David A. Gilder

Acculturation stress, anxiety disorders, and alcohol dependence in a select population of young adult Mexican Americans.

Objectives:Mexican Americans comprise one of the most rapidly growing populations in the United States, and within this population, the process of acculturation has been suggested to be associated with some mental health problems. This study sought to ascertain quantitative information indexing acculturation stress and its association with mental health disorders in a select community sample of Mexican Americans. Methods:Demographic information, Diagnostic and Statistical Manual-III-R diagnoses, and information on cultural identity and acculturation stress were obtained from 240 Mexican American young adults that were recruited by fliers and were residing in selected areas of San Diego. Results:No associations were found between measures of cultural identification and lifetime diagnoses of drug or alcohol dependence, major depressive disorder, anxiety disorders, or antisocial personality disorder or conduct disorder in this sample of Mexican American young adults. However, lifetime diagnoses of alcohol dependence, substance dependence, and anxiety disorders were associated with elevations in acculturation stress. Conclusion:Quantitative measures of acculturation stress, but not cultural identity per se, were found to be associated significantly with substance dependence and anxiety disorders in this select population of Mexican American young adults. These data may be helpful in designing prevention and intervention programs for this high-risk population.

Lifetime history of traumatic events in an American Indian community sample: Heritability and relation to substance dependence, affective disorder, conduct disorder and PTSD

American Indians appear to experience a higher rate of traumatic events than what has been reported in general population surveys. American Indians also suffer higher alcohol related death rates than any other ethnic group in the U.S. population. Therefore efforts to delineate factors which may uniquely contribute to increased likelihood of trauma, post traumatic stress disorder (PTSD), and substance use disorders (SUD) over the lifetime in American Indians are important because of the high burden of morbidity and mortality that they pose to American Indian communities. Participants were American Indians recruited from reservations that were assessed with the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA), family history assessment and the stressful-life-events scale. Of the 309 participants, equivalent numbers of men and women (94%) reported experiencing traumas; however, a larger proportion of women received a PTSD diagnosis (38%) than men (29%). Having experienced multiple trauma and sexual abuse were most highly associated with PTSD. Having experienced assaultive trauma and having PTSD symptoms were both found to be moderately heritable (30-50%). Logistic regression revealed that having an anxiety and/or affective disorder and having a substance dependent diagnosis, but not having antisocial personality disorder/conduct disorder, were significantly correlated with having a diagnosis of PTSD. These studies suggest that trauma is highly prevalent in this American Indian community, it is heritable, is associated with PTSD, affective/anxiety disorders and substance dependence. Additionally, trauma, PTSD and substance dependence appear to all co-emerge in early adulthood in this high-risk population.

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.

Heritability and a genome-wide linkage analysis of a Type II/B cluster construct for cannabis dependence in an American Indian community

Subtyping of substance dependence disorders holds promise for a number of important research areas including phenotyping for genetic studies, characterizing clinical course, and matching treatment and prevention strategies. This study sought to investigate whether a dichotomous construct similar to Babors Types A/B and Cloningers Types I/II for alcohol dependence can be identified for cannabis dependence in a Native American sample. In addition, heritability of this construct and its behavior in a genetic linkage analyses were evaluated. Information on cannabis use and dependence symptoms and other psychiatric disorders was obtained using the Semi‐Structured Assessment for the Genetics of Alcoholism from a community sample of 606 American Indians. Hierarchical average linkage and K means cluster analysis was used, and a three‐cluster solution was found to generate the best separation of variables. Ninety‐one per cent of cannabis‐dependent participants fell into one of the two subtypes: Type A/I cluster (n = 114, 56%) and Type B/II cluster (n = 70, 35%). Heritability (estimated using Sequential Oligogenic Linkage Analysis Routines) was only significant for the Type B/II cluster (h2 = 0.44, SE = 0.18, P < 0.01). Evidence for linkage was found for the Type B/II cluster (versus no diagnosis) on chromosome 16 [at 139 centimorgans (cM), Log of the Odds (LOD) score = 4.4], and on chromosome 19 (at 74 cM, LOD score = 6.4). Regions of interest for this phenotype (LOD > 1.5) were also located on chromosomes 14, 21, 22. These findings suggest that a Type B/II cannabis dependence phenotype can be identified in this population and that it is in part heritable and linked to areas of the genome identified previously for drug dependence phenotypes in this population as well as in other studies.

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.

Externalizing disorders in American Indians: comorbidity and a genome wide linkage analysis.

Alcohol dependence is one of the leading causes of morbidity and mortality in Native Americans. Externalizing disorders such as conduct disorder (CD) and antisocial personality disorder (ASPD) have been demonstrated to have significant comorbidity with alcohol dependence in the general population. This studys aims were to: assess the comorbidity of DSM‐III‐R ASPD and CD with alcohol dependence, to map susceptibility loci for ASPD and CD, and to see if there is overlap with loci previously mapped for alcohol dependence phenotypes in 587 American Indians. Alcohol dependence was found to be comorbid with DSM‐III‐R ASPD but not CD. However, the amount of alcohol dependence in the population attributable to ASPD and/or CD is low. ASPD and the combined phenotype of participants with ASPD or CD were both found to have significant heritability, whereas no significant evidence was found for CD alone. Genotypes were determined for a panel of 791 micro‐satellite polymorphisms in 251 of the participants. Analyses of multipoint variance component LOD scores, for ASPD and ASPD/CD, revealed six locations that had a LOD score of 2.0 or above: on chromosome 13 for ASPD and on chromosomes 1, 3, 4, 14, 17, and 20 for ASPD/CD. These results corroborate the importance of several chromosomal regions highlighted in prior segregation studies for externalizing diagnoses. These results also further identify new regions of the genome, that do not overlap with alcohol dependence phenotypes previously identified in this population, that may be unique to either the phenotypes evaluated or this population of American Indians.

Age at regular drinking, clinical course, and heritability of alcohol dependence in the San Francisco family study: a gender analysis.

We examined gender differences in age of onset, clinical course, and heritability of alcohol dependence in 2,524 adults participating in the University of California San Francisco (UCSF) family study of alcoholism. Men were significantly more likely than women to have initiated regular drinking during adolescence. Onset of regular drinking was not found to be heritable but was found to be significantly associated with a shorter time to onset of alcohol dependence. A high degree of similarity in the sequence of alcohol-related life events was found between men and women, however, men experienced alcohol dependence symptoms at a younger age and women had a more rapid clinical course. Women were found to have a higher heritability estimate for alcohol dependence (h(2)= .46) than men (h(2)= .32). These findings suggest that environmental factors influencing the initiation of regular drinking rather than genetic factors associated with dependence may in part underlie some of the gender differences seen in the prevalence of alcohol dependence in this population. (Am J Addict 2010;00:1-10).

Factors Associated with Remission from Cannabis Dependence in Southwest California Indians

Abstract Cannabis is the most widely used illicit substance in the United States, and rates of cannabis use disorders in some Native American samples have been reported to be higher than in the general U.S. population. However, little is known about factors which are associated with remission from cannabis dependence in any ethnicity. Using the SSAGA, this study examined variables associated with complete remission (defined as no symptoms of dependence for 6 months or more) from DSM-III-R cannabis dependence in 159 Southwest California Indians living on contiguous reservations. Female gender, employment, having more cannabis-induced symptoms, and a shorter duration of dependence were all associated with an increased likelihood of remission. Attention to factors associated with remission from cannabis dependence may be important in designing more effective treatment and intervention programs in this high-risk population.

Measuring historical trauma in an American Indian community sample: Contributions of substance dependence, affective disorder, conduct disorder and PTSD

BACKGROUND The American Indian experience of historical trauma is thought of as both a source of intergenerational trauma responses as well as a potential causative factor for long-term distress and substance abuse among communities. The aims of the present study were to evaluate the extent to which the frequency of thoughts of historical loss and associated symptoms are influenced by: current traumatic events, post traumatic stress disorder (PTSD), cultural identification, percent Native American Heritage, substance dependence, affective/anxiety disorders, and conduct disorder/antisocial personality disorder (ASPD). METHODS Participants were American Indians recruited from reservations that were assessed with the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA), The Historical Loss Scale and The Historical Loss Associated Symptoms Scale (to quantify frequency of thoughts and symptoms of historical loss) the Stressful-Life-Events Scale (to assess experiences of trauma) and the Orthogonal Cultural Identification Scale (OCIS). RESULTS Three hundred and six (306) American Indian adults participated in the study. Over half of them indicated that they thought about historical losses at least occasionally, and that it caused them distress. Logistic regression revealed that significant increases in how often a person thought about historical losses were associated with: not being married, high degrees of Native Heritage, and high cultural identification. Additionally, anxiety/affective disorders and substance dependence were correlated with historical loss associated symptoms. CONCLUSIONS In this American Indian community, thoughts about historical losses and their associated symptomatology are common and the presence of these thoughts are associated with Native American Heritage, cultural identification, and substance dependence.

Linkage analyses of stimulant dependence, craving, and heavy use in American Indians

Amphetamine‐type substances are the second most widely used illicit drugs in the United States. There is evidence to suggest that stimulant use (cocaine and methamphetamine) has a heritable component, yet the areas of the genome underlying these use disorders are yet to be identified. This studys aims were to map loci linked to stimulant dependence, heavy use, and craving in an American Indian community at high risk for substance dependence. DSM diagnosis of stimulant dependence, as well as indices of stimulant “craving,” and “heavy use,” were obtained using the Semi‐Structured Assessment for the Genetics of Alcoholism (SSAGA). Genotypes were determined for a panel of 791 microsatellite polymorphisms in 381 members of multiplex families using SOLAR. Stimulant dependence, stimulant “craving,” and “heavy stimulant use,” were all found to be heritable. Analyses of multipoint variance component LOD scores, failed to yield evidence of linkage for stimulant dependence. For the stimulant “craving” phenotype, linkage analysis revealed a locus that had a LOD score of 3.02 on chromosome 15q25.3‐26.1 near the nicotinic receptor gene cluster. A LOD score of 2.05 was found at this same site for “heavy stimulant use.” Additional loci with LOD scores above 2.00 were found for stimulant “craving” on chromosomes 12p13.33‐13.32 and 18q22.3. These results corroborate the importance of “craving” as an important phenotype that is associated with regions on chromosome 12, 15, and 18, that have been highlighted in prior segregation studies in this and other populations for substance dependence‐related phenotypes.