Kristina Berglund

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.

Personality profile in type I alcoholism: long duration of alcohol intake and low serotonergic activity are predictive factors of anxiety proneness

Summary.The aim of the present study was to further investigate personality profiles in male type I alcohol-dependent subjects (n = 33), in relation to central serotonergic neurotransmission, history of excessive alcohol consumption and present use of tobacco. Central serotonergic neurotransmission was assessed by the prolactin (PRL) response to D-fenfluramine. By using the Temperament and Character Inventory and the Karolinska Scales of Personality, all subjects self-rated their personality profile. The results showed that individuals with low PRL response and long duration of excessive alcohol consumption had significantly higher anxiety proneness, and that years of excessive alcohol consumption was the strongest predictor. Long duration of excessive alcohol consumption thus appears to have an influence on personality traits in male type I alcohol-dependent individuals and these personality traits may therefore be a consequence of, rather than preceding, alcoholism in these individuals.

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.

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.

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.

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.

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 patters 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.

Changes in mental well-being during Minnesota treatment

The present study assessed mental well-being daily in 28 alcohol-dependent patients who underwent 28 days of Minnesota inpatient treatment. The Swedish Mood Adjective Check List (sMACL) with six bipolar dimensions was used for daily self-reports. At start of treatment, patients had lower levels in four dimensions of mental well-being compared to those of a norm group. Moreover, patients showed significant improvements in all levels of mental well-being during treatment, and at the end of treatment patients had values within the normal range, except for one dimension (activation/deactivation), in which the levels were significantly higher. The findings may suggest a beneficial effect of this type of treatment on mental well-being, although findings may also reflect a mere effect of adjustment to treatment or the social situation.

Predicting Treatment Outcome on the Basis of Temperament in Patients Who Are Socially Stable and Alcohol Dependent

ABSTRACT The literature on predictors of treatment outcome is relatively extensive, but results on personality factors that predicts treatment outcome among alcohol dependent patients are still inconclusive. The aim of this study was to investigate if the scales of the Temperament and Character Inventory could predict treatment outcome after 18 months in a sample of patients who were socially well adjusted and alcohol dependent (N = 202). Bivariate comparisons indicate that patients with higher levels of harm avoidance showed a lower probability of successful treatment. Further, exploratory analysis of specific configurations associated with treatment success or failure was presented. The results indicate that harm avoidance seem to be a key factor for this specific sample of patients who are socially well adjusted and alcohol dependent, results that might be useful in clinical practice.