Papers by Laurence Karper
Archives of General Psychiatry
To characterize further behavioral, cognitive, neuroendocrine, and physiological effects of suban... more To characterize further behavioral, cognitive, neuroendocrine, and physiological effects of subanesthetic doses of ketamine hydrochloride in healthy human subjects. Ketamine, a phencyclidine hydrochloride derivative, is a dissociative anesthetic and a noncompetitive antagonist of the N-methyl-D-aspartate subtype of excitatory amino acid receptor. Nineteen healthy subjects recruited by advertisements from the community participated in this randomized, double-blind, placebo-controlled study. Subjects completed three test days involving the 40-minute intravenous administration of placebo, ketamine hydrochloride (0.1 mg/kg), or ketamine hydrochloride (0.5 mg/kg). Behaviors associated with the positive and negative symptoms of schizophrenia were assessed by using the Brief Psychiatric Rating Scale. Changes in perception and behaviors associated with dissociative states were assessed by the Perceptual Aberration Subscale of the Wisconsin Psychosis Proneness Scale and the Clinician-Adminis...
The Journal of neuropsychiatry and clinical neurosciences, 1992
Two patients with prolonged postictal encephalopathy lasting 63 and 72 hours, respectively, follo... more Two patients with prolonged postictal encephalopathy lasting 63 and 72 hours, respectively, following seizures with clozapine are reported. Clozapine alters the EEG in a majority of patients treated, with seizure frequency as high as 5-10% in doses above 600 mg/d. Prolonged postictal encephalopathy following a clozapine-induced seizure has not been previously reported but may be an important side effect of this medication. Pharmacologic and clinical issues are discussed.
Journal of Dual Diagnosis, 2008
Psychiatric symptoms and alcohol and drug use disorders are often diagnosed in individuals who fr... more Psychiatric symptoms and alcohol and drug use disorders are often diagnosed in individuals who frequent shelters and programs for homelessness. Services are often provided in a fragmented, uncoordinated manner. This study evaluates a care coordination program in dual-diagnosis patients by comparing data on 50 patients treated with standard methods and 50 patients enrolled in the care coordination program. Clinical outcomes were measured with the Hamilton Depression Scale, Positive and Negative Syndrome scale, BASIS-32, service utilization, and alcohol use. We found that care coordination is a relatively low intensity but promising intervention that may improve clinical outcomes of homeless dual-diagnosis patients.
Archives of General Psychiatry, 1998
This study evaluated the dose-related ethanol-like subjective effects of the N-methyl-D-aspartate... more This study evaluated the dose-related ethanol-like subjective effects of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine hydrochloride in recently detoxified alcoholics. Twenty male inpatients meeting DSM-III-R criteria for alcohol dependence and who had not consumed alcohol for 10 to 27 days prior to the study completed 3 test days that involved the intravenous infusion of ketamine hydrochloride (0.1 mg/kg or 0.5 mg/kg) or saline solution under randomized double-blind conditions. Ethanol-like subjective effects were assessed using the Sensation Scale; the Biphasic Alcohol Effects Scale; visual analog scales to measure "high" and degree of similarity to ethanol, cocaine, and marijuana; a scale assessing the number of standard alcohol drinks producing similar subjective effects; and visual analog scales measuring ethanol craving. Ketamine produced dose-related ethanol-like effects on each scale measuring its similarity to ethanol. Its effects were more similar to the sedative or descending limb effects of ethanol than to the stimulant or ascending limb effects. Ketamine effects also were more like ethanol than marijuana or cocaine. Ethanol-like effects were more prominent at the higher ketamine dose, a dose rated as similar to greater levels of ethanol intoxication. However, ketamine did not increase craving for ethanol. The production of ethanol-like subjective effects by ketamine supports the potential clinical importance of NMDA receptor antagonism among the mechanisms underlying the subjective effects of ethanol in humans.
Psychiatric Services, 2008
Schizophrenia Research, 1993
similar on most clinical and neuropsychological measures, and both groups are cognitively more im... more similar on most clinical and neuropsychological measures, and both groups are cognitively more impaired than normal controls. There are, however, some interesting differences between LOS and EOS groups-e.g., greater impairment on Wisconsin Card Sorting Testin the EOS than LOS patients. Comment: We will discuss our findings from the view-point of factors that may be associated with a delayed onset of schizophrenia.
Schizophrenia Research, 1993
enhances the signal to noise ratio thus highlighting the differences between schizophrenics and n... more enhances the signal to noise ratio thus highlighting the differences between schizophrenics and normals.
Biological Psychiatry, 1994
35428, but not to BZT. WIN 35428 curves in cocaine users was shifted to the right of the control ... more 35428, but not to BZT. WIN 35428 curves in cocaine users was shifted to the right of the control curve while BZT inhibition curves in cocaine addicts overlapped with the controls. Similarly, there was a decrease in responsiveness of [3H]GBR 12935 binding to nomifensine in rats 6 weeks following withdrawal from a week-long cocaine treatment; the nomifensine curve was shifted to the right of the saline control curve, in the saline treated group, the estimated ICso was 0.001 mM, while in the cocaine group it was I mM. These results are consistent with an altered pharmacological profile of DATR associated with chronic intake of cocaine.
Biological Psychiatry, 2000
The amino acid glycine, modulates neurotransmission via actions at GLY-A receptor and GLY-B recep... more The amino acid glycine, modulates neurotransmission via actions at GLY-A receptor and GLY-B receptor. The latter are coagonist sites associated with N-Methyl-D-Aspartate (NMDA) glutamate receptors. The central bioavailability of peripherally administered glycine has not been adequately characterized in humans. Methods: Healthy human subjects were administered either oral D-cycloserine (50 mg or placebo) and intravenous glycine (saline, 100 mg/kg or 200 mg/kg) in random order over 4 test days under double-blind conditions. Cerebrospinal fluid was collected by lumbar puncture performed on the first test day was analyzed to determine amino acid levels. The acoustic startle response was measured on the second test day. Results: Intravenous glycine dose-dependently increased both serum and CSF glycine and serine levels. Neither glycine nor DCS produced any significant effects on behavior, cognition or the acoustic startle response. Neither IV glycine nor DCS were associated with any toxicity. Conclusions: Thus, peripheral glycine administration raised CSF glycine levels without producing any clear central nervous system effects. Glycine and D-cycloserine did not worsen cognitive test performance and did not induce behavioral symptoms on their own. The possibility that glycine and D-cycloserine enhanced cognitive test performance cannot be excluded given the psychometric limitations of the test battery.
Schizophrenia Research, 2010
Journal of Clinical Psychopharmacology, 1994
Psychopharmacology, 2005
Rationale Sensitization to the effects of N-methyl-d-aspartate (NMDA) glutamate receptor antagoni... more Rationale Sensitization to the effects of N-methyl-d-aspartate (NMDA) glutamate receptor antagonists is robust in animals. However, the applicability of this model to humans is unclear because it currently rests on highly confounded retrospective studies of individuals who experienced protracted psychoses following repeated binges with NMDA receptor antagonists. Objectives The purpose of the current study was to determine whether there was evidence of sensitization to the behavioral effects of ketamine in healthy human subjects with repeated exposure to this drug. Methods Data were studied from 295 healthy human subjects who participated in one or more of 11 separate studies that involved ketamine administration over 14 years. Positive and negative symptoms (Brief Psychiatric Rating Scale: BPRS), perceptual alterations (Clinician-Administered Dissociative States Scale: CADSS), and “high” and “anxiety” states (Visual Analog Scale: VAS) that were measured in all studies were included as outcome measures. Results After including the number of previous exposures, number of previous studies, and time since first exposure as variables, repeated exposure to ketamine did not result in increased behavioral responses, suggestive of behavioral sensitization. Conclusions The current data do not provide evidence that repeated exposure to ketamine, albeit limited, is associated with sensitization to the behavioral effects of ketamine.
Biological Psychiatry, 1994
the qualitative ratings were more sensitive to the group differences, explaining significantly mo... more the qualitative ratings were more sensitive to the group differences, explaining significantly more between group variance than the quantitative measures. The results suggest that human observers may be sensitive to important features of pathologic anatomy that are not fully revealed through quantitative methods.
Schizophrenia Research, 1995
Psychomotor stimulation is mediated by the basal ganglia especially the striatum and the nucleus ... more Psychomotor stimulation is mediated by the basal ganglia especially the striatum and the nucleus accumbens (NAc) by disinhibition of the thalamus. Blockade of excitatory glutamatergic input of the striatum or the NAc by NMDA receptor antagonists induces psychomotor stimulation in rats as well as in man. Because the symptoms resemble those of schizophrenic patients, pharmacologically induced hypofunction of the glutamatergic transmission is the best accepted model of schizophrenia. The NMDA receptor complex possesses a strychnineinsensitive glycine receptor which positively modulates the glutamatergic transmission at the NMDA receptor complex. If a hypofunction of the glutamatergic system underlies schizophrenia (Kim et al., 1980), a glycine substitution therapy may be beneficial in the treatment of schizophrenia.
Journal of Clinical Psychopharmacology, 1992
Schizophrenia Research, 1995
Psychomotor stimulation is mediated by the basal ganglia especially the striatum and the nucleus ... more Psychomotor stimulation is mediated by the basal ganglia especially the striatum and the nucleus accumbens (NAc) by disinhibition of the thalamus. Blockade of excitatory glutamatergic input of the striatum or the NAc by NMDA receptor antagonists induces psychomotor stimulation in rats as well as in man. Because the symptoms resemble those of schizophrenic patients, pharmacologically induced hypofunction of the glutamatergic transmission is the best accepted model of schizophrenia. The NMDA receptor complex possesses a strychnineinsensitive glycine receptor which positively modulates the glutamatergic transmission at the NMDA receptor complex. If a hypofunction of the glutamatergic system underlies schizophrenia (Kim et al., 1980), a glycine substitution therapy may be beneficial in the treatment of schizophrenia.
Schizophrenia Research, 1995
Current Opinion in Psychiatry, 1994
Archives of General Psychiatry, 1998
This study evaluated the dose-related ethanol-like subjective effects of the N-methyl-D-aspartate... more This study evaluated the dose-related ethanol-like subjective effects of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine hydrochloride in recently detoxified alcoholics. Twenty male inpatients meeting DSM-III-R criteria for alcohol dependence and who had not consumed alcohol for 10 to 27 days prior to the study completed 3 test days that involved the intravenous infusion of ketamine hydrochloride (0.1 mg/kg or 0.5 mg/kg) or saline solution under randomized double-blind conditions. Ethanol-like subjective effects were assessed using the Sensation Scale; the Biphasic Alcohol Effects Scale; visual analog scales to measure "high" and degree of similarity to ethanol, cocaine, and marijuana; a scale assessing the number of standard alcohol drinks producing similar subjective effects; and visual analog scales measuring ethanol craving. Ketamine produced dose-related ethanol-like effects on each scale measuring its similarity to ethanol. Its effects were more similar to the sedative or descending limb effects of ethanol than to the stimulant or ascending limb effects. Ketamine effects also were more like ethanol than marijuana or cocaine. Ethanol-like effects were more prominent at the higher ketamine dose, a dose rated as similar to greater levels of ethanol intoxication. However, ketamine did not increase craving for ethanol. The production of ethanol-like subjective effects by ketamine supports the potential clinical importance of NMDA receptor antagonism among the mechanisms underlying the subjective effects of ethanol in humans.
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Papers by Laurence Karper