Southwest California Indians Research Articles

CLINICAL STUDY: 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.

Association Between Single Nucleotide Polymorphisms in the Cannabinoid Receptor Gene (CNR1) and Impulsivity in Southwest California Indians

Impulsivity is a personality trait characterized by acting suddenly in an unplanned manner in order to satisfy a desire without consideration for the consequences of such behavior. There are several psychiatric disorders that include the term impulsivity as a criterion and, therefore, it has been suggested that impulsivity may be an important phenotype that may link a number of different behavioral disorders, including substance abuse. This study's aims were to determine if a significant association could be detected between the (AAT)n triplet repeat polymorphism as well as 5 single nucleotide polymorphisms (SNPs) in or near the CNR1 receptor gene and impulsivity in Southwest California 'Mission' Indians (SWC). Impulsivity was assessed using a scale derived from the Maudsley personality inventory, and blood samples were collected for DNA analyses from 251 individuals recruited from local Indian reservations. The estimated heritability (h(2)) for the impulsivity phenotype was 0.20 + 0.12 (p < .004). Impulsivity was significantly associated with the 6-repeat allele of the triplet repeat polymorphism (AATn/A6; p < .0001), as well as four SNPs in or near the CNR1 receptor gene: rs1535255 (p = .001), rs2023239 (p = .004), rs1049353 (p < .001) and rs806368 (p < .0006). These studies provide data to suggest that the CNR1 receptor gene may be significantly associated with impulsivity in SWC Indians.

Electrophysiological Responses to Affective Stimuli in Southwest California Indians: Relationship to Alcohol Dependence

Native Americans have some of the highest rates of alcohol abuse and dependence, yet potential risk factors associated with the problem drinking seen in some tribes remain relatively unknown. The present investigation evaluated associations between the P350 and P450 components of the event-related potential (ERP) elicited by affective stimuli and potential vulnerability factors associated with risk of alcohol dependence in Southwest California (SWC) Indian adults. Data from 517 Native American SWC Indian adults between the ages of 18 and 70 were used in the analyses. ERPs were collected using a task that required discrimination among faces with neutral, sad, and happy facial expressions. P450 amplitudes were significantly reduced in participants who met lifetime Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, criteria for alcohol dependence in centroparietal leads. In contrast, participants who met personal lifetime criteria for affective disorder were found to have higher P350 and P450 amplitudes in frontal leads. Neither P350 nor P450 component amplitudes were significantly altered based on a family history of alcohol dependence, a personal history of antisocial personality disorder/conduct disorder, or the presence of drug dependence other than alcohol. These findings suggest, in this select population, that P450 amplitudes are selectively affected by both alcohol dependence and affective disorder. However, reductions in P450 amplitude were restricted to those participants with alcohol dependence, confirming that it may be an important putative endophenotype for genetic studies of that disorder in this high-risk population.

Factors Associated with Remission from Cannabis Dependence in Southwest California Indians

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.

Heritability of illicit drug use and transition to dependence in Southwest California Indians

Native Americans have high rates of drug use and dependence yet little is known concerning its etiology or clinical course. These analyses were conducted to describe the heritability of the use of a variety of illicit drugs, as well as the conditional probability of transitioning from use to dependence for each drug class in a community sample of Native American men and women. The sample included 460 participants (190 men and 270 women), recruited through community effort, from eight contiguous Indian reservations in Southern California. Participants were assessed using the Semi-Structured Assessment for the Genetics of Alcoholism. The Semi-Structured Assessment for the Genetics of Alcoholism interview retrospectively asks about the initial use and drug dependence of the following illicit drug classes: marijuana, cocaine, stimulants, sedatives, opiates, hallucinogens, and solvents. Heritability of initial use was determined using SOLAR (http://www.sfbr.org/solar/). Ninety-one percent of this select Indian population had tried at least one of the illicit drug classes. The most commonly tried substance was marijuana (88%), followed by stimulants (60%), cocaine (44%), hallucinogens (34%), and solvents (20%). The heritability of initiation of drug use ranged from 0.14 for cocaine to 0.59 for marijuana. The conditional probability of transition from initiation to drug dependence ranged from 0.66 for stimulants to 0.06 for hallucinogens. These findings suggest that heritability of the initiation of substance use, in Southwest California Indians, may be similar to other population samples. In this population, however, high rates of dependence on marijuana, opiates, and stimulants are seen once initiation of the use of the substance has occurred.

Association Between Single Nucleotide Polymorphisms in the Cannabinoid Receptor Gene (CNR1) and Impulsivity in Southwest California Indians

Association Between Single Nucleotide Polymorphisms in the Cannabinoid Receptor Gene (CNR1) and Impulsivity in Southwest California Indians

P3 components and adolescent binge drinking in Southwest California Indians

In adolescence, consuming a large number of drinks over a short interval of time (e.g. binging) is not an uncommon occurrence. Since adolescence is an important neurodevelopmental period, the effect of binge drinking on brain and behavior has become a significant health concern. The present study evaluated event-related potentials (ERPs) in young adult Southwest California Indians who had a history of binge drinking during their adolescence. One hundred twenty five participants who were currently 18–25 yrs of age who were free of Axis I psychiatric diagnoses were categorized as: 1) reporting no binge drinking during adolescence (> 5 drinks per occasion before age 18) or drug dependence diagnoses 2) reporting binge drinking during adolescence with no drug dependence diagnoses 3) reporting binge drinking during adolescence and drug dependence diagnoses. ERPs were collected using a facial discrimination task. Adolescent alcohol and drug exposure was found to be associated with decreases in the latency of an early P3 component (P350). Decreases in a later component amplitude (P450) were also found in young adults exposed to alcohol, and those exposed to alcohol and drugs. However, that finding appears to be a combined result of predisposing factors such as family history of alcoholism and presence of other externalizing diagnoses. Taken together these preliminary studies suggests that adolescent binge drinking may result in a decreases in P3 component latencies and amplitudes perhaps reflecting a loss or delay in the development of inhibitory brain systems.

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

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.

Age at First Intoxication and Alcohol Use Disorders in Southwest California Indians

In several national surveys, a younger age of onset of first drink and/or regular drinking has been associated with a higher likelihood of the development of alcohol dependence. Some studies have suggested that age at first drink is primarily an environmentally driven variable whereas others suggest that it may be partially mediated by a general vulnerability to exhibit problem behaviors. Although Native Americans, overall, have the highest prevalence of alcohol dependence of any U.S. ethnic group, the relationship of age of onset of intoxication with alcohol dependence in Native American populations is relatively unknown. Demographic information and DSM-III-R diagnoses were obtained from 525 Southwest California (SWC) Indian adults residing on contiguous reservations. Survival analyses and Cox and logistic regression were used to investigate the relationship between age of onset of first intoxication and the development of alcohol dependence. Heritability of the age of onset of first intoxication was also determined using SOLAR. Age at first intoxication was not found to be heritable in this population. Early onset of intoxication, however, was found to be significantly associated with both a shorter time to onset of alcohol dependence and increased prevalence in this population, even on taking into account several other risk factors including externalizing diagnoses. These data suggest that effective environmental prevention efforts at reducing underage drinking may be an important strategy to lower the prevalence of alcohol dependence in this high-risk population.

Age of first marijuana use and the occurrence of marijuana use disorders in Southwest California Indians

In several national surveys a younger age of substance usage has been associated with a higher likelihood of the development of dependence. Some studies have suggested that age at first use is primarily an environmentally driven variable, whereas others suggest that it may be partially mediated by a general vulnerability to exhibit problem behaviors. Although Native Americans, overall, have the highest prevalence of substance dependence of any US ethnic group, the relationship of age of first marijuana use on the development of dependence in Native American populations is relatively unknown. Demographic information and DSM-III-R diagnoses were obtained from 525 Southwest California Indian adults residing on contiguous reservations. Multinomial logistic regression was used to investigate the relationship between age of first use and marijuana use disorders. Early marijuana use was found to be strongly associated with abuse and dependence in this population, even in the presence of several other risk factors including externalizing diagnoses. These data suggest that effective environmental prevention efforts at reducing early marijuana use may be an important strategy to lower the prevalence of use disorders in this high risk population.

Genomic screen for substance dependence and body mass index in southwest California Indians

Substance abuse and obesity are health disparities that may afflict Native Americans more than some other ethnic groups. One theoretical assumption concerning Native people is that the long history of dependence on foraging and subsistence agriculture may have led to selective enrichment of traits that improve genetic fitness, so called 'thrifty' or 'fat sparing' genes. We have speculated that this same selective pressure may have enriched for genetic variants that increase the risk for consumption of alcohol and drugs of abuse. Here, we report the results of a genome scan that compared findings for two consumption phenotypes: 'any drug dependence and/or regular tobacco use' and body mass index (BMI) in southwest California (SWC) Indian families. Variance component analyses from SOLAR were used to generate log of the odds ratio (LOD) scores. Evidence for linkage was found on chromosome 6 for both the 'any drug' (LOD score = 3.3) and BMI (LOD score = 2.3) phenotypes. Bivariate analyses of the two phenotypes revealed a combined LOD score of 4.1 at that location. Additional loci on chromosomes 6, 15, 16 and 21 were found for the 'any drug' phenotype, and on chromosomes 8, 16 and 18 for BMI (LOD scores ranged between 1.2 and 2.3). These results provide suggestive evidence for linkage for substance abuse and BMI in this Mission Indian population and, furthermore, provide preliminary data suggesting that 'consumption phenotypes' may share some genetic determinants.

Heritability of substance dependence in a native American population

To estimate the heritability of substance dependence and associated symptoms in a sample of Southwest California (Mission) Indians. Families from eight contiguous Indian reservations were recruited in order to ascertain information on substance dependence symptoms and diagnoses using a semi-structured diagnostic interview. Dependence diagnoses for alcohol, marijuana, stimulants and a measure of regular tobacco usage, any drug dependence or tobacco usage were obtained. Composite measures of alcohol dependence symptoms for withdrawal, drinking severity, antisocial problems and interpersonal problems were constructed from the nine groups of symptoms summarized in the diagnostic interview. Heritability estimates were calculated using variance component methods, as implemented in SOLAR. In this population, marijuana dependence (0.38) and regular tobacco use (0.43), alcohol dependence (DSM-III-R 0.19; ICD-10, 0.29) and stimulant dependence (0.25) showed evidence for moderate genetic influences as determined by heritability estimates. Four phenotypes constructed using the composite symptoms of alcohol dependence revealed that withdrawal had the highest heritability estimate (0.71), followed by antisocial problems (0.36) and drinking severity (0.34). Symptom clusters reflecting interpersonal problems did not appear to be highly heritable (0.19). Marijuana dependence, regular tobacco usage and composite phenotypes constructed from alcohol dependence symptoms for antisocial problems, drinking severity and withdrawal generally have patterns of familial aggregation, suggesting that they can be successfully used for linkage analysis in this Southwest California Indian sample.

Comorbidity of Select Anxiety and Affective Disorders With Alcohol Dependence in Southwest California Indians

Native Americans, overall, have the highest prevalence of alcohol dependence of any US ethnic group. In several large national surveys, alcohol dependence has been significantly associated with higher rates of anxiety and affective disorders (comorbidity). However, the frequencies of these disorders and their comorbidity with alcohol dependence in Native American populations are relatively unknown. Demographic information and DSM-III-R diagnoses were obtained by using the Semi-Structured Assessment for the Genetics of Alcoholism developed for the Collaborative Study on the Genetics of Alcoholism from 483 Southwest California Indian adults residing on contiguous reservations. The Semi-Structured Assessment for the Genetics of Alcoholism allowed differentiation of each anxiety and affective disorder into one of three types: independent of substance use, concurrent with alcohol use, and concurrent with drug use. Sixty-six percent of the men and 53% of the women sampled had a lifetime diagnosis of alcohol dependence. Fourteen percent of the sample had a lifetime independent anxiety disorder, and 14% of the sample had a lifetime independent affective disorder. Alcohol- and/or drug-concurrent major depression occurred in 8%, and other alcohol- and/or drug-concurrent anxiety and affective disorders each occurred in less than 1.1% of the sample. No significant comorbidity was found between alcohol dependence and independent agoraphobia, social phobia, or major depressive disorder. In this Southwest California Indian sample, rates of anxiety and affective disorders were substantially similar to those reported in the National Comorbidity Survey; however, comorbidity of independent disorders with alcohol dependence was not as pervasive as in the National Comorbidity Survey. Rates of concurrent anxiety and affective disorders were low. These data support the hypothesis that despite high rates of alcohol dependence, Southwest California Indians do not have higher rates of anxiety and affective disorders or comorbidity of these disorders with alcohol dependence than those reported in large surveys of non-American Indian populations.

Association of ALDH1 Promoter Polymorphisms With Alcohol‐Related Phenotypes in Southwest California Indians

Cytosolic aldehyde dehydrogenase (ALDH1A1) is an important enzyme in the metabolism of acetaldehyde and the synthesis of retinoic acid. Two polymorphisms in the promoter region of ALDH1A1-ALDH1A1*2 and ALDH1A1*3-have recently been identified and described in small samples of Asian, Caucasian, and African individuals. The aim of this study was to determine the prevalence of these polymorphisms in a sample of Southwest California Indians and to test for associations with alcohol dependence and other substance-related behaviors. The participants in this study were 463 adult men and women recruited from 8 contiguous Indian reservations. A structured interview was used to gather information on demographics, psychiatric diagnoses, and personal drinking and drug use history. A blood sample was obtained from each participant, and leukocyte DNA was extracted and used to genotype for the presence of the ALDH1A1 promoter polymorphisms. Twenty-seven participants (6%) possessed ALDH1A1*2 (frequency, 0.03), two participants possessed ALDH1A1*3, and one participant displayed both of these alleles. Individuals with an ALDH1A1*2 allele had lower rates of alcohol dependence and regular tobacco use than those without this allele. Individuals with ALDH1A1*2 also reported a significantly lower maximum number of drinks ever consumed in a 24-hr period, reported drinking fewer drinks per occasion when they first started drinking regularly, and reported lower expectations of alcohol's effects compared with individuals without this allele. Results from this study suggest that ALDH1A1*2 may be associated with protection from the development of alcohol and other substance use disorders.