Hazardous alcohol use and alcohol use disorders in women : characteristics and vulnerability factors

Abstract: The overall aim of this thesis was to study vulnerability factors associated with hazardous alcohol consumption during pregnancy and alcohol use disorders among Swedish women. Different risk-factors and characteristics were studied, and examined for their ability to discriminate or identify different subtypes (type I/late onset and type II/early onset) of alcohol dependence ( alcoholism ). In study I, an RCT at ANC in Stockholm (control, n = 156, intervention, n =147) we examined the ability of Swedish antenatal care to identify alcohol-related risk pregnancies, and the utility of some tools that could improve its performance (AUDIT, TLFB and biomarkers). In study II, a pilot cohort (n = 139) was screened for alcohol use disorders, and assessed for psychopathology, personality traits, and alcohol use during the first trimester. Subjects reporting consumption exceeding a conservative threshold for harmful use were offered a diagnostic psychiatric interview. The main findings of the pilot study were replicated using a large sample of women in the third trimester (n = 715). In study III and IV, a case-control study, detailed assessment was obtained from 200 treatment-seeking alcohol dependent women and 189 healthy population controls. All women were assessed for alcohol-related behaviors, sexual abuse history, psychiatric problems, and personality traits. Cases and controls were genotyped for markers in the CRHR1, MAOA and OPRM1 genes. In study V, female twins from the Swedish Twin Registry (n =13 501) answered questions to establish lifetime alcohol use disorders, and subjects with alcoholism were classified for subtype. Heritability estimates were obtained, and environmental factors associated with alcoholism and its subtypes were studied. Sixteen percent of pregnant women drank at levels that could be defined as riskconsumption . Significantly more of these were identified by intensified screening compared to regular antenatal screening procedures (p = 0.0001), while biomarkers were of little use. Only a minority of women with hazardous alcohol consumption during pregnancy fulfilled alcohol dependence criteria. Psychiatric distress in those with risk-consumption did not differ from those with low or no consumption during pregnancy, but subjects with continued alcohol use scored higher on novelty seeking. Among women with alcohol dependence, early onset/type II alcoholism is a valid construct. We found that alcohol dependent women classified as type II had more severe alcohol problems and significantly higher rates of illicit drug use. Family history of alcoholism was also considerably more common among type II than subjects than those classified as type I. Both alcoholism subtypes scored higher than normal on anxiety and impulsivity traits, but type II subjects scored markedly higher than either of the other groups on aggression (p = 0.00004). Despite a higher density of family history among type II subjects in the clinical cohort, our twin study did not support a difference in heritability between early onset/type II and late onset/type I alcoholism. Both genetic and environmental factors play an important role for susceptibility to alcoholism in women, in particular the early onset subtype. Childhood trauma is a category of environmental factors that plays a major role. The effect of emotional neglect and physical trauma was accounted for by familial background factors, which can be both genetic and environmental. In addition, childhood sexual abuse was an independent individual risk factor for alcohol dependence. Effects of sexual abuse were in part mediated trough psychiatric problems. Overall, treatment-seeking alcohol dependent women with a history of abuse have distinct features as compared to other alcohol dependent women.