Analysis of monocyte chemotactic protein-1 gene polymorphism in patients with spontaneous bacterial peritonitis.

AIM: To investigate a genetic polymorphism of the monocyte chemotactic protein-1 (MCP-1) gene in patients with spontaneous bacterial peritonitis (SBP). METHODS: MCP-1 genotyping was performed in 23 patients with SBP and 83 cirrhotic control patients with non-infected ascites. RESULTS: The frequency of carriers of the G-allele was lower in SBP patients but this difference did not reach statistical significance. However, in the subgroup of patients with alcoholic cirrhosis (n = 80), carriers of the G-allele were significantly less frequent in SBP-patients (38.1%) than in cirrhotic controls (67.8%, P = 0.021). CONCLUSION: In patients with alcoholic liver cirrhosis, the -2518 MCP-1 genotype AA is a risk factor for the development of SBP.

Genetic and environmental influence on attachment disorganization.

BACKGROUND: Empirical studies demonstrate that maternal sensitivity is associated with attachment security in infancy, while maternal frightening/frightened behavior is related to attachment disorganization. However, attachment disorganization is also predicted by individual dispositions in infancy. Indeed, recent studies indicate a link between attachment disorganization and DRD4 gene polymorphisms, thus suggesting a genetic vulnerability for attachment disorganization. The aims of our study were twofold, to test a) a possible direct link between molecular genetic variations and attachment disorganization, and b) a possible gene-environment interaction with a moderating effect of early maternal caregiving. METHODS: Attachment security and disorganization, as well as quality of maternal behavior were assessed in the infants of the Regensburg Longitudinal Study IV (N = 106) at the age of 12 months. DNA samples were collected in order to assess the exon III repeat polymorphism in the coding region and the -521 C/T single nucleotide polymorphism (SNP) in the regulatory region of the DRD4 gene and a repeat polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene. RESULTS: Significant associations were found between attachment disorganization and the short polymorphism of the serotonin transporter gene. Also, a gene-environment interaction indicated that this genetic association was only valid for infants of mothers exhibiting low responsiveness. No other significant genetic associations with attachment disorganization were apparent. CONCLUSIONS: The study suggests a gene-environment interaction whereby biological determinants of attachment disorganization are moderated by social experiences. Different pathways of the development of attachment disorganization are discussed based on a bio-behavioral model of development.

Elevated adiponectin serum levels in patients with chronic alcohol abuse rapidly decline during alcohol withdrawal.

BACKGROUND: Adiponectin is a circulating protein with hepatoprotective effects. AIMS: To study the relationship of excessive alcohol consumption and serum adiponectin levels (SAL). PATIENTS AND METHODS: The SAL were determined in (i) heavy drinkers without advanced liver damage during the course of alcohol withdrawal, (ii) patients with chronic hepatitis C virus (HCV) infection, (iii) patients with alcohol-associated cirrhosis, and (iv) healthy volunteers that consumed excessive amounts of alcohol for only a short period of time. Further, primary human hepatocytes (PHH) and adipocytes were incubated in vitro with alcohol or serum of patients. RESULTS: Patients with chronic alcohol consumption had significantly higher SAL than HCV-patients with comparable degrees of liver damage. In alcoholics, but not in HCV patients, SAL positively correlated with serum levels of aminotransferases. Further, SAL correlated with the amount of alcohol consumption but declined during the course of alcohol abstinence. After short-term excessive alcohol consumption SAL were not elevated in healthy individuals. Adiponectin mRNA was detectable in adipocytes but not in hepatocytes, and alcohol failed to induce adiponectin in both cell types. In contrast, serum of active drinkers induced adiponectin expression in adipocytes while serum from the same individuals collected after alcohol withdrawal had no effect. CONCLUSIONS: Alcohol exhibits a specific effect on SAL that is dose and time dependent, and correlates with the degree of hepatic damage. Alcohol does not seem to affect adiponectin expression directly in adipocytes but potentially via mediators systemically released as a result of the chronic alcohol intake.

Systematic analysis of glutamatergic neurotransmission genes in alcohol dependence and adolescent risky drinking behavior.

CONTEXT: Glutamatergic neurotransmission is implicated in alcohol-drinking behavior in animal models. OBJECTIVE: To investigate whether genetic variations in glutamatergic neurotransmission genes, which are known to alter alcohol effects in rodents, contribute to the genetic basis of alcoholism in humans. DESIGN: Association analysis of alcohol dependence and haplotype-tagging single nucleotide polymorphisms (SNPs) covering 10 glutamatergic genes. Resequencing of functional domains of these genes identified 204 SNPs. Haplotypes with a frequency of 5% or greater could be discriminated by 21 haplotype-tagging SNPs analyzed for association in 2 independent samples of alcohol-dependent adult patients and controls as well as adolescent trios. SETTING: Four university medical centers in the south of Germany. PARTICIPANTS: One thousand three hundred thirty-seven patients and 1555 controls (study 1: 544 patients, 553 controls; study 2: 793 patients, 1002 controls). One hundred forty-four trios of 15-year-old adolescents assessed for risky drinking behavior. MAIN OUTCOME MEASURES: Genotype profiles for GLAST; N-methyl-d-aspartate-receptor subunits NR1, NR2A, and NR2B; MGLUR5; NNOS; PRKG2; CAMK4; the regulatory subunit of PI3K; and CREB were analyzed for association with alcohol dependence using multivariate statistical analysis. Risky adolescent drinking was tested using the transmission disequilibrium test. RESULTS: Analysis of study 1 revealed that NR2A and MGLUR5 have the greatest relevance for human alcohol dependence among the genes selected with odds ratios of 2.35 and 1.69, respectively. Replication analysis in study 2 confirmed an association of alcohol dependence with NR2A (odds ratio, 2.01) but showed no association with MGLUR5. Combined analysis of study 1 and study 2 exhibited a more significant association on the Cochran-Mantel-Haenszel test (P < .001) for NR2A; NR2A was associated with positive family history, early onset of alcoholism, and maximum number of drinks in adults as well as risky drinking patterns in adolescents. CONCLUSION: Genetic variations in NR2A have the greatest relevance for human alcohol dependence among the glutamatergic genes selected for their known alteration of alcohol effects in animal models.

Performance of diadochokinetic movements in schizophrenic patients.

Motor deficits are common and disabling symptoms in schizophrenic patients, which have enormous impact on the long-term outcome of the disease by affecting work performance and daily functioning. They are attributed to the disorder itself, as well as to treatment with dopamine-blocking antipsychotics. This study assessed the kinematic parameters of motor performance of a diadochokinetic hand movement in 20 drug-naïve, 20 conventionally treated (haloperidol or fluphenazine), and 20 atypically treated (olanzapine) patients, as well as in 20 healthy controls using a three-dimensional ultrasonic movement analysis system. It also tested differences in motor enhancement as induced by an attentional strategy and in dexterity advantages of motor performance for the dominant hand between the four study groups. Amplitude and peak velocity of diadochokinetic hand movements were significantly reduced in all patient groups compared to the controls, while frequency of the repetitive movement remained unaffected. The reduction was most pronounced in the conventionally treated patients. In addition, movement automation was impaired, primarily under conventional antipsychotic treatment. The study also revealed weaker effects of an attentional enhancing strategy on the movement amplitude in atypically and conventionally treated patients compared to both controls and drug-naïve patients. Alterations of dexterity could not be detected either in the drug-naïve or in the treated patients. The results indicate that patients with schizophrenia suffer from a specific primary motor deficit in diadochokinesia with reduction of amplitude and peak velocity. This deficit is significantly worsened by conventional antipsychotic treatment. Antipsychotic treatment additionally reduces the enhancing effect of an attentional strategy on motor performance.

Association of the -141C Del variant of the dopamine D2 receptor (DRD2) with positive family history and suicidality in German alcoholics.

Several lines of evidence indicate an involvement of the dopaminergic system in alcoholism, withdrawal, suicidality, and attention-deficit hyperactivity disorder (ADHD). The functionally relevant -141C Ins/Del polymorphism located upstream to exon 1 in the 5'-region of the dopamine D2 receptor (DRD2) gene might be an interesting candidate gene. We investigated a sample of 1,126 well-characterized, primary chronic alcoholics of German descent according to a phenotype-genotype strategy, i.e., alcoholics suffering from severe withdrawal complications such as seizure or delirium, family history positive (FH+) alcoholics, alcoholics with an antisocial personality disorder (ASPD), alcoholics with an ADHD, and type 1 or type 2 alcoholics according to Cloninger's typology. Compared to the control subjects, there was a significant excess of the -141C Del allele in alcoholics with a paternal and grandpaternal history of alcoholism and in alcoholic subgroups with suicidality or without a history of withdrawal symptoms. There were no significant differences in allele frequency between the entire group or subgroups of alcoholics and healthy controls. Therefore, the -141C Del variant of the DRD2 might be a protective factor against the development of withdrawal symptoms. However, it might also be a risk factor in a highly burdened subgroup of alcoholics with a paternal and grandpaternal history of alcoholism and it might contribute to the substantially higher likelihood of suicide in alcoholics.

[Outcome of a substitution therapy program in an outpatient treatment setting of a psychiatric hospital]. / Ergebnisse der Substitutionsbehandlung in einer psychiatrischen Klinikambulanz.

We look at 42 opiate addicts being in substitution therapy at a certain date (24.9.2003) in an outpatient treatment setting of a psychiatric hospital. Treatment outcome is described with amount of take home, reduced delinquency, increased social reintegration as well as pharmacological treatment. 25 men and 17 women, age from 20 to 49 (29) have been in our treatment between 1 to 52 months (29). 20 of them (48 %) got an additional psychiatric medication, mostly antidepressants (42 %) but also neuroleptics (9,5 %). 21 patients had a drug free urine test (including cannabis) during the last month and could take their opiate medication at home. Necessity of support by social security declines from 25 % before to 16 % in substitution treatment. Also the need of unemployment benefit could be reduced from 36 % before to 26 % in treatment. Full time jobs increase from 31 % to 48 %, part time jobs from 3 % to 7 % in treatment.

[Use of cigarettes, alcohol and drugs by adolescents--a questionnaire survey among 9th grade students]. / Konsum psychoaktiver Substanzen durch Jugendliche--Eine Erhebung bei Schülern der 9. Klassen.

INTRODUCTION: For the planning of further substance abuse prevention programs it is necessary to obtain data about the patterns of region-specific substance use in adolescents. METHOD: In 2002 a questionnaire survey on substance use among the 9 (th) graders of all school types in the city and in the county of Regensburg was carried out (mean age 15,3 years, N = 1580). RESULTS: The first substance ever used by adolescents are cigarettes, starting at an average age of 12.2 years. 30 % of the students are current daily smokers with 43 % fulfilling criteria of nicotine dependence. When used several times per week 53 % regard the use of spirits being very dangerous, whereas the same rate considers the danger of drinking wine or beer at the same frequency being rather small. The level of information about institutions offering help for substance abuse and dependence problems is being considered as poor or zero by 67 %. DISCUSSION: The primary prevention of smoking as early as possible should be a priority of school-based prevention programs. The study also reveals a deficit of information on substances and institutions offering help for substance abuse and dependence problems which should be faced in school lessons.

[Attention-deficit hyperactivity disorder and alcohol dependence: a risk constellation]. / Aufmerksamkeitsdefizit-Hyperaktivitätssyndrom (ADHS) und Alkoholabhängigkeit: Eine Risikokonstellation.

INTRODUCTION: The estimated prevalence for attention-deficit hyperactivity disorder (ADHD) in adulthood is 2 - 6 %. Patients with a substance use disorder met the criteria for ADHD between 30 and 50 %. ADHD and conduct disorders are discussed to increase risk of developing substance abuse and increase severity of disorder. METHOD: We compared epidemiological and clinical characteristics and comorbidity in subgroups of 314 adult alcoholics of German descent with or without persistent symptoms of attention-deficit hyperactivity disorder (ADHD). Aim of the study was to identify specific pathophysiological mechanisms that could contribute to vulnerability, severity or complication of alcohol dependence. RESULTS: 21.3 % of the alcoholics fulfilled DSM-IV-criteria of ADHD with ongoing symptoms in adulthood and had a Wender-Utah-Rating-Scale score > 90. Subgroup of alcoholics with ADHD were significantly younger at age of onset of alcoholism (24 years versus 30 years), had a significantly higher daily alcohol intake (253 g versus 196 g EtOH), had significantly more social stress, lifetime experiences in court proceedings against them (11 versus 2 %) and suicidal ideation (25 versus 11 %). In the subgroup of alcoholics with ADHD 51 % fulfilled criteria of antisocial personality disorder. The early onset of alcoholism was most pronounced in this subgroup. CONCLUSION: In our sample, persistence of ADHD symptoms from childhood into adulthood and antisocial personality disorder contributes to vulnerability and morbidity of alcohol dependence with early onset and greater severity of disorder.

[Attachment styles in German alcoholics with or without attention-deficit hyperactivity disorder (ADHD)]. / Bindungsstile bei deutschen Alkoholabhängigen mit und ohne Aufmerksamkeitsdefizit-Hyperaktivitätssyndrom (ADHS).

INTRODUCTION: Attachment theory yields empirical constructs for development of human self, personality and cognition. Insecure attachment strategies were associated with various psychiatric disorders. METHOD: We investigated distribution of attachment styles in 368 adult alcoholics of German descent with or without persistent symptoms of attention-deficit hyperactivity disorder (ADHD) and in 402 healthy individuals. RESULT: Insecure attachment styles were significantly overrepresented compared to healthy controls. The subgroup of alcoholics with ADHD showed significantly more frequent enmeshed (74.1 %), the subgroup of alcoholics without persistent ADH-associated symptoms showed more frequent dismissing (35 %) attachment strategies. CONCLUSION: In our sample, insecure attachment styles are associated with alcoholism. The subgroup of alcoholics with persistent ADHD shows a specific attachment behavior that could contribute to different therapy response or to early onset or severity of alcoholism.

[ADHD and alcohol dependence: a common genetic predisposition?]. / ADHS und Alkoholabhängigkeit: Gemeinsame genetische Grundlagen?

INTRODUCTION: Nearly 50 % of subjects with continuing symptoms of attention-deficit hyperactivity disorder (ADHD) in adulthood show a comorbid substance use disorder. Both, ADHD and alcohol dependence have a high genetic load and might even share overlapping sources of genetic liability. METHOD: We investigated phenotype and 5-HTT/5-HT2c allelic characteristics in 314 alcoholics of German descent. RESULT: 21 % of the alcoholics fulfilled DSM-IV-criteria of ADHD with ongoing symptoms in adulthood. There was no significant difference in 5-HTT- or 5-HT2c-allele distribution between alcoholics and matched controls or between alcoholics with or without ADHD. CONCLUSION: In our sample the functional relevant 5-HTT-promoter and the 5-HT2c-receptor Cys23Ser polymorphism do not contribute to the supposed common genetic predisposition of ADHD and alcohol dependence.

Comorbidity of alcohol dependence with attention-deficit hyperactivity disorder: differences in phenotype with increased severity of the substance disorder, but not in genotype (serotonin transporter and 5-hydroxytryptamine-2c receptor).

BACKGROUND: Nearly 50% of subjects with continuing symptoms of attention-deficit hyperactivity disorder (ADHD) in adulthood have been reported to show a comorbid substance use disorder. Both ADHD and alcohol dependence have a high genetic load and might even share overlapping sources of genetic liability. Recently, the functional relevant polymorphism within the promoter region of the serotonin transporter gene (5-HTT) and the 5-hydroxytryptamine-2c (5-HT2c) receptor Cys23Ser have been proposed as candidate genes for both entities. METHODS: We investigated phenotype and 5-HTT/5-HT2c genotype characteristics in 314 alcoholics of German descent. RESULTS: There was no significant difference in 5-HTT genotype or 5-HT2c allele distribution between alcoholics and matched controls. Sixty-seven alcoholics fulfilled DSM-IV criteria of ADHD with ongoing symptoms in adulthood and had a Wender Utah Rating Scale score greater than 90. Thirty had ADHD plus antisocial personality disorder. The subgroup of alcoholics with ADHD (ADHD+) showed a significantly higher daily and record ethanol intake per month, an earlier age at onset of alcohol dependence, and a higher frequency of suicidal ideation, court proceedings, and antisocial personality disorder. In our sample, more than 50% of type 2 alcoholics according to Cloninger consist of the ADHD+ and/or antisocial personality disorder-positive subjects. There were no differences in 5-HTT genotype or 5-HT2c allele distribution between the ADHD+ subgroups and alcoholics without comorbidity and matched controls, respectively. CONCLUSIONS: Comorbidity of alcoholism and ADHD forms a distinct phenotype that shows an increased severity of the substance disorder. This phenotype contributes substantially to the so-called type 2 alcoholics according to Cloninger. In our sample, the functional relevant 5-HTT promoter and the 5-HT2c receptor Cys23Ser polymorphism do not contribute to the supposed common genetic predisposition of ADHD and alcohol dependence.

[Chronic Alcoholics with Multiple Impairments] / Chronisch mehrfach beeinträchtigte Alkoholabhängige - Praxisnahe Evaluation eines Vorschlages zur operationalisierten Diagnostik und alternativer Modelle -

To improve reliability of diagnosis of a specific subgroup of chronic alcoholics with multiple impairments (CMA), operational criteria have been proposed. To evaluate usability and sensitivity vs. specifity, all in-patients fulfilling ICD-10 criteria of alcohol dependence were screened on two randomly chosen dates. Two clinically "extreme" groups were extracted: patients in a 8-week short-term residential treatment vs. patients in a residential program specifically designed for chronic alcoholics with severe somatic, psychic and/or social consequences. More quantitative operational criteria, such as "treatment experience" and "consumptive behaviour" revealed much lower discriminative power than more qualitative criteria, such as "comorbidity" and "social and legal status". Substantially revised and simplified operational criteria exhibited comparable sensitivity and specifity for the classification of chronic alcoholics with multiple impairments (CMA).

[Relapse Prevention Program in German Alcoholics] / Rückfallpräventionsgruppe bei alkoholabhängigen Patienten.

Relapse prevention plays an important role in the treatment of alcoholics. Positive predictors are high self-efficacy and confidence in high-risk situations, positive outcome expectancies, sufficient coping-skills and low craving. We examined 64 primary German alcoholics. Each person met the criteria of alcohol dependence of DSM-IV and ICD-10. Subjects were included in an in-patient 4-step relapse prevention program. This manual-guided group psychotherapy is based on cognitive-behavioral approach focused on high-risk situations, phases of relapse, stress/relax and resources. Craving before and after treatment did not differ, so that using this kind of relapse prevention training might be suitable in both in- and out-patient programs. High values for insight, optimism, self-efficacy and confidence in high-risk situations might enhance individual coping-skills to balance patient's lifestyle focussing on an abstinent way of life.

[Repetitiv Transcranial Magnetic Stimulation in Nicotine Dependence] / Transkranielle Magnetstimulation bei Nikotinabhängigkeit.

70 - 80 % of regular smokers fulfill the ICD-10-criteria of dependence. In Germany, approximately 120 000 deaths per year are caused by tobacco-associated diseases. In contrast, therapeutic interventions, such as nicotine substitution or bupropione, yield poor abstinence rates of 30 % after 12 months, at best. In animal experiments, repetitive transcranial magnetic stimulation (rTMS) exhibited modulatory effects on dopaminergic neurotransmission in regions of the so-called reward system. This pilot study should evaluate, if rTMS could modulate subjective craving for tobacco, which quite often leads to relapse to smoking. Therefore, 11 tobacco-dependent cigarette smokers were randomly assigned to a course of verum- and placebo-rTMS on consecutive days. Craving, as measured by a visual analogue scale, is significantly decreased after Verumstimulation compared to placebostimulation intra-individually. This encourages further studies to clarify, if rTMS might be helpful in achieving higher tobacco abstinence rates in smokers willing to quits.

[Chronic alcoholic patients with multiple comorbidity. Community outpatient evaluation of a recommendation for operationalized diagnosis and alternative models]. / Chronisch mehrfach beeinträchtigte Alkoholabhängige. Praxisnahe Evaluation eines Vorschlages zur operationalisierten Diagnostik und alternativer Modelle.

To improve reliability of diagnosis of a specific subgroup of chronic alcoholics with multiple impairments (CMA), operational criteria have been proposed. To evaluate usability and sensitivity vs. specificity, all in-patients fulfilling ICD-10 criteria of alcohol dependence were screened on two randomly chosen dates. Two clinically "extreme" groups were extracted: patients in a 8-week short-term residential treatment vs. patients in a residential program specifically designed for chronic alcoholics with severe somatic, psychic and/or social consequences. More quantitative operational criteria, such as "treatment experience" and "consumptive behaviour" revealed much lower discriminative power than more qualitative criteria, such as "comorbidity" and "social and legal status". Substantially revised and simplified operational criteria exhibited comparable sensitivity and specificity for the classification of chronic alcoholics with multiple impairments (CMA).

[Relapse prevention group for alcohol dependent patients]. / Rückfallpräventionsgruppe bei alkoholabhängigen Patienten.

Relapse prevention plays an important role in the treatment of alcoholics. Positive predictors are high self-efficacy and confidence in high-risk situations, positive outcome expectancies, sufficient coping-skills and low craving. We examined 64 primary German alcoholics. Each person met the criteria of alcohol dependence of DSM-IV and ICD-10. Subjects were included in an in-patient 4-step relapse prevention program. This manual-guided group psychotherapy is based on cognitive-behavioral approach focused on high-risk situations, phases of relapse, stress/relax and resources. Craving before and after treatment did not differ, so that using this kind of relapse prevention training might be suitable in both in- and out-patient programs. High values for insight, optimism, self-efficacy and confidence in high-risk situations might enhance individual coping-skills to balance patient's lifestyle focussing on an abstinent way of life.

[Transcranial magnetic stimulation for nicotine dependence]. / Transkranielle Magnetstimulation bei Nikotinabhängigkeit.

70-80% of regular smokers fulfill the ICD-10-criteria of dependence. In Germany, approximately 120,000 deaths per year are caused by tobacco-associated diseases. In contrast, therapeutic interventions, such as nicotine substitution or bupropione, yield poor abstinence rates of 30% after 12 months, at best. In animal experiments, repetitive transcranial magnetic stimulation (rTMS) exhibited modulatory effects on dopaminergic neurotransmission in regions of the so-called reward system. This pilot study should evaluate, if rTMS could modulate subjective craving for tobacco, which quite often leads to relapse to smoking. Therefore, 11 tobacco-dependent cigarette smokers were randomly assigned to a course of verum- and placebo-rTMS on consecutive days. Craving, as measured by a visual analogue scale, is significantly decreased after Verumstimulation compared to placebo-stimulation intra-individually. This encourages further studies to clarify, if rTMS might be helpful in achieving higher tobacco abstinence rates in smokers willing to quits.

High-frequency repetitive transcranial magnetic stimulation decreases cigarette smoking.

BACKGROUND: The mesolimbic dopaminergic reward system seems to play a crucial role in reinforcing effects of nicotine. Recently, acute high-frequency repetitive transcranial magnetic stimulation (rTMS) of frontal brain regions has been shown to efficiently modulate the mesostriatal and mesolimbic dopaminergic system in both animals and humans. For this reason, we investigated whether high-frequency rTMS would be able to influence nicotine-related behavior by studying rTMS effects on craving and cigarette smoking. METHOD: Fourteen treatment-seeking smokers were included in a double-blind crossover trial, conducted in 2002, comparing single days of active versus sham stimulation. Outcome measures were rTMS effects on number of cigarettes smoked during an ad libitum smoking period and effects on craving after a period of acute abstinence. RESULTS: High-frequency (20-Hz) rTMS of left dorsolateral prefrontal cortex reduced cigarette smoking significantly (p <.01) in an active stimulation compared with sham stimulation. Levels of craving did not change significantly. CONCLUSION: High-frequency rTMS may be useful for treatment in smoking cessation.