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Biomedical subjects

Thomas Hillemacher

Publications and source records attributed to Thomas Hillemacher.

At least 19 recordsLinked to original sources

Depressive symptoms may explain elevated plasma levels of homocysteine in females with eating disorders.

Elevated plasma homocysteine levels have been found in different psychiatric disorders, including major depression and eating disorders. The aim of the present study was to evaluate whether presence of depression or depressive symptoms is associated with elevated homocysteine levels in patients with eating disorders. Total plasma homocysteine levels were assessed in 44 females with anorexia nervosa (n = 21) or bulimia nervosa (n = 23). Comorbid major depressive disorder (MDD) was diagnosed according to DSM-IV criteria using a semi-structured interview (SCID-I). Furthermore, depressive symptoms were assessed using Beck's depression inventory (BDI). Presence of MDD was not associated with elevated homocysteine levels (t-test: T = 0.42; df = 42; P = 0.68). However, self-rated presence of clinically relevant depressive symptoms (BDI score18) was associated with elevated homocysteine (T = -2.8; df = 42; P = 0.008). Presence of depressive symptoms may explain elevated homocysteine levels previously reported in patients with eating disorders or vice versa. Longitudinal studies are needed to unravel this hen or egg problem.

Adolescent↗

Alcoholism and homicide with respect to the classification systems of Lesch and Cloninger.

AIMS: Worldwide criminal statistics show a disproportionately high incidence of violent offences committed under the influence of alcohol. A psychopathological subtyping of alcohol dependence in offenders who committed homicide has mainly been related to impulsive and dissocial personalities up to now. METHODS: In an investigation on 48 alcohol-dependent offenders who committed homicide, a subtyping according to the multidimensional classification systems of Lesch and Cloninger has now been conducted for the first time. RESULTS: In Lesch's classification, there was a high incidence of homicides committed by type II and type III subjects with the comorbidity anxiety and cyclothymia. While type III offenders were more often repeat offenders, there was a remarkably high rate of first offenders among type II subjects (Chi-squared test; chi(2) = 30.0, df = 3, P < 0.001). With respect to Lesch's typology, the blood alcohol concentrations did differ significantly in the group of offenders (Kruskal-Wallis, chi(2) = 18.3, df = 3, P < 0.001), whereas the blood alcohol concentration of type II offenders at the time of offence was significantly lower than in type III offenders (Mann-Whitney-U, Z = -3.47; P = 0.001). Regarding to the Cloninger's typology, no significant differences in the aforementioned parameters could be found. DISCUSSION: An excessive noradrenergic reaction of anxiety offenders with initial withdrawal is discussed as a possible explanatory model.

Adult↗

Evidence of an association of leptin serum levels and craving in alcohol dependence.

Recent studies have described an association of leptin serum levels and craving in alcohol dependent patients. The aim of the present study was to investigate a large patients' sample using a power-based statistical analysis. We included 156 male and 33 female patients suffering from alcohol dependence admitted for detoxification treatment. Leptin serum levels were measured using a commercial ELISA kit. The Obsessive Compulsive Drinking Scale (OCDS) was used to assess alcohol craving at admission. For both genders Spearman's correlation revealed significant results. These findings could be confirmed using multiple linear regression models (males: r=1.881, t=4.338, p<0.001; females: r=6.160, t=5.793, p<0.001) with a power of 1.00. In contrast to previous results describing an association only in female patients, this power-based analysis shows that leptin is associated with alcohol craving in both genders.

Adult↗

Treating dopamimetic psychosis in Parkinson's disease: structured review and meta-analysis.

Psychosis due to dopamimetic treatment is a difficult problem in patients with Parkinson's disease (PD). The aim of this structured review with meta-analysis was to evaluate which neuroleptic drugs can efficiently be used to treat drug-induced psychosis (DIP) in Parkinson's disease. Electronic databases were screened for the key words Parkinson's disease and psychosis. Only 7 trials with a satisfactory allocation concealment and data reporting were included into the study. Two trials compared low-dose clozapine versus placebo with a significantly better outcome for clozapine regarding efficacy and motor functioning. In one trial clozapine was compared against quetiapine showing equivalent efficacy and tolerability. However, in two placebo controlled trials quetiapine failed to show efficacy. In two further placebo controlled trials olanzapine did not improve psychotic symptoms and significantly caused more extrapyramidal side effects. Based on randomized trial-derived evidence which is currently available, only clozapine can be fully recommended for the treatment of DIP in PD. Olanzapine should not be used in this indication.

Antipsychotic Agents↗

Apolipoprotein E gene polymorphism and previous alcohol withdrawal seizures.

Aim of this study was to investigate the possible association of apolipoprotein E (ApoE) gene polymorphism with a history of alcohol withdrawal seizures. We included 194 patients with alcohol dependence who were divided into patients with (SZ+) and without (SZ-) previous alcohol withdrawal seizures. ApoE genotypes were determined using PCR. For statistical analysis we examined the number of ApoE alleles (ApoE2: n=36; ApoE3: n=311; ApoE4: n=41). A significant positive association with a positive history of withdrawal seizures (SZ+) was found in the ApoE3 allele group (Fisher's exact test: p=0.006) while a significant negative association was observed in the ApoE2 allele group (Fisher's exact test: p=0.029). For the ApoE4 allele group no significant differences were found regarding a history of withdrawal seizures. Our findings suggest an association between the apolipoprotein E3 gene variant and an elevated risk of alcohol withdrawal seizures. These preliminary results must be validated in further studies.

Adult↗

Different allele-distribution of mthfr 677 C -> T and mthfr -393 C -> a in patients classified according to subtypes of Lesch's typology.

AIMS: The typology by Lesch distinguishes between four subtypes: type 1 (model of allergy), type 2 (model of anxiety or conflict), type 3 (alcohol as an antidepressant), and type 4 (alcohol as adaptation). Taking into account that alcohol dependence is associated with elevated homocysteine levels, this study was undertaken to investigate different MTHFR (methylenetetrahydrofolate reductase) genotypes related to homocysteine metabolism in patients with alcohol dependence who were classified according to Lesch's typology (LT). SUBJECTS AND METHODS: 134 non-abstinent chronic alcoholics (112 males, 22 females; mean age 44.2 (SD 8.9) years) were classified according to LT and divided into four groups: LT 1 (n = 26), LT 2 (n = 65), LT 3 (n = 58), and LT 4 (n = 18). Total plasma homocysteine levels and MTHFR genotypes -393, 677, and 1,793 were determined. RESULTS: We observed a significantly higher frequency of the thermolabile MTHFR 677 C-->T variant (TT) in patients classified as subtype LT4 when compared with subtypes LT2 and LT3 (P = 0.005). Furthermore, for the MTHFR -393 C --> A-polymorphism, significantly more AC/AA variants were found in subtype LT4 (P = 0.034). No differences in allele-distribution were detected for MTHFR 1793. CONCLUSION: To our knowledge, this is the first study evaluating MTHFR genotypes in patients who were classified according to LT. Significantly different distributions of MTHFR 677 and -393 variants within Lesch Type 4 as compared with Types 2 and 3 hint at genetic determination of Lesch subtypes.

Adult↗

Prolactin serum levels and alcohol craving - an analysis using Lesch's typology.

BACKGROUND: Prolactin secretion is closely connected to dopaminergic transmission that is known to play a crucial role in mediating reinforcement and craving in alcoholism. OBJECTIVES: The study was performed to analyze the association between prolactin serum levels and alcohol craving during withdrawal differentiating alcohol-dependent patients using Lesch's typology. METHODS: We assessed 115 male patients with the Obsessive Compulsive Drinking Scale at early alcohol withdrawal. In addition, serum was obtained to measure prolactin concentration and the patients were classified according to Lesch's typology into one of four subgroups. RESULTS: Correlation analysis showed a significant association between prolactin serum levels and the extent of craving in Lesch's type 2 patients (r=0.32, p=0.015; n=57); however, no association was found for any other subgroup. The results were confirmed comparing patients with low and high craving (Mann-Whitney U test: Z=-2.805, p=0.005). CONCLUSIONS: In patients of Lesch's type 2, who are characterized to suffer from anxiety and to use alcohol because of its anxiolytic effects, prolactin is associated with craving during early alcohol withdrawal.

Adult↗

Elevated prolactin serum levels and history of alcohol withdrawal seizures.

BACKGROUND: Prolactin has been discussed to be useful for differential diagnosis in epilepsia. Aim of the present study was to investigate the association between prolactin serum levels and previous alcohol withdrawal seizures. METHODS: We assessed 118 male patients admitted for detoxification treatment. Previous withdrawal seizures were recorded and prolactin serum levels were measured using an enzymatic immunoassay. RESULTS: Patients with a history of alcohol withdrawal seizures had significantly higher prolactin levels (17.8 ng/ml, SD=12.1) than patients without previous seizures (13.0 ng/ml, SD=8.1, p<0.05). Logistic regression revealed significant predictive qualities for prolactin serum levels (B=0.05, Wald=5.30, p=0.021, OR=1.06, 95%CI=1.01-1.11). CONCLUSIONS: The present findings show an association between elevated prolactin serum levels and a history of withdrawal seizures. Hence, the results suggest that prolactin elevation at admission may be a clinical marker for an increased risk of withdrawal seizures.

Adult↗

Association of catecholamine-O-methyltransferase and 5-HTTLPR genotype with eating disorder-related behavior and attitudes in females with eating disorders.

OBJECTIVE: There is growing evidence, that genetic variants contribute to the pathogenesis of anorexia nervosa and bulimia nervosa. Genetic studies have revealed candidate genes, but no satisfactory associations with the disorders have been found so far. The aim of the present study was to evaluate, whether behavioral and attitudinal traits of the disorders can serve as phenotypes with a possible association with two common functional polymorphisms of the monoaminergic pathways. METHOD: Forty-five female in-patients of a specialized hospital for eating disorders were included into the study. Eating disorder symptomatology was assessed using the Eating Disorder Inventory-2. The functional catecholamine-O-methyltransferase (COMT) 158 Val-->Met polymorphism and the deletion/insertion polymorphism of the serotonin transporter promoter 5-HTTLPR were determined. RESULTS: Carriers of at least one Met-allele of the COMT gene had significantly higher total scores of the Eating Disorder Inventory-2, as well as significantly higher scores on the subscales bulimia, ineffectiveness, interoceptive awareness, maturity fears and impulse regulation. Carriers of the deletion of the 5-HTTLPR had significantly higher scores on the subscales drive for thinness and body dissatisfaction. CONCLUSION: We found associations between the COMT and the 5-HTTLPR polymorphisms and specific clinical, behavioral and attitudinal traits of eating disorders. These polymorphisms may predispose their carriers to exhibit certain symptoms of eating disorders or confer a general risk for more severe forms of these disorders.

Adolescent↗

Obsessive-compulsive alcohol craving is not associated with Apolipoprotein E genotype.

This study examined a possible association with obsessive and compulsive alcohol craving in 192 alcohol-dependent patients undergoing detoxification treatment. Statistical analysis revealed no significant association between Apolipoprotein E polymorphism and obsessive-compulsive alcohol craving (analysis of variance: F=1.11, P=0.358).

Alcohol Drinking↗

Nicotine dependence is associated with compulsive alcohol craving.

AIMS: To investigate a possible association of nicotine dependence and alcohol craving. DESIGN: A prospective cross-sectional study on patients diagnosed with alcohol dependence. SETTING: Detoxification unit of a regional psychiatric hospital. PARTICIPANTS: A total of 127 smoking male patients were included in the study at admission for detoxification from alcohol. MEASUREMENTS: The Fagerström Test for Nicotine Dependence (FTND) was used to assess the severity of nicotine dependence while the Obsessive Compulsive Craving Scale (OCDS) was used to measure alcohol craving. The OCDS was assessed at admission and after 7 days of withdrawal treatment, distinguishing the total score, the obsessive and the compulsive subscale. FINDINGS: Spearman's correlation revealed a significant association between the extent of alcohol craving and the FTND score (day 0, n = 127: OCDS total score r = 0.238, P = 0.007; OCDS compulsive score r = 0.280, P = 0.001; day 7; n = 94: OCDS total score r = 0.212, P = 0.040; OCDS compulsive score r = 0.225, P = 0.029). CONCLUSIONS: The severity of nicotine dependence is associated with higher craving in alcohol-dependent patients. These results point towards shared pathophysiological mechanisms in alcohol craving and nicotine addiction.

Adult↗

An assessment of the potential value of elevated homocysteine in predicting alcohol-withdrawal seizures.

PURPOSE: Higher homocysteine levels were found in actively drinking patients with alcohol dependence. Recent studies have shown that high homocysteine levels are associated with alcohol-withdrawal seizures. The aim of the present study was to calculate the best predictive cutoff value of plasma homocysteine levels in actively drinking alcoholics (n = 88) with first-onset alcohol-withdrawal seizures. METHODS: The present study included 88 alcohol-dependent patients of whom 18 patients had a first-onset withdrawal seizure. All patients were active drinkers and had an established diagnosis of alcohol dependence, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Sensitivity and specificity were calculated by using every homocysteine plasma level found in the study population as cut-off value. A Bayes theorem was used to calculate positive (PPV) and negative (NPV) predictive values for all cutoff values used. RESULTS: The highest combined sensitivity and specificity was reached at a homocysteine plasma cutoff value of 23.9 microM. Positive predictive values ranged from 0.23 to 0.745; the maximum was reached at a homocysteine plasma level of 41.7 microM. Negative predictive values ranged from 0.50 to 0.935, with a maximum at a homocysteine plasma level of 15.8 microM. CONCLUSIONS: Homocysteine levels above this cutoff value on admission are a useful screening tool to identify actively drinking patients at higher risk of alcohol-withdrawal seizures. This pilot study gives further hints that biologic markers may be helpful to predict patients at risk for first-onset alcohol-withdrawal seizures.

Adult↗

Volume intake and craving in alcohol withdrawal.

AIMS: It has been shown that beer consumption is associated with alcohol craving, in contrast to wine or spirits consumption. The present study was undertaken to evaluate whether the daily volume intake of alcoholic beverages is associated with craving in patients undergoing alcohol withdrawal. METHODS: A total of 158 male patients were assessed using the obsessive compulsive drinking scale (OCDS) at admission. The daily volume intake of alcoholic beverages was calculated by adding the volume of all regularly consumed alcoholic beverages, disregarding their alcohol percentage. Lesch's typology was used to classify patients for subgroup analysis. RESULTS: The daily volume intake of alcoholic beverages correlated significantly with the extent of the OCDS (r = 0.33; P < 0.001). With general linear models, we found a significant association of the calculated daily volume intake of all alcoholic beverages with craving (F = 6.426; P = 0.012), but not for the daily ethanol intake. Differentiating the patients according to Lesch's typology a significant association was particularly found in Lesch Type 2 (model of anxiety) patients (F = 11.31; P = 0.001). CONCLUSION: Our results support the hypothesis that volume intake is associated with craving and suggest a role of pathophysiological changes in volume regulating mechanisms (such as vasopressin or ANP) in the neurobiology of alcohol craving, particularly in male patients of Lesch's Type 2 undergoing alcohol withdrawal.

Adult↗

Recurrent detoxifications are associated with craving in patients classified as type 1 according to Lesch's typology.

AIMS: Recurrent detoxifications have been suggested to be associated with elevated alcohol craving. The aim of this investigation was to study the influence of preceding detoxifications on craving in patients with alcoholism classified according to Lesch's typology. METHODS: We examined 192 patients (154 men, 38 women) after admission for detoxification treatment. Craving was assessed using the Obsessive Compulsive Drinking Scale, and patients were classified into one of the four subgroups of Lesch's typology. The number of preceding detoxifications was assessed with a structured interview. RESULTS: Lesch's typology type 4 patients showed significantly higher craving scores than type 1-3 patients (Mann-Whitney U-Test; P < 0.05). With respect to the influence of recurrent detoxifications, we found a significant correlation between the number of preceding detoxifications and the extent of craving for the whole population (Spearman's rho r = 0.241, P = 0.001, N = 192), particularly for patients of Lesch's type 1 (Spearman's rho r = 0.534, P = 0.001, N = 37). No significant association was found for patients of the other subgroups (Lesch's type 2-4). CONCLUSION: The influence of recurrent detoxifications on craving is especially important in patients with Lesch's type 1. Our results underline the importance of the kindling effect particularly in this group of patients, possibly mediated by an increase of glutamatergic neurotransmission. Furthermore, our results emphasize the need to classify patients with alcohol-dependency in addiction research.

Adult↗