Age-dependent changes in electroencephalographic responses to alcohol consumption in subjects with aldehyde dehydrogenase-2 genetic variations.

BACKGROUND: We have recently reported that alcohol consumption resulted in a significant increase in alpha power of the EEGs in aldehyde dehydrogenase-2 (ALDH2)-normal (NN) subjects but not in ALDH2-deficient heterozygote (ND) subjects. The purpose of the present study was to investigate interactive effects of individual factors such as age and ALDH2 genotype on alcohol-induced EEG changes. METHODS: We examined EEG power spectral changes induced by 0.4 ml/kg of alcohol ingestion in 53 NN and 21 ND subjects of two different age groups: younger and older groups. Blood ethanol and acetaldehyde levels were also determined in 17 NN and 13 ND subjects in separate studies. RESULTS: Alcohol consumption markedly increased EEG power in the NN subjects of the older group, especially in theta and slow alpha power, whereas only slight increases were noted in fast alpha and beta power in the NN subjects of the younger group. However, no such differences between the two age groups were observed in the ND subjects. It should be noted that there were no differences in blood ethanol and acetaldehyde level at 30 min after alcohol ingestion between the different age groups in both genotypes. However, there was a significant increase in frequency of alcohol intake in the older group of both genotype groups. The multiple regression analysis indicated that both alcohol use habits and genotype, as well as aging, significantly modulated EEG changes after alcohol ingestion. CONCLUSIONS: The results suggest that both ALDH2 genotype and age as well as alcohol use habits modify alcohol sensitivity in the central nervous system, resulting in greater increases in EEG energy in response to alcohol intake in the older group of the NN subjects.

Effects of aldehyde dehydrogenase-2 genotype on cardiovascular and endocrine responses to alcohol in young Japanese subjects.

The present study was designed to investigate the effects of aldehyde dehydrogenase-2 (ALDH2) genotype on cardiovascular and endocrine responses to alcohol ingestion in young, healthy Japanese subjects. For this purpose, we monitored changes in the electrocardiogram (ECG), blood pressure (BP), finger blood flow (BF) and facial skin temperature (FST) during and after alcohol ingestion (0.4 ml/kg body weight). Spectral analyses of beat-to-beat variations of heart rate (HR), BP and BF were applied. Two major spectral components were examined at low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-10.4 Hz) bands for HR and BP variability (BPV). Significant effects for ALDH2 genotype were observed in HR variability (HRV) analysis; HF power of HRV was markedly depressed and the LF/HF ratio was significantly higher with alcohol in ALDH2-deficient (ND) subjects, while ALDH2-normal (NN) subjects did not display such changes. Analysis of BP variability showed increased LF and HF power after alcohol ingestion in the NN subjects, but there were no significant differences between genotypic groups. We also examined BF variability (BFV) in six major spectral components; power of the 0.8-2.2 Hz frequency band was significantly affected by genotype and higher power was observed in the ND subjects. Plasma concentrations of both epinephrine and norepinephrine increased after alcohol ingestion only in the ND subjects. Furthermore, plasma concentrations and urinary excretion of epinephrine, but not norepinephrine, were higher after alcohol ingestion in the ND than in the NN subjects. Blood acetaldehyde levels were about 10-fold higher in the ND than in the NN subjects although blood alcohol levels similarly increased in the ND and NN subjects. Our results also indicated that alcohol ingestion increased secretion of pituitary-adrenal hormones including ACTH, beta-endorphin and cortisol in the ND subjects. The present results along with previous studies suggest that alcohol-induced tachycardia in the ND subjects was probably mediated by acetaldehyde-induced rise in epinephrine secretion from the adrenal medulla and/or changes in the autonomic nervous system. Alcohol-induced relative predominance of cardiac sympathetic activity in the ND subjects might be ascribed partly to increased norepinephrine secretion from sympathetic nerve terminals. Effects of acetaldehyde on these cardiovascular and endocrine systems were discussed in terms of their effects on the central nervous system.