Alcohol use disorders among adult children of alcoholics (ACOAs): Gene-environment resilience factors.

Both genetic and early environmental factors contribute to the pathogenesis of Alcohol Use Disorder (AUD). Gender and psychopathology symptoms might further moderate this association, resulting in an impairment of both the dopaminergic and serotoninergic pathways that sustain the binge, withdrawal and craving cycle. In a sample of of adult children of alcoholic parents (ACOAs) (n = 107) we compared those with and without an AUD, on socio-demographic variables, adverse childhood experiences, psychopathology symptoms and two polymorphisms associated with an impaired serotoninergic and dopaminergic neurotransmission (5HTTLPR and Taq1A/DRD2). A logistic regression revealed that an early caring environment might lower the risk of developing an AUD. When controlling for the actual psychopathology symptoms, being male and having the genotype associated with an impaired dopaminergic neurotransmission were still associated with AUD. Results were confirmed by an unsupervised approach that showed how the clusters characterised by being male and having the high risk genotypes were still associated with AUD compared to being female without the unfavourable dopamine genotype.Our results point to the need for implementing prevention strategies aimed at creating a caring environment especially in those families with an alcoholic parent. We further suggest that psycho-education as a symptom recognition and avoiding self-medication could improve the outcome in those subjects at higher risk, especially males.

Endothelial dysfunction and high cardiovascular risk profile in severe alcoholics improve only partially following a medium-term alcohol withdrawal.

BACKGROUND: Little is known about brachial artery flow-mediated vasodilatation (FMD) in active and medium-term withdrawing heavy alcoholics (HA). METHODS: FMD and some parameters of cardiovascular (CV) risk were measured in 29 HA (average alcohol intake 135, range 86 to 215 g per day) at baseline and after a 9 ± 7 months withdrawal and in 35 teetotalers. RESULTS: HA showed baseline impaired maximal % FMD (8.5 ± 5.4 SD vs. 14.9 ± 7.4, <0.001 vs. teetotalers), higher systolic (SBP) and diastolic (DBP) blood pressure (+24 mm Hg, <0.001; +15 mm Hg, <0.01), uric acid (5.3 ± 1.1 vs. 4.4 ± 0.8 mg/dl, <0.05), high-sensitivity C-reactive protein (hs-CRP; 2.7 ± 2.0 vs. 1.0 ± 0.9 mg/l, <0.02), endothelin-1 (ET-1, 0.88 ± 0.36 vs. 0.37 ± 0.10 pg/ml,<0.001), asymmetric dimethylarginine (ADMA, 0.50 ± 0.21 vs. 0.41 ± 0.12 µmol/l, p < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (2.3 ± 1.1 vs. 1.2 ± 0.4, <0.001), and urinary 8-isoprostane (U8-iso-PGF2α) (237.2 ± 172.4 vs. 168.5 ± 96.6 pg/mg creatinine, <0.05). After withdrawal, SBP fell by 15 mm Hg, DBP by 11 mm Hg (p < 0.001), and hs-CRP by 0.94 mg/l (p < 0.02), all remaining still higher than teetotalers (<0.05, 0.01, 0.05 respectively). ET-1, HOMA-IR, and U8-iso-PGF2α were unchanged (p = NS vs. baseline, <0.05 to 0.001 vs. teetotalers). Maximal % FMD rose (to 10.6 ± 6.2, p < 0.04), but it still remained impaired (<0.04 vs. teetotalers). ADMA increased further to 0.64 ± 0.15 µmol/l (<0.05 vs. baseline, <0.02 vs. teetotalers). CONCLUSIONS: HA show marked endothelial dysfunction (ED) and high BP, impaired insulin sensitivity, inflammation, increased oxidative stress, and elevated ET-1 and ADMA, which are unaffected or only partially reversed by a medium-term alcohol withdrawal. ED and related abnormalities persist in detoxified alcoholics, thus contributing to a greater CV morbidity and mortality.

Effects of moderate ethanol drinking on the GH and cortisol responses to physical exercise.

OBJECTIVE: To evaluate the effects of moderate amounts of ethanol on the GH and cortisol responses to physical exercise. METHODS: Ten normal men underwent three bicycle ergometer tests. Test were carried out in basal conditions (control test) or after drinking 0.5 or 0.75 g/kg BW ethanol. Tests lasted 15 min in all subjects; the workload was increased at 3 min intervals from time 0 until exhaustion. Non-endocrine physiological parameters (NEPP), such as heart rate, blood pressure, ventilation, frequency of breathing, tidal volume, oxygen consumption, carbon oxide production and respiratory exchange ratio were measured from time 0 until exhaustion. Serum GH and cortisol levels were evaluated in blood samples taken at 5-10 min intervals over a 50 min period from time 0. RESULTS: Neither basal values, nor exercise-induced changes in NEPP were altered by ethanol drinking. Both GH and cortisol levels significantly rose during the exercise control test. The hormonal responses did not change after 0.5 g/kg BW ethanol, whereas they significantly decreased after 0.75 g/kg BW ethanol. CONCLUSIONS: Modification of the GH and cortisol responses to exercise represents an "endocrine window" of the effects that even moderate ethanol drinking produces in the CNS. The data show that 0.75 g/kg BW ethanol is the minimal amount producing significant inhibitory effects on the GH and cortisol responses to physical exercise. In view of the important roles played by GH and cortisol during physical activity, even moderate ethanol drinking must be avoided before sport.

Endothelial dysfunction and cardiovascular risk profile in long-term withdrawing alcoholics.

BACKGROUND: Rates of cardiovascular morbidity and mortality are greater in heavy alcoholics than in either teetotallers or light-to-moderate drinkers. OBJECTIVE: On the assumption that factors leading to atherosclerotic damage remain operative even after long-term alcohol withdrawal, we studied the possible mechanisms of raised cardiovascular risk in former heavy alcoholics. METHODS: Forty-two apparently disease-free, normotensive alcoholics detoxified for 37.1 +/- 31.9 (SD) months, median 24, participated in the study. They were compared with 39 lifetime alcohol-abstaining control subjects, carefully matched for age, sex, body mass index, smoking and dietary habits, physical activity, lipids and fasting glucose. Endothelial function (flow-mediated dilation of brachial artery, high-resolution ultrasound technique), blood pressure, and some parameters of endothelial activation, oxidative stress, vascular inflammation and insulin sensitivity were measured. RESULTS: The maximal percentage of flow-mediated dilatation was reduced in detoxified alcoholics (10.1 +/- 4.6 versus 14.9 +/- 7.4, P < 0.001) who also showed significantly higher blood pressure (systolic 127.5 +/- 12.9 versus 118.2 +/- 10.7 mmHg, P < 0.001; diastolic 79.4 +/- 7.1 versus 74.6 +/- 6.4 mmHg, P < 0.01; mean 95.4 +/- 8.2 versus 89.1 +/- 7.3 mmHg, P < 0.001), uric acid (5.0 +/- 1.1 versus 4.4 +/- 0.8 mg/dl, P < 0.05), high-sensitivity C-reactive protein (2.1 +/- 2.0 versus 1.0 +/- 0.9 mg/l, P < 0.01), endothelin-1 (0.38 +/- 0.11 versus 0.17 +/- 0.10 pg/ml, P < 0.001) and fasting insulin (10.4 +/- 4.5 versus 5.6 +/- 1.6 muU/ml, P < 0.001) with abnormal homeostasis model assessment index of insulin resistance (2.3 +/- 1.1 versus 1.2 +/- 0.4, P < 0.001). CONCLUSION: Previous heavy alcoholism, in spite of long-term withdrawal, is associated with endothelial dysfunction and a wide cluster of haemodynamic, vascular and metabolic abnormalities that indicate an unfavourable cardiovascular and metabolic risk profile even in apparently disease-free former alcoholics.

Sodium sensitivity as a main determinant of blood pressure changes during early withdrawal in heavy alcoholics.

BACKGROUND: Stimulated sympathetic nervous system, renin-angiotensin-aldosterone system, vasopressin, and cortisol are thought to affect blood pressure in early withdrawal of alcoholics. Hyperactivity of sodium-retaining systems with consequent volume expansion also could interact with sodium sensitivity as previously found in long-term withdrawing alcoholics. METHODS: To investigate this hypothesis, blood pressure and sodium balance were measured during the first 8 days of withdrawal in 18 chronic alcoholics on a 150 mM Na diet. Results were related to the Salt Sensitivity Index of blood pressure as measured in the same alcoholics after 1 year of abstinence. RESULTS: Early withdrawal study: there was a positive sodium balance (+288.6 +/- 45.6 mM; p < 0.0001) and rise in mean arterial pressure (+11.8 +/- 2.9 mm Hg; p = 0.001) during early withdrawal on 150 mM Na diet. Salt Sensitivity Study after long-term detoxification: the shift from low (55 mM) to high sodium (260 mM) intake produced a larger (p = 0.04) increase in mean arterial pressure in alcoholics (+9.3 +/- 2.0 mm Hg) than in 30 teetotal controls (+5.1 +/- 1.1) (Salt Sensitivity Index, 0.047 +/- 0.008 vs. 0.023 +/- 0.0053; p < 0.05). Changes in mean blood pressure during withdrawal were highly related to sodium sensitivity index (r = 0.8; p < 0.001). CONCLUSIONS: Early withdrawing alcoholics exposed to a normal sodium intake experience positive Na balance and increase in blood pressure that is related to sodium sensitivity measured after long-term detoxification. This suggests that salt sensitivity plays a key role in blood pressure regulation in early withdrawing alcoholics.