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Biomedical subjects

L E Adler

Publications and source records attributed to L E Adler.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1987

Family diagnoses missed on a clinical inpatient service.

Methods for taking family psychiatric histories have been developed primarily for research rather than clinical settings. The authors compared family histories obtained independently by a research team and by PGY-3 residents on 52 consecutively admitted adult psychiatric inpatients. In contrast to the residents, the research team used a family tree, screening questions, and a structured interview based on diagnostic criteria and identified more than four times as many diagnoses in relatives as did the residents. The results demonstrate that a family history strategy derived from research methodology significantly enhances the gathering of important diagnostic information in a clinical inpatient setting.

Data Collection↗
PubMed1986

Neurophysiological studies of sensory gating in rats: effects of amphetamine, phencyclidine, and haloperidol.

Central mechanisms of sensory gating were assessed in Sprague-Dawley rats by an evoked potential technique similar to one that we have previously used to show diminished sensory gating in psychotic patients. Middle latency (15-50 msec) auditory evoked potential responses were recorded at the skull in unanesthetized freely moving animals. Gating mechanisms were assessed in a conditioning-testing paradigm by measuring the suppression of response to a 74 dB click test stimulus following an earlier identical conditioning stimulus at 0.5-sec intervals. The rats demonstrated significant suppression of the N50 response to the second auditory stimulus. Amphetamine treatment significantly interfered with the suppression of the response to the second stimulus; haloperidol, injected after the amphetamine, returned the conditioning-testing ratio toward normal values. Phencyclidine caused a similar decrease in suppression and was similarly antagonized by haloperidol. During some periods of hyperarousal, animals showed spontaneous loss of suppression; this condition could be reversed by haloperidol treatment. These results with psychotomimetic drugs in an animal model parallel abnormalities in sensory gating previously observed in psychotic human subjects.

Animals↗
PubMed1985

Neurophysiologic studies of sensory gating in schizophrenia: comparison of auditory and visual responses.

Gating of visual and auditory evoked responses was assessed in chronic schizophrenic patients treated with neuroleptic drugs. Middle latency components of the visual evoked response (N90-P130) were recorded at the occiput after flash stimulus. Possible inhibitory mechanisms of sensory gating were assessed in a conditioning-testing paradigm by measuring the change in amplitude of response to a second stimulus, relative to the response to the first stimulus. Simultaneous electrooculograms were recorded to detect contamination of recordings by eye movement. Neither schizophrenic patients nor normal control subjects demonstrated significant suppression of visual evoked responses in the conditioning-testing paradigm. These results differed markedly from similar measurements of a middle latency component of the auditory evoked response (P50) recorded using the same conditioning-testing paradigm in these subjects. Normal controls showed significant decrements of the P50 response to the second auditory stimulus (mean decrement over 80%), whereas schizophrenic patients failed to show a significant decrement (mean less than 40%). This finding for auditory evoked responses replicated previous studies of normal and schizophrenic subjects. Multiple conditioning stimuli were substituted for the single conditioning stimulus used previously in an attempt to enhance gating of auditory responses, but suppression of the P50 test response did not increase in either normal or schizophrenics.

Adult↗
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↗
PubMed1983

Neurophysiological evidence for a defect in inhibitory pathways in schizophrenia: comparison of medicated and drug-free patients.

Central nervous system inhibitory neuronal mechanisms were assessed in clinically stable chronic schizophrenic patients treated with neuroleptic drugs to provide data for comparison with those obtained previously from acutely psychotic, unmedicated patients. An early positive component of the auditory average evoked response recorded at the vertex 50 msec after a click stimulus (P50) was studied. After stimuli were delivered at 10-sec intervals to establish a baseline response, inhibitory mechanisms were assessed in a conditioning-testing paradigm, by measuring the change in response to a second stimulus following the first at either 0.5-, 1.0-, or 2.0-sec intervals. At the 0.5-sec interval, normal controls had over an 80% mean decrement in response, whereas schizophrenics showed a mean decrement of less than 10% but there was no significant difference in suppression between medicated and unmedicated patients. However, the amplitude of P50, which was smaller in unmedicated schizophrenics than in normal subjects, was significantly increased in the medicated patients. The data suggest that inhibitory mechanisms which are dysfunctional in acutely psychotic.

Acoustic Stimulation↗
PubMed1983

Neurophysiological studies of sensory gating in mania: comparison with schizophrenia.

The action of central nervous system mechanisms involved in sensory gating was assessed in acutely psychotic manic patients. An early positive component of the auditory average evoked response, recorded at the vertex 50 msec after a click stimulus, was studied. Stimuli were delivered at 10-sec intervals to establish a base-line response. Sensory gating mechanisms were then tested using a conditioning-testing paradigm to assess the change in response to a second stimulus following the first at either 0.5-, 1.0- or 2.0-sec intervals. A similar paradigm had been used previously to assess deficits in this function in acute and chronic schizophrenics. We found a deficit in sensory gating in acutely manic patients. similar to that found in schizophrenics, although the variability in response was more marked in the manic patients. We followed these patients during their treatment on lithium carbonate and found a return of these neuronal functions towards normal values which corresponded to their clinical improvement. A series of stable euthymic bipolar patients were found to have responses indistinguishable from normal controls. The data suggest that deficits in neuronal gating functions, similar to those found in schizophrenia, can be seen during acute mania but these deficits return to normal as the acute psychosis abates.

Adolescent↗
PubMed1982

Clonidine treatment of schizophrenia. Double-blind comparison to placebo and neuroleptic drugs.

Antipsychotic effects of clonidine were evaluated in one schizoaffective and seven schizophrenic patients, using a double-blind, cross-over design to compare placebo, clonidine, and standard neuroleptic drugs. Mean improvement on clonidine and neuroleptics was equal, and improvement scores on the two treatments were closely correlated for individual patients. Clonidine was selected because it blocks noradrenergic but not dopaminergic neurotransmission. Patients were selected because of co-existing psychosis and tardive dyskinesia, a movement disorder thought to be caused by the antidopaminergic properties of the neuroleptics. For all patients, dyskinesia improved when neuroleptics were discontinued during clonidine and placebo periods of the study. The data provide preliminary evidence that clonidine may be an effective alternative to neuroleptics, particularly for patients for whom the dopaminergic blocking action of the neuroleptics is undesirable. The study also prompts re-evaluation of theories of a unique role for dopamine in schizophrenia.

Adolescent↗
PubMed1982

Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia.

The action of CNS inhibitory neuronal mechanisms was tested in acutely psychotic unmedicated schizophrenic patients and in normal controls. An early positive component of the auditory average evoked response recorded at the vertex 50 msec after a click stimulus was studied. Stimuli were delivered at 10-sec intervals to establish a base-line response. Inhibitory mechanisms were then tested using a conditioning-testing paradigm by assessing the change in response to a second stimulus following the first at either 0.5, 1.0, or 2.0-sec intervals. At the 0.5-sec interval, normal controls had over a 90% mean decrement in response, whereas schizophrenics showed less than a 15% mean decrement. At 2-sec intervals, responses from normals were still 30 to 50% diminished, but those from schizophrenics showed an increased response to the stimulus compared to base line. The data suggest that normally present inhibitory mechanisms are markedly reduced in schizophrenics. Failure of these inhibitory mechanisms may be responsible for the defects in sensory gating which are thought to be an important part of the pathophysiology of schizophrenia.

Acoustic Stimulation↗
PubMedDate not supplied

Defects in auditory sensory gating and their apparent compensation in relatives of schizophrenics.

Auditory sensory processing is defective at several stages in schizophrenics, as revealed by electrophysiological recordings. The purpose of this study was to assess the relationship between two of these defects in schizophrenics and their relatives. One defect is illustrated by the failure to gate the P50 wave of the auditory evoked potential in the conditioning-testing paradigm. In this paradigm, paired clicks are presented to the subject. Normals suppress or gate the P50 response to the second or test click. Schizophrenics fail to suppress the test response. This defect has been related to schizophrenics' inability to filter out noise in their environment. A second defect is illustrated by schizophrenics' lower than normal N100 wave, which has been related to failure to attend to particular features of interest in the stimulus. The question addressed in this study was whether these two defects inevitably occur together. While they do occur together in schizophrenics, even in very good prognosis, mildly ill subjects, they do not occur together in the relatives of schizophrenics. The defect in the gating of P50 occurs in half these relatives, but N100 amplitudes are not diminished. Instead, relatives with abnormal P50 gating have N100 amplitudes which are larger than normal. One interpretation of the data is that the relatives with the sensory gating defect can compensate for that defect at a subsequent stage of information processing, as demonstrated by their large amplitude N100 wave, whereas schizophrenic patients cannot.

Adult↗
PubMedDate not supplied

Lack of relationship of auditory gating defects to negative symptoms in schizophrenia.

The differences between schizophrenic patients with positive and negative symptoms have been the subject of extensive investigations. Psychophysiologists have proposed that there are elementary auditory sensory processing deficits in schizophrenia, but their prevalence in particular positive or negative subtypes has not been described. Our previous studies have shown that schizophrenics have impaired auditory sensory gating relative to normal controls, as demonstrated by the P50 auditory evoked potential conditioning-testing paradigm. In this paradigm, schizophrenics fail to show the normally expected diminished response to the second or 'test' stimulus. In the present study we assessed the possible relationship of this defect to negative symptoms in 20 schizophrenic patients treated with neuroleptics. Nine patients met the Andreasen criteria for predominantly 'negative schizophrenia'. 12 normal controls with no family history of schizophrenia were also studied electrophysiologically. Negative schizophrenics showed greater impairment than patients without such symptoms on the Trails B test of organic impairment, but there were no differences between groups on electrophysiological measurements of auditory sensory gating. Both schizophrenic groups showed impaired P50 auditory gating compared to normal controls. Both groups of schizophrenics also had a significantly diminished amplitude of the N100 waveform in the conditioning response, compared to normal controls. Auditory sensory processing defects in schizophrenia appear to be independent of negative symptoms.

Adult↗
PubMedDate not supplied

Gating of auditory response in schizophrenics and normal controls. Effects of recording site and stimulation interval on the P50 wave.

Auditory evoked potentials were recorded using a paired stimulus, conditioning-testing paradigm from 14 schizophrenic patients and 13 normal subjects with no family history of psychotic disorder. Previous studies of the vertex P50 wave using this paradigm have demonstrated a possible sensory gating deficit in schizophrenics, as shown by their failure to diminish the response to a test stimulus presented 500 ms after a conditioning stimulus. Recordings were made at Cz, Fz, C3, T3, C4, and T4, to compare effects at different recording sites with this paradigm. Schizophrenics had significantly poorer sensory gating than normals, with the most significant difference between the groups at Cz. In addition to the 500 ms interval, subjects were also recorded at a conditioning-testing interval of 100 ms. Most schizophrenics showed normal sensory gating at the 100 ms interval, despite their abnormalities at 500 ms. The results indicate that Cz is optimal recording site for this paradigm, and that gating abnormalities in schizophrenic subjects are limited to specific interstimulus intervals.

Adult↗
PubMedDate not supplied

Concurrent medical illness in the schizophrenic patient. Epidemiology, diagnosis, and management.

The management of the medically ill schizophrenic patient presents a dual dilemma for the physician. The patient may have a serious medical illness that must be diagnosed and effectively treated, yet the patient's psychiatric disorder may interfere with effective management. Thus, undiagnosed and untreated medical illness can result in significant morbidity for schizophrenic patients. Because schizophrenic patients may appear to be less cooperative than medical patients without concurrent psychiatric illness, they can cause countertransference reactions on the part of physicians and nursing staff that can interfere with treatment. Schizophrenic patients also have deficits in the processing of sensory information. These deficits require the staff to make changes in management in order to facilitate the patient's ability to cooperate with treatment and to give reliable informed consent. A host of other factors complicate the medical management and treatment of schizophrenic patients. Such factors include medication side effects of psychotropic medication, the potential interactions between medications used to treat the patient's physical illness with psychotropics, pregnancy in the female patient, and the strength of the patient's support system. The ability to successfully diagnose and treat concurrent medical illness in the schizophrenic patient will depend on the physician's ability to be flexible and to understand the implications of the patient's underlying disorder for his relationship to hospital staff. This paper reviews some of the relevant literature and describes possible treatment strategies integrating what we know about schizophrenia with medical management.

Adult↗
PubMedDate not supplied

Risk factors for burns as a consequence of seizures in persons with epilepsy.

To explore the risk factors and circumstances for burns in a population of persons with epilepsy, we surveyed 244 University of Colorado Health Sciences Center Seizure Clinic patients. Twenty-five had at least one seizure-related burn requiring medical attention (12 were hospitalized), 21 reported burns requiring medical attention not related to seizure activity, and 199 reported no burns. All patients with seizure-related burns had alteration of consciousness during most seizures. Statistical models with logistic regression indicated that a useful model for assessing risk of seizure-related burns in this population of patients could be constructed using three significant variables; lifetime total number of seizures experienced by the patient, the presence of interictal neurologic impairment, and gender. The remainder of the variables studied (percentage of seizures that occurred nocturnally, percentage of seizures preceded by a simple partial seizure (SPS) warning, self-care status, number of seizures in adult life, seizure type, patient age, age of onset of seizure disorder, and presence of burns not associated with seizure) were either not significantly correlated with seizure-related burns or did not significantly improve the success of the statistical model in light of the other variables studied. Most injuries occurred in the home during activities that might have been avoided. They included 10 burns incurred while cooking, 5 incurred while showering (with a plumbing system that permitted exposure to scalding water), and 3 caused by exposed room heaters. A subset of epileptic patients are at increased risk for burns and should minimize situations in which they can be burned.

Accident Prevention↗
PubMedDate not supplied

Schizophrenia and nicotinic receptors.

Patients with schizophrenia often cannot respond to important features of their environment and filter out irrelevant stimuli. This dysfunction could be related to an underlying defect in inhibition--i.e., the brain's ability to alter its sensitivity to repeated stimuli. One of the neuronal mechanisms responsible for such inhibitory gating involves the activation of cholinergic nicotinic receptors in the hippocampus. These receptors are diminished in many specimens of hippocampal brain tissue obtained postmortem from schizophrenic patients. In living schizophrenic patients, stimulation of cholinergic receptors by nicotine transiently restores inhibitory gating of evoked responses to sensory stimuli. Many people with schizophrenia are heavy smokers, but the properties of the nicotinic receptor favor only short-term activation, which may explain why cigarette smoking is only a transient symptomatic remedy. This paper reviews the clinical phenomenology of inhibitory gating deficits in people with schizophrenia, the neurobiology of such gating mechanisms, and the evidence that some individuals with the disorder may have a heritable deficit in the nicotinic cholinergic receptors involved in this neurobiological function. Inhibitory gating deficits are only partly normalized by neuroleptic drugs and are thus a target for new therapeutic strategies for schizophrenia.

Antipsychotic Agents↗