D Medoff

University of Maryland, Baltimore, Baltimore, MD, United States

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Publications (17)104.35 Total impact

  • Schizophrenia Research - SCHIZOPHR RES. 01/2003; 60(1):245-246.
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    ABSTRACT: Metabolites of the kynurenine pathway of tryptophan degradation may play a role in the pathogenesis of several human brain diseases. One of the key metabolites in this pathway, kynurenine, is either transaminated to form the glutamate receptor antagonist, kynurenate, or hydroxylated to 3-hydroxykynurenine, which in turn is further degraded to the excitotoxic N-methyl-D-aspartate receptor agonist quinolinate. Because a hypoglutamatergic tone may be involved in the pathophysiology of schizophrenia, it is conceivable that alterations in kynurenine pathway metabolism may play a role in the disease. The tissue levels of kynurenine, kynurenate, and 3-hydroxykynurenine were measured in brain tissue specimens obtained from the Maryland Brain Collection. All three metabolites were determined in the same samples from three cortical brain regions (Brodmann areas 9, 10, and 19), obtained from 30 schizophrenic and 31 matched control subjects. Kynurenate levels were significantly increased in schizophrenic cases in Brodmann area 9 (2.9 +/- 2.2 vs. 1.9 +/- 1.3 pmol/mg protein, p <.05), but not in Brodmann areas 10 and 19. Kynurenine levels were elevated in schizophrenic cases in Brodmann areas 9 (35.2 +/- 28.0 vs. 22.4 +/- 14.3 pmol/mg protein; p <.05) and 19 (40.3 +/- 23.4 vs. 30.9 +/- 10.8; p <.05). No significant differences in 3-hydroxykynurenine content were observed between the two groups. In both groups, significant (p <.05) correlations were found in all three brain areas between kynurenine and kynurenate, but not between kynurenine and 3-hydroxykynurenine (p >.05). In rats, chronic (6-months) treatment with haloperidol did not cause an increase in kynurenate levels in the frontal cortex, indicating that the elevation observed in schizophrenia is not due to antipsychotic medication. The data demonstrate an impairment of brain kynurenine pathway metabolism in schizophrenia, resulting in elevated kynurenate levels and suggesting a possible concomitant reduction in glutamate receptor function.
    Biological Psychiatry 10/2001; 50(7):521-30. · 9.25 Impact Factor
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    J D Sherr, D Medoff, G Thaker
    American Journal of Psychiatry 08/1999; 156(7):1125-6. · 14.72 Impact Factor
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    ABSTRACT: The authors tested the hypothesis that eye tracking disorder in schizophrenia is associated with neurological signs. The subjects were 93 normal comparison subjects and 59 schizophrenic patients. They were evaluated with the Neurological Evaluation Scale, a standardized rating instrument that assesses sensory integration, motor coordination, sequencing of complex motor acts, and other neurological signs. Also, the schizophrenic patients' smooth-pursuit eye movements were tested in response to a 0.3-Hz sinusoidal target by means of infrared oculography. They were divided into those with (N=18) and without (N=41) eye tracking disorder by using a previously described method, which was based on mixture analysis of the distribution of position root mean square error. The patients with eye tracking disorder had significantly worse performance than the patients without eye tracking disorder with respect to sensory integration, and the effect size was moderate to large. In comparison with the normal subjects, both patient subgroups had significantly worse performance on all of the Neurological Evaluation Scale subscales. Although neurological signs are present generally in schizophrenia, poor sensory integration is particularly pronounced in patients with eye tracking disorder. A review of the literature shows that the two abnormalities have strikingly similar patterns of validators, including 1) familial aggregation, 2) premorbid presence, 3) syndromal specificity, 4) trait status, and 5) association with the deficit syndrome. Poor sensory integration and eye tracking disorder in schizophrenia may be various manifestations of a common, underlying pathophysiological process.
    American Journal of Psychiatry 11/1998; 155(10):1352-7. · 14.72 Impact Factor
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    ABSTRACT: To examine the relationship between smooth pursuit eye movements and tardive dyskinesia (TD) in schizophrenia. Forty schizophrenic patients with TD and 25 non-TD patients had smooth pursuit eye movements tested with infrared oculography. In addition to the diagnosis of TD (present or absent), each patient had ratings of severity of TD. There was no significant or strong association between TD and poor smooth pursuit eye movements. The results stand in contrast to those of several previous studies, which were based on limited methodology. However, this study was not able to exclude definitively the possibility that TD is associated with poor smooth pursuit, perhaps with a small to moderate effect. Furthermore, these conclusions are limited to simple eye tracking protocols in which distractions are minimized. The question of whether or not TD is associated with poor smooth pursuit in schizophrenia needs to be resurrected.
    Schizophrenia Research 06/1998; 31(2-3):141-50. · 4.59 Impact Factor
  • Archives of General Psychiatry 03/1998; 55(2):184-6. · 13.77 Impact Factor
  • Schizophrenia Research 01/1998; 29(1):173-173. · 4.59 Impact Factor
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    ABSTRACT: The objective was to determine the relationships between eye tracking disorder (ETD) in schizophrenia, specific ocular motor measures, and the deficit syndrome. Twenty-five normal comparison subjects and 53 schizophrenic patients had eye movements tested with infrared oculography using a sinusoidal target. Patients were assessed with the Schedule for the Deficit Syndrome. For the patients, the distribution of position root mean square error (a global measure of pursuit) was best fit by a mixture of two normal distributions. This information was used to divide the patients into two subgroups, those with and those without ETD. ETD was almost completely accounted for by several specific ocular motor measures and was significantly associated with the deficit syndrome. The finding that ETD was almost completely accounted for by specific measures bridges a gap of interpretation in this field. ETD and the deficit syndrome of schizophrenia may share a common pathophysiology of cerebral cortical-subcortical circuits.
    Biological Psychiatry 12/1997; 42(9):781-96. · 9.25 Impact Factor
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    ABSTRACT: The overall goals of the studies presented here were to compare (1) the accuracies of saccades to moving targets with either a novel or a known target motion, and (2) the relationships between the measures of target motion and saccadic amplitude during pursuit initiation and maintenance. Since resampling of position error just prior to saccade initiation can confound the interpretation of results, the target ramp was masked during the planning and execution of the saccade. The results suggest that saccades to moving targets were significantly more accurate if the target motion was known from the early part of the trial (e.g., during pursuit maintenance) than in the case of novel target motion (e.g., during pursuit initiation); both these types of saccades were more accuate than those when target motion information was not available. Using target velocity in space as a rough estimate of the magnitude of the extra-retinal signal during pursuit maintenance, the saccadic amplitude was significantly associated with the extra-retinal target motion information after accounting for the position error. In most subjects, this association was stronger than the one between retinal slip velocity and saccadic amplitude during pursuit initiation. The results were similar even when the smooth eye motion prior to the saccade was controlled. These results suggest that different sources of target motion information (retinal image velocity vs internal representation of previous target motion in space) are used in planning saccades during different stages of pursuit. The association between retinal slip velocity and saccadic amplitude is weak during initiation, thus explaining poor saccadic accuracy during this stage of pursuit.
    Experimental Brain Research 03/1997; 113(2):371-7. · 2.22 Impact Factor
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    ABSTRACT: The authors' goal was to test the hypothesis that abnormal smooth pursuit eye movements in schizophrenic patients are associated with the deficit syndrome. The eye movements of 24 normal comparison subjects, 32 patients with nondeficit schizophrenia, and 11 patients with deficit schizophrenia were tested with infrared oculography using foveapetal step-ramp targets. The group of schizophrenic patients had normal latency to pursuit onset, abnormally decreased open-loop acceleration and abnormally decreased velocity during the periods of closed-loop acceleration and steady-state pursuit. The subgroup of schizophrenic patients with the deficit syndrome had particularly poor performance during the periods of open- and closed-loop acceleration. Patients with schizophrenia have abnormal smooth pursuit eye movements in response to a step-ramp stimulus, and the defects are particularly pronounced in patients with the deficit syndrome. Abnormal smooth pursuit eye movements in schizophrenia and related disorders have been consistently linked with primary and enduring negative symptoms.
    American Journal of Psychiatry 10/1996; 153(9):1158-65. · 14.72 Impact Factor
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    ABSTRACT: Using positron emission tomography with the tracer 18-fluoro-D-deoxyglucose, we assessed regional cerebral glucose utilization patterns (rCMRglu) associated with three performance levels in a forced choice, tone recognition task. Four normal subjects responded with one hand when they heard a high-frequency tone (1500 Hz), and with the other hand when they recognized a low-frequency tone (750 Hz). The EASY (EAS) condition accuracy average was 96%, the INTERMEDIATE level accuracy averaged 89%, and the DIFFICULT (DIF) recognition task accuracy average was 77%. Statistical parametric mapping (SPM94) analysis revealed that the DIF minus EAS contrast is associated with a marked metabolic elevation in the right middle and inferior temporal gyri and the gyrus fusiformis. The EAS minus DIF contrast revealed greater rCMRglu in the right medial geniculate body. Enhanced activity in right temporal lobe structures may reflect a role in auditory memory and "image" visualization. The medial geniculate enhancement may reflect tone frequency assessment.
    Biological Psychiatry 07/1996; 39(12):1013-22. · 9.25 Impact Factor
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    ABSTRACT: Although an abnormality of smooth pursuit eye movement has been consistently noted in schizophrenia, the underlying ocular motor pathophysiology is unknown. It is unclear whether the abnormality represents deficits in processing of information provided by the moving target, generation of pursuit eye movements, or other ocular motor and related cognitive processes. To evaluate the ability to process information provided by a moving target, saccadic accuracies were studied in step-ramp and single step tasks. Schizophrenic (with and without tardive dyskinesia [TD]) and normal subjects made equally accurate initial corrective saccades to the moving target. Thus, when the target jumped and then smoothly moved (creating a position and a velocity error on the retina), the patients were able to process retinal motion information and generate a normally accurate saccadic response. After the initial corrective saccade, both groups followed the target with a combination of pursuit eye movements and occasional catch-up saccades. During this period, the retinal velocity error is minimal because the eye approximates the target motion, and the major source of target motion information both for the smooth pursuit and saccadic responses is extra-retinal (i.e., predictive mechanism). The accuracies of catch-up saccades were significantly lower in the schizophrenic patients than in the normal subjects. During this period, overall pursuit performance, measured by pursuit gain, was also significantly worse in the patients. Accuracies of subsequent catch-up saccades, but not initial corrective saccades, significantly predicted the pursuit gain. Low pursuit gain was associated with high numbers of saccades per time spent in pursuit, which were similar in both schizophrenic subgroups (i.e., with and without TD), but were only significantly higher in the patients with TD than in the normal subjects. These preliminary data suggest that schizophrenic patients are able to process retinal motion information but have difficulties in using extra-retinal motion information to generate an appropriate saccadic response.
    Psychiatry Research 02/1996; 59(3):221-37. · 2.68 Impact Factor
  • Schizophrenia Research 01/1996; 18(2):194-194. · 4.59 Impact Factor
  • Schizophrenia Research - SCHIZOPHR RES. 01/1995; 15(1):122-123.
  • Schizophrenia Research - SCHIZOPHR RES. 01/1995; 15(1):84-84.
  • Schizophrenia Research - SCHIZOPHR RES. 01/1995; 15(1):184-184.
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    ABSTRACT: Identifying substance use disorders in persons with mental illness is often difficult. In this study prevalence rates of substance use disorders among state psychiatric hospital patients were obtained by six different methods: DSM-III-R substance use diagnoses and five additional strategies based on frequency of use and past substance abuse treatment. Overlaps and differences between patients identified by the six methods were examined. Chart review and a structured substance use screening interview were used with a random sample of 20 percent (N = 474) of the population of the Maryland state hospital system. Comparisons focused on cohorts identified by two of the methods: DSM-III-R substance use diagnoses and recent regular use (any past period of daily or weekly use plus any use during the 30 days before hospitalization). The prevalence rates of substance use identified by the six strategies ranged from 23 percent to 55 percent. The recent-regular-use criteria identified 176 patients, and DSM-III-R diagnoses identified 111. The recent-regular-use criteria also identified a greater number of patients as likely to benefit from substance use treatment. Patients identified by both methods were significantly younger and more likely to be male and nonschizophrenic than patients without substance use disorders. The need for substance use treatment may be underestimated if discharge planners consider only DSM-III-R diagnoses. A brief screen for recent regular use may be a better way to assess treatment needs in a state hospital population.
    Hospital & community psychiatry 09/1993; 44(8):748-52.