Prevalence and heritability of alcohol use disorders in 18-year old Swedish twins.

Background: Heritability of alcohol use disorders (AUDs) varies widely, with reported estimates of 30-78% in twin studies. This variation might be due to methodological differences (e.g., using different thresholds for AUDs, age differences between samples). Aim: To investigate the heritability of AUDs in a nation-wide sample of male and female twins in late adolescence (18 years). Participants: The study is based on data from 8,330 18-year-old Swedish monozygotic (MZ) and dizygotic (DZ) twins from the Child and Adolescent Twin Study (Sweden). Method: Univariate sex-limitation twin analyses were performed using (a) total AUDIT score, (b) different AUDIT cut-offs (AUDIT-10: potentially harmful alcohol use and most likely alcohol dependent ; AUDIT-C: potential hazardous alcohol consumption/active alcohol use disorders), and (c) a risk-group classification for alcohol dependence based on AUDIT total score. Results: Prevalence of potential hazardous alcohol consumption/active alcohol use was 57.1%, and for potentially harmful alcohol use prevalence was 26.5%. Prevalence was higher among females (59.0% and 31.1% respectively) than males (54.4% and 20.0% respectively). Overall, the results of the univariate model fitting indicated that there were qualitative sex differences in the genetic and environmental influences on AUDs, with generally moderate heritability estimates ranging between 0.37 and 0.50. Discussion: At odds with previous research, a harmful/hazardous drinking pattern was more common in this age group among females than a low-risk drinking pattern (where males were overrepresented). Heritability estimates were moderate throughout all measures and cut-offs, with equally high contributions from shared and non-shared environment. Sex-limitation models revealed qualitative sex differences for AUDs, suggesting that different genetic and/or environmental factors influence variation in AUDs in males and females.

Outcome in Relation to Drinking Goals in Alcohol-Dependent Individuals: A Follow-up Study 2.5 and 5 Years After Treatment Entry.

AIMS: To evaluate the long-term treatment outcome (up to 5 years) with respect to different drinking goals of patients. METHODS: Alcohol-dependent individuals (n = 349) were recruited from three alcohol treatment units. They were interviewed using the Addiction Severity Index (ASI). They were sub-grouped according to their goal at treatment entry: abstinence, low- risk drinking and no decided goal. RESULTS: Patients with abstinence as a goal at treatment entry reported at 2.5 years follow-up a higher abstinence rate, a more pronounced reduction in alcohol consumption, reduction in total number of DSM-IV criteria, higher frequency of low-risk drinking and fewer diagnoses of alcohol dependence compared to the groups who had low risk drinking as a goal or no decided goal. This improvement remained basically unchanged in all three groups at 5 years follow-up, suggesting long-term stability after the treatment interventions. CONCLUSIONS: The findings suggest that: (1) alcohol-dependent patients who have abstinence as their own drinking goal have a more favorable treatment outcome than those who have low-risk drinking as a goal or no decided goal. (2) Abstinence as a drinking goal should be considered for those who have a longer duration (for example more than 10 years) of their alcohol-related problems. (3) Patients who have no decided goal should be recommended abstinence as a drinking goal.

TAQ1A1 Allele of the DRD2 Gene Region Contribute to Shorter Survival Time in Alcohol Dependent Individuals When Controlling for the Influence of Age and Gender. A Follow-up Study of 18 Years.

AIMS: To investigate the influence of the A1 allele of the TAQ1A polymorphism in the dopamine D2 receptor (DRD2) gene region on mortality in adult individuals with alcohol dependence. METHODS: The study sample consisted of 359 alcohol-dependent individuals treated for severe alcohol withdrawal symptoms in 1997. Years of survival was studied in an 18-year follow-up. In the analyses, gender and age were controlled for. RESULTS: At the 18-year follow-up, 53% individuals had deceased. The analyses showed that older age (P < 0.001), male gender (P < 0.05) and carrying the A1 allele (P < 0.01) all significantly and independently contributed to shorten years of survival. Among the deceased individuals, the genotype A1+ was the only significant contributor to shorten years of survival. CONCLUSIONS: An important contribution of the present study is that in alcohol dependence the Taq1A1 allele of the DRD2 gene region is a risk factor for premature death of similar importance as the well-known risk factors of age and gender. SHORT SUMMARY: We investigated the influence of A1 allele of the TAQ1A polymorphism in DRD2 receptor gene region on mortality in alcohol-dependent individuals in an 18-year follow-up. Age, gender and the A1 allele contributed to shorten years of survival. Among the deceased, the A1+ was the only contributor to shorten years of survival.

The Influence of Smoking and Smokeless Tobacco on the Progression, Severity and Treatment Outcome in Alcohol-Dependent Individuals.

AIMS: The influence of tobacco use in alcohol-dependent individuals is not well understood, especially the role of snuffing, which is common in Northern Europe. The aim was therefore to investigate the influence of smoking and snuffing on the progression, severity and treatment outcome in alcohol-dependent individuals. The hypotheses were that concomitant tobacco use (i.e. smoking or snuffing) would enhance the progression and severity of alcohol dependence and be less beneficial for treatment outcome, relative to tobacco non-users. METHODS: Alcohol-dependent individuals (n = 347) were recruited from three treatment units specialized in alcohol use disorders. Participants were interviewed about their current and past alcohol and tobacco use at treatment entry and at a follow-up interview 2.5 years thereafter. RESULTS: The tobacco users (smokers and snuffers) had an earlier alcohol debut compared to the tobacco never-users. Snuffers reported regular alcohol consumption and inebriation at an earlier age in contrast to smokers and tobacco never-users. There were no difference between the groups regarding treatment outcome. CONCLUSIONS: This study highlights the importance of studying not only the influence of smoking but also of snuffing on the progression, severity and treatment outcome in individuals with alcohol dependence.

Is There a Need for Congruent Treatment Goals Between Alcohol-Dependent Patients and Caregivers?

BACKGROUND: Alcohol-dependent patients have different treatment goals when entering treatment. Furthermore, different treatment settings advocate different treatment goals. Earlier studies have pointed out that treatment goal is important for treatment outcome, both in the treatment setting as well as in the patients themselves. However, to our knowledge, no study has so far investigated the interaction between patient's goal and the goal of the treatment setting. The aim of the study was therefore to study the interaction between these 2 factors on treatment outcome. METHODS: Patients' (n = 201) goals from 2 treatment settings-one that had an abstinence-oriented goal and one with a low-risk drinking goal-were investigated. The patients were followed up 2.5 years after treatment entry and effectiveness of congruent treatment goals on treatment outcome was investigated. RESULTS: There was no significant association between congruent goals and treatment outcomes (p = 0.060). However, when comparing the effectiveness of congruent treatment goal between the 2 treatment settings, the abstinence-oriented treatment setting was significantly more effective (p < 0.01). CONCLUSIONS: The major finding was that there appeared to be no association between congruence itself and treatment outcome. On the other hand, we found that the treatment outcome was more successful if the patient as well as the treatment setting had abstinence as a goal (i.e., congruent goals of abstinence).

Childhood maltreatment affects the serotonergic system in male alcohol-dependent individuals.

BACKGROUND: Reduced central serotonergic neurotransmission has been demonstrated in individuals with excessive alcohol consumption and/or alcohol dependence. Childhood maltreatment has also been found to have a negative impact on central serotonergic neurotransmission. The aim of this study was to evaluate the impact of childhood maltreatment on central serotonergic dysfunction in alcohol-dependent individuals. METHODS: Adult men with a diagnosis of alcohol dependence (n = 18) were recruited from outpatient treatment units for alcoholism. Central serotonergic neurotransmission was assessed by a neuroendocrine method, that is, the prolactin (PRL) response to the selective 5-HT reuptake inhibitor citalopram. Childhood maltreatment was assessed retrospectively by the Childhood Trauma Questionnaire. RESULTS: Alcohol-dependent individuals with childhood experience of emotional abuse had significantly lower PRL response compared with those without such abuse (3 ± 5 and 64 ± 24 mU/l, respectively; t = 6.51, p < 0.001). Among those who reported childhood emotional abuse, 4 of 7 individuals had flat PRL responses in comparison with none in those with no report of such abuse (p < 0.01). CONCLUSIONS: This is the first study to show that self-reported childhood maltreatment, in particular emotional abuse, in male alcohol-dependent individuals is associated with a quite dramatic (more than 90%) reduction in central serotonergic neurotransmission. It should, however, be noted that the number of individuals is relatively small, and the results should therefore be considered as preliminary.

Neuroendocrine assessment of serotonergic, dopaminergic, and noradrenergic functions in alcohol-dependent individuals.

BACKGROUND: Alcohol dependence has been associated with reduced function of serotonin, dopamine as well as noradrenaline activities in several neuroendocrine studies. To our knowledge, there is, however, no study investigating all these 3 systems with the use of neuroendocrine methods in one and the same alcohol-dependent individual. METHODS: Alcohol-dependent individuals (n = 42) and controls (n = 28) participated in the neuroendocrine test series. Central serotonergic neurotransmission was assessed by the prolactin (PRL) response to citalopram (CIT). The postsynaptic DRD2 function was measured by the growth hormone (GH) response to apomorphine (APO) and the postsynaptic α2-adrenoceptor function by GH response to clonidine (CLON). RESULTS: In the alcohol-dependent individuals, the PRL concentrations were significantly lower at the time points 240 minutes and 300 minutes after CIT administration and mean delta PRL value was significantly reduced by 45% in comparison with controls. There were no significant differences in APO-GH and CLON-GH concentrations at any time points or in mean delta GH values between the groups. An impaired monoaminergic profile, including all 3 systems, was significantly more frequent in alcohol-dependent individuals than controls (43% vs. 6% respectively). CONCLUSIONS: The monoaminergic dysfunction was restricted to an impairment of the serotonergic system, suggesting that this system is especially vulnerable to long-term and excessive alcohol consumption. Moreover, impaired monoaminergic profiles, including low responses in 2 or 3 systems, were more frequently observed in alcohol-dependent individuals than in controls. Such impaired profiles may be of clinical importance, but further studies are needed.

Do alcohol-dependent individuals with DRD2 A1 allele have an increased risk of relapse? A pilot study.

AIMS: The TaqIA polymorphism of the dopamine D2 receptor (DRD2) gene has been extensively studied in relation to alcoholism, and the TaqI A1 allele appears to be over-represented in alcohol-dependent individuals. In a recent study, this allele has also been associated with a highly increased mortality rate in alcohol-dependent individuals. In the present study, we investigated whether the TaqI A1 allele of the DRD2 gene region was associated with a higher relapse rate in alcohol-dependent individuals. METHODS: Adult women (n = 10) and men (n = 40) with a diagnosis of alcohol-dependence were recruited from two Swedish 12-step treatment units for alcoholism. Subjects were genotyped for the TaqIA polymorphism. On average, 1½ year after the end of the treatment program, subjects were re-interviewed by using the alcohol-related items from the Addiction Severity Index follow-up version. RESULTS: Thirty-three (66%) subjects self-reported relapse and 17 (34%) abstinence during the follow-up period. Thirty-sex percent (18/50) were carriers of the A1 allele of the DRD2 gene region, and 64% (32/50) were non-carriers. Among the carriers of the A1 allele, 89% (16/18) reported relapse in contrast to 53% (17/32) in the non-carriers (P = 0.01; odds ratio = 7.1). CONCLUSION: The present study is, to our knowledge, the first report of an association between the TaqI A1 allele and a substantially increased relapse rate. It should be emphasized that the number of subjects is relatively small, and this investigation should therefore be considered as a pilot study.

Reward-related genes and personality traits in alcohol-dependent individuals: a pilot case control study.

Components of the brain reward system, i.e. the mesolimbic dopamine, laterodorsal cholinergic and ghrelin signaling systems, have been implicated in alcohol reward in preclinical studies. Genetic variants of these systems have previously been linked to alcohol dependence. Here, we genotyped 31 single nucleotide polymorphisms (SNPs): 1 SNP in the dopamine D2 receptor (DRD2) gene, 20 SNPs in 5 different nicotinic acetylcholine receptor subunit (CHRN*) genes, and 10 SNPs in the genes encoding pro-ghrelin (GHRL) and its receptor (GHSR), in a pilot study of type 1 alcoholics (n = 84) and healthy controls (n = 32). These individuals were characterized using the Temperament and Character Inventory. None of the SNPs were associated with risk of alcohol dependence in this population. The GG genotype of SNP rs13261190 in the CHRNB3 was associated with increased novelty seeking, while SNPs of the ghrelin signaling system were associated with decreased self-directedness (AA of rs495225, GHSR) and alterations in self-transcendence (AA of both rs42451 and rs35680, GHRL). In conclusion, this pilot study suggests that reward-related genes are associated with altered personality scores in type 1 alcohol dependence, which warrants future studies of these associations in larger study samples.

Do men with excessive alcohol consumption and social stability have an addictive personality?

The existence of an "addictive" personality has been extensively debated. The current study investigated personality in male individuals with excessive alcohol consumption (n=100) in comparison to a population-based control group (n=131). The individuals with excessive alcohol consumption were recruited by advertisements in a regional daily newspaper and controls from a population based Swedish Twin Registry. Personality was assessed by the Karolinska Scales of Personality (KSP). Comparisons were made with normative data. Furthermore, by using a multivariate projection-based approach (Principal Component Analysis; PCA), hidden structures of traits and possible relationships among the individuals with excessive consumption and the controls was investigated. The individuals with excessive alcohol consumption as well as the controls had mean values within the normative range in all scales of the KSP. Moreover, the PCA analysis revealed no systematic between-group separation. Taken together, this result demonstrates that male individuals with excessive alcohol consumption do not have a personality different from that of a general population, which supports the notion of no "addictive personality".

Psychosocial and dental factors in the maintenance of severe dental fear.

The aim was to study the relationship between psychosocial factors and dental status in adult subjects with severe dental fear (DF). A consecutive sample of 148 adults (mean age 36.1 yrs, range 21-69 yrs) referred for dental fear treatment was investigated using an intake questionnaire on dental attendance and history, psychometric questionnaires on dental fear, general anxiety and depression and a radiographic examination. The subjects had a mean DFMT (Decayed, Filled, Missed Teeth) score of 18.6 (SD = 5.6). A deterioration in dental status defined as the presence of root remnants was present in 57% of the subjects and was related to the negative consequences of dental fear, general anxiety and depression. Most subjects (84%) reported clinical levels of general anxiety and 46% reported clinical levels of depression. In conclusion, subjects with severe DF often suffer from psychosocial consequences and distress.This is even more marked if their dental status has deteriorated.The findings support a biopsychosocial vicious circle understanding of the maintenance of DF.

Possible predictors of discontinuation of specialized dental treatment among children and adolescents with dental behaviour management problems.

This study aimed to identify potential predictors of non-attendance among children and adolescents with dental behaviour management problems (DBMP). A group of 179 patients, 7.5-19 yr of age, was grouped into 56 'non-attenders' (discontinued treatment, missed appointments, or >or= 20% cancellations) and 123 'attenders'. In addition to data from an introductory interview and dental recordings, baseline data from psychometric measures of fear and other personal and parental characteristics were included in logistic regression analyses and tree-based modelling. The non-attenders had higher scores on impulsivity and sociability and lower socio-economic status (SES) than the attenders, and they lived more often in single-parent families. Logistic regression analyses and tree-based modelling point to SES and parental anxiety as important predictors for non-attendance within this group of children and adolescents. To predict, and possibly to prevent, non-attendance among children and adolescents referred for specialized dental care because of DBMP, we must consider their lives and family situations as well as their personal characteristics and oral health status. Further research should focus on whether the observed associations between non-attendance and factors such as personal characteristics, family and psychosocial factors, and previous dental experiences, also hold for those who remain in regular dental care.

Dental behaviour management problems: the role of child personal characteristics.

AIM: This study aimed to investigate the role of dental fear (DF) and other personal characteristics in relation to dental behaviour management problems (DBMP). DESIGN: A study group of 230 patients (7.5-19 years old; 118 girls), referred because of DBMP, was compared to a reference group of 248 same-aged patients (142 girls) in ordinary dental care. Patients and their parents independently filled in questionnaires including measures of fear and anxiety, behavioural symptoms, temperamental reactivity, and emotion regulation. RESULTS: Study group patients referred because of DBMP differed from the reference group in all investigated aspects of personal characteristics. In the multivariate analyses, DF was the only variable with consistent discriminatory capacity through all age and gender subgroups. Aspects of anxiety, temperament, and behavioural symptoms contributed, but differently for different subgroups and at different levels of dental fear. CONCLUSIONS: Among older children and adolescents, DF deserves to be re-established as the single most important discriminating variable for DBMP at clearly lower scores than commonly used. Further research should focus on the different patterns of DBMP development, considering various personal characteristics that may trigger, maintain, or exacerbate young patients' vulnerability to DF and DBMP.

Gamma-glutamyltransferase in alcohol use disorders: Modification of decision limits in relation to treatment goals?

Serum gamma-glutamyltransferase (GGT) is recommended as a marker for alcohol use disorders by the Swedish National Guidelines for Addiction, although it has a low sensitivity and specificity. GGT is inexpensive and easily accessible but additional knowledge is required on how to use the marker in patients with various levels of alcohol intake. Levels of GGT were obtained from 37 male social drinkers (< 100 grams pure alcohol weekly) and 18 former alcohol-dependent males with long-term (6 +/- 5 years) abstinence. Reproducibility was calculated through repeated blood samplings. Mean serum activity of GGT, in former alcohol-dependent males, was 0.26 microkat/L with an intra-class correlation coefficient of 0.85. In social drinkers, these figures were 0.34 microkat/L and 0.92, respectively. In treatment of males, with the goal of abstinence, upper reference limit is suggested to be 0.40 microkat/L. Goals of non-harmful drinking (< 100 grams weekly) suggest higher limits (0.62 microkat/L). Thirty percent increase of GGT should be suggestive of relapse.

Dopamine D2 receptor genotype is associated with increased mortality at a 10-year follow-up of alcohol-dependent individuals.

AIMS: Because the TAQ1 A1 allele may be associated with alcohol-related medical illnesses, and medical illnesses in alcohol-dependent individuals are associated with increased mortality, we test the hypothesis that the TAQ1 A1 allele of the DRD2 gene is associated with increased mortality in alcohol-dependent individuals. METHODS: Following an index treatment episode, a 10-year follow-up study in 366 alcohol-dependent individuals was performed. The TAQ1 A1/A2 DRD2 genotype and allele frequencies were compared between those deceased and those still living at the 10-year point. In addition, the genotype and allele frequencies of these alcohol-dependent individuals were compared to that in 578 control subjects. RESULTS: The prevalence of the A1 allele differed between the deceased and living patients and the controls: 47% of the deceased were A1+, compared to 37% of the living patients and 32% of the controls. The frequency of the TAQ1 A1/A2 genotype also differed between the groups. Thus, 43% had the A1/A2 genotype in comparison with 32% in the living patients and 29% in the controls. The TAQ 1 A1 allele frequency differed between the groups. The frequency of A1 allele was 25% in the deceased patients compared to 21% in the living patients and 17% in the controls. CONCLUSION: The TAQ I A1 allele of the DRD2 gene (or DRD2 gene region) was associated with increased mortality over a 10-year period in alcohol-dependent individuals.

Everyday- and dental-pain experiences in healthy Swedish 8-19 year olds: an epidemiological study.

BACKGROUND: Very little is known about children's everyday pains and dental treatment pains. A child's gender, age, and level of dental anxiety are factors that could interplay with the perception of pain and are thus worth studying. AIM: The objectives of this study were to investigate the frequency and reported intensity levels of children's everyday- and dental-pain experiences, and to study the reported pains in relation to gender, age, and dental anxiety. DESIGN: Three hundred and sixty-eight consecutive patients (8-19 years, mean age 13.5 years) from three different Public Dental Service were recruited. Pain ratings were obtained using McGrath's Children's Pain Inventory list and some additional items. Dental anxiety was estimated by the Dental Anxiety Scale. RESULTS: Most frequently experienced everyday pains were headache and tummy/stomach ache. Among dental treatment events, dental injection was reported to be most often ranked as painful, and more frequently by girls. Both dental and everyday pains were rated higher grouping children with high dental anxiety. CONCLUSIONS: The frequency of pain experiences are the same in Swedish children as in other populations. There is a relation between dental anxiety and the perception of pain.

Thrombocytopenia in early alcohol withdrawal is associated with development of delirium tremens or seizures.

AIMS: In several studies, possible risk factors/predictors for severe alcohol withdrawal syndrome (AWS), i.e. delirium tremens (DT) and/or seizures, have been investigated. We have recently observed that low blood platelet count could be such a risk factor/predictor. We therefore investigated whether such an association could be found using a large number of alcohol-dependent individuals (n = 334). METHODS: This study is a retrospectively conducted cohort study based on data from female and male patients (>20 years of age), consecutively admitted to an alcohol treatment unit. The individuals had to fulfil the discharge diagnoses alcohol dependence and alcohol withdrawal syndrome according to DSM-IV. RESULTS: During the treatment period, 3% of the patients developed DT, 2% seizures and none had co-occurrence of both conditions. Among those with DT, a higher proportion had thrombocytopenia. Those with seizures had lower blood platelet count and a higher proportion of them had thrombocytopenia. The sensitivity and specificity of thrombocytopenia for the development of DT during the treatment period was 70% and 69%, respectively. The positive predictive value (PPV) was 6% and the negative predictive value (NPV) was 99%. For the development of seizures, the figure for sensitivity was 75% and for specificity 69%. The figures for PPV and NPV were similar as those for the development of DT. CONCLUSIONS: Thrombocytopenia is more frequent in patients who develop severe AWS (DT or seizures). The findings, including the high NPV of thrombocytopenia, must be interpreted with caution due to the small number of patients who developed AWS. Further studies replicating the present finding are therefore needed before the clinical usefulness can be considered.

Self-reported health functioning in Swedish alcohol-dependent individuals: age and gender perspectives.

The aim of this study was to investigate health functioning and drinking patterns in a Swedish alcohol-dependent treatment sample. Gender and two age groups were, respectively, compared in these characteristics. Data for demographic characteristics, substance use and health functioning were collected by a structured interview, using the Addiction Severity Index. A total sample of 125 individuals (30 women and 95 men) was interviewed shortly after arrival to the inpatient treatment. Differences between genders were found in drinking patterns, where men had earlier onset of first drink, earlier onset of problematic alcohol consumption and longer duration of problematic consumption. No differences between genders were found regarding somatic and psychiatric health. When comparing the two age groups (29-47 years and 49-69 years), the younger individuals had more lifetime and current psychiatric symptoms (including depression, anxiety, suicidal ideation etc.), whereas the older individuals had more chronic somatic disorders. The younger individuals had also an earlier onset of first drink of alcohol and had started a problematic consumption at earlier ages. They had also more lifetime experience of illicit drugs (including benzodiazepines and analgesics). The findings from the present study indicate that an age-perspective in treatment planning may be of more importance than a gender perspective, where younger individuals probably need more of psychiatric consultation and their older counterparts need more of consultations by medical professionals.