so that they can either detect all sounds in the environment or ignore most of them, in favor of narrowing the focus of their concentration. In schizophrenia, this mechanism is usually deficient; patients are in a state of hypervigilance and have diminished abilities to focus their attention. The deficiency appears to be genetically determined and to involve the brainstem control of sensory input to the hippocampus. Such sensory gating deficits may underlie more complex psychotic symptoms, such as hallucinations and delusions. Further studies of their neurobiology could lead to increased understanding of the pathophysiology of schizophrenia.

Arousal↗
PubMedDate not supplied

Linkage analysis of schizophrenia: the D1 dopamine receptor gene and several flanking DNA markers.

Alterations in dopaminergic activity may play an important role in the pathogenesis of schizophrenia. The central effects of dopamine are mediated by at least five G protein-coupled receptors, D1, D2, D3, D4 and D5. The D1 receptor maps to 5q35.1 and it identifies an Eco RI as well as a Taq I RFLP. In the present study we undertook a linkage analysis between the D1 receptor RFLPs and schizophrenia in 9 multigenerational families in which segregation of disease was consistent with autosomal dominant inheritance and reduced penetrance. Several flanking DNA markers were also analyzed as the D1 receptor RFLPs were relatively uninformative in our families. Pairwise analyses of schizophrenia and several flanking markers indicate that inheritability of this region is unlikely to be involved in the pathogenesis of schizophrenia in the 9 families studied.

Chromosome Mapping↗
PubMedDate not supplied

Human dopamine transporter gene not linked to schizophrenia in multigenerational pedigrees.

A large body of data suggests that perturbations in brain dopaminergic transmission play a role in the pathogenesis of schizophrenia. Recently, the gene for the human dopamine transporter has been cloned and polymorphisms have been identified. Because mutations of the dopamine transporter gene might underlie the cause of schizophrenia in a subset of families, we undertook a linkage analysis between schizophrenia in 9 families and a dopamine transporter gene polymorphism. Evidence of linkage was not found in most families assuming autosomal dominant or recessive inheritance.

Carrier Proteins↗