Robert W. Robin

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.

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.

Naltrexone Alone and With Sertraline for the Treatment of Alcohol Dependence in Alaska Natives and Non-Natives Residing in Rural Settings: A Randomized Controlled Trial

BACKGROUND Access to specialty alcoholism treatment in rural environments is limited and new treatment approaches are needed. The objective was to evaluate the efficacy of naltrexone alone and in combination with sertraline among Alaska Natives and other Alaskans living in rural settings. An exploratory aim examined whether the Asn40Asp polymorphism of the mu-opioid receptor gene (OPRM1) predicted response to naltrexone, as had been reported in Caucasians. METHODS Randomized, controlled trial enrolling 101 Alaskans with alcohol dependence, including 68 American Indians/Alaska Natives. Participants received 16 weeks of either (1) placebo (placebo naltrexone + placebo sertraline), (2) naltrexone monotherapy (50 mg naltrexone + sertraline placebo) and (3) naltrexone + sertraline (100 mg) plus nine sessions of medical management and supportive advice. Primary outcomes included Time to First Heavy Drinking Day and Total Abstinence. RESULTS Naltrexone monotherapy demonstrated significantly higher total abstinence (35%) compared with placebo (12%, p = 0027) and longer, but not statistically different, Time to First Heavy Drinking Day (p = 0.093). On secondary measures, naltrexone compared with placebo demonstrated significant improvements in percent days abstinent (p = 0.024) and drinking-related consequences (p = 0.02). Combined sertraline and naltrexone did not differ from naltrexone alone. The pattern of findings was generally similar for the American Indian/Alaska Native subsample. Naltrexone treatment response was significant within the group of 75 individuals who were homozygous for OPRM1 Asn40 allele. There was a small number of Asp40 carriers, precluding statistical testing of the effect of this allele on response. CONCLUSIONS Naltrexone can be used effectively to treat alcoholism in remote and rural communities, with evidence of benefit for American Indians and Alaska Natives. New models of care incorporating pharmacotherapy could reduce important health disparities related to alcoholism.

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. “Our grandmother, the earth, is a woman, and in mistreating your wife, you will be mistreating her. Most assuredly you will be abusing our grandmother if you act thus.” (Winnebago man)

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.

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.

Schizophrenia and psychotic symptoms in families of two American Indian tribes

BackgroundThe risk of schizophrenia is thought to be higher in population isolates that have recently been exposed to major and accelerated cultural change, accompanied by ensuing socio-environmental stressors/triggers, than in dominant, mainstream societies. We investigated the prevalence and phenomenology of schizophrenia in 329 females and 253 males of a Southwestern American Indian tribe, and in 194 females and 137 males of a Plains American Indian tribe. These tribal groups were evaluated as part of a broader program of gene-environment investigations of alcoholism and other psychiatric disorders.MethodsSemi-structured psychiatric interviews were conducted to allow diagnoses utilizing standardized psychiatric diagnostic criteria, and to limit cultural biases. Study participants were recruited from the community on the basis of membership in pedigrees, and not by convenience. After independent raters evaluated the interviews blindly, DSM-III-R diagnoses were assigned by a consensus of experts well-versed in the local cultures.ResultsFive of the 582 Southwestern American Indian respondents (prevalence = 8.6 per 1000), and one of the 331 interviewed Plains American Indians (prevalence = 3.02 per 1000) had a lifetime diagnosis of schizophrenia. The lifetime prevalence rates of schizophrenia within these two distinct American Indian tribal groups is consistent with lifetime expectancy rates reported for the general United States population and most isolate and homogeneous populations for which prevalence rates of schizophrenia are available. While we were unable to factor in the potential modifying effect that mortality rates of schizophrenia-suffering tribal members may have had on the overall tribal rates, the incidence of schizophrenia among the living was well within the normative range.ConclusionThe occurrence of schizophrenia among members of these two tribal population groups is consistent with prevalence rates reported for population isolates and in the general population. Vulnerabilities to early onset alcohol and drug use disorders do not lend convincing support to a diathesis-stressor model with these stressors, commonly reported with these tribes. Nearly one-fifth of the respondents reported experiencing psychotic-like symptoms, reaffirming the need to examine sociocultural factors actively before making positive diagnoses of psychosis or schizophrenia.