PubMed Health⌕ Search

Biomedical subjects

D Hommer

Publications and source records attributed to D Hommer.

At least 37 records · Page 2Linked to original sources
PubMed1996

Early expression of smooth-pursuit eye movement abnormalities in children of schizophrenic parents.

OBJECTIVE: Disordered smooth-pursuit eye movements (SPEM) and, specifically, small anticipatory saccades that disrupt SPEM have been hypothesized to be a marker of genetic vulnerability to schizophrenia. This study compares SPEM in children of schizophrenic parents with normally developing control children to assess whether SPEM abnormalities are also present in a subset of at-risk children. METHOD: With infrared oculography, SPEM was examined in 13 children of schizophrenic parents and 19 normally developing controls (aged 6 to 15 years). Measures of smooth-pursuit gain and root mean square error were used in addition to more specific measures of catch-up saccades and anticipatory saccades. RESULTS: Children of schizophrenic parents differed from normally developing controls on gain and root mean square error, but not on catch-up saccades. Small anticipatory saccades were significantly more frequent in the at-risk group. The percentage of total eye movements due to anticipatory saccades identified 54% of the at-risk group (compared with none of the control group) as performing more than two standard deviations above (worse than) the control mean. CONCLUSIONS: The presence of increased anticipatory saccades is evidence for an oculomotor dysfunction that may be a phenotype of the genetic risk for schizophrenia, expressed years prior to the possible development of clinical illness.

Adolescent↗
PubMed1995

Dissociations in the expression of the sedative effects of triazolam.

Fifteen normal volunteers were administered 0.250, 0.375, and 0.500 mg of triazolam and placebo in a double-blind repeated measures cross-over design. Subjects demonstrated dose-dependent impairments in free recall, a test of explicit memory requiring awareness and reflection, and sedation as assessed by objective behavioral measures (the digit symbol substitution task) and subjective visual analogue scales. The sedative drug response did not account for the impairment in free recall. Differences in performance of the two tests of sedation indicated that the effect of this drug on reflective processes accounts for impairment in episodic memory and the inability to track the sedative effects of this drug at the higher doses tested in this study.

Administration, Oral↗
PubMed1995

Cerebral glucose metabolism, CSF 5-HIAA levels, and aggressive behavior in rhesus monkeys.

OBJECTIVE: Considerable evidence suggests that low concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in CSF are associated with a history of aggressive behavior in both human and nonhuman primates. The purpose of this investigation was to examine the relationships among CSF 5-HIAA concentration, history of aggressive behavior, and cerebral glucose metabolism in a group of nonhuman primates whose CSF 5-HIAA had been sampled several times over the preceding 2 years and whose social behavior had been observed since birth. METHOD: The subjects were nine adult male rhesus monkeys studied under isoflurane anesthesia. Cerebral glucose utilization was measured by [18F]fluorodeoxyglucose positron emission tomography. Aggressiveness ratings were made by a primatologist who had had frequent contact with the animals over several years. RESULTS: There was a significant negative correlation between ratings of aggressive behavior and CSF 5-HIAA concentrations. There was also a negative correlation between the dose of pentobarbital required to induce anesthesia and level of CSF 5-HIAA. Moreover, there were significant negative correlations between CSF 5-HIAA levels and both whole brain glucose utilization and regional glucose utilization in the orbital-frontal cortex. CONCLUSIONS: These results suggest that both increased aggressiveness and low concentrations of CSF 5-HIAA are associated with higher brain glucose metabolism in rhesus monkeys under standardized anesthesia. Aggressive nonhuman primates with low CSF 5-HIAA concentrations may have "innate" tolerance toward functional gamma-aminobutyric acid A receptor agonists such as pentobarbital, isoflurane, and possibly alcohol.

Aggression↗
PubMed1994

Childhood-onset schizophrenia: an NIMH study in progress.

An ongoing study of the phenomenology, genetics, neuropsychology, physiology (eye tracking, autonomic responsivity), neuroimaging, biochemistry, and pharmacology of childhood-onset schizophrenia is described, and pilot data are presented for the first 22 subjects. Differentiation from autism "spectrum" disorders and other poorly defined, severe neurodevelopmental disorders is needed. Eye tracking and autonomic results are similar to patterns seen in later-onset schizophrenia and possibly more striking. Magnetic resonance imaging showed larger left frontal ventricular horn area for the schizophrenia subjects, larger left caudate, and lack of normal caudate asymmetry. Fluorodeoxyglucose positron emission tomography during an auditory continuous performance task revealed decreased right parietal/occipital glucose metabolic rate in the schizophrenia subjects, which may be secondary to poor attentional performance, and increased glucose metabolic rate in three left frontal regions, a left parietal region, and the right putamen. Clozapine has been effective and well tolerated in an open trial with 12 adolescents who responded poorly to typical neuroleptics; 16 subjects have been enrolled in a double-blind comparison of haloperidol and clozapine. Longitudinal study of this narrowly defined and possibly more homogeneous group of very early-onset schizophrenia subjects will be relevant to current neurodevelopmental theories addressing the role of puberty, progression of pathology, and continuity or discontinuity with later-onset schizophrenia.

Adolescent↗
PubMed1994

Impairments in reflective cognitive functions in alcoholics: a neuropharmacological model.

The ability to make use of reflective cognitive operations in monitoring and evaluating remembered events is impaired in subgroups of nominally cognitively unimpaired, detoxified alcoholics. Alcoholics, relative to controls, make more errors in identifying the source of remembered information (i.e. whether a remembered word was self-generated or was a stimulus word presented by the experimenter), and are impaired in their ability to inhibit confabulatory errors (intrusions). The cognitive-memory impairment expressed in benzodiazepine-treated normal volunteers mimics this impairment in alcoholics. Disturbances in prefrontal and frontal lobe functions may be involved in this selective impairment in cognition in many alcoholics and may also contribute to what accounts for the failures in reflective cognitive operations observed in amnestic patients.

Alcoholism↗
PubMed1993

Dissociation of benzodiazepine-induced amnesia from sedation by flumazenil pretreatment.

The human amnestic syndrome associated with lesions of the hippocampus and amygdala is characterized by a selective impairment of recent (explicit, episodic) memory. Benzodiazepine (BZ) treated normal subjects demonstrate similar, marked impairments in episodic memory, but in addition, BZ also induces sedation and inattention. Thus, the amnestic effects of BZ may be secondary to drug-induced sedation. However, when subjects were pretreated with the specific BZ receptor antagonist, flumazenil, the sedative and attentional effects of diazepam were blocked, but a marked impairment in episodic memory still occurred. This demonstrates that, using neuropharmacological methods, it is possible to produce a dissociation of memory impairment from inattention and sedation. Such distinct patterns of cognitive dysfunction may serve as models for clinical cognitive syndromes.

Adult↗
PubMed1993

Benzodiazepine pharmacodynamics: utility of eye movement measures.

The utility of several measures of saccadic and smooth pursuit eye movements as benzodiazepine pharmacodynamic measures was explored in 24 psychiatrically and medically health control subjects. Measures of sedation and memory impairment were also included. Subjects received four logarithmically increasing doses of intravenous diazepam at 15-min intervals on 1 day resulting in monotonically increasing plasma diazepam levels, and placebo on another day in random order 1 week apart. Measures were collected twice at baseline, once after each dose of diazepam/placebo and twice more, 15 and 30 min after the last dose. Peak saccadic velocity and smooth pursuit gain showed the greatest overall and dose-dependent drug effect among eye movement measures. Although effect sizes at the highest dose for memory impairment and self-rated sedation were comparable to these two measures, reliability (i.e., placebo-day fluctuation) with these measures was considerably poorer. Log-linear pharmacodynamic modeling was used to calculate the effective dose (ED30) or concentration (EC30) required to reduce saccadic velocity or pursuit gain by 30%. Almost all (23/24) subjects had linear and easily interpretable plots for saccadic velocity, while a majority (19/24) of subjects had interpretable plots for smooth pursuit gain. The distribution of ED30 and EC30 values showed a wide range of sensitivities to diazepam. These findings suggest that saccadic velocity and smooth pursuit gain are sensitive, reliable, quantitative benzodiazepine pharmacodynamic measures.

Adolescent↗
PubMed1992

Selective effects of triazolam on memory.

The effects of benzodiazepine (triazolam 0.25 and 0.50 mg) on different aspects of cognitive function were assessed. Triazolam impaired free recall and recognition of information presented after drug administration. In contrast to these impairments in explicit memory, a memory function that did not require conscious awareness was not altered by triazolam. Similarly, triazolam did not affect subjects' abilities to access semantic memory.

Adult↗
PubMed1992

Effect of acute and chronic benzodiazepines on plasma GABA in anxious patients and controls.

The acute effects of diazepam on plasma GABA were determined in 18 patients with panic disorder, 13 patients with generalized anxiety disorder and 20 healthy controls. All subjects were benzodiazepine-naive. Four logarithmically increasing doses of diazepam/placebo were administered intravenously at 15-min intervals on 2 separate days. Plasma GABA was measured at baseline and 3 min after the highest dose of diazepam/placebo. There was an overall decrease in plasma GABA that was significantly greater following diazepam compared with placebo, but no group differences in response. In a separate group of 18 panic disorder patients receiving chronic benzodiazepine treatment with alprazolam, the same diazepam infusion procedure (no placebo day) produced decreases in plasma GABA similar to those seen in the untreated panic disorder patients. The clinical and physiologic implications of these findings are discussed.

Adult↗
PubMed1991

Neuroendocrine effects of diazepam in panic and generalized anxiety disorders.

The adrenocorticotropic hormone (ACTH), cortisol, and growth hormone responses to four consecutive, logarithmically increasing doses of intravenous diazepam compared with placebo given at 15-min intervals were examined in patients with panic disorder (n = 13), generalized anxiety disorder (n = 8), and healthy controls (n = 13). Diazepam caused dose-dependent decreases in cortisol and increases in GH and dose-independent decreases in ACTH. There were no patient-control differences, possibly due to either the small sample size of the experimental paradigm, which tested subjects in an upright, sitting position in mildly arousing circumstances.

Adrenocorticotropic Hormone↗
PubMed1990

Effects of the acute administration of caffeine in patients with schizophrenia.

Caffeine, 10 mg/kg, was administered to 13 schizophrenic patients in a double-blind placebo-controlled study of its behavioral effects. Some measures of psychopathology were significantly increased: Brief Psychiatric Rating Scale (BPRS) total, BPRS subscales thought disorder, unusual thought content, and euphoria-activation, and several individual BPRS items. Nurses' Bunney-Hamberg ratings of psychosis and mania, comparing the day before with the day after pharmacological challenge, increased significantly. Compared to placebo, caffeine also produced significant increases of diastolic blood pressure and cortisol. Thus, these findings indicate that caffeine increases arousal and has a psychotogenic effect when administered to schizophrenic patients. The possible roles of various neurotransmitters is discussed with special emphasis on caffeine's actions on dopaminergic and adenosinergic systems.

Adolescent↗
PubMed1990

Reduced benzodiazepine sensitivity in panic disorder.

We evaluated the functional sensitivity of the gamma-aminobutyric acid-benzodiazepine supramolecular complex in 9 patients with panic disorder and 10 psychiatrically healthy control subjects by comparing the effects of four logarithmically increasing doses of intravenous diazepam on saccadic eye movement velocity, memory, and self-rated sedation. Patients with panic disorder were less sensitive than controls to diazepam using eye velocity as the dependent measure. Sedation and memory effects did not distinguish the two groups. These findings suggest that panic disorder is associated with functional subsensitivity of the gamma-aminobutyric acid-benzodiazepine supramolecular complex in brain-stem areas controlling saccadic eye movements.

Adult↗
PubMed1988

Benzodiazepine withdrawal: overview and implications for the treatment of anxiety.

The authors critically review 20 reports (studies and large case series) detailing the nature, severity, and variability of benzodiazepine withdrawal syndromes. Factors affecting the frequency and intensity of withdrawal are identified, and methodologic problems limiting the generalizability of certain findings are pointed out. Treatment approaches for minimizing withdrawal are reviewed, and implications for the problem of long-term benzodiazepine use and dependence are discussed.

Anti-Anxiety Agents↗
PubMed1985

Pharmacological and neurochemical properties of 1,4-diazepines with two annelated heterocycles ('hetrazepines').

1,4-Diazepines with two annelated heterocycles ('hetrazepines') such as brotizolam (WE 941), WE 973 and WE 1008 bind with high affinities to benzodiazepine receptors in the central nervous system. Brotizolam has a pharmacologic spectrum of action similar to clinically useful benzodiazepines, while the closely related derivatives WE 973 and WE 1008 appear to lack hypnotic action. Unlike other benzodiazepine receptor ligands which share common pharmacologic properties with the benzodiazepines, the apparent affinities of WE 973 and WE 1008 are not increased significantly in the presence of GABA, even at an elevated incubation temperature. Furthermore, the apparent affinities of these compounds do not appear to be reduced as a result of increasing the incubation temperature. Brotizolam, like the benzodiazepines, facilitates GABAergic transmission in zona recitulata neurons of the substantia nigra. In contrast, at a dose which inhibits cell firing, WE 973 does not appear to significantly augment the inhibitory action of GABA in these cells. These observations suggest that the so-called 'GABA shift' may not be a valid means of distinguishing benzodiazepine-like compounds in vitro. Furthermore, these data suggest that facilitation of GABAergic transmission may be necessary for the hypnotic action of benzodiazepine receptor ligands, but not for the anticonflict or the anticonvulsant actions of such compounds.

Action Potentials↗
PubMed1985

Atrophy limited to the third ventricle in chronic schizophrenic patients. Report of a controlled series.

Computed tomographic scans of 30 chronic schizophrenic patients and 26 matched medical controls were blindly assessed for ventricular brain ratio, cortical atrophy, third-ventricle diameter, and cerebellar atrophy. Schizophrenic patients had significantly larger third ventricles than the medical controls. There was no difference in the other brain morphologic variables. Phenomenology, drug response, CSF levels of 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, and a wide variety of clinical variables did not correlate with any measure of brain morphology. Clinicopathologic correlates of brain morphology may be limited to those patients with significant atrophy.

Adult↗
PubMed1984

Neuroleptic-induced decrease in plasma homovanillic acid and antipsychotic activity in schizophrenic patients.

Plasma-free homovanillic acid, a major metabolite of dopamine, was measured in chronically ill schizophrenic patients both before and during treatment with the antipsychotic phenothiazine, fluphenazine. Neuroleptic treatment was associated with a significant time-dependent decrease in plasma homovanillic acid from pretreatment values, which were significantly elevated when compared with those of age- and sex-matched healthy control subjects. Further, both the absolute concentrations as well as the neuroleptic-induced reductions in plasma homovanillic acid determined over 5 weeks of neuroleptic treatment were statistically significantly correlated with ratings of psychosis and improvement in psychosis, respectively. These findings suggest that the delayed effects of neuroleptic agents on presynaptic dopamine activity may more closely parallel their therapeutic actions than do their immediate effects in blocking postsynaptic dopamine receptors and that a decrease in dopamine "turnover" may be responsible for their antipsychotic effects.

Adult↗
PubMed1984

Electrophysiological and pharmacological actions of the convulsant benzodiazepine Ro 5-4864.

Ro 5-4864 (4'-chlorodiazepam) elicited convulsions in mice with a CD50 of 23.5 mg/kg (i.p.) and increased the firing rate of substantia nigra zona reticulata neurons in a dose dependent fashion (0.5-4 mg/kg i.v.). Diazepam and clonazepam, but not Ro 15-1788, were potent inhibitors of Ro 5-4864 induced convulsions. Ro 15-1788 was also ineffective in reversing Ro 5-4864 induced increases in cell firing of zone reticulata neurons. Muscimol potently inhibited the seizures and reversed increases in cell firing elicited by Ro 5-4864. Phenobarbital and pentobarbital inhibited Ro 5-4864 induced convulsions with moderate potencies, while phenytoin and carbamazepine were ineffective at doses of up to 100 mg/kg. These observations suggest that Ro 5-4864 does not elicit its pharmacologic actions through a direct action at a 'brain-type' benzodiazepine receptor. However, both the profile and potency of compounds effective in inhibiting the electrophysiological and pharmacological effects of Ro 5-4864 suggest that this compound may act by perturbation of a component of the GABA-benzodiazepine receptor chloride ionophore complex. These findings do not, however, rule out a direct involvement of the high affinity 'peripheral-type' benzodiazepine receptors found in brain.

Animals↗