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ABSTRACT: One month before (T-1) and 12 months after (T12) controlled i.v. administration of pharmaceutical heroin-HCl (10-100 mg/day) in the context of a heroin maintenance program (HMP), concentrations of opiates and cocaine as well as its metabolites were determined in head hair (n = 46) using a validated gas chromatographic-mass spectrometric method. In addition, a patient collective of a methadone maintenance program (MMP, daily doses 15-260 mg) was examined (n = 35). The incidence of additional cocaine consumption decreased in both groups during the study period (T-1 to T12): in HMP from 64.6% to 45.8% and in MMP from 71.4% to 60.0%. A significant reduction of cocaine consumption was defined as an at least 30% reduction of analyte concentrations in hair (Deltac > 30%). Accordingly, in HMP, a decrease in 45.8% of initially (T-1) cocaine-positive patients was determined; in MMP, the reduction was 48.6%. In 22.9% of HMP and 37.1% of MMP, an increase of cocaine concentrations was detected. Codeine and acetylcodeine were found in 50.0% and 43.5% (T-1) and 13.0% and 10.9% (T12) of the samples of the HMP, as well as in 45.7% and 25.7% (T-1) and 17.1% and 5.7% (T12) in MMP, respectively. The missing of acetylcodeine, in particular at T-1, questions its applicability as a characteristic marker of a preceding consumption of illicit heroin in hair analysis.
Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 09/2009; 123(5):363-9. · 2.59 Impact Factor
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ABSTRACT: Urine samples of patients from a heroin maintenance program (HMP) and a methadone maintenance program (MMP) were chromatographically analyzed 1 month before and 6 and 12 months into treatment for the presence of classical markers of heroin use as well as for the presence of markers for illicit heroin abuse. Furthermore, the samples were immunochemically tested for cannabinoids, cocaine metabolites, amphetamine, methylendioxyamphetamines and benzodiazepines. A co-consumption of illicit heroin (HER) in the HMP was determined to be 50% but was significantly lower compared to the MMP with a co-use of 71%. The incidence was high because not only acetylcodeine (AC) as a very specific marker was considered but also other marker substances for illicit HER use. Amphetamines played only a minor part in both collectives, and the proportion of HER and methadone patients using cocaine was similar and decreased during treatment. Also, the benzodiazepine use decreased, and cannabis use was high in both collectives during treatment. Considering only the AC in the present study, a co-use of illicit HER in the HMP was similar to previous reports concerning HER-assisted treatment programs. If additional marker substances were examined, the suspicion of a co-use of illicit HER is markedly enhanced.
Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 09/2009; 124(5):499-503. · 2.59 Impact Factor
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Ke Xu, Dirk Lichtermann,
Robert H Lipsky,
Petra Franke,
Xiehe Liu,
Ying Hu,
Liping Cao,
Sibylle G Schwab,
Dieter B Wildenauer,
Claiton H D Bau,
Erica Ferro,
Will Astor,
Thembi Finch,
Jeanietta Terry,
Julie Taubman,
Wolfgang Maier,
David Goldman
Archives of general psychiatry 08/2006; 63(8):939-940. · 12.26 Impact Factor
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ABSTRACT: The brain synaptic vesicular amine transporter SLCA18A2 is a key component for the uptake of monoamines like dopamine or serotonin into vesicles. We have analyzed seven DNA polymorphisms located in the genomic region of SLC18A2 for association with alcohol- and nicotine dependence, using a family-based design. Our sample comprised 131 families with alcohol-dependent offspring and 96 families with at least one nicotine-dependent offspring. For the alcohol-dependent sample, we found statistical significant association for two single markers (rs363387, P=0.03; rs363333, P=0.0066) as well as for several haplotypes (minimal P=0.0038). When the sample with alcohol dependence was stratified according to gender, we observed increased association for the male subgroup (rs363387, P=0.0011). None of the markers showed association in the sample of families with nicotine dependence. However, analysis of a combined sample of alcohol and nicotine-dependent families resulted in single markers as well as several haplotypes showing statistical significant association with substance dependence (minimal P=0.0044). We conclude that DNA polymorphisms located in SLC18A2 might contribute to the development of substance dependence.
Neuropsychopharmacology 01/2006; 30(12):2263-8. · 7.99 Impact Factor
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ABSTRACT: High-dose methadone is well known to cause testosterone deficiency and sexual dysfunction in opioid-dependent men. Buprenorphine is a new drug for the pharmacotherapy of opioid dependence. Its influence on the gonadal axis has not been investigated to date. We therefore assayed testosterone, free testosterone, estradiol, SHBG, LH, FSH, and prolactin in 17 men treated with buprenorphine. Thirty-seven men treated with high-dose methadone and 51 healthy blood donors served as controls. Sexual function and depression were assessed using a self-rating sexual function questionnaire and the Beck Depression Inventory. Patients treated with buprenorphine had a significantly higher testosterone level [5.1 +/- 1.2 ng/ml (17.7 +/- 4.2 nmol/liter) vs. 2.8 +/- 1.2 ng/ml (9.7 +/- 4.2 nmol/liter); P < 0.0001] and a significantly lower frequency of sexual dysfunction (P < 0.0001) compared with patients treated with methadone. The testosterone level of buprenorphine-treated patients did not differ from that of healthy controls. In conclusion, we demonstrated for the first time that buprenorphine, in contrast with high-dose methadone, seems not to suppress plasma testosterone in heroin-addicted men. To this effect, buprenorphine was less frequently related to sexual side effects. Buprenorphine might therefore be favored in the treatment of opioid dependence to prevent patients from the clinical consequences of methadone-induced hypogonadism.
Journal of Clinical Endocrinology & Metabolism 02/2005; 90(1):203-6. · 6.50 Impact Factor
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Nadia Chabane,
Bruno Millet,
Richard Delorme, Dirk Lichtermann,
Flavie Mathieu,
Jean Louis Laplanche,
Isabelle Roy,
Marie Christine Mouren,
Regis Hankard,
Wolfgang Maier,
Jean Marie Launay,
Marion Leboyer
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ABSTRACT: Association studies of the serotonin transporter (SLC6A4) gene in obsessive-compulsive disorder (OCD) have generated discrepant results. Here, we genotyped the 5-HTTLPR polymorphism in 106 French OCD patients and 171 healthy controls (case control study). We also performed a family association study on 116 trios including an OCD patient (73 French and 43 German). No association was detected between the 5-HTTLPR polymorphism and OCD in either the case control study or the family study.
Neuroscience Letters 07/2004; 363(2):154-6. · 2.11 Impact Factor
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Ke Xu, Dirk Lichtermann,
Robert H Lipsky,
Petra Franke,
Xiehe Liu,
Ying Hu,
Liping Cao,
Sibylle G Schwab,
Dieter B Wildenauer,
Claiton H D Bau,
Erica Ferro,
Will Astor,
Thembi Finch,
Jeanietta Terry,
Julie Taubman,
Wolfgang Maier,
David Goldman
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ABSTRACT: Dopamine receptor-mediated pathways play critical roles in the mechanism of addiction. However, associations of the D(2) dopamine receptor gene (DRD2) with substance abuse are controversial.
To determine whether susceptibility sites resided at DRD2.
Haplotype-based case-control analysis of 2 distinct populations using 10 single nucleotide polymorphisms (SNPs) with heroin dependence.
Universities of Mainz and Bonn, Germany, and 3 local hospitals in southwestern China. Patients Cases and control subjects recruited from China (486 cases, 313 controls) and Germany (471 cases, 192 controls).
Genotyping for 10 SNPs by 5'-exonuclease fluorescence assays. The D' value of linkage disequilibrium and haplotypes were generated by the expectation-maximization algorithm.
Genotype, allele, and haplotype frequencies were compared between cases and controls by chi(2) tests constructed for each population. An additional 32 SNPs randomly distributed in the genome were genotyped for detecting population admixture in the 2 populations.
A haplotype block of 25.8 kilobases (kb) was defined by 8 SNPs extending from SNP3 (TaqIB) at the 5' end to SNP10 site (TaqIA) located 10 kb distal to the 3' end of the gene. Within this block, specific haplotype cluster A (carrying TaqIB1 allele) was associated with a high risk of heroin dependence in Chinese patients (P = 1.425 x 10(-22); odds ratio, 52.80; 95% confidence interval, 7.290-382.5 for 8-SNP analysis). A putative recombination "hot spot" was found near SNP6 (intron 6 ins/del G), creating 2 new daughter haplotypes that were associated with a lower risk of heroin dependence in Germans (P = 1.94 x 10(-11) for 8-SNP analysis). There was no evidence of population stratification in either population.
These results strongly support a role of DRD2 as a susceptibility gene with heroin dependence in Chinese patients and was associated with low risk of heroin dependence in Germans.
Archives of General Psychiatry 07/2004; 61(6):597-606. · 12.02 Impact Factor
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Thomas Rohrmeier,
Albert Putzhammer,
Heino Sartor,
Michael Knapp,
Margot Albus,
Margitta Borrmann-Hassenbach, Dirk Lichtermann,
Dieter Wildenauer,
Sibylle Schwab,
Wolfgang Maier,
Helmfried E Klein,
Peter Eichhammer
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ABSTRACT: Recently, a putative functional polymorphism (-141C Ins/Del) in the 5'-flanking region of the dopamine D2 receptor was found. An association of the Ins allele with schizophrenia has been described in a Japanese sample. In the present study this association was examined in a German schizophrenia patient population. In a family based approach 190 German family trios were analyzed for the -141C Ins/Del genotype. Using the transmission disequilibrium test (TDT) we found no evidence for an association of the Ins allele with schizophrenia (TDT = 0.152, P = 0.696). In parallel, we performed an independent case control study with 268 schizophrenic patients and 244 controls. Again, we did not detect an overrepresentation of the Ins allele in patients (P = 0.124). Thus, our data do not support the hypothesis that the -141C Ins variant plays a major role in predisposition to schizophrenia. To confirm our conclusion further preferentially family based studies are needed.
Psychiatrische Praxis 06/2003; 30 Suppl 2:S212-5. · 1.64 Impact Factor
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Thomas Rohrmeier,
Albert Putzhammer,
Heino Sartor,
Michael Knapp,
Margot Albus,
Margitta Borrmann-Hassenbach, Dirk Lichtermann,
Dieter Wildenauer,
Sibylle Schwab,
Wolfgang Maier,
Helmfried E. Klein,
Peter Eichhammer
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ABSTRACT: Recently, a putative functional polymorphism (- 141C Ins/Del) in the 5'-flanking region of the dopamine D (2) receptor was found. An association of the Ins allele with schizophrenia has been described in a Japanese sample. In the present study this association was examined in a German schizophrenia patient population. In a family based approach 190 German family trios were analyzed for the - 141C Ins/Del genotype. Using the transmission disequilibrium test (TDT) we found no evidence for an association of the Ins allele with schizophrenia (TDT = 0.152, P = 0.696). In parallel, we performed an independent case control study with 268 schizophrenic patients and 244 controls. Again, we did not detect an overrepresentation of the Ins allele in patients (P = 0.124). Thus, our data do not support the hypothesis that the - 141C Ins variant plays a major role in predisposition to schizophrenia. To confirm our conclusion further preferentially family based studies are needed.
Psychiatrische Praxis 06/2003; 30(Suppl 2):212-215. · 1.64 Impact Factor
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ABSTRACT: The paper reports the first controlled family study investigating not only 1st but also 2nd and 3rd degree relatives of patients with schizophrenia by direct diagnostic interviews. Regardless of their degree of relationship, all biological relatives of the patients were found to be at an elevated risk of schizophrenia (5.0% in 1st, 3.1% in 2nd, 1.5% in 3rd degree relatives compared to 0.8% among controls). Schizoaffective and affective disorders have also been found to be more common in the three groups of relatives but without a monotone decline of prevalence rates across the groups. Other psychiatric disorders were not found to be at an elevated risk in relatives of patients compared to controls. Thus, our findings support the hypothesis that psychotic, as well as affective disorders, aggregate in families of individuals with schizophrenia.However, in our study, the risk of schizophrenia and the risk of affective disorders correlated. Particularly, the magnitude of the risk of schizophrenia among relatives of probands with schizophrenia varied with the occurrence of affective disorders in relatives. In relatives, the risk of schizophrenia was maximal in absence of a family history of affective disorder. This constellation holds true even if only families of index cases without any affective syndrome during lifetime are considered.
Schizophrenia Research 11/2002; 57(2-3):259-66. · 4.75 Impact Factor
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Sven Cichon,
Johannes Schumacher,
Daniel J Müller,
Martina Hürter,
Christine Windemuth,
Konstantin Strauch,
Susanne Hemmer,
Thomas G Schulze,
Gabriele Schmidt-Wolf,
Margot Albus, [......],
Jürgen Minges, Dirk Lichtermann,
Bernhard Lerer,
Kyra Kanyas,
Max P Baur,
Thomas F Wienker,
Wolfgang Maier,
Marcella Rietschel,
Peter Propping,
Markus M Nöthen
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ABSTRACT: Bipolar affective disorder (BPAD), also known as manic depressive illness, is a severe psychiatric disorder characterized by episodes of mania and depression. It has a lifetime prevalence of ∼1% in all human populations. In order to identify chromosomal regions containing genes that play a role in determining susceptibility to this psychiatric condition, we have conducted a complete genome screen with 382 markers (average marker spacing of 9.3 cM) in a sample of 75 BPAD families which were recruited through an explicit ascertainment scheme. Pedigrees were of German, Israeli and Italian origin, respectively. Parametric and non-parametric linkage analysis was performed. The highest two-point LOD score was obtained on 8q24 (D8S514; LOD score = 3.62), in a region that has not attracted much attention in previous linkage studies of BPAD. The second best finding was seen on 10q25–q26 (D10S217; LOD score = 2.86) and has been reported in independent studies of BPAD. Other regions showing ‘suggestive’ evidence for linkage localized to 1p33–p36, 2q21–q33, 3p14, 3q26–q27, 6q21–q22, 8p21, 13q11 and 14q12–q13. In addition, we aimed at detecting possible susceptibility loci underlying genomic imprinting by analyzing the autosomal genotype data with the recently developed extension of the GENEHUNTER program, GENEHUNTER-IMPRINTING. Putative paternally imprinted loci were identified in chromosomal regions 2p24–p21 and 2q31–q32. Maternally imprinted susceptibility genes may be located on 14q32 and 16q21–q23.
Human Molecular Genetics 01/2002; · 7.64 Impact Factor
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Petra Franke,
Markus M. Nöthen,
Tao Wang,
Helge Neidt,
Michael Knapp, Dirk Lichtermann,
Olaf Weiffenbach,
Peter Mayer,
Volker Höllt,
Peter Propping,
Wolfgang Maier
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ABSTRACT: In the present study, we tested the hypothesis that addictive behavior may be influenced by genetic variation in the human δ-opioid receptor gene. We investigated the contribution of a silent T to C change in the coding region to the development of heroin and alcohol dependence using large case-control and family-based association samples. Presence of the C allele was previously reported to significantly increase the risk for heroin dependence. In the present study, however, we did not find statistically significant differences between patients and controls nor did we find preferential transmission of the C allele from parents to affected offspring. Our results, therefore, do not support an association between genetic variation of the δ-opioid receptor and addictive behavior in man. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:462–464, 1999. © 1999 Wiley-Liss, Inc.
American Journal of Medical Genetics 09/1999; 88(5):462 - 464.
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Sibylle G. Schwab,
Joachim Hallmayer,
Margot Albus,
Bernard Lerer,
Claudia Hanses,
Kyra Kanyas,
Ronnen Segman,
Margitta Borrman,
Bettina Dreikorn, Dirk Lichtermann,
Marcella Rietschel,
Matyas Trixler,
Wolfgang Maier,
Dieter B. Wildenauer
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ABSTRACT: Recent reports on potential linkage by Faraone and the NIMH Genetics Initiative-Millennium Schizophrenia Consortium [1997: Am J Med Genet 74:557], and by Straub et al. [1997: Am J Med Genet 74:558], prompted us to study chromosome 10 in a sample of 72 families containing 2 or more affected sibs with schizophrenia for additional evidence of linkage. We obtained highest allele sharing for the two markers D10S582 (61.5% allele sharing, χ2 = 7.6, P = 0.0058) and D10S1423 (59% allele sharing, χ2 = 4.76, P = 0.029). D10S1423 is one of the markers with the highest lod scores in the study of Faraone and the NIMH Genetics Initiative-Millennium Schizophrenia Consortium [1997: Am J Med Genet 74:557]. GENEHUNTER analysis revealed a nonparametric lod score (NPL) of 3.2 (P = 0.0007) for the marker D10S1714, which lies in the same region. Multipoint affected sib-pair lod score analysis (identity by descent) calculated by ASPEX revealed a lod score of 1.72 for all possible sib-pair combinations (107) and of 2.13, when only independent sib-pairs (87) were counted. Our study provides further evidence for a potential susceptibility locus for schizophrenia on chromosome 10p. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:302–307, 1998. © 1998 Wiley-Liss, Inc.
American Journal of Medical Genetics 07/1998; 81(4):302 - 307.
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ABSTRACT: Replication was attempted of a recent report on linkage between bipolar affective disorder and pericentrometric loci on chromosome 18. Linkage to these markers was excluded in a sample of five extended multiplex families using lodscore and affected-pedigree-member methods. In one family, however, the lod score exceeded 1.0. Although the proposed susceptibility genes are unlikely to have a major impact on the occurrence of bipolar disorder, they might modify the genetic risk in a minority of familial cases.
Psychiatry Research 12/1995; · 2.52 Impact Factor
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ABSTRACT: One month before (T-1) and 12 months after (T12) controlled intravenous administration of pharmaceutical heroin-HCl (10-1000 mg/d) in the context of a heroin-maintenance program, concentrations of opiates in head hair were determined (n = 46), using a validated gas chromatography-mass spectrometry method with limits of detection (LOD) between 0.02 and 0.04 ng/mg. In addition, a collective of opiate-associated fatalities was examined (n = 24). The obtained concentrations in the proximal segment (1 cm) of the patients were between 0.04 and 1.16 ng/mg (mean 0.13 ng/mg) for heroin (HER), between 0.02 and 32.41 ng/mg (mean 1.48 ng/mg) for 6-monoacetylmorphine (MAM) and between 0.03 and 11.79 ng/mg (mean 1.19 ng/mg) for morphine (MOR). With the exception of the analyte HER, there was no other statistically significant difference in the concentrations in comparison to the opiate fatalities [HER 1.55-5.20 ng/mg mean 3.38 ng/mg), MAM 0.04-30.01 ng/mg (mean 2.14 ng/mg), and MOR 0.03-11.87 ng/mg (mean 1.15 ng/mg) in the proximal segments]. After controlled HER administration, a correlation between the dose and the total opiate concentration in the hair was found (r = 0.66). These results disagree with the observations of authors who found only limited dose-concentration relationships after heroin abuse in hair. When considering a single analyte, the coefficient of correlation increased in correspondence to the respective plasma half-life (r = 0.42, r = 0.58, and r = 0.69 for HER, MAM, and MOR). The latter findings are in agreement with the report that states that this correlation is influenced by the plasma half-lifes of analytes. Codeine and acetylcodeine (AC) were detected in 50% and 43.5% (T-1) and 13% and 10.9% (T12) of the samples of the HER-maintenance program, as well as in 33.3% and 16.7% in opiate-associated fatalities, respectively. The lack of differences between obtained opiate concentrations in the hair of participants in a controlled heroin maintenance program and of opiate-associated fatalities does not support the hypothesis that an absence of tolerance can be regarded as a potential cause of death. In addition, the lack of AC, which was also observed in the majority of the deaths, questions its applicability as a characteristic marker of the consumption of illicit heroin.
Journal of analytical toxicology 29(5):345-52. · 2.02 Impact Factor
