Evelyn Phillips

Genomic screen for loci associated with alcohol dependence in Mission Indians

Alcohol dependence is a leading cause of morbidity and mortality in Native Americans, yet biological factors underlying the disorder in this ethnic group remain illusive. This studys aims were to map susceptibility loci for DSM‐III‐R alcohol dependence and two narrower alcohol‐related phenotypes in Mission Indian families. Each participant gave a blood sample and completed an interview using the Semi‐Structured Assessment for the Genetics of Alcoholism (SSAGA) that was used to make alcohol dependence diagnoses and the narrower phenotypes of withdrawal, and drinking severity. Genotypes were determined for a panel 791 microsatellite polymorphisms. Analyses of multipoint variance component LOD scores for the dichotomous DSM‐III‐R phenotype revealed no peak LOD scores that exceeded 2.0 at any chromosome location. Two chromosomes, 4 and 12, had peak LOD scores that exceeded 2 for the alcohol use severity phenotype and three chromosomes 6, 15, 16 were found to have peaks with LOD scores that exceeded 2 for the withdrawal phenotype. Evidence for linkage to chromosomes 4 and 15, and 16 have been reported previously for alcohol related phenotypes whereas no evidence has as yet been reported for chromosomes 6 and 12. Combined linkage and association analysis suggest that alcohol dehydrogenase 1B gene polymorphisms are partially responsible for the linkage result on chromosome 4 in this population. These results corroborate the importance of several chromosomal regions highlighted in prior segregation studies in alcoholism and further identify new regions of the genome that may be unique to either the restricted phenotypes evaluated or this population of Mission Indians.

Electrophysiological findings during the menstrual cycle in women with and without late luteal phase dysphoric disorder: relationship to risk for alcoholism?

This study evaluated electrophysiological (EEG, ERGs), and cognitive (neuropsychological testing) responses in patients with late luteal phase dysphoric disorder (LLPDD, DSM-III-R) and controls over the menstrual cycle. In both groups, the frequency and stability of electroencephalogram (EEG) alpha activity significantly differed over the menstrual cycle. The latency of the P3 components of the auditory event-related potentials (ERPs) did not vary as a function of the menstrual cycle, but the P3 latency was found to be later in LLPDD subjects as a group. When the LLPDD subjects were assessed based on family history of alcoholism, it was found that those with alcoholic relatives had more high-frequency alpha (9-12 Hz) in their EEG, lower P3 component amplitudes, and longer P3 component latencies when compared to LLPDD subjects without alcoholic relatives or controls. These data suggest that LLPDD may have persistent neurophysiological correlates, some of which are also in common with risk for alcoholism.

Co-Morbidity of Select Anxiety, Affective, and Psychotic Disorders with Cannabis Dependence in Southwest California Indians

Abstract Cannabis dependence is co-morbid with psychiatric disorders in general population surveys, but whether co-morbidity exists in American Indian populations is unknown. The aim of this study was to assess co-morbidity between cannabis dependence and psychiatric disorders in a community sample of Southwest California (SWC) Indians. Demographic information and DSM-III-R diagnoses, including differentiation of independent and cannabis-induced psychiatric disorders, were obtained using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) developed for the Collaborative Study on the Genetics of Alcoholism (COGA) from 513 SWC Indian adults residing on contiguous reservations. Although SWC Indians in this sample had high rates of cannabis dependence (43% in men and 24% in women), cannabis-induced psychiatric disorders each occurred in 1% or less of the sample. No significant co-morbidity with independent psychiatric disorders was found. In SWC Indians, cannabis dependence may be less etiologically related to psychiatric disorders than in the general population.

EEG asymmetry: relationship to mood and risk for alcoholism in Mission Indian youth

BACKGROUND Left frontal electroencephalogram (EEG) alpha dominance has been hypothesized to be related to depressed mood as well as aversive motivation and emotion. However, few studies have prospectively evaluated electroencephalogram asymmetry during development in high-risk adolescents and children. METHODS EEG alpha asymmetry was investigated in 134 Mission Indian children who were between 7 and 13 years of age. The relationships between electroencephalogram alpha asymmetry and age, gender, parental history of alcohol dependence, Native American heritage, and mood/ approach behaviors were explored. RESULTS No significant relationship was found between frontal alpha asymmetry and age, gender, or behavioral measures of depressed mood and/or approach behaviors. However, participants with > or = 50% Native American heritage were significantly more likely to have greater electroencephalogram alpha power in the left frontal cortex than in the right. CONCLUSIONS The present findings suggest that the hypothesized relationship between EEG alpha asymmetry and measures of depressed mood, aversive motivation, and emotion may not be universal in all age or ethnic groups. Additionally, though the relationship between greater degrees of Native American heritage and alpha asymmetry are not as yet clear, we suggest it may be more related to substance abuse than depression in this population of Mission Indians.

EEG spectral phenotypes: heritability and association with marijuana and alcohol dependence in an American Indian community study.

Native Americans have some of the highest rates of marijuana and alcohol use and abuse, yet neurobiological measures associated with dependence on these substances in this population remain unknown. The present investigation evaluated the heritability of spectral characteristics of the electroencephalogram (EEG) and their correlation with marijuana and alcohol dependence in an American Indian community. Participants (n=626) were evaluated for marijuana (MJ) and alcohol (ALC) dependence, as well as other psychiatric disorders. EEGs were collected from six cortical sites and spectral power determined in five frequency bands (delta 1.0-4.0 Hz, theta 4.0-7.5 Hz, alpha 7.5-12.0 Hz, low beta 12.0-20.0 Hz and high beta/gamma 20-50 Hz). The estimated heritability (h(2)) of the EEG phenotypes was calculated using SOLAR, and ranged from 0.16 to 0.67. Stepwise linear regression was used to detect correlations between MJ and ALC dependence and the spectral characteristics of the EEG using a model that took into account: age, gender, Native American Heritage (NAH) and a lifetime diagnosis of antisocial personality and/or conduct disorder (ASPD/CD). Increases in spectral power in the delta frequency range, were significantly correlated with gender (p<0.001) and marijuana dependence (p<0.003). Gender, age, NAH and ASPD/CD were all significantly (p<0.001) correlated with theta, alpha and beta band power, whereas alcohol dependence (p<0.01), gender (p<0.001), and ASPD/CD (p<0.001) were all correlated with high beta/gamma band power. These data suggest that the traits of EEG delta and high beta/gamma activity are correlated with MJ dependence and alcohol dependence, respectively, in this community sample of Native Americans.

Electrophysiological Responses to Affective Stimuli in American Indians Experiencing Trauma With and Without PTSD

Abstract:  American Indians are at high risk for exposure to violence and other traumatic events, yet few studies have investigated posttraumatic stress disorder (PTSD) or its neurobiological consequences in Indian communities. In the present study, a sample of American Indians (n= 146) were given a structured diagnostic interview that additionally indexed traumatic life events and symptoms emerging following those events. Electroencephalogram (EEG) spectra and visual event‐related potentials (ERPs) to happy, sad, and neutral faces were also recorded from each participant. Ninety‐nine percent of the sample had experienced at least one category of trauma with the mean number being 5, 27% had experienced at least 8 categories, and 13% met DSM‐IV criteria for PTSD. The PTSD group did not differ on any demographic or diagnostic variables from the larger sample. An electrophysiological signature for PTSD was found that included increases in high‐frequency gamma activity (20–40 Hz, F= 8.7, P < 0.004) in frontal leads, higher N1 amplitudes to sad stimuli in frontotemporal leads (F= 12.4, P < 0.001, F= 5.0, P < 0.03) , and longer latency P3 components to happy stimuli in midline, central, and right frontal leads(F= 4.7, P < 0.03; F= 4.1, P < 0.04; F= 4.0, P < 0.05). These findings were observed in participants with PTSD, but not in a group with equivalently high trauma counts. These findings suggest that PTSD is associated with EEG hyperarousal, higher attentional levels to sad stimuli, and slower processing of happy stimuli. They also partially confirm ERP data reported in combat victims with PTSD suggesting that PTSD may induce neurobiological consequences that transcend type of eliciting trauma as well as ethnic and cultural factors.

EEG Low-Voltage Alpha and Alpha Power in African American Young Adults: Relation to Family History of Alcoholism

BACKGROUND Several studies support an association between having a low-voltage EEG and alcohol dependence; however, it is not clear whether this measure represents a risk marker or is a result of years of heavy drinking. The present studys aims were to investigate the prevalence of low-voltage alpha EEG variants in African American young adults who have not yet developed alcohol dependence and to test for associations between low-voltage alpha (LVA) EEG, alpha power, and a family history of alcohol dependence. METHODS Clinical ratings and spectral characteristics of the EEG, collected using bipolar recordings, were investigated in 81 African American young adult men and women (18-25 years old) who had no personal history of alcohol dependence. Information on psychiatric diagnoses, personality features, personal drinking and drug use history, and family history (FH) of alcoholism was obtained. RESULTS Thirty-two percent (n = 26) of the participants had an LVA EEG variant, and an additional 22% (n = 18) had borderline LVA. The presence of an LVA variant was not associated with drinking status, a family history of alcoholism, or a personal history of anxiety disorders but was associated with significantly higher extroversion scores. Participants who had an FH of alcoholism had significantly higher spectral power in the slow alpha frequencies (7.5-9 Hz). FH was not associated with any significant differences in any other EEG frequency band. CONCLUSIONS These findings suggest that considerable ethic variation may exist in the prevalence of LVA EEG variants. In addition, like findings in other populations of non-African descent, having an FH of alcohol dependence may be associated with significantly higher voltage in the alpha frequency ranges.

EEG alpha phenotypes: linkage analyses and relation to alcohol dependence in an American Indian community study

BackgroundEvidence for a high degree of heritability of EEG alpha phenotypes has been demonstrated in twin and family studies in a number of populations. However, information on linkage of this phenotype to specific chromosome locations is still limited. This studys aims were to map loci linked to EEG alpha phenotypes and to determine if there was overlap with loci previously mapped for alcohol dependence in an American Indian community at high risk for substance dependence.MethodsEach participant gave a blood sample and completed a structured diagnostic interview using the Semi Structured Assessment for the Genetics of Alcoholism. Bipolar EEGs were collected and spectral power determined in the alpha (7.5-12.0 Hz) frequency band for two composite scalp locations previously identified by principal components analyses (bilateral fronto-central and bilateral centro-parietal-occipital). Genotypes were determined for a panel of 791 micro-satellite polymorphisms in 410 members of multiplex families using SOLAR.ResultsSixty percent of this study population had a lifetime diagnosis of alcohol dependence. Analyses of multipoint variance component LOD scores, for the EEG alpha power phenotype, revealed two loci that had a LOD score of 3.0 or above for the fronto-central scalp region on chromosomes 1 and 6. Additionally, 4 locations were identified with LOD scores above 2.0 on chromosomes 4, 11, 14, 16 for the fronto-central location and one on chromosome 2 for the centro-parietal-occipital location.ConclusionThese results corroborate the importance of regions on chromosome 4 and 6 highlighted in prior segregation studies in this and other populations for alcohol dependence-related phenotypes, as well as other areas that overlap with other substance dependence phenotypes identified in previous linkage studies in other populations. These studies additionally support the construct that EEG alpha recorded from fronto-central scalp areas may represent an important endophenotype associated with alcohol and other substance dependence.

P3 components of the event-related potential and marijuana dependence in Southwest California Indians.

Native Americans have some of the highest rates of marijuana use and abuse, yet neurobiological measures associated with addiction to marijuana in this population remain unknown. The present investigation evaluated associations between the P350 and P450 components of the event‐related potential (ERP) elicited by affective stimuli, and marijuana dependence in a population of Southwest California (SWC) Indian adults. Three hundred and seventeen participants with a mean age of 30 years who were free of major Axis I and psychiatric diagnoses and antisocial personality disorder were categorized as: (1) no marijuana use disorders or other drug dependence diagnoses; (2) marijuana dependence and no other drug dependence diagnoses; and (3) marijuana dependence and other drug dependence diagnoses. ERPs were collected using a facial discrimination task that generated a late positive component with two peaks at approximately P350 and P450 milliseconds. Multivariate analyses of variance was used to detect associations between the two component peaks and the three participant groups taking into consideration age, gender and the presence of a lifetime diagnosis of alcohol dependence. Increases in the latency of both the P350 and P450 component peaks were found to be associated with the diagnosis of marijuana dependence and marijuana dependence co‐morbid with other drug dependence. Women appeared to be more impacted than men are. A diagnosis of marijuana dependence was not associated with any changes in late component amplitudes. Taken together these studies suggest that marijuana dependence may be associated with delays in the evaluation and identification of emotional stimuli in SWC Indians.

N4 component responses to pre-pulse startle stimuli in young adults: Relationship to alcohol dependence

Both physiological and behavioral studies provide evidence to suggest that deficits in frontal cortical control circuits may contribute to the risk for developing alcohol dependence. Event-related potential (ERP) and eye blink responses to startle and short delay prepulse-plus-startle stimuli, and psychiatric diagnoses were investigated in young adult (age 18-30 years) men (n=135) and women (n=205) Mexican Americans. Women displayed a significant increase in the amplitude of the eye blink response to both the startle and pre-pulse-plus-startle stimuli. None of the psychiatric diagnoses were associated with differences in eye blink responses. ERP responses to the startle and prepulse-plus startle stimuli included a negative polarity wave at approximately 400 ms that was of the highest amplitude in the frontal leads (N4S). Women were found to have significantly higher amplitude N4S responses than men. Participants with alcohol dependence demonstrated significantly less inhibition and more facilitation of the N4S component by the pre-pulse stimuli. This finding was not associated with a diagnosis of: any other drug dependence disorder (including nicotine), anxiety or affective disorder, or conduct/antisocial personality disorder. The present study suggests that gender and a lifetime diagnosis of alcohol dependence may selectively contribute to this frontal late wave electrophysiological response to prepulse-plus-startle stimuli.