Relationships of plasma tryptophan availability to course of illness and clinical features of alcoholism: a preliminary study

Ac, Swann; Ba, Johnson; Cr, Cloninger; Yr, Chen

doi:10.1007/s002130050962

Cited by 31 publications

(15 citation statements)

References 30 publications

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“…effectiveness as adjunctive treatment to cognitive behavioral therapy in early and late onset alcoholics was presented at a meeting of the American Society of Addiction Medicine (Johnson et al 1999). These data showed that ondansetron (particularly 4 µg/kg b.i.d) was significantly superior to placebo in reducing alcohol drinking and increasing abstinence rates among early but not late onset alcoholics.…”

Section: -Ht 3 Antagonistsmentioning

confidence: 92%

“…Broken lines indicate reduced function. Solid lines represent normal function who have an early alcoholism onset, compared with those who develop the disease in later life, are more prone to serotonergic dysfunction (Ballenger et al 1979;BuydensBranchey et al 1989;Vikkunen andLinnoila, 1990, 1997;Fils-Aime et al 1996;George et al 1999;Swann et al 1999). While this 5-HT dysfunction among EOA has been postulated to be a deficiency state (LeMarquand et al 1994a(LeMarquand et al , 1994b, our results would argue for a more fundamental and complex interaction between mechanisms controlling serotonin regulation at the transporter and their interaction with drinking (see Fig.…”

Section: -Ht 3 Antagonistsmentioning

confidence: 97%

“…Preclinical studies would also suggest that the combination of ondansetron and naltrexone would be useful as there does appear to be some synergism of action at reducing ethanol consumption in animals (Le and Sellers 1994). Additionally, since both may be useful in alcoholics with a biological predisposition to disease (King et al 1997;Johnson et al 1999), it is scientifically interesting that preliminary clinical evidence would suggest that the addition of naltrexone to ondansetron may be more effective than either alone in treating early onset alcoholics (Johnson et al 2000). Development of future clinical studies should be based upon mechanistic pharmacological principles to afford us the optimal opportunity to find effective medication combinations for the treatment of alcoholism.…”

Section: Combination Treatmentsmentioning

confidence: 98%

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Neuropharmacological treatments for alcoholism: scientific basis and clinical findings

Johnson¹,

Ait-Daoud

2000

Psychopharmacology

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160

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Preclinical studies have exploded our knowledge about the behavioral and biological underpinnings of alcoholism. These studies suggest that certain neurotransmitters, particularly those interacting with the opioid, N-methyl-D-aspartate, and monoamine systems, may play a critical role in the expression of alcohol-drinking and other behaviors associated with its abuse liability. Built upon this foundation, important advances have been made in the development of therapeutic medications for the treatment of alcoholism. Of the medications reviewed, acamprosate's potential appears to be the most widely established. In the USA, naltrexone was approved by the Food and Drug Administration in 1995 for the treatment of alcoholism; however, the results of some studies have been less encouraging. Naltrexone's reliance on high compliance rates for efficacy may, eventually, limit its potential in clinical settings offering generic treatment for alcoholism. The relative paucity of dose-response studies on naltrexone's effects in treating alcoholics is an important gap in the literature. Recent data from a large clinical trial suggests that ondansetron, a serotonin3 antagonist, offers new hope for the treatment of early onset alcoholics; a type of alcoholism most difficult to manage with psychosocial measures alone. Different subtypes of alcoholic may, therefore, have varying treatment responses to serotonergic agents. Matching subtypes of alcoholic to effective treatment medications based upon their different biologies remains an important therapeutic goal. Combinations of effective pharmacological agents need exploration as they may prove to be synergistic, and could shepherd in a new era of treatments aimed at multiple neurotransmitter targets associated with the alcoholism disease. The coming decade promises more powerful tools for characterizing drug effects on alcohol drinking, thereby closing the gap between animal models of addiction and the human condition.

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Section: -Ht 3 Antagonistsmentioning

confidence: 92%

Section: -Ht 3 Antagonistsmentioning

confidence: 97%

Section: Combination Treatmentsmentioning

confidence: 98%

See 1 more Smart Citation

Neuropharmacological treatments for alcoholism: scientific basis and clinical findings

Johnson¹,

Ait-Daoud

2000

Psychopharmacology

Self Cite

160

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“…Among EOAs (who reported more frequent incarceration for violent crimes, more suicide attempts, and more frequent depression than LOAs), central serotonergic activity (i.e., measured as the ratio of plasma tryptophan to other amino acids competing for brain entry) was inversely related to depression and aggression. Swann et al (1999) found that individuals with low activity on this measure of serotonergic function were more anxious and had antisocial personality characteristics and an early age of onset of alcoholism. In another sample of recently abstinent alcoholics, EOAs also had a more severe course of alcoholism and a lower mean cerebrospinal fluid concentration of 5-hydroxyindoleacetic acid, the major serotonin metabolite, than LOAs (Fils-Aime et al 1996).…”

Section: Introductionmentioning

confidence: 87%

Comparison of Alcoholism Subtypes as Moderators of the Response to Sertraline Treatment

Kranzler

Feinn²,

Armeli³

et al. 2011

Alcoholism Clin & Exp Res

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Background A variety of typologies have been used to categorize alcoholism’s diverse manifestations. Although the most widely studied typologies are dichotomous ones based on genetic epidemiologic findings or using cluster analytic methods, recent efforts have utilized a single item or the onset of a diagnosis of alcohol dependence to subtype individuals based on the age of alcoholism onset. We compared three different methods to subtype alcoholics. Methods This secondary analysis used data from 134 alcohol-dependent participants in a placebo-controlled trial of sertraline (Kranzler et al. 2011). We compared cluster analysis to distinguish two risk/severity subtypes (Babor et al. 1992) with two age-of-onset subtypes (i.e., based on the age of onset of problem drinking or the age at which alcohol dependence criteria were first met). Results Each method yielded subgroups that differed significantly from one another on demographic and clinical measures. Although concordance was high between the two age-of-onset methods, it was poor between the age-of-onset methods and the cluster analysis-derived approach. All three subtyping approaches significantly moderated the effects of sertraline or placebo, but only in the L′L′ genotype group, as originally reported (Kranzler et al. 2011). In all cases, sertraline treatment was superior to placebo in later-onset individuals and inferior to placebo in the earlier-onset groups. Conclusions Because age-of-onset subtypes can be defined retrospectively on an individual basis, they may be more clinically useful than cluster-derived subtypes, which require group data. Because the two age-of-onset measures we examined appear to have comparable validity, a single item is easier to use as a measure of the age of onset of problem drinking.

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“…In the case of quinolinic acid neurotoxicity will be increased, whereas neuroprotection will be afforded by kynurenic acid (see Fig. 2) [85][86][87][88][89][90][91][92][93]. Abuse of alcohol will also impair the effectiveness of hepatic tryptophan pyrrollase, an effect which will be exacerbated in chronic problem drinkers, due to increasing liver damage, and may be implicated in the neurocognitive deficits associated with alcohol dependency [94][95][96].…”

Section: Neurochemistrymentioning

confidence: 99%

Towards an Integrated Clinical Psychobiology of Alcoholism

Martin¹,

Bonner

2005

CPSR

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Alcohol dependency is a complex multi-factorial clinical presentation characterized by etiological ambiguity, poor treatment adherence and unfavorable prognosis. Recent evidence suggest considerable heterogeneity in this patient group across a number of neurological, genetic, psychological and personality parameters which relate directly to the clinical manifestation and course of this chronic condition. The current review examines contemporary cross-disciplinary research reports to present an integrated psychobiological synthesis of the main themes. The psychobiological model proposed offers a template for both clinicians and researchers to evaluate the relative contribution of key indicators to the end-point gestalt of alcohol dependency. Analysis and integration of psychobiological risk factors are illuminated within the context of sub-type identification, tailored treatment interventions and clinical outcome prediction. Implications for current psychiatric practice and the direction of future research are discussed.

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Relationships of plasma tryptophan availability to course of illness and clinical features of alcoholism: a preliminary study

Abstract: These data suggest that a low plasma TRYP/LNAA ratio is associated with susceptibility to anxiety, antisocial-type personality characteristics, and an early age of onset for alcoholism. In contrast, a high plasma TRYP/LNAA ratio is associated with a later onset of alcoholism and dysphoria.

Cited by 31 publications

References 30 publications

Neuropharmacological treatments for alcoholism: scientific basis and clinical findings

Neuropharmacological treatments for alcoholism: scientific basis and clinical findings

Comparison of Alcoholism Subtypes as Moderators of the Response to Sertraline Treatment

Towards an Integrated Clinical Psychobiology of Alcoholism

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