Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women.

Women who have experienced childhood sexual abuse (CSA) have an increased risk of alcoholism and antisocial personality disorder (ASPD). Among male subjects, a functional polymorphism (MAOA-LPR, monoamine oxidase A linked polymorphic region) in the promoter region of the monoamine oxidase A gene (MAOA) appears to moderate the effect of childhood maltreatment on antisocial behavior. Our aim was to test whether MAOA-LPR influences the impact of CSA on alcoholism and ASPD in a sample of 291 women, 50% of whom have experienced CSA; we also tested whether haplotypes covering the region where both MAOA and monoamine oxidase B (MAOB) genes are located predict risk of alcoholism and ASPD better than the MAOA-LPR locus alone. Participants included 168 alcoholics (39 with ASPD (antisocial alcoholics) and 123 controls (no alcoholics, no ASPD). Antisocial behavior was also modeled as a continuous trait: ASPD symptoms count. The MAOA-LPR low activity allele was associated with alcoholism (P=0.005), particularly antisocial alcoholism (P=0.00009), only among sexually abused subjects. Sexually abused women who were homozygous for the low activity allele had higher rates of alcoholism and ASPD, and more ASPD symptoms, than abused women homozygous for the high activity allele. Heterozygous women displayed an intermediate risk pattern. In contrast, there was no relationship between alcoholism/antisocial behavior and MAOA-LPR genotype among non-abused women. The MAOA-LPR low activity allele was found on three different haplotypes. The most abundant MAOA haplotype containing the MAOA-LPR low activity allele was found in excess among alcoholics (P=0.008) and antisocial alcoholics (P=0.001). Finally, a MAOB haplotype, which we termed haplotype C, was significantly associated with alcoholism (P=0.006), and to a lesser extent with antisocial alcoholism (P=0.03). In conclusions, MAOA seems to moderate the impact of childhood trauma on adult psychopathology in female subjects in the same way as previously shown among male subjects. The MAOA-LPR low activity allele appears to confer increased vulnerability to the adverse psychosocial consequences of CSA. Haplotype-based analysis of the MAOA gene appeared to strengthen the association, as compared to the MAOA-LPR locus alone. A MAOB haplotype was associated with alcoholism independently from ASPD.

Validity of the CAGE questionnaire in an American Indian population.

OBJECTIVE: This study evaluated the performance of the CAGE questionnaire (a set of four questions about alcoholism) in an American Indian population. METHOD: We analyzed data from a cross-sectional study of 275 individuals (179 women) aged 21 years or older. Alcohol dependence was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised (DSM-III-R), based on a detailed psychiatric interview using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version. Accuracy of the CAGE questionnaire was quantified as sensitivity, specificity, likelihood ratios and the area under receiver operating characteristics (ROC) curves, using the DSM-III-R diagnosis as the reference. RESULTS: Of participants interviewed, 85% of men and 53% of women had a diagnosis of alcohol dependence by DSM-III-R. A CAGE score of > or = 2 had a sensitivity and specificity of 68% and 93%, respectively, in men and 62% and 79% in women, for the diagnosis of alcohol dependence. CAGE scores of 0, 1 and > or = 2 were associated with likelihood ratios of 0.3, 0.3 and 9.5, respectively, in men and 0.4, 0.7 and 1.5 in women. The area under the ROC curve was 81% for men and 75% for women. CONCLUSIONS: These findings suggest that the CAGE questionnaire is a valid screening method, in this population, for identifying people likely to have alcohol dependence.

Association of low-voltage alpha EEG with a subtype of alcohol use disorders.

BACKGROUND: Neurophysiological traits may identify more homogeneous subgroups of alcoholics. Such discoveries could yield information regarding pathophysiological development, leading to more specific preventive measures and treatments. In an earlier study of 127 individuals, 59 of whom were unrelated, we found that a heritable resting Electroencephalographic (EEG) phenotype, i.e., the low-voltage alpha (LVA) trait, was associated with alcohol use disorders and anxiety disorders. METHODS: We evaluated these findings using an independent, similarly established, dataset of 120 subjects. We also extended the study to a larger set of 149 unrelated individuals from a total sample of 247 subjects for whom psychiatric diagnoses and resting EEG phenotypes were available. Blind-rated psychiatric diagnoses were formulated according to DSM-III-R criteria. RESULTS: In the replication sample, the LVA trait was again more common among subjects with anxiety disorders than among those without. In the total group of unrelated individuals, alcoholics were significantly (3 times) more likely to show the LVA trait than were nonalcoholics. Again, individuals with anxiety disorders were significantly (3 times) more likely to exhibit the LVA trait than were those without anxiety disorders. Of 11 unrelated alcoholics with anxiety disorders, seven showed the LVA trait. It was specifically the LVA trait and not low-amplitude alpha activity that was associated with alcohol use disorders. CONCLUSIONS: The results of this replication study and the analysis of the total sample of unrelated individuals support an association between LVA EEG and the subtype of alcohol use disorders associated with anxiety disorders. The LVA phenotype may be a vulnerability factor for alcohol use disorders and anxiety disorders.

Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations.

BACKGROUND: In mice, quantitative trait locus studies and behavioral evaluation of animals deleted for 5-HT1B have implicated this serotonin autoreceptor in alcohol consumption and aggressive behavior. We therefore investigated whether the 5-HT1B gene (HTR1B) is linked to alcoholism with aggressive and impulsive behavior in the human, as represented by 2 psychiatric diagnoses: antisocial personality disorder and intermittent explosive disorder comorbid with alcoholism. METHODS: Linkage was first tested in 640 Finnish subjects, including 166 alcoholic criminal offenders, 261 relatives, and 213 healthy controls. This was followed by a study in a large multigenerational family derived from a Southwestern American Indian tribe (n=418) with a high rate of alcoholism. All subjects were psychiatrically interviewed, blind-rated for psychiatric diagnoses, and typed for a HTR1B G861C polymorphism and for a closely linked short-tandem repeat locus, D6S284. Linkage was evaluated in sib pairs, and by using an association approach in which pedigree randomization corrects for nonindependence of observations on related subjects. RESULTS: In Finnish sib pairs, antisocial alcoholism showed significant evidence of linkage to HTR1B G861C (P=.04) and weak evidence with D6S284 (P=.06). By association analysis, the 183 Finnish antisocial alcoholics had a significantly higher HTR1B-861C allele frequency than the other 457 Finns we studied (P=.005). In the Southwestern American Indian tribe, significant sib pair linkage of antisocial alcoholism to HTR1B G861C (P=.01) was again observed, and there was also significant linkage to D6S284 (P=.01). CONCLUSION: These results suggest that a locus predisposing to antisocial alcoholism may be linked to HTR1B at 6q13-15.

Intimate violence in a southwestern American Indian tribal community.

Much has been written about intimate violence and American Indians, but little empirical data are available. This study investigated the prevalence and characteristics of intimate violence among 104 members of a Southwestern American Indian tribe. A semistructured psychiatric interview and a measure of intimate violence were administered to 104 tribal community members from an overall study sample of 582. Both men and women reported high rates of lifetime (91%) and recent (31%) intimate violence; much of this behavior was interactive. However, female victims were more likely to require medical attention because of sustained injuries and to have their children involved with the violence than were male victims. For women in this study, forced sex was the only incident significantly associated with lifetime affective disorders and lifetime posttraumatic stress disorder. In this Southwestern American Indian community, intimate violence appears to be another variable in an environmental context that includes alcoholism, other psychiatric disorders, and traumatic events.

Evidence for genetic linkage to alcohol dependence on chromosomes 4 and 11 from an autosome-wide scan in an American Indian population.

To identify specific genes affecting vulnerability or resistance, we performed a whole-autosomal genome scan for genetic linkage to alcohol dependence in a Southwestern American Indian tribe. Genotypes at 517 autosomal microsatellite loci and clinical evaluations were available for 152 subjects belonging to extended pedigrees and forming 172 sib-pairs. Highly suggestive evidence for linkage emerged for two genomic regions using two- and multipoint sib-pair regression methods; both regions harbored neurogenetic candidate genes. The best evidence is seen with D11S1984 (nominal P = 0.00007, lod approximately equal to 3.1) on chromosome 11p, in close proximity to the DRD4 dopamine receptor and tyrosine hydroxylase (TH) genes. Good evidence is seen with D4S3242 (nominal P = 0.0002, lod approximately equal to 2.8) on chromosome 4p, near the beta1 GABA receptor gene. Interestingly, three loci in the alcohol dehydrogenase gene cluster on chromosome 4q showed evidence for linkage with two-point analyses, but not multipoint analysis.

Relationship of binge drinking to alcohol dependence, other psychiatric disorders, and behavioral problems in an American Indian tribe.

The hypothesis that binge drinking is a benign behavior not associated with alcohol dependence, other psychiatric disorders, or problem areas, in American Indians, was tested in a sample of 582 adult Southwestern American Indian males and females in large multigenerational pedigrees. All information was obtained from semistructured psychiatric interviews that were independently blind-rated for DSM-III-R diagnoses. Three main outcome measures were used: the relationship between binge drinking and (1) alcohol dependence and other psychiatric disorders, (2) substance abuse treatment, and (3) four behavioral problem categories-violence/lawlessness, physical, social, and work. Binge drinking and alcohol dependence were strongly associated. Most binge drinkers were diagnosed as alcohol dependent. However, when controlling for alcohol dependence and other covariates, binge drinking was independently associated with an increase in odds for positive diagnoses for multiple psychiatric disorders, and for social, work, physical, and violence/lawlessness behavioral problems. In sum, binge drinking was found to be a common and severe problem with deleterious consequences in multiple domains of functioning. Assessment instruments should be designed to elicit information on binge patterns of drinking and strategies devised to provide appropriate treatment.

Prevalence and characteristics of trauma and posttraumatic stress disorder in a southwestern American Indian community.

OBJECTIVE: High rates of violence and trauma in many American Indian communities have been reported. The authors investigated the relationship between both the frequency and type of traumatic events and the prevalence of posttraumatic stress disorder (PTSD) in a Southwestern American Indian tribe. METHOD: A structured psychiatric interview and the Traumatic Events Booklet were administered to a subset of 247 tribal members from an overall study population of 582. Subjects were recruited from the community on the basis of membership in pedigrees, and not by convenience. DSM-III-R diagnoses were assigned by consensus after the interviews were evaluated blindly by independent raters. RESULTS: The prevalence of lifetime PTSD was 21.9% (N = 54), and 81.4% of the subjects (N = 201) had experienced at least one traumatic event apiece. The most predictive factor for lifetime PTSD among women was the experience of physical assault, and for men the most predictive factors were a history of combat and having experienced more than 10 traumatic events. CONCLUSIONS: In this Southwestern American Indian community, the prevalences of lifetime PTSD and of exposure to a traumatic event were higher than in the general U.S. population. However, the nearly 4:1 ratio of subjects who reported at least one traumatic event to those with PTSD diagnoses is similar to findings from studies of non-Indians. Individuals with a history of multiple traumatic events (66.0%, N = 163) had a significantly higher risk of developing PTSD. Chronic and multiple trauma did not preclude the identification of acute and discrete traumatic events that resulted in PTSD.

Prevalence, characteristics, and impact of childhood sexual abuse in a Southwestern American Indian tribe.

OBJECTIVE: There were two objectives; first, to investigate the prevalence and characteristics of child sexual abuse in an American Indian community, and second, to determine whether persons with histories of child sexual abuse are at greater risk to develop psychiatric disorders and behavioral problems than persons who report no such history. METHOD: A sample of 582 Southwestern American Indian tribal members was collected for a genetic and linkage study on alcoholism and psychiatric disorders in three large and interrelated pedigrees. Subjects were recruited from the community without knowledge of their clinical histories or those of their relatives. Child sexual abuse and psychiatric disorders were assessed using a semi-structured psychiatric interview. RESULTS: Females were more likely to be sexually abused as children (49%) than were males (14%). Intrafamilial members accounted for 78% of the reported child sexual abuse. Sexually abused males and females were more likely to report childhood and adult behavioral problems than were nonabused subjects. There was a strong relationship between multiple psychiatric disorders and child sexual abuse, with sexually abused males and females more likely to be diagnosed with > or = 3 psychiatric disorders, both including and excluding alcohol dependence or abuse, than were nonabused subjects. CONCLUSION: Child sexual abuse in this population is both an index of family dysfunction and community disorganization as well as a predictor of later behavioral patterns and psychopathology.

Factors influencing utilization of mental health and substance abuse services by American Indian men and women.

OBJECTIVE: This study investigated the effects of gender, number of lifetime psychiatric diagnoses, and childhood victimization on utilization of mental health and substance abuse treatment services in a Southwestern American Indian tribe. METHODS: A total of 582 individuals were recruited based on tribal enrollment and membership in large multigenerational pedigrees. Subjects were interviewed using a modified version of the Schedule for Affective Disorders and Schizophrenia-Lifetime Version, a semistructured psychiatric interview. For this study the definition of childhood victimization was limited to childhood sexual abuse. RESULTS: Fifty-six percent of the subjects had received mental health treatment, substance abuse treatment, or both. Patterns of service utilization differed by gender with the odds of inpatient and substance abuse treatment higher for men than for women. Women were more likely than men to receive mental health treatment. Subjects who had been sexually abused as children were more likely to have three or more psychiatric diagnoses and to have received extensive treatment, compared with subjects who reported no childhood sexual abuse history. Logistic regression demonstrated strong relationships between number of psychiatric diagnoses and the likelihood of treatment among both men and women. CONCLUSIONS: Gender, number of psychiatric diagnoses, and childhood sexual abuse are strong predictors of utilization of mental health and substance abuse treatment services. These factors should be considered in designing treatment interventions.

Grandmother dishonored: violence against women by male partners in American Indian communities.

Extensive and scrupulously conducted research during the past decade has established the issue of violence against women by male partners as both an international human rights issue and a public health problem of national concern. This research has rarely been extended into communities of color, and, in particular, to American Indian women. This article presents conceptual and methodological factors involved in conducting research with American Indian women, a comprehensive literature review of available data, assertions regarding abuse of women by male partners in American Indian communities, and directions for future research.

Alcoholism and substance abuse among selected southern Cheyenne Indians.

This family and small community-based study reports the occurrence of alcoholism and co-occurring substance abuse in Southern Cheyenne Indians living in western Oklahoma. Sociocultural factors complicate operationalization of clinical data into standard (DSM-III-R) psychiatric disorder terminology; understanding sociocultural factors is essential for assessing the high rate of addictive disorders in this group. To obtain reliable and valid clinical diagnoses, data from several sources were utilized within a blind rating system: 1) SADS-L, a clinician-administered research diagnostic instrument; 2) MAST; 3) relatives; 4) medical records; 5) other official documents. The sample consisted of 69 males (45 alcoholics) and 97 females (36 alcoholics). Among clinically significant substance abusers (moderate impairment of function), 22 of 24 were alcoholics. In non-alcoholics, mean MAST scores were 8.8 (males) and 5.1 (females); in alcoholics, 32.0 (males) and 38.7 (females). Mean age of onset on heavy use of alcohol was 20.1 yrs. (males) and 22.8 (females) (p = 0.047); among all alcoholics, 86% (males) and 64% (females) had early onset (< 25 yrs. old). When data from 98 unrelated subjects were analyzed separately, similar findings were observed except that mean age of onset of heavy use of alcohol was more discrepant between males and females, viz. 20.1 versus 22.8 yrs. (p = 0.02). Among those with substance abuse disorders, early age of onset was present in all but one female. In these Cheyenne, alcoholism is usually clinically severe and early in onset; it often co-occurs with substance abuse, also early in onset.