Symposium 11 Monday Sept. 24th 9 am–10.30 am; Room: Lecture Hall 3
Typologies in alcohol dependence—basic and clinical results. First Part: Chairpersons: Lesch OM (Austria), Reynaud M (France)
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Abstract |
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Presentation S11-1
Alcoholic patients overlap among different typological classification schemes
Pombo S, Ismail F, Reizinho R, Neves Cardoso JM (Portugal)
Aims. This study aims to assess patients classification concordance among six different alcoholic typological models: Cloninger's Type I/II Von Knorring, Sullivan and Gilligan operationalized criteria; Babor Type A/B; NETER Alcoholic Typology and Lesch Subtypes.
Methods. A sample of 318 alcohol-dependent patients recruited in the alcoholism unit (NETER) of the Psychiatric Service of Santa Maria University Hospital in Lisbon (Portugal) was eligible for study entry. All subjects were evaluated during the outpatient therapeutical programme for operacionalized criteria, reported by each alcoholism typology.
Results. Regarding concordance agreement (kappa values) for the three types I/II classifications, Von Knorring vs Sullivan yielded the higher rate of agreement, followed by Von Knorring vs Gilligan and Gilligan vs Sullivan criteria. Chi-square comparisons showed a significant overlap between Babor type A and Cloninger type I of Von Knorring (72.7% concordance) and Sullivan (74.4%). Over-two type classifications showed the following significant positive relations: Lesch type I vs NETER heredopathic subtype; Lesch type II vs NETER anxiopathic subtype and Babor type A; Lesch type III vs NETER tymopathic subtype; Lesch type IV vs Cloninger type II of Von Knorring and Sullivan criteria and NETER addictopathic subtype vs Cloninger type II of Von Knorring, Sullivan and Gilligan criteria.
Conclusions. Like in other studies it was verified a low level of agreement between the proposed methods for identifying Cloninger's type I/II alcoholics. We also observed a significantly overlap between Cloninger's type I and Babor's type A patients and anxiety and depression classification criteria methods of over-two types solutions.
Presentation S11-2
Adolescent sensitivity and alcohol induced brain damage
Crews FT, He J (USA)
Aims. To determine if adolescents represent an age with a unique response to alcohol we investigated the effects of ethanol treatment on neurogenesis and binge drinking induced neurodegeneration.
Methods. Rats and mice of various ages were treated with ethanol. Neurodegeneration and neurogenesis monitored by histochemistry.
Results. Adolescents are much more sensitive to ethanol neurotoxic effects. Neurogenesis is inhibited by lower doses of ethanol in adolescents rather than adults. We found that neurogenesis is reduced at blood levels in adolescents which are half that found to effect adults. Further, silver stain shows that adolescents have much more frontal damage than adults following a model of binge drinking. Adolescent binge drinking induces long-lasting changes in the brain that persist into adulthood.
Conclusions. The adolescent brain is sensitive to ethanol induced disruption. Adolescent brain development may represent a critical period of sensitivity to ethanol induced neuropathology.
Presentation S11-3
Phenotypes of alcohol dependence and genetic analyses
Hesselbrock V, Hesselbrock MN (USA)
Aims. Drinking, as an example of drug use behavior in the general population, varies considerably from severe alcohol dependence through simple abuse, to ‘normal drinking’ to abstinence. Although many drug dependencies are often defined in clinical studies as a single diagnostic entity, their clinical expression is likely to be heterogeneous. Indeed, persons with alcohol or other drug dependencies are heterogeneous in terms of their substance use history, demography, patterns of use, and other co-occurring psychiatric conditions. Further, different family backgrounds and rearing patterns and a variety of biological, social, and psychiatric problems have been associated with chronic drug use. These factors may influence treatment seeking behavior, treatment outcomes, and the life course of substance abuse or dependence by moderating or mediating its clinical expression.
Methods. Studies using multivariate statistical methods for identifying homogeneous groups of subjects were selected for inclusion. Theoretically-based typologies were not included in this review.
Results. Several studies using different statistical methods suggest as many as four homogeneous types of alcoholism: a chronic/severe type, a depressed/anxious type, a mildly affected type and an antisocial type.
Conclusions. Different classification systems may capture different aspects of the clinical phenomenon and also suggest differences in genetic vulnerability. This presentation will review published and unpublished findings from the COGA study and other studies demonstrating that clinical, diagnosis-based phenotypes of ‘alcoholism’ provide different linkage findings from those based upon specific symptoms or multivariate statistically derived phenotypes.
Presentation S11-4
The dopamine transporter gene polymorphism and dopamine receptor DRD2 gene haplotypes in Lesch and Cloninger typologies of alcoholism
Samochowiec J, Kucharska-Mazur J, Grzywacz A, Pelka-Wysiecka J, Samochowiec A (Poland)
Aims. The aim of our study was to evaluate the genetic background of Lesch and Cloninger typologies in respect to genes polymorphisms that as reported previously may alter dopaminergic neurotransmission and are associated with alcoholism: the dopamine transporter (DAT-40 bp VNTR) and DRD2 genes. We studied haplotypes from 3 SNP's in DRD2 gene: promoter –141C ins/del, exon 8 (A/G) and Taq I A.
Methods. We investigated 122 alcoholics, age 35 ± 9. According to Lesch typology 58 patients were type I, 36 type II, 11 type III, 17 type IV alcoholics. According to Cloninger typology, 86 patients were type I, 36 were type II. Alcohol and family history was assessed by means of structured interview, based on SSAGA. We recruited gender, ethnically and age matched 409 controls, with excluded psychiatric disorders (using PRIME-MD), mean age of 35 ± 14. The polymorphisms were detected by PCR.
Results. A significant increase of the A9 repeat alleles frequency of DAT polymorphism was noticed in Lesch type I alcoholics (p = 0.04; OR = 1.61), (but neither in Cloninger I, II nor in the whole group of alcoholics) when compared with controls. The most frequent haplotype in the whole group of alcoholics and subgroups divided by Lesch and controls were: I (insertion), A (adenine), A2. Although this haplotype was statistically less frequent in both types of Lesch I and II types of alcoholics when compared to controls (Lesch type I: 0.382; Lesch type II: 0.381; controls: 0.524; p = 0.014 and 0.031 respectively). Haplotype I, G (guanine), A2 was more frequent in alcoholics (Lesch type I: 0.299; type II: 0.319; controls: 0.215, p = 0.07 and 0.05 respectively). There were no frequency differences between haplotypes in Lesch type I and II subgroups. No differences were found examining haplotypes in subgroups of alcoholics divided according to Cloninger' typology. We did not calculate Lesch type III and IV alcoholics' alleles and haplotypes frequencies since the number of individuals was too low for genetic examinations.
Conclusions. Our results indicate a possible genetic role of dopamine transporter polymorphism in Lesch type I alcoholics.
Presentation S11-5
Amino acids in alcohol dependence defined by the Lesch typology
Walter H, Lesch OM, Skala K, Hartl D, De Witte P (Austria)
Aims. Though some amino acids, like e.g. glutamic acid are well known as working excitatory in the CNS, its impact on the modulation of alcohol withdrawal symptoms and withdrawal fits are not yet clear. The study has been undertaken to examine the levels of glutamic acid and other amino acids in chronic alcohol dependent patients.
Methods. Excitatory and inhibitory amino acids were measured in a total of 216 alcohol dependent patients (male = 149; female = 67). 159 patients were assessed according to both Coninger's typology (Cloninger type I 71.7%, type II 28.3%) and Lesch's typology (Lesch type I 11.3%, type II 55% type III 22%, type IV 11.3%). The distribution of glutamic acid, glutamine, aminobutyric acid, glycine, alanine, aspartic acid, citrulline, valine, cystine, methionine, isoleucine, leucine, tyrosine, phenylalanine, ornithine, lysine, serine, histidine, L3-methyhistidine, proline, taurine, phosphoserine, threonine, phosphoethanolamine and urea was analysed according to the Lesch typology as well as according to gender and age.
Results. Varying serum amino acids concentrations were observed in relation to age and gender. Glycine was significantly higher in the age group of –50 compared to 50+ age group. Significantly higher levels of aminobutyric acid, valine, leucine, lysine, tyrosine, citrulline and urea, were found for the age +50, compared to –50 group. Cystine levels were higher in female patients. Higher serine and histidine levels were found in male patients, aged +50. Glutamic acid levels did not differ according to Cloninger's types. For Lesch's types I and IV significantly higher glutamic acid values (type I: mean value 142.98 umol/l; SD113.20; type II: 76.53 umol/l; SD 60.79; type III: 80.52 umol/l; SD 64.31; type IV: 134.05 umol/l; SD 99.78), without any age difference, were found. In LES-type I the frequent occurrence of high values of glutamic acid is interpreted as a kindling phenomenon, while in type IV the high frequency of elevated glutamic acid values seemed to relate either to compulsivity and/or to the frequent repetition of drinking and withdrawal.
Conclusions. Following these results it seems that phenotypes using weighted severity degrees of different categories as it is used in the decision tree developed by the research group of Lesch lead to new hypotheses explaining different mechanisms of craving and withdrawal.