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CSF monoamine metabolites in alcoholics with and without nicotine addiction
Abstracts
BIOI. PSYCilfATRY t996;39:500-666
436. NEUROPSYCHOLOGICAL ASSESSMENTS IN DETOXIFIED ALCOHOLICS I.W. Chung. S.J. Kim, & K.Y, Won Dcpnrtment of Nettropsychi:ltry. School of Ml!dicine. Chung-Buk Nationtll University llnd Hospital, Korea Chronic alcoholics oflen show specific deficits in perceptual capacities. motor perfonnances, memory functions, and problem·solving llnd abstracting abilities (Eckllrdt MJ and Martin PRo 1986. Parsons OA and Leber WR. 1981). Cognitive deficits relale to years of excessive consumption of alcoholic beverages and to the pattern of recent con· sumption. However. the relationships have nol been reported consistenlly using present neuropsychological tcst material or as§cssment tools. Recently, computer·based neurops)'chological assessments have been applied for brain-behavior disorder. Consislent presentation of test stimuli is the main Ildv:mtage of lhis method. The objective of the present study is 10 investigate cognitive fllnctiOllins in detoxified :llcoholics. The goal of the study is to diffcrenti:lte alcoholics from conlrols and 10 detennine the multivariate relationship among alcohol consumption patterns, age, education. familial alcoholism. and neuropsycholo~ical performance in alcoholics. The study group consisled of 20 deto,ufied mule alcoholics admitted for treatmen~ to Chungbuk National University Hospital and Chcongju Medical Center. Diagnosis of alcohol dependence was based on OSM-IfI-R. Excludcd ffom the study were palients who previously had any of the following characteristics: history of drug abuse. previous major hend injury or current medical condition that might aller cognition. or history of trealment for any major psychiatric disorder. Their mean age was 41 :!: 4 years (melln ± SD) and mean educational years were 8.6 :!: 3.4 yeurs. Their mean abstinence period was 121 ± 34 days, mean alcohol consumption period was 21 :t 3 years. All p03lients were free of medication for at lellst 7 days before neuropsychological testing. The test measures were Vienna system with test items of Standard Progressive Matrices. Cognitrone. Oetennination Unit. Motor Performance Series. Lifetime fumilial alcohol abuse or dependence was b::lSCd on self-report by the proband. The dalu were analyzcd with Sllliistical methods of Wilcoxon rank sum ICSI and multivnrinte-rnultiplc regression nnnlyscs. The results were sueh thai alcoholics performed slgnilicllnlly poorer 00 sublcsl~ of Delermination Unit. Motor Performance Series. excepl Stllndard Progressive Matrices llnd Cognitrone. Relalionships of cognition to Iifelime estimates of alcohol consumption and number of days from last drink to testing were found to be nonlinear. This suggests that greater consumption predicts worse performance. while longer abstinence predicts better perfomlaoce. Further extensive sludy is warranted to confirm these results.
437. CSF MONOAMINE METABOLITES IN ALCOHOLICS WITH AND WITHOUT NICOTINE ADDICTION P.W. Ragan, D.T, George, S. Shoaf, M. Eckardt, & M. Linnoila Laborlltory of Clinical Studies. OICBR. NIAAA. NIH. Bethesda. MD 20892·1250 Chronic alcohol consumption differentially llffect~ monoamine neuro· transmitter function by increasing mcsolimbic dopaminergic transmis·
627
sian. while decrensinI; scrolonergic and noradrenergic neurotransmisIlion. Of nOle. at least tWo-lhirds of alcoholics are cigarette smokers. Nicotine has also been shown to variably nffect monoaminergic neurons. Using CSF monoomine m~taboliles :15 an index of central mOl1oaminergic function. we measured CSF levels of 5-HIAA, HVA. and MHPG in carerully.screened medication-free alcoholics. Nicotine-dependent alcoholics were mndomized to either continue or stop smoking during their second week of hospitalillllion. Lumbar punctures were perfonned after 7-10 days of sobricly In: (1) smoking alcoholics (n 10): (2) alcoholics 48 hours into nicotine withdrawal (verilicd by plasma nicotine/colinine levels; n;::: II): (3) nonsmoking alcoholics Cn "" 8); and (4) nonsmoking. nondrinking controls (n = 20). There was a significant (ANOVA, p ;::: 0.046) elevation in CSF HVA - but not in j-H1AA or MHPG - in nonsmoking llicoholics (196 pmoVml, SD 33) compared to the smoking (126 pmoVml; SO 33) or stopped smoking (147 pmoVml. SD 71) 31coholics with intermediale levels (156 pmollml. SD 51) in ccnlro1s. The lumbar puncture was repealed in 17 alcoholics 31-35 days afler their last drink. Two-way ANOVA with repeated measures (p
=
438. NEURAL MECHANISMS UNDERLYING ALCOHOL'S REINFORCING PROPERTIES R.L. Ownby & BJ. Mason Alcohol Disorders Research Unit. University of Miami School of Medicine. j\.Ham~ FL A neural circuit comprising medial rorcbrain and other brain stRIctures ma)' be aClivated by ethanol intake (Koob 1992). It is widely believed that ethanol's reinforcing effects, and presumably its poten( effect on behavior, is at least partially mediated by opiate ncurotransmiucr systems in this circuit. The primary purpose of this study was to develop 11 neural network model of brain struclUtes underlying the reinforcement circuitry affecled by ethanol ;/1 vl\'o. Using standard ncuml network simulation software (Zell ct:lI 1995), n network b:lsed on neuroanatomic structures was created. The network waslrained with two diSlinct sets of inplIIllml output values. The behavior of the actual network could be reproduced during learning two different sets of a.~socialions. a.~ might happen when learning occurs under the innuence of alcohol. The network rapidly learned to discriminate between stimuli associated or not with olher inputs simulating the presence or absence of alcohol. Results of Ihis study show thllt 11 neural network model of the circuits underlying ethanol's reinforcing effects can simuillte one aspecl of the dcvclopment of alcohol dependcnce-the acquisition of llicohol's discriminative stimulus proper· tics. Further development of the network. including aherations in the way opiate neurotrnnsmiuer systems function. may simulate other a~l'Ccts of nlcohol dcpendence. In this way. modeling the effects of opiate nntago· nist medications on the syslcm may olso bc possible. our long-lerm goal in this simulation.
BIOI. PSYCilfATRY t996;39:500-666
436. NEUROPSYCHOLOGICAL ASSESSMENTS IN DETOXIFIED ALCOHOLICS I.W. Chung. S.J. Kim, & K.Y, Won Dcpnrtment of Nettropsychi:ltry. School of Ml!dicine. Chung-Buk Nationtll University llnd Hospital, Korea Chronic alcoholics oflen show specific deficits in perceptual capacities. motor perfonnances, memory functions, and problem·solving llnd abstracting abilities (Eckllrdt MJ and Martin PRo 1986. Parsons OA and Leber WR. 1981). Cognitive deficits relale to years of excessive consumption of alcoholic beverages and to the pattern of recent con· sumption. However. the relationships have nol been reported consistenlly using present neuropsychological tcst material or as§cssment tools. Recently, computer·based neurops)'chological assessments have been applied for brain-behavior disorder. Consislent presentation of test stimuli is the main Ildv:mtage of lhis method. The objective of the present study is 10 investigate cognitive fllnctiOllins in detoxified :llcoholics. The goal of the study is to diffcrenti:lte alcoholics from conlrols and 10 detennine the multivariate relationship among alcohol consumption patterns, age, education. familial alcoholism. and neuropsycholo~ical performance in alcoholics. The study group consisled of 20 deto,ufied mule alcoholics admitted for treatmen~ to Chungbuk National University Hospital and Chcongju Medical Center. Diagnosis of alcohol dependence was based on OSM-IfI-R. Excludcd ffom the study were palients who previously had any of the following characteristics: history of drug abuse. previous major hend injury or current medical condition that might aller cognition. or history of trealment for any major psychiatric disorder. Their mean age was 41 :!: 4 years (melln ± SD) and mean educational years were 8.6 :!: 3.4 yeurs. Their mean abstinence period was 121 ± 34 days, mean alcohol consumption period was 21 :t 3 years. All p03lients were free of medication for at lellst 7 days before neuropsychological testing. The test measures were Vienna system with test items of Standard Progressive Matrices. Cognitrone. Oetennination Unit. Motor Performance Series. Lifetime fumilial alcohol abuse or dependence was b::lSCd on self-report by the proband. The dalu were analyzcd with Sllliistical methods of Wilcoxon rank sum ICSI and multivnrinte-rnultiplc regression nnnlyscs. The results were sueh thai alcoholics performed slgnilicllnlly poorer 00 sublcsl~ of Delermination Unit. Motor Performance Series. excepl Stllndard Progressive Matrices llnd Cognitrone. Relalionships of cognition to Iifelime estimates of alcohol consumption and number of days from last drink to testing were found to be nonlinear. This suggests that greater consumption predicts worse performance. while longer abstinence predicts better perfomlaoce. Further extensive sludy is warranted to confirm these results.
437. CSF MONOAMINE METABOLITES IN ALCOHOLICS WITH AND WITHOUT NICOTINE ADDICTION P.W. Ragan, D.T, George, S. Shoaf, M. Eckardt, & M. Linnoila Laborlltory of Clinical Studies. OICBR. NIAAA. NIH. Bethesda. MD 20892·1250 Chronic alcohol consumption differentially llffect~ monoamine neuro· transmitter function by increasing mcsolimbic dopaminergic transmis·
627
sian. while decrensinI; scrolonergic and noradrenergic neurotransmisIlion. Of nOle. at least tWo-lhirds of alcoholics are cigarette smokers. Nicotine has also been shown to variably nffect monoaminergic neurons. Using CSF monoomine m~taboliles :15 an index of central mOl1oaminergic function. we measured CSF levels of 5-HIAA, HVA. and MHPG in carerully.screened medication-free alcoholics. Nicotine-dependent alcoholics were mndomized to either continue or stop smoking during their second week of hospitalillllion. Lumbar punctures were perfonned after 7-10 days of sobricly In: (1) smoking alcoholics (n 10): (2) alcoholics 48 hours into nicotine withdrawal (verilicd by plasma nicotine/colinine levels; n;::: II): (3) nonsmoking alcoholics Cn "" 8); and (4) nonsmoking. nondrinking controls (n = 20). There was a significant (ANOVA, p ;::: 0.046) elevation in CSF HVA - but not in j-H1AA or MHPG - in nonsmoking llicoholics (196 pmoVml, SD 33) compared to the smoking (126 pmoVml; SO 33) or stopped smoking (147 pmoVml. SD 71) 31coholics with intermediale levels (156 pmollml. SD 51) in ccnlro1s. The lumbar puncture was repealed in 17 alcoholics 31-35 days afler their last drink. Two-way ANOVA with repeated measures (p
=
438. NEURAL MECHANISMS UNDERLYING ALCOHOL'S REINFORCING PROPERTIES R.L. Ownby & BJ. Mason Alcohol Disorders Research Unit. University of Miami School of Medicine. j\.Ham~ FL A neural circuit comprising medial rorcbrain and other brain stRIctures ma)' be aClivated by ethanol intake (Koob 1992). It is widely believed that ethanol's reinforcing effects, and presumably its poten( effect on behavior, is at least partially mediated by opiate ncurotransmiucr systems in this circuit. The primary purpose of this study was to develop 11 neural network model of brain struclUtes underlying the reinforcement circuitry affecled by ethanol ;/1 vl\'o. Using standard ncuml network simulation software (Zell ct:lI 1995), n network b:lsed on neuroanatomic structures was created. The network waslrained with two diSlinct sets of inplIIllml output values. The behavior of the actual network could be reproduced during learning two different sets of a.~socialions. a.~ might happen when learning occurs under the innuence of alcohol. The network rapidly learned to discriminate between stimuli associated or not with olher inputs simulating the presence or absence of alcohol. Results of Ihis study show thllt 11 neural network model of the circuits underlying ethanol's reinforcing effects can simuillte one aspecl of the dcvclopment of alcohol dependcnce-the acquisition of llicohol's discriminative stimulus proper· tics. Further development of the network. including aherations in the way opiate neurotrnnsmiuer systems function. may simulate other a~l'Ccts of nlcohol dcpendence. In this way. modeling the effects of opiate nntago· nist medications on the syslcm may olso bc possible. our long-lerm goal in this simulation.