Effects of a Fermented Dairy Drink Containing Lacticaseibacillus paracasei subsp. paracasei CNCM I-1518 (Lactobacillus casei CNCM I-1518) and the Standard Yogurt Cultures on the Incidence, Duration, and Severity of Common Infectious Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There is considerable interest in the role of probiotics in immune function. The objective of this systematic review and meta-analysis was to assess the effects of the consumption of a fermented dairy drink containing Lacticaseibacillus paracasei subsp. paracasei CNCM I-1518 (the previous taxonomic nomenclature was Lactobacillus casei CNCM I-1518, prior to the nomenclature change in April 2020) and the standard yogurt cultures (hereinafter referred to collectively as "FDD") on common infectious diseases (CIDs) in generally healthy children and adults. Nine literature databases were searched, and nine randomized controlled trials from eight publications were eligible for inclusion. Combined effect sizes were determined for three metrics of CID incidence, two metrics of CID duration, and one metric of CID severity. Compared to the control, the consumption of the FDD resulted in (1) a significant reduction in the odds of experiencing ≥1 CID (odds ratio (OR) (with a 95% confidence interval (CI)): 0.81 (0.66, 0.98); p = 0.029); (2) a significant reduction in mean CIDs per subject (-0.09 (-0.15, -0.04); p = 0.001); and (3) a trend towards reduced risk in cumulative CIDs (relative risk (RR): 0.91 (0.82, 1.01); p = 0.082). The consumption of the FDD had no significant effect on CID duration or severity. Based on the studies conducted thus far, these results suggest that the FDD may reduce CID incidence in the general population.

A functional serotonin transporter gene polymorphism and depressive effects associated with interferon-alpha treatment.

BACKGROUND: Interferon-alpha (IFN-alpha) treatment frequently induces depression, potentially leading to early dose reductions or a shorter duration of treatment, which can adversely affect outcomes, including quality of life. OBJECTIVE: Defining relevant risk factors for IFN-alpha-induced depression is essential in order to identify prophylactic treatment strategies. METHOD: The authors examined whether a functional polymorphism (5-HTTLPR) in the gene encoding the serotonin transporter moderates IFN-alpha-induced depressive symptoms in 1,015 patients with chronic hepatitis C (CHC) receiving pegylated IFN-alpha and ribavirin. Depressive symptoms were assessed at baseline, 12 weeks, and 20 weeks of treatment. RESULTS: Depression symptoms increased during antiviral treatment; 5-HTTLPR genotype moderated IFN-alpha-induced depression symptoms in both non-Hispanic Caucasians and Hispanic patients, although the opposite risk allele was associated with depression in the two populations. CONCLUSION: 5-HTTLPR may moderate risk for the development of depressive symptoms during IFN-alpha therapy for CHC in a population-specific manner.

Effects of aripiprazole on subjective and physiological responses to alcohol.

BACKGROUND: Aripiprazole is an atypical antipsychotic with partial agonist activity at D(2) receptors, which could reduce the reinforcing effects of alcohol. The present study examined whether aripiprazole modifies the behavioral and physiological effects of a moderate dose of alcohol in a group of social drinkers. METHODS: Eighteen healthy subjects (9 men; mean age = 27.6 years) completed a double-blind, within-subject study with 3 experimental sessions in a randomized sequence, during which they received no medication, aripiprazole 2.5 mg, or aripiprazole 10 mg on the day prior to the laboratory session. During the session, subjects consumed alcohol that was served as three standardized drinks (i.e., a total of 0.8 g/kg for men and 0.7 g/kg for women). Breath alcohol concentration (BrAC), heart rate, blood pressure, static ataxia, and subjective effects were measured regularly throughout the laboratory sessions. RESULTS: Alcohol consumption produced physiological and subjective responses that were consistent with the literature on its effects. Pre-treatment with aripiprazole was generally well tolerated, with tiredness being the most commonly reported adverse event. The medication was associated with modest physiological effects. It also significantly and dose-dependently increased the sedative effects of alcohol and, to a lesser degree, decreased the euphoric effects of alcohol. CONCLUSIONS: These findings require replication in a larger subject sample that includes heavy drinkers and in a study that employs a placebo session. Based on its capacity to increase the sedative effects and decrease the euphoric effects of alcohol, aripiprazole could be of value in the treatment of heavy drinking.

Reliability of DSM-IV diagnostic criteria using the semi-structured assessment for drug dependence and alcoholism (SSADDA).

UNLABELLED: The semi-structured assessment for drug dependence and alcoholism (SSADDA) yields reliable DSM-IV diagnoses for a variety of psychiatric disorders, including alcohol and drug dependence. This study examines the reliability of individual DSM-IV criteria for lifetime substance dependence diagnoses and the impact of those criteria on diagnostic reliability. METHODS: Two hundred ninety-three subjects (52.2% women; 38.2% African American, 46.8% European American, 7.5% Hispanic) were interviewed twice over a 2-week period to examine the inter-rater reliability (n=173) or test-retest reliability (n=120) of the SSADDA. Cohen's kappa-statistic and its confidence interval were used to assess the reliability of individual diagnostic criteria. RESULTS: Overall, the inter-rater reliability estimates were excellent for individual DSM-IV criteria for nicotine and opioid dependence; good for alcohol and cocaine dependence, and fair for dependence on cannabis, sedatives and stimulants. The impact of any individual criterion on diagnostic reliability was minimal, consistent with the notion that the DSM-IV diagnosis of substance dependence measures an underlying construct that is relatively consistent across specific groups of substances. CONCLUSIONS: These results, combined with results from a study of the SSADDA's diagnostic reliability [Pierucci-Lagha, A., Gelernter, J., Feinn, R., Cubells, J.F., Pearson, D., Pollastri, A., Farrer, L., Kranzler, H.R., 2005. Diagnostic reliability of the semi-structured assessment for drug dependence and alcoholism (SSADDA). Drug Alcohol Depend. 80, 303-312], show that the instrument can be used reliably to assess substance dependence.

Subjective effects and changes in steroid hormone concentrations in humans following acute consumption of alcohol.

BACKGROUND: GABAA receptors are an important site of action of endogenous neurosteroids and an important mediator of several behavioral effects of alcohol. This study examined the effects of alcohol on plasma steroid hormone concentrations on the hypothesis that the endocrine effects mediate some of the subjective effects of alcohol. METHODS: Thirty-two healthy subjects (17 men) with no history of a substance use disorder participated in this human laboratory study. All subjects consumed three standard drinks of grain alcohol. Subjective measures and blood samples for steroid concentrations were collected at baseline and 40 min after alcohol consumption. RESULTS: Alcohol increased self-reported stimulation, alcohol liking, and desire for more alcohol. Alcohol also increased pregnenolone (PREG) and dehydroepiandrosterone (DHEA) concentrations, while it decreased progesterone (PROG) and allopregnanolone (ALLO) concentrations, as well as ALLO/PREG and PROG/PREG ratios. In men, the change in PREG concentration was significantly correlated with alcohol liking, while the alcohol-induced change in ALLO concentration correlated significantly with both alcohol liking and desire for more alcohol. DISCUSSION: These findings provide preliminary support for the hypothesis that endogenous neurosteroids mediate some of the subjective effects of alcohol. Efforts to replicate these findings should aim to specify more clearly the nature and time course of the effects.

Diagnostic reliability of the Semi-structured Assessment for Drug Dependence and Alcoholism (SSADDA).

UNLABELLED: The Semi-structured Assessment for Drug Dependence and Alcoholism (SSADDA) is a diagnostic instrument developed for studies of the genetics of substance use and associated disorders. The SSADDA provides more detailed coverage of specific drug use disorders, particularly cocaine and opioid dependence, than existing psychiatric diagnostic instruments. A computerized version of the SSADDA was developed to permit direct entry of subject responses by the interviewer. This study examines the diagnostic reliability of the SSADDA for substance use disorders and for other DSM-IV disorders that are commonly associated with substance use disorders. METHODS: Two hundred and ninety-three subjects (mean age = 39 yr, 52.2% women) were interviewed twice over a 2-week period in two sub-studies examining the inter-rater (n = 173) or test-retest reliability (n = 120) of the SSADDA. The kappa statistic and Yule's Y were used to measure reliability. RESULTS: The reliability of most substance dependence diagnoses was good to excellent, although the reliability of substance abuse diagnoses was substantially lower. The reliability of the associated psychiatric diagnoses varied from fair to excellent. CONCLUSIONS: The SSADDA yields reliable diagnoses for a variety of psychiatric disorders, including alcohol and drug dependence. Although developed for use in genetic studies, its broad and detailed coverage of disorders and computer-assisted format will allow it to be used in a variety of applications requiring careful diagnostic assessment.

GABRA2 alleles moderate the subjective effects of alcohol, which are attenuated by finasteride.

GABA(A) receptors are involved in the subjective effects of alcohol. Endogenous neuroactive steroids interact with GABA(A) receptors to mediate several behavioral effects of alcohol in rodents. Based on a haplotypic association of alcohol dependence with the gene encoding the GABA(A) receptor alpha-2 subunit (GABRA2), we examined whether GABRA2 alleles are associated with the subjective response to alcohol. We also examined whether finasteride (a 5-alpha steroid reductase inhibitor), which blocks the synthesis of some neuroactive steroids, reduces the subjective response to alcohol. In all, 27 healthy social drinkers (15 males) completed a randomized, double-blind, placebo-controlled study of high-dose finasteride. After being pretreated with study drug, subjects consumed three alcoholic drinks. Subjective effects were measured repeatedly over the ascending blood alcohol curve. To examine the moderating role of genetic variation in GABRA2, a single-nucleotide polymorphism that was informative in association studies was included as a factor in the analysis. Subjects homozygous for the more common A-allele (n=7) showed more subjective effects of alcohol than did individuals with one or two copies of the alcohol dependence-associated G-allele (n=20, including two homozygotes). Among the A-allele homozygotes, there was a greater reduction in several subjective effects during the finasteride session compared to the placebo session. These findings provide preliminary evidence that the risk of alcoholism associated with GABRA2 alleles may be related to differences in the subjective response to alcohol. The effects of finasteride provide indirect evidence for a mediating role of neuroactive steroids in some of the subjective effects of alcohol.

Effects of rapid tryptophan depletion on mood and urge to drink in patients with co-morbid major depression and alcohol dependence.

RATIONALE: Rapid tryptophan depletion (RTD) has been used to study central serotonin function and may therefore be useful in understanding co-morbid alcohol dependence (AD) and major depressive disorder (MDD). OBJECTIVES: To examine (1) the effect of RTD on mood and urge to drink among patients with AD and MDD and (2) the association of RTD effects with alleles of a functional polymorphism in the gene encoding the serotonin transporter protein. METHODS: Double-blind, placebo-controlled study, in which 14 treatment responders recruited from one of two placebo-controlled trials of serotonergic antidepressants were enrolled. Patients underwent two day-long sessions, which were either a tryptophan depletion session or a sham session. During each session, mood and urge for alcohol were measured at regular intervals. RESULTS: Five hours after RTD, plasma TRP concentrations decreased by 73.1%. There was a significant effect of session on both mood and the urge to drink. Genotype moderated the effect of session on mood, such that, during RTD, individuals homozygous for the long allele reported greater depression than did subjects with one or two copies of the S allele. CONCLUSIONS: This study provides support for the role of serotonergic neurotransmission in modulating mood and alcohol urges, and underscores the utility of these effects as a phenotype for genetic analysis. These findings may also help to identify alcoholics who are at greatest risk for MDD.

Effects of ondansetron in early- versus late-onset alcoholics: a prospective, open-label study.

BACKGROUND: Early-onset alcoholics (EOAs) have a greater familial loading for alcoholism, more severe progression of the disorder, a greater severity of comorbid psychopathology, and a poorer response to treatment than late-onset alcoholics (LOAs). Ondansetron, a 5-hydroxytryptamine-3 antagonist, was found to be superior to placebo in the treatment of EOAs, but not of LOAs. This study compared the tolerability and potential efficacy of an oral solution of ondansetron in EOAs versus LOAs. METHODS: Forty outpatients with alcohol dependence (67.5% male; 87.5% European American; 20 EOAs; 20 LOAs) received an oral solution of ondansetron at a dosage of 4 microg/kg twice daily for 8 weeks, together with weekly relapse-prevention therapy. RESULTS: EOAs had a significantly greater decrease in drinks per day, drinks per drinking day, and alcohol-related problems than LOAs. Changes in the level of carbohydrate-deficient transferrin were consistent with changes in self-reported drinking behavior. CONCLUSIONS: An oral solution of ondansetron seems suitable for the treatment of alcohol dependence, yielding findings consistent with evidence from a placebo-controlled trial that ondansetron, at a dosage of 4 microg/kg twice daily, is of value in the treatment of EOAs.

[Alcoholism and aging. 1. Epidemiology, clinical aspects and treatment]. / Alcool et vieillissement. 1. Aspects épidémiologiques, cliniques et thérapeutiques.

Demographic trends reveal the elderly to be the fastest growing segment of the population. Physicians can therefore anticipate to be faced with a growing number of older patients with alcohol-related problems. It is now being increasingly recognized that alcoholism does not only concern the young population, but can appear for the first time late in life. One third of older alcoholic people develop a problem with alcohol in later life, while the other two thirds grow older with the medical and psychosocial sequelae of early-onset alcoholism. In addition, as the number of the elderly increases, clinicians are more faced with patients who began drinking earlier in life and who continue to do so late on life. Furthermore, increasing age is associated with a higher prevalence of chronic disease and use of medication that may interact to amplify the effects of alcohol. Alcohol may cause or worsen chronic illnesses or symptoms such as insomnia, depression, and hypertension. On the other hand, older drinkers are therefore more likely to have adverse consequences of drinking at lower levels of alcohol consumption, and these consequences are likely to be more severe. In this paper, we review the prevalence of geriatric alcoholism, the drinking pattern seen in the elderly i.e., early vs. late onset alcoholism, and we expose the danger of alcohol problems underdiagnosis. In addition, we review the comorbidities associated with alcohol use and finally we discuss treatment options.

[Alcoholism and aging. 2. Alcoholic dementia or alcoholic cognitive impairment?]. / Alcool et vieillissement. 2. Démence alcoolique ou déficit cognitif alcoolique?

Chronic alcohol consumption results in considerable damage to many of the body's organs, and particularly to the brain. Beyond the confusional state occurring with acute intoxication or withdrawal, alcohol abuse is responsible of a constellation of neuropsychiatric syndromes including cognitive dysfunction, Wernicke-Korsakoff Syndrome, alcoholic cerebellar degeneration, Marchiafava-Bignami disease and alcohol-related dementia, ARD. ARD would account for nearly 20% of all admissions to state mental hospitals in the United-States. According to the DSM-IV, ARD is defined by a dementia associated with alcohol abuse. However, the concept of a dementia directly related to the neurotoxicity of alcohol for brain neurons is still a matter of debate. Several hypotheses have been proposed to explain the mechanisms of cognitive deficits related to chronic alcohol intoxication. This paper presents the epidemiological, neuropathological, neurochemical and clinical data on ARD. Alcoholism is responsible for cognitive deficits of various severity, which could be reversible or not with alcohol abstinence, but can also participate to the cognitive impairment related to other pathologies, such as Alzheimer disease. On account of this review, it is suggested that the term alcohol-related cognitive impairment should be more convenient than that of ARD, more restrictive and more confusing. Presently, there are no established treatment for alcohol-related cognitive impairment. Alcohol abstinence is a most important step. Psychosocial interventions are essential to support the patients in the daily life.