Epistasis between IL1A, IL1B, TNF, HTR2A, 5-HTTLPR and TPH2 variations does not impact alcohol dependence disorder features.

We assessed a set of biological (HDL, LDL, SGOT, SGPT, GGT, HTc, Hb and T levels) and psychometric variables (investigated through HAM-D, HAM-A, GAS, Liebowitz Social Anxiety Scale, Mark & Mathews Scale, Leyton scale, and Pilowski scale) in a sample of 64 alcohol dependent patients, at baseline and after a detoxification treatment. Moreover, we recruited 47 non-consanguineous relatives who did not suffer alcohol related disorders and underwent the same tests. In both groups we genotyped 11 genetic variations (rs1800587; rs3087258; rs1799724; 5-HTTLPR; rs1386493; rs1386494; rs1487275; rs1843809; rs4570625; rs2129575; rs6313) located in genes whose impact on alcohol related behaviors and disorders has been hypothesized (IL1A, IL1B, TNF, 5-HTTLPR, TPH2 and HTR2A). We analyzed the epistasis of these genetic variations upon the biological and psychological dimensions in the cases and their relatives. Further on, we analyzed the effects of the combined genetic variations on the short - term detoxification treatment efficacy. Finally, being the only not yet investigated variation within this sample, we analyzed the impact of the rs6313 alone on baseline assessment and treatment efficacy. We detected the following results: the couple rs6313 + rs2129575 affected the Leyton -Trait at admission (p = 0.01) (obsessive-compulsive trait), whilst rs1800587 + 5-HTTLPR impacted the Pilowski test at admission (p = 0.01) (hypochondriac symptoms). These results did not survive Bonferroni correction (p < or = 0.004). This lack of association may depend on the incomplete gene coverage or on the small sample size which limited the power of the study. On the other hand, it may reflect a substantial absence of relevance of the genotype variants toward the alcohol related investigated dimensions. Nonetheless, the marginal significance we detected could witness an informative correlation worth investigating in larger samples.

TPH2 gene variants and anxiety during alcohol detoxification outcome.

Clinical outcome of alcoholism may be partly under genetic control. The serotonergic system is involved in alcohol intake, and it has been widely investigated in alcohol dependence. Recently, attention has been focused on the neuronal tryptophan hydroxylase 2 gene (TPH2). TPH2 variants have been consistently associated with anxiety-related traits; since anxiety is critical for alcohol dependence treatment, in the present paper we investigated 9 SNPs within the THP2 gene in anxiety symptoms during the detoxification procedure. The sample comprised 68 alcohol-dependent patients who where evaluated with the Hamilton Rating Scale for Anxiety, before and after the detoxification procedure. Other psychopathological indicators of outcome, such as depression and anxiety sub-features were also investigated. We did not observe a role for TPH2 variants in the efficacy of treatment in relieving anxiety and other psychopathological symptoms. However, a haplotype that included the promoter rs4570625 polymorphism (associated with anxiety-related traits in previous studies) showed an association with the severity of anxiety symptoms on admission. This preliminary finding, although obtained on a small sample, may provide further support for a role of the TPH2 gene in emotional behaviors. Furthermore, the present study suggests the possible functional significance of the promoter rs4570625 polymorphism. The present preliminary results are of interest in alcoholism, given that comorbidity with anxiety represents a critical problem in treatment settings and response to detoxification.

Evaluation of apolipoprotein E (apoE) and lipoprotein profile in severe alcohol-dependent individuals.

BACKGROUND: Chronic alcohol consumption down-regulates the expression of sialytransferase genes resulting in impaired sialylation of apolipoprotein E (apoE) and decreased association with HDL. There are a limited number of studies with contradictory data on the effect of alcohol dependence on human plasma apoE. The aim of the present work is to determine and compare the levels of apoE in relation to the other lipoproteins in alcohol-dependent individuals in order to evaluate the possible role of apoE in lipoprotein metabolism in conditions of severe alcohol dependence. PATIENTS AND METHODS: The sample of our study comprised 43 DSM-IV diagnosed alcohol-dependent/abusing subjects (33 males and 10 females), treated on an inpatient basis according to a standard detoxification protocol, and 27 healthy people (9 males and 18 females, as a control group). Serum concentration of hepatic enzymes (AST, ALT, gammaGT), as well as measures of cholesterol and lipoproteins were obtained at baseline and at discharge after a detoxification period of 4-5 weeks. RESULTS: Upon admission, all alcohol-dependent individuals had significantly higher hepatic enzyme levels, apoE and HDL values compared to controls. After completion of alcohol detoxification, all the above parameters returned to normal levels. Additionally, a significant correlation was observed between alcohol consumption during the previous year of alcohol abuse and the apoE values both upon admission to and on discharge from the detoxification program. CONCLUSION: The statistical correlation between apoE on admission and discharge with alcohol consumption during the previous year suggests that apoE is dependent on alcohol consumption and can serve as a sensitive marker of severe alcohol abuse.

Vitamin B12 and hepatic enzyme serum levels correlate with interleukin-6 in alcohol-dependent individuals without liver disease.

Alcohol abuse is a major cause of liver cirrhosis as well as chronic liver disease. The aim of the present study was to investigate the possible correlation, between liver dysfunction biological markers and vitamin B12, with interleukin-6, in the serum of alcohol-dependent individuals without liver disease (AWLD). In a sample of 43 alcohol abusing/dependent subjects (33 males and 10 females) treated on an inpatient basis according to a standard detoxification protocol, the serum activities of the hepatic enzymes (ASAT, ALAT, gamma-GT), as well as the concentration of B12 and IL-6, were determined on admission. A strong positive correlation has been observed between IL-6 and B12, ASAT, ALAT, and gamma-GT at the beginning of the detoxification period. The results confirmed that in alcohol-dependent individuals, the median serum concentration of IL-6, before the beginning of the treatment, had a significant positive correlation with the liver dysfunction biological markers and B12. In conclusion, IL-6 might be used as an additional diagnostic marker for the degree of liver dysfunction in alcohol dependent individuals.

Depression and social phobia secondary to alcohol dependence.

BACKGROUND: According to the self-medication hypothesis, individuals with depression and anxiety disorders use alcohol to control their symptoms and subsequently become dependent. Conversely, alcohol dependence disorder (ADD) can cause or exacerbate psychiatric disorders. This study analyzed the characteristics of depression and social phobia secondary to ADD. (1) What is their functional impact? (2) Are they independent or associated conditions? (3) Do they completely remit in abstinent individuals? (4) Is the remission of one disorder associated with the remission of the other disorder? METHODS: Sixty-four inpatients with ADD were evaluated with depression and anxiety disorder scales upon admission to hospital and after 5 weeks of detoxification. RESULTS: Baseline comparisons differentiated patients with a Hamilton Rating Scale for Depression (HDRS) score > 35 (n = 50; 78%) from those with an HDRS score < or = 35 by higher levels of generalized anxiety and lower global functioning. Patients with generalized social phobia [Leibowitz Social Anxiety Scale (LSAS) score > 60: n = 20; 31.2%] were not distinguishable from those with an LSAS score < or = 60 by depressive and anxiety disorder symptoms. In postdetoxification assessment, patients who remitted from depression (HDRS score < 7: n = 35; 54.6%) had a lower generalized anxiety and marginally higher levels of hypochondriasis compared to nonremitter subjects (HDRS score > or = 7). Patients who remitted from social phobia (LSAS score < 30: n = 32; 50%) did not significantly differ from nonremitter subjects in depressive and anxiety disorder symptoms. Generalized anxiety (Hamilton Rating Scale for Anxiety) and hypochondriasis (Whiteley Index) were the significant predictors of global functioning (Global Assessment Scale). CONCLUSIONS: Depression and social phobia secondary to ADD are independent conditions that do not completely remit after cessation of drinking. Specific treatments are needed to reduce residual depressive and anxiety symptoms in abstinent alcoholics.

Effect of alcohol detoxification on serum S-100B levels of alcohol-dependent individuals.

BACKGROUND: Chronic alcohol consumption has been associated with both liver dysregulation and neurotoxic effects in the central nervous system of human beings and experimental animals. Serum levels of S100B protein have been extensively studied in several conditions of neural tissue injury but not in alcohol abuse. The aim of this study was to evaluate the serum levels of S100B in alcohol-dependent individuals and to further investigate the effect of alcohol detoxification on the levels of S100B. PATIENTS AND METHODS: Our study included 20 alcohol dependent/abusing subjects, diagnosed based on the DSM-IV criteria and treated on an inpatient basis according to a standard detoxification protocol. The serum concentration of hepatic enzymes (ASAT, ALAT, gammaGT), as well as measurements of anxiety, depression and global functioning were obtained at baseline and at weekly intervals over the period of 4-5 weeks, while S100B levels were measured on admission and discharge. RESULTS: Upon admission, hepatic enzyme levels were found increased compared to normal levels and correlated positively with the degree of alcohol consumption of the last year. Interestingly, the ALAT levels correlated positively with S100B levels upon admission. After completion of alcohol detoxification, the hepatic enzyme levels returned to normal. The S100 B levels decreased in 10 patients with a moderate alcohol-consumption over the last year, but increased in 10 patients with high alcohol consumption over the last year. Additionally, a significant correlation was found between the levels of S100B and the global functioning scale at the end of detoxification treatment. CONCLUSION: S100B protein levels are affected differently in alcohol-dependent individuals with either mild or high alcohol consumption during the period of up to one year before assessment. A good correlation between the release pattern of S100B and global functioning scale was found. Although this is a preliminary study, the present data suggest a possible use of S100B protein measurements in detecting alcohol-dependent individuals with high alcohol consumption and in further monitoring the alcohol detoxification treatment.

Interleukin-1 alpha and beta, TNF-alpha and HTTLPR gene variants study on alcohol toxicity and detoxification outcome.

Genetic factors may influence the liability to treatment outcome and medical complications in alcoholism. In the present study we investigated the IL-1A rs1800587, IL-1B rs3087258, TNF-alpha rs1799724 and the HTTLPR variants in a sample of 64 alcohol dependents and 47 relatives versus a set of clinical parameters and outcome measures. Alcohol dependents had a less favorable clinical profile compared to relatives (higher cholesterol, triglycerides, glucose, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, gamma-glutamyltransferase). After detoxification, all clinical indexes improved and hepatic enzyme levels were similar in alcohol dependents and relatives, except for the GGT that remained significantly higher in alcohol dependents. Alcoholic depressive and anxiety scores were significantly reduced after detoxification. IL-1A, IL-1B, TNF-alpha and HTTLPR variants were not associated with any baseline clinical index or change after detoxification. In our sample IL-1A, IL-1B, TNF-alpha and HTTLPR do not appear as liability factors for alcohol toxicity or detoxification outcome, however the small sample size may influence the observed results.

Interrelationship of hepatic function, thyroid activity and mood status in alcohol-dependent individuals.

BACKGROUND: Alcohol-induced changes in thyroid function may contribute to the development of mood disorders such as depression and anxiety that almost invariably coexist in alcohol-dependent individuals. The aim of the present study was to investigate the severity of liver dysfunction and thyroid activity in correlation with anxiety and depressive-like symptomatology before and after a detoxification period. PATIENTS AND METHODS: In a sample of 100 alcohol-abusing/dependent subjects treated on an in-patient basis according to a standard detoxification protocol, measurements of the serum levels of hepatic enzymes (ASAT, ALAT, gammaGT) and thyroid hormones (T3, T4, TSH) as well as measures of anxiety, depression and global functioning were obtained at baseline and at weekly intervals over the period of 4-5 weeks. RESULTS: After completion of the alcohol detoxification, most measurements returned to normal levels and correlations were observed between the levels of hepatic enzymes and thyroid hormones. Additionally, a significant correlation was obtained between the levels of thyroid hormones and the mood status scales. CONCLUSION: Our results indicated a dysfunction of the hypothalamic-pituitary-thyroid axis in alcohol dependence with possible implications in the diagnosis and treatment of mood disorders associated with alcohol abuse.

Correlation of liver dysfunction biological markers to the mood status of alcohol-dependent individuals.

OBJECTIVE: Alcohol intake is a major cause of liver cirrhosis as well as chronic liver disease, and commonly coexists with mood disorders such as depression and anxiety. The aim of the present study was to investigate the possible correlation between liver dysfunction related to alcohol intake with anxiety and depressive-like symptomatology prior to and after the detoxification period. METHODS: One hundred alcohol abusing/dependent subjects (81 males and 19 females) were treated on an inpatient basis according to a standard detoxification protocol and measurements of serum levels of hepatic enzymes (ASAT, ALAT, γGT), and measures of anxiety (HARS), depression (HDRS) and global functioning (GAS) were also obtained at baseline and at weekly intervals over a period of 4 weeks. RESULTS: Increased levels of hepatic enzymes were observed upon admission that were significantly reduced (P<0.001) following completion of the detoxification treatment. In addition, the psychopathological profile was improved at the end of the detoxification period and a significant correlation was obtained between the levels of hepatic enzymes and the global functioning of alcohol-dependent individuals. CONCLUSION: This observation further supports a relationship between the depressogenic action of alcohol and the disordered liver function observed in alcohol-dependent individuals, with possible implications in the diagnosis and treatment of mood disorders associated to alcohol abuse.