RESUMO
BACKGROUND: Electrophysiological variables may represent sensitive biomarkers of vulnerability to or endophenotypes for alcohol use disorders (AUD). METHODS: Young adults (age 18-30 yrs, nâ¯=â¯580) of Mexican American heritage were assessed with the Semi-Structured Assessment for the Genetics of Alcoholism and event-related oscillations (EROs) generated in response to a task that used pictures of objects, food, and alcohol-related and non-alcohol-related drinks as stimuli. RESULTS: Decreases in energy in the alpha and beta frequencies and higher phase synchrony within cortical brain areas were seen in response to the alcohol-related as compared to the non-alcohol-related stimuli. Differences in ERO energy and synchrony responses to alcohol-related stimuli were also found as a function of age, sex, AUD status and comorbidity. Age-related decreases in energy and increases in synchrony were found. Females had significantly higher energy and lower synchrony values than males. Participants with AUD had higher synchrony values specifically in the beta frequencies, whereas those with a lifetime diagnosis of conduct disorder and/or antisocial personality disorder had lower alpha power and synchrony, and those with any affective disorder had lower ERO energy in the beta frequencies. Those with substance-associated affective "dark-side" symptoms had slower reaction times to the task, lower energy in the beta frequencies, lower local synchrony in the theta frequencies, and higher long-range synchrony in the delta and beta frequencies. CONCLUSIONS: These findings suggest that EROs recorded to alcohol-related stimuli may be biomarkers of comorbid risk factors, symptoms and disorders associated with AUD that also can differentiate those with "dark-side symptoms".
Assuntos
Sintomas Afetivos/fisiopatologia , Alcoolismo/fisiopatologia , Potenciais Evocados , Americanos Mexicanos/psicologia , Análise e Desempenho de Tarefas , Adolescente , Adulto , Sintomas Afetivos/etnologia , Sintomas Afetivos/psicologia , Fatores Etários , Alcoolismo/etnologia , Alcoolismo/psicologia , Ritmo alfa , Transtorno da Personalidade Antissocial/etnologia , Transtorno da Personalidade Antissocial/fisiopatologia , Transtorno da Personalidade Antissocial/psicologia , Ritmo beta , Encéfalo/fisiopatologia , Comorbidade , Transtorno da Conduta/etnologia , Transtorno da Conduta/fisiopatologia , Transtorno da Conduta/psicologia , Feminino , Humanos , Masculino , Americanos Mexicanos/genética , Transtornos do Humor/etnologia , Transtornos do Humor/fisiopatologia , Transtornos do Humor/psicologia , Tempo de Reação , Fatores Sexuais , Adulto JovemRESUMO
Neurophysiological measurements of the response to pre-pulse and startle stimuli have been suggested to represent an important endophenotype for both substance dependence and other select psychiatric disorders. We have previously shown, in young adult Mexican Americans (MA), that presentation of a short delay acoustic pre-pulse, prior to the startle stimuli can elicit a late negative component at about 400 msec (N4S), in the event-related potential (ERP), recorded from frontal cortical areas. In the present study, we investigated whether genetic factors associated with this endophenotype could be identified. The study included 420 (age 18-30 years) MA men (n = 170), and women (n = 250). DNA was genotyped using an Affymetrix Axiom Exome1A chip. An association analysis revealed that the CCKAR and CCKBR (cholecystokinin A and B receptor) genes each had a nearby variant that showed suggestive significance with the amplitude of the N4S component to pre-pulse stimuli. The neurotransmitter cholecystokinin (CCK), along with its receptors, CCKAR and CCKBR, have been previously associated with psychiatric disorders, suggesting that variants near these genes may play a role in the pre-pulse/startle response in this cohort.
Assuntos
Americanos Mexicanos/genética , Receptor de Colecistocinina A/genética , Receptor de Colecistocinina B/genética , Reflexo de Sobressalto/genética , Adolescente , Adulto , Estudos de Coortes , Fenômenos Eletrofisiológicos , Feminino , Humanos , Masculino , Medição de Risco , Adulto JovemRESUMO
Several studies support an association between electroencephalogram (EEG) voltage and alcohol dependence. However, the distribution of EEG variants also appears to differ depending on an individual's ethnic heritage, suggesting significant genetic stratification of this EEG phenotype. The present study's aims were to investigate the incidence of EEG alpha variants and spectral power in the alpha frequency range in Mexican American young adults based on gender, and personal and family history of alcohol dependence. Clinical ratings (high-, medium-, and low alpha voltage variants) and spectral characteristics of the EEG in the alpha frequency range (7.5-12 Hz) were investigated in young adult (age 18-25 years) Mexican American men (n=98) and women (n=138) who were recruited from the community. Nineteen percent (n=45) of the participants had a low-voltage alpha EEG variant, 18% had a high-voltage variant, and 63% had a medium-voltage variant. There were no significant differences in the distribution of the EEG variants based on family history of alcohol dependence. There was a significant relationship between gender and the three alpha variants (chi2=9.7; df=2; P<.008), and there were no male participants with alcohol dependence with high alpha variants (chi2=5.8; df=2; P<.056). Alcohol dependence, but not a family history of alcohol dependence, was associated with lower spectral power in the alpha frequency range in the right (F=4.4; df=1,96; P<.04) and left (F=5.3; df=1.96; P<.02) occipital areas in the men but not in the women. In conclusion, in this select population of Mexican American young adults, male gender and alcohol dependence are associated with an absence of high-voltage alpha variants and lower alpha power in the EEG. These data suggest that EEG low voltage, a highly heritable trait, may represent an important endophenotype in male Mexican Americans that may aid in linking brain function with genetic factors underlying alcohol dependence in this ethnic group.
Assuntos
Alcoolismo/fisiopatologia , Ritmo alfa , Encéfalo/fisiopatologia , Americanos Mexicanos , Adulto , Alcoolismo/epidemiologia , Alcoolismo/etnologia , Alcoolismo/genética , California/epidemiologia , Feminino , Análise de Fourier , Predisposição Genética para Doença , Humanos , Masculino , Americanos Mexicanos/estatística & dados numéricos , Linhagem , Fenótipo , Fatores SexuaisRESUMO
Since the classic description by Fuller Albright in the 1940s, primary hyperparathyroidism has evolved from a disease with classic signs and symptoms to a disease in search of symptoms! Since that time, two major events have occurred. First, in the United States, United Kingdom, and in most European countries, there has been a steady rise in the apparent incidence of the disease. Second, there has been a dramatic shift in the pattern of presentation. A majority of patients with primary hyperparathyroidism in countries with multichannel screening panels are asymptomatic. Skeletal and renal complications are uncommon, and osteitis fibrosa is rare. In contrast, the clinical presentation of primary hyperparathyroidism has changed very little in other regions such as the East, the Middle East, and some parts of the southern hemisphere over the same period of observation. Accordingly, we assessed the influence of vitamin D and calcium nutrition on the disease expression and parathyroid tumor growth in patients with primary hyperparathyroidism from different parts of the world. Between 1945 and 1950, both the prevalence of osteitis fibrosa and parathyroid tumor weight declined dramatically in the United States, coinciding with fortification of milk with vitamin D. In contrast, osteitis fibrosa and parathyroid tumor weight changed very little in parts of the world where vitamin D depletion is endemic. Furthermore, for a comparable degree of vitamin D depletion, Asian Indians have significantly larger tumors compared with Americans (3.95 +/- 2.23 vs. 0.66 +/- 2.84 g; p < 0.001). Within the United States, blacks have larger tumors compared with whites (0.78 +/- 2.87 vs. 0.58 +/- 2.78 g; p < 0.01). However, the slopes of regression between serum 25-hydroxyvitamin D, the best index of vitamin D nutrition, and parathyroid tumor weight, the best available index of parathyroid growth, were not significantly different between Asian Indians, whites, and blacks. We conclude that vitamin D and calcium nutrition of the population affect both the clinical expression and parathyroid tumor growth in patients with primary hyperparathyroidism. It will be of interest to see if the pattern of presentation of primary hyperparathyroidism changes when better nutritional policies are implemented in developing countries.