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L E Adler

Publications and source records attributed to L E Adler.

At least 55 records · Page 3Linked to original sources
PubMed1993

Neurophysiological and neuropsychological evidence for attentional dysfunction in schizophrenia.

The behavior of the P50 wave of the auditory evoked potential in a paired stimulus or conditioning-testing paradigm has been used as a measure of sensory gating disturbance in schizophrenia. Schizophrenics fail to decrement the P50 response to the second stimulus of the pair, so that the ratio of the test to the conditioning amplitude is elevated over normal values. The aim of this study was to compare this neurophysiological measure to neuropsychological measures of attention and memory. As expected, schizophrenics performed worse than controls on most measures. The time to complete a digit cancellation test, a measure of sustained attention, was found to be particularly longer in schizophrenics than in control subjects. Furthermore, the increased time to complete this task correlated with the increased ratio of the amplitude of the test P50 response to the conditioning response in the schizophrenics. Thus, a neurophysiological defect in sensory gating may relate to a disorder in sustained attention in schizophrenia. Although the P50 wave may come from the hippocampus, neuropsychological measures of verbal learning and memory were not correlated with alterations in the P50 ratio.

Adult↗
PubMed1993

Normalization of auditory physiology by cigarette smoking in schizophrenic patients.

OBJECTIVE: Because many schizophrenic patients are heavy smokers, it has been suggested that nicotine normalizes some neuronal deficit involved in their illness. Schizophrenic subjects have various difficulties with maintenance of attention and selective processing of sensory information. One defect in sensory gating in schizophrenia has been characterized by recording auditory evoked potentials. Most normal subjects have a decrease in the evoked response to the second of two closely paired stimuli, whereas most schizophrenic subjects do not. The aim of this study was to determine whether smoking normalizes this deficit in auditory sensory gating in schizophrenia. METHOD: Changes in auditory sensory gating in response to smoking cigarettes were studied in 10 smokers without psychiatric illness and 10 schizophrenic smokers. Both groups were asked to abstain from smoking from 11:00 p.m. until 8:00 a.m. the next morning, when their auditory evoked responses to pairs of clicks were recorded. The ability to gate sensory information is reflected in a decrease in the P50 wave amplitude in response to the second of the two stimuli. After baseline recordings, the subjects smoked as much as they wished, and then two postsmoking recordings were performed. RESULTS: The schizophrenic patients had a marked but brief improvement in P50 auditory gating immediately after smoking, whereas P50 gating for the normal smokers was slightly impaired. CONCLUSIONS: This study suggests that cigarette smoking can transiently normalize the impairment of auditory sensory gating in schizophrenic patients.

Adult↗
PubMed1992

Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics.

Diminished gating of the P50 auditory evoked response to repeated stimuli is a psychophysiological feature of schizophrenia, that is also present in many relatives of patients. Animal models of auditory sensory gating indicate that nicotinic cholinergic neurotransmission is a critical neuronal substrate. The aim of this experiment was to determine if the deficit in sensory gating could be reversed by nicotine administration. Nonsmoking relatives of schizophrenics with abnormal sensory gating were selected as subjects for this initial double-blind trial, to avoid effects of psychotropic medications that might complicate trials in schizophrenic patients themselves. Nicotine-containing gum increased P50 sensory gating to near normal levels within 30 min of administration. The effect was transient; the gating of P50 returned to baseline levels within 1 hr. There was no change observed after placebo administration. In one of the subjects, the anticholinesterase inhibitor physostigmine similarly normalized P50 gating. The results are consistent with the hypothesis that nicotinic cholinergic neurotransmission may mediate a familial psychophysiological deficit in schizophrenia.

Adult↗
PubMed1992

Phencyclidine and auditory sensory gating in the hippocampus of the rat.

The psychotomimetic drug 1-(1-phenylcyclohexyl) piperidine (PCP, phencyclidine) was found to cause a deficit in the gating of the response of the hippocampal neuron to repeated auditory stimuli, which is similar to a particular physiological feature observed in human psychosis. Other drugs, with sigma agonist and/or N-methyl-D-aspartate (NMDA) antagonist effects, were administered and their ability to cause a loss of auditory gating was compared to that of PCP. The rank order of effectiveness was levoxodrol > PCP and (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801) > N-allylnormetazocine (SKF 10047) > dexoxodrol > 3-(+/-)2-carboxypiperazine-4-yl) propyl-1-phosphonate (CPP). Further studies of two of the drugs, PCP and MK-801, showed that selective lesioning of the noradrenergic input with the neurotoxin DSP4, as well as less selective depletion of monoamines with reserpine, blocked the loss of gating. Phencyclidine, and other drugs with the same spectrum of action, most likely disrupt gating by increasing noradrenergic activity through a sigma mechanism.

Acoustic Stimulation↗
PubMed1991

Codistribution of a sensory gating deficit and schizophrenia in multi-affected families.

Because the clinical diagnosis of schizophrenia has not generally been an adequate phenotypic marker to detect the genes that convey risk for schizophrenia, efforts have been directed toward the identification of more elementary neuronal dysfunctions in schizophrenic patients and their families. Psychophysiological studies of sensory gating and selective attention suggest that defects in these brain functions are present in schizophrenic patients and some of their relatives. This study examines one of these defects in sensory gating, failure to suppress the P50 evoked response to repeated auditory stimuli. Six pedigrees, chosen because of the presence of large sibships containing several cases of schizophrenia, were studied. A mathematical model was developed to assess the familial association of the P50 defect with schizophrenia. The model preserves the quantitative nature of the data and is suitable for use in a sample with small numbers of pedigrees comprising many individuals. It is thus suitable for the evaluation of putative phenotypes in families to be studied by linkage analysis with polymorphic genetic markers. The results suggest that the P50 defect is familially associated with schizophrenia.

Adult↗
PubMed1991

Counterpoint: a sensory gating--hippocampal model of schizophrenia.

We propose a model for schizophrenia that incorporates findings of impaired auditory sensory gating with a possible structural abnormality of the hippocampus. The deficit in auditory sensory gating would be a genetic schizotaxic factor, necessary in the development of schizophrenia but not sufficient by itself. Genetic or acquired hippocampal dysgenesis or frank damage in combination with the sensory gating deficit would be necessary to produce the full-blown syndrome. We review the relevant literature and reply to Dr. E. Fuller Torrey's hypothesis.

Attention↗
PubMed1991

Lithium carbonate and mood disorder in recently detoxified alcoholics: a double-blind, placebo-controlled pilot study.

The effects of lithium carbonate were assessed in a double-blind, placebo-controlled study of a small group of recently detoxified alcoholics. The patients were treated during their 2nd and 3rd week of abstinence. A previous study demonstrated the existence in these patients of a syndrome of mildly elevated psychomotor rate, including irritability, grandiosity, an increased need for social contact, loquaciousness, and sexual preoccupation. The intensity of this syndrome was significantly decreased by treatment with low dose lithium carbonate, with no effect of placebo treatment.

Adult↗
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↗
PubMed1990

Auditory sensory gating in hippocampal neurons: a model system in the rat.

Diminished evoked response to repeated auditory stimuli, an example of sensory gating normally present in human subjects, is often absent in schizophrenics. To examine the mechanism of the normal response and to delineate possible sites of its abnormality in psychosis, it would be desirable to reproduce the phenomenon in laboratory animals. In this study, we show that the pattern of diminished response to the second of paired auditory stimuli is found in activity recorded from the CA3 region of the hippocampus of anesthetized rats. The evoked potential recorded from this area is predominantly an N40 wave, at identical latency to the prominent negative wave recorded from the skull surface of unanesthetized rats. Similar responses were not found in other areas, including the auditory neocortex and the medial geniculate nucleus. Amphetamine, which diminished sensory gating in both animals and humans, diminished the gating of the evoked potential recorded in the hippocampus. The effect of amphetamine was reversed by haloperidol. The rat hippocampus may therefore contain neurons that can be used to study the neurobiology of sensory gating.

Action Potentials↗
PubMed1990

Sensory physiology and catecholamines in schizophrenia and mania.

Hypersensitivity to sensory stimulation is a prominent characteristic of both schizophrenia and mania. Neurophysiological recordings suggest a common deficit in a central neuronal sensory gating mechanism which regulates sensitivity to repeated auditory stimuli. Dopamine and norepinephrine are hypothesized to have major roles in these illnesses, but their role in aberrant sensory processing has not yet been proved. Presumptive evidence for effects of catecholamines on sensory processing comes from psychophysiological studies of normal subjects challenged with stimulants who show decreased sensory gating, and studies of psychotic patients treated with neuroleptics who show improved function. Studies of similar phenomena in animals show comparable effects of catecholamines on sensory processing, both behaviorally and at the single neuron level. In this study, gating of auditory evoked potentials (EPs) during treatment of both illnesses was compared with plasma dopamine and norepinephrine metabolites. Comparisons of medicated and unmedicated states showed that schizophrenic patients have a fixed deficit in sensory gating, which is a familial trait, unchanged by medication. During acute illness, they have an additional transient hypersensitivity to stimuli, manifested as smaller EPs, which seems to be mediated by dopamine. Manic patients have only the deficit in sensory gating, which is transient and seems to be mediated by norepinephrine. Thus, similar neurophysiological deficits in the two psychoses are associated with different biochemical abnormalities, which may explain similarities in acute symptoms and differences in other aspects of the illnesses, such as their response to treatment.

Adult↗
PubMed1989

Sensory gating in schizophrenics and normal controls: effects of changing stimulation interval.

Auditory evoked potentials were recorded using a paired click, conditioning-testing paradigm in 10 schizophrenics and in 10 normal subjects with no family history of psychotic disorder. The paradigm is used to demonstrate central nervous system gating of responsiveness to auditory stimuli by examining the extent to which the response to the conditioning stimulus diminishes the response to a test stimulus occurring a short time later. Recordings were made at conditioning-testing intervals of 500 msec, 150 msec, and 75 msec to determine subjects' gating of responsiveness to stimuli repeated at various intervals. The schizophrenics had conditioning-testing ratios indicative of poor gating of the auditory P50 wave at the 500-msec and 150-msec intervals, but most patients had good sensory gating at the 75-msec interval. Normal subjects showed good sensory gating at all three intervals. Results suggest that although sensory gating mechanisms responsible for changes in neuronal response at longer intervals are chronically defective in schizophrenics, other gating mechanisms functioning at shorter intervals appear to be intact and function well in most patients. The results may lead to increased specification of the neurobiological basis of sensory abnormalities in schizophrenia.

Adult↗
PubMed1989

Bereitschaftspotential in tardive dyskinesia.

The bereitschaftspotential or motor readiness potential is a slow negative electroencephalographic wave occurring 150-1500 ms prior to the onset of a voluntary movement. It was measured in 33 subjects: 11 normal controls, 11 medicated schizophrenics with no tardive dyskinesia or evidence of drug-induced parkinsonism, and 11 patients with tardive dyskinesia. The bereitschaftspotential amplitude was more than two times larger in patients with tardive dyskinesia than in normal controls or schizophrenic patients without tardive dyskinesia. The increased amplitude correlated with the degree of severity of the tardive dyskinesia as measured on the Abnormal Involuntary Movement Scale (AIMS). The finding of the increased bereitschaftspotential amplitude in tardive dyskinesia, taken together with earlier findings of low amplitude in Parkinson's disease, suggests that this potential may reflect the level of dopaminergic activity in the basal ganglia.

Adult↗
PubMed1988

Modulation of the gating of auditory evoked potentials by norepinephrine: pharmacological evidence obtained using a selective neurotoxin.

Central mechanisms of sensory gating were assessed in Sprague-Dawley rats using an evoked potential technique similar to one that we have previously employed to show diminished sensory gating in psychotic patients. Gating mechanisms were examined using a conditioning-testing paradigm in which pairs of 74-dB clicks were delivered; the interval between the conditioning and test stimuli was 0.5 sec. A middle latency auditory evoked response (N50) recorded from the skull of unanesthetized, freely moving rats demonstrated significant suppression to the test click. Systemic administration of amphetamine (1 mg/kg, ip) significantly reduced the amount of suppression of the response to the test stimulus; haloperidol (1 mg/kg), injected after the amphetamine, returned the conditioning-testing suppression ratio toward normal values. Amphetamine also decreased the latency and amplitude of the conditioning response, an effect that was also reversed by haloperidol. Both decreased suppression of the test response and reduced amplitude and latency of the conditioning response have been observed in schizophrenia. To aid in determining the underlying mechanism of these effects, the animals were treated with two doses, given at a 1-week interval, of N-(2-chloroethyl-N-ethyl-2-bromobenzylamine) (DSP4; 50 mg/kg, ip), an agent that selectively depletes central norepinephrine. The extent and selectivity of the depletions were confirmed by chemical analysis. Following DSP4, the effects of amphetamine on the amplitude and latency of the conditioning response were largely unchanged. However, pretreatment with DSP4 significantly attenuated the reduction in conditioning-testing suppression observed following the administration of amphetamine. The data suggest a specific role for norepinephrine in the modulation of sensory processing.

Amphetamine↗
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

Premenstrual mood changes and gating of the auditory evoked potential.

To assess the effect of the menstrual cycle on a measure of brain physiology known to be affected in psychiatric illness, auditory-evoked electroencephalographic potentials were recorded from 12 women on the day prior to menstruation and nine days after the initiation of their cycle. Eight were normal college students, and four were patients in a premenstrual syndrome clinic. The women showed significant changes in self-ratings of mood between the two recordings. The P50 wave of the auditory-evoked response was evaluated in a conditioning-testing paradigm, in which stimuli were presented in pairs, allowing assessment of putative excitatory and inhibitory processes involved in the gating of central nervous system sensory responsiveness to auditory stimuli. The auditory-evoked potentials were unchanged between the two recording periods. There was also no difference between the women and age-matched male controls. The data suggest that these central nervous system functions are not responsive to hormonal fluxes in menstruation. Since inhibitory gating of the P50 wave is lost in the manic phase of manic-depressive illness, the data also suggest that premenstrual mood changes in normal women do not share electrophysiological properties of mania.

Adult↗