The Combined Dexamethasone-Suppression/CRH-Stimulation Test in Alcoholics During and After Acute Withdrawal

Hundt, Walter; Zimmermann, U.; P??ttig, M.; Spring, K.; Holsboer, Florian

doi:10.1097/00000374-200105000-00009

Cited by 14 publications

(15 citation statements)

References 30 publications

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“…Finally, up-regulation of hypothalamic-pituitary-adrenal (HPA)-axis reactivity, measured by dex-CRH responses, has been reported in the first weeks following initiation of alcohol abstinence 43 , and may offer a window on central CRH activity, which is suggested by animal studies to be up-regulated following a prolonged history of brain alcohol exposure 44 . We therefore explored whether a modulation of dex-CRH test responses by acamprosate would indicate that glutamatergic and CRH-related neuroadaptations in alcoholism are related to each other.…”

Section: Commentmentioning

confidence: 99%

Effect of Acamprosate on Magnetic Resonance Spectroscopy Measures of Central Glutamate in Detoxified Alcohol-Dependent Individuals

Umhau¹,

Momenan²,

Schwandt³

et al. 2010

Arch Gen Psychiatry

139

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Context Acamprosate is approved for treatment of alcoholism, but its mechanism of action remains unclear. Animal studies suggest that a persistent hyperglutamatergic state contributes to the pathophysiology of alcoholism, and that acamprosate may exert its actions by intervening in this process. Human translation of these findings is lacking. Objective To examine whether acamprosate modulates indices of central glutamate levels in recently abstinent alcohol dependent patients, as measured by proton nuclear magnetic resonance spectroscopy (1H-MRS). Design A 4 week, double-blind, placebo-controlled randomized controlled experimental medicine study, with 1H-MRS measures obtained on day 4 and 25. Setting NIAAA inpatient research unit at the NIH Clinical Center. Patients Thirty three patients who met the DSM-IV criteria for alcohol dependence and were admitted for medically supervised withdrawal from ongoing alcohol use. Intervention Four weeks of acamprosate (initial oral loading followed by 1998mg daily) or matched placebo, initiated at the time of admission. Outcome measures The main outcome was the glutamate/creatine ratio (Glu) as determined by single voxel 1H-MRS within the anterior cingulate. Exploratory neuroendocrine, biochemical and behavioral outcomes were also collected, as well as safety/tolerability – related measures. Result There was a highly significant suppression of Glu over time by acamprosate (time × treatment interaction: F[1, 29]=13.5, p<0.001). Cerebrospinal fluid (CSF) levels of glutamate obtained in a subset of patients 4 weeks into abstinence were uncorrelated with the MRS measures and were unaffected by treatment, but were strongly correlated (R2=0.48, p<0.001) with alcohol dependence severity. Other exploratory outcomes, including repeated Dex/CRH tests, as well as psychiatric ratings were unaffected. Among tolerability measures, gastrointestinal symptoms were significantly greater in acamprosate treated subjects, in agreement with the established profile of acamprosate. Conclusion MRS measures of central glutamate are reduced over time when acamprosate is initiated at the onset of alcohol abstinence. Trial registration www.clinicaltrials.gov Identifier: NCT00106106

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Section: Commentmentioning

confidence: 99%

Effect of Acamprosate on Magnetic Resonance Spectroscopy Measures of Central Glutamate in Detoxified Alcohol-Dependent Individuals

Umhau¹,

Momenan²,

Schwandt³

et al. 2010

Arch Gen Psychiatry

139

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“…2003). Furthermore, a blunted response of ACTH to stimulation by various methods was noticed during the withdrawal phase (Wand & Dobs 1991; Hundt et al . 2001).…”

Section: Introductionmentioning

confidence: 99%

CLINICAL STUDY: Cortisol concentrations, stress‐coping styles after withdrawal and long‐term abstinence in alcohol dependence

et al. 2006

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Alcohol-dependent patients face a substantial risk of relapse after detoxification. A major risk factor for relapse is stress which is reflected biologically by various physiological changes that include an activation of the hypothalamic-pituitary-adrenal (HPA) axis and release of glucocorticoids. The prospective study examined cortisol concentrations and stress-coping styles in relation to abstinence 1 year following discharge from treatment. Cortisol concentrations were measured in the plasma of 46 alcohol-dependent patients (12 women) on initial presentation for treatment (day 1), and again in plasma and in cerebrospinal fluid (CSF) after 6 weeks of abstinence (day 40). These results were compared with those of 26 age- and sex-matched, healthy control subjects. After withdrawal, the patients completed a comprehensive baseline assessment including a stress-coping questionnaire (Stressverarbeitungsfragebogen SVF120) and were monitored for 1 year after discharge. Negative stress-coping styles (e.g. flight, resignation) positively correlated with higher cortisol concentration in plasma and in CSF after withdrawal (day 40). Compared with relapsers after 1 year, abstainers had significantly lower levels for cortisol in CSF, whereas the stress-coping styles did not differ between abstainers and relapsers in this sample. These findings suggest that relatively stable personality traits like stress-coping styles have no measurable influence on abstinence. The lower cortisol concentration in CSF as an indicator for HPA axis functioning is associated with long-term abstinence in detoxified alcoholics.

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“…A VARIETY OF studies provided evidence of alterations in adrenocorticotropic hormone (ACTH)/cortisol secretion in alcoholic patients (Adinoff et al, 1991; Bruijnzeel and Gold, 2005; Hundt et al, 2001; Inder et al, 1995; Wand and Dobs, 1991). Evidence of altered regulation of the hypothalamic–pituitary–adrenal (HPA) system in alcoholic patients was reported by studies showing abnormal cortisol responses to the dexamethasone suppression test during alcohol drinking and withdrawal periods (Abou‐Saleh et al, 1984; Del Porto et al, 1985; Kirkman and Nelson, 1988; Newson and Murray, 1983; Swartz and Dunner, 1982).…”

mentioning

confidence: 99%

Adrenocorticotropic Hormone/Cortisol Response to Physical Exercise in Abstinent Alcoholic Patients

Coiro

Casti

Jotti

et al. 2007

Alcoholism Clin & Exp Res

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The Combined Dexamethasone-Suppression/CRH-Stimulation Test in Alcoholics During and After Acute Withdrawal

Abstract: We conclude that the HPA system is severely disturbed during alcohol withdrawal, possibly reflecting an exaggerated release of hypothalamic corticotropin and vasopressin.

Cited by 14 publications

References 30 publications

Effect of Acamprosate on Magnetic Resonance Spectroscopy Measures of Central Glutamate in Detoxified Alcohol-Dependent Individuals

Effect of Acamprosate on Magnetic Resonance Spectroscopy Measures of Central Glutamate in Detoxified Alcohol-Dependent Individuals

CLINICAL STUDY: Cortisol concentrations, stress‐coping styles after withdrawal and long‐term abstinence in alcohol dependence

Adrenocorticotropic Hormone/Cortisol Response to Physical Exercise in Abstinent Alcoholic Patients

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