The contribution of parental alcohol use disorders and other psychiatric illness to the risk of alcohol use disorders in the offspring

Background: Few population‐based studies have investigated associations between parental history of alcoholism and the risk of alcoholism in offspring. The aim was to investigate in a large cohort the risk of alcohol use disorders (AUD) in the offspring of parents with or without AUD and with or without hospitalization for other psychiatric disorder (OPD). Methods: Longitudinal birth cohort study included 7,177 men and women born in Copenhagen between October 1959 and December 1961. Cases of AUD were identified in 3 Danish health registers and cases of OPD in the Danish Psychiatric Central Register. Offspring registration with AUD was analyzed in relation to parental registration with AUD and OPD. Covariates were offspring gender and parental social status. Results: Both maternal and paternal registration with AUD significantly predicted offspring risk of AUD (odds ratios 1.96; 95% CI 1.42 to 2.71 and 1.99; 95% CI 1.54 to 2.68, respectively). The association between maternal, but not paternal, OPD and offspring AUD was also significant (odds ratios 1.46; 95% CI 1.15 to 1.86 and 1.26; 95% CI 0.95 to 1.66, respectively). Other predictors were male gender and parental social status. A significant interaction was observed between paternal AUD and offspring gender on offspring AUD, and stratified analyses showed particularly strong associations of both paternal and maternal AUD with offspring AUD in female cohort members. Conclusions: Parental AUD was associated with an increased risk of offspring AUD independent of other significant predictors, such as gender, parental social status, and parental psychiatric hospitalization with other diagnoses. Furthermore, this association appeared to be stronger among female than male offspring. The results suggest that inherited factors related to alcoholism are at least as important in determining the risk of alcoholism among daughters as among sons.     

Multicenter validation study of the %CDT TIA kit in alcohol abuse and alcohol dependence

Background: Carbohydrate-deficient transferrin (CDT) and γ-glutamyl transferase (GGT) are used as biomarkers of alcohol misuse. The aim of this study was to evaluate, in terms of sensitivity and specificity, the performance of the new Bio-Rad %CDT TIA kit and GGT assay for identifying alcohol abuse and alcohol dependence (according to the DSM-IV criteria).
Methods: An open multicenter study (30 centers) over 3 months, including patient groups of "abusers,""dependents," and controls, was conducted in France.
Results: In alcohol abuse, the sensitivity of GGT was 0.56, and that of CDT was 0.80; in alcohol dependence, the sensitivity of GGT was 0.86, and that of CDT was 0.91. The specificity of GGT was 0.77, and that of CDT was 0.83. The association of GGT with CDT increased sensitivity for alcohol abuse to 0.90 and for alcohol dependence to 0.99, but it appreciably decreased specificity (0.63).
Conclusions: %CDT is the better screening marker for alcohol abuse and dependence, but GGT is still a useful marker for the detection of alcohol dependence. As an assay method, the second-generation Bio-Rad %CDT immunoassay can be recommended for routine CDT measurement.     

Coadministration of disulfiram and lorazepam in the treatment of alcohol dependence and co-occurring anxiety disorder: an open-label pilot study

ABSTRACT

Background: Anxiety is common among persons with alcohol use disorder during early abstinence from alcohol. Although benzodiazepines are effective for short-term treatment of anxiety, they are rarely used beyond acute detoxification due to concerns about misuse or interactions with alcohol. Objectives: We conducted an open-label trial to explore the effects of coadministering lorazepam and disulfiram to alcohol-dependent patients with anxiety disorder symptoms. The rationale for this model is to minimize the risks of the benzodiazepine, while also potentially enhancing adherence to disulfiram. Methods: Forty-one participants with DSM-IV alcohol dependence who also met syndromal criteria for anxiety disorder with or without co-occurring major depressive syndrome initiated treatment with lorazepam (starting dose 0.5 mg three times daily) and disulfiram (starting dose 500 mg three times weekly). Participants received 16 weeks of monitored pharmacotherapy with manualized medical management. Results: Adherence to treatment decreased steadily with time (85.4% at 4 weeks, 36.6% at 16 weeks). Participants showed significant increases in percent abstinent days during treatment and at 24 weeks follow-up. Large reductions in anxiety, depression, and craving were observed during treatment, and improvement remained significant at 24 weeks. Duration of adherence with disulfiram strongly predicted abstinence at 16 weeks. There was no evidence of misuse of lorazepam or dose escalation during the study. Conclusion: Lorazepam can be safely used for short-term treatment of anxiety in combination with disulfiram treatment of alcohol use disorder. However, it is not clear that making lorazepam dispensing contingent on adherence to disulfiram enhances retention in disulfiram treatment.     

Mediterranean alcohol-drinking pattern,low to moderate alcohol intake and risk of atrial fibrillation in the PREDIMED study

Background and aimsThere is ongoing controversy about the effect of a low to moderate alcohol consumption on atrial fibrillation (AF). Our aim is to assess the association between adherence to a Mediterranean alcohol drinking pattern and AF incidence.Methods and resultsA total 6527 out of the 7447 participants in the PREDIMED trial met our inclusion criteria. A validated frequency food questionnaire was used to measure alcohol consumption. Participants were classified as non-drinkers, Mediterranean alcohol drinking pattern (MADP) (10–30 g/d in men and 5–15 g/day in women, preferably red wine consumption with low spirits consumption), low-moderate drinking (<30 g/day men y and < 15 g/day women), and heavy drinking. We performed multivariable Cox regression models to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) of incident AF according to alcohol drinking patterns. After a mean follow up of 4.4 years, 241 new incident AF cases were confirmed. Alcohol consumption was not associated to AF incidence among low-moderate drinkers (HR: 0.96; 95%CI: 0.67–1.37), adherents to MADP (HR: 1.15 95%CI: 0.75–1.75), or heavy drinkers (HR: 0.92; 95%CI: 0.53–1.58), compared with non-drinkers.ConclusionsIn a high cardiovascular risk adult population, a Mediterranean alcohol consumption pattern (low to moderate red wine consumption) was not associated with an increased incidence of AF.Clinical trialsURL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.     

Effects of chronic alcohol consumption on the broad phospholipid signal in human brain: an in vivo 31P MRS study

BACKGROUND: Phosphorus magnetic resonance spectroscopy (31P MRS) allows for the measurement of phospholipids and their breakdown products in the human brain. Fairly mobile membrane phospholipids give rise to a broad signal that co-resonates with metabolic phosphodiesters. Chronic alcohol exposure increases the rigidity of isolated brain membranes and, thus, may affect the amount and transverse relaxation times (T2) of MRS-detectable phospholipids. We tested the hypothesis that subjects who were heavy drinkers have stiffer membranes than controls who were light drinkers, as reflected in a smaller broad signal component and a shorter T2 of the broad signal in 31P MR spectra of the brain. METHODS: Thirteen alcohol-dependent heavy drinkers (mean age 44 years) were studied by localized 31P MRS in the centrum semiovale and compared with 17 nondependent light drinkers of similar age. The broad component signal was separated from the metabolite signal by convolution difference, which is based on the large difference in line widths of these two signals. Longitudinal and T2 relaxation times were measured using standard methods. RESULTS: The broad component integral was 13% lower in the brain of heavy drinkers compared with light drinkers (p < 0.001) and remained significantly smaller after corrections for both longitudinal and transverse relaxations (p < 0.01). The T2 distribution of the broad component consistently showed two resolvable components in both groups. The fast relaxing component had the same T2 in both groups (T2 = 1.9 msec). The slower relaxing component T2 was 0.6 msec shorter in heavy drinkers compared with light drinkers (p = 0.08). CONCLUSIONS: These results, observed in the absence of white matter volume loss, are consistent with biochemical alterations and higher rigidity of white matter phospholipids associated with long-term chronic alcohol abuse. The observed smaller broad signal component in these relatively young heavy drinkers is a sensitive measure of white matter phospholipid damage.     

Abstention, alcohol use and risk of myocardial infarction in men and women taking account of social support and working conditions: the SHEEP case-control study

Aims Very few studies indicating that low–moderate alcohol consumption protects from myocardial infarction (MI) controlled for social support and working conditions, which could confound the findings. Therefore, a first aim was to study the risk of non‐fatal and total MI in relation to volume of alcohol consumption and measures of social support and working conditions. A second aim was to analyse the impact of the volume of earlier alcohol use in abstainers. Design Data came from a case–control study, the Stockholm Heart Epidemiology Program (SHEEP), including first MI among Swedish citizens 45–70 years old. Setting Stockholm County 1992–94. Participants There were 1095 cases of MI in men and 471 in women (928 and 372 were non‐fatal), and 2339 living controls from the general population. Measurement Information about alcohol use at different periods in life and job strain, social anchorage and life control besides pre‐existing health problems, smoking, physical activity, socio‐economic status and marital status was obtained by a questionnaire from the cases and the controls. Findings In multivariate logistic regression analyses, the relative risk for MI (especially non‐fatal) was reduced among alcohol consumers. RR for non‐fatal MI was 0.52 (95% confidence intervals 0.32, 0.85) in men with a consumption of 50–69.9 g 100% ethanol/day and 0.21 (95% confidence interval 0.06, 0.77) in women with a consumption of 30 g or more per day (reference category 0.1–5 g 100% ethanol/day). Men who were abstainers during the previous 1–10 years and with an earlier average consumption of 5–30 g 100% ethanol/day had a significantly lower relative risk compared to such abstainers with an earlier higher consumption. Earlier consumption among abstainers may also have an impact on gender differences in MI. Analyses showed positive interaction between abstention and low life‐control in women, but only 4% of the female cases were due to this interaction. There were no other interactions between measures of alcohol use and social anchorage, life control and working situations. Conclusion Alcohol use had a protective impact on MI, with little impact of job strain, social anchorage and life control, giving increased support for a protective impact of low‐moderate alcohol use. The level of previous alcohol consumption among male 1–10‐year‐long abstainers influenced the risk of MI.     

Effects of abstinence from alcohol on the broad phospholipid signal in human brain: an in vivo 31P magnetic resonance spectroscopy study

BACKGROUND: In vivo phosphorus magnetic resonance spectroscopy (31P MRS) at a magnetic field strength of 1.5 T allows measurement of fairly mobile membrane phospholipids in the human brain. We previously showed that subjects who are heavy drinkers had a smaller signal and a shorter transverse relaxation time (T2) of white matter phospholipids than light drinkers, which suggested lower concentrations and molecular mobility of phospholipids in heavy drinkers. The purpose of the present study was to measure if such chronic alcohol-induced white matter tissue changes are persistent in long-term abstinent alcoholics. METHODS: Fourteen abstinent alcoholics (mean age 45 years, seven men and seven women) were studied by localized 31P MRS in the centrum semiovale and were compared with 13 male, alcohol-dependent, heavy drinkers and 23 nondependent light drinkers (17 men, 6 women) of similar age. Methods for measurements of the broad membrane phospholipid signal and its relaxation time were described previously. RESULTS: Phospholipid concentrations and relaxation times in alcoholics abstinent for an average of 31 months were not significantly different from those measured in light drinkers. The contribution of fast and slowly relaxing signal components to the broad phospholipid signal, however, was still different in abstinent alcoholics compared with light drinkers. No effects of sex or of family history of alcoholism were noted on any of our spectroscopic measures within the light-drinking or abstinent groups. CONCLUSIONS: Most of our results suggest at least partial recovery of chronic alcohol-induced white matter phospholipid damage with long-term abstinence. They offer myelination changes and/or dendritic rearborization as a possible mechanism for the commonly observed white matter volume gain with prolonged abstinence. But the results also suggest a persistent abnormality in the nature and/or physical properties of white matter phospholipids in long-term abstinent alcoholics.     

Age- and sex-based ranges of platelet count and cause-specific mortality risk in an adult general population: prospective findings from the Moli-sani study

Platelet count varies by age, sex and ethnicity. However, previous studies have adopted standard ranges to identify subjects with thrombocytopenia or thrombocytosis. The aim of this study was to test the predictive role of age-sex-based cut-offs of platelet count proposed by an Italian collaborative study, towards the risk of cause-specific death. We conducted a prospective analysis on 21,563 adult subjects (mean age 55.6 ± 11.8) randomised from the general population of the Moli-sani study.

Hazard ratios (HR) were calculated by multivariable Cox-proportional hazard models with 95% confidence intervals. Over a median follow-up of 8.2 years (interquartile range: 7.3 to 9.2 years; 175,972 person-years), we ascertained and validated 1,130 deaths, 415 of which are from cardiovascular disease, 439 from cancer and 276 from non-vascular/non-cancer causes.

As opposed to the normal ranges defined by age and sex (extreme values from 122 to 405 x10⁹/L), lower platelet number (87.7% of values being higher than 100x10⁹/L) was associated with increased risk of total (HR = 1.92; 95%CI 1.38–2.67), cancer (HR = 1.77; 95%CI 1.03–3.05), and non-cardiovascular/non-cancer mortality (HR = 3.16; 95%CI 1.84–5.42) but was unrelated to cardiovascular mortality. Higher platelet count was not associated with any death risk.

In conclusion, age-sex-based low platelet count, well above the traditional lower normal range of <100 x10⁹/L, is associated with increased total and specific mortality risk in a general population.