The gene for the human dopamine transporter DAT1 displays several polymorphisms, including a 40-bp variable number of tandem repeats (VNTR) ranging from 3 to 13 copies in the 3'-untranslated region (UTR) of the gene. Some hints for an association of certain VNTR with psychiatric disorders, behavioural problems and temperament traits have been found. This study explored possible associations between the most frequent DAT1 polymorphism, namely the A10 VNTR, and personality traits as measured by the Temperament and Character Inventory (TCI) and the NEO Five Factor Inventory (NEO-FFI) in alcohol-dependent patients (ADP). One hundred and forty-four ADP and 144 age-, educational level- and sex-matched controls (CO) were genotyped and interviewed with the TCI and NEO-FFI. ADP showed higher neuroticism, lower extraversion, lower openness, lower agreeableness and lower conscientiousness than CO on the NEO-FFI and higher scores in harm avoidance, reward dependence and self transcendence and lower scores in self directedness and cooperativeness on the TCI than controls. There were no genetic links regarding those personality traits, the diagnosis of alcohol dependence and the VNTR. Only in a subgroup of ADP, those without psychiatric co-diagnoses and homozygous for A10, significantly lower scores in novelty seeking and higher scores in self directedness than in all the other ADP and CO could be detected. Summarizing, the 40-bp VNTR did not help to differentiate between ADP and CO, but might contribute to some personality dimensions in certain ADP subgroups.

Zusammenfassung: Es wurden alkoholabhängige Patienten unter Stressbedingungen neuropsychologisch untersucht. Fragestellung: Zeigt sich wie bei depressiven Patienten eine abnorme Reaktion auf negative Rückmeldung oder gar eine generelle Stressanfälligkeit? Die alkoholabhängigen Patienten wurden in der Testbatterie zur Aufmerksamkeitsprüfung (TAP) nach negativer Rückmeldung tendenziell langsamer und die Kontrollpersonen tendenziell schneller. Insgesamt ergab sich ein signifikanter Unterschied in Visuellem Scanning und Reaktionswechsel. Damit ist die “abnormal response to negative feedback” nicht spezifisch für depressive Patienten. Unter 90 dBA Lärm als Stressor zeigten sich dagegen keine Effekte auf die Leistungsfähigkeit oder die Stressverarbeitung. Eine Leistungsminderung durch generelle Stressanfälligkeit konnte somit nicht beobachtet werden. Kontinuierliches Stressmonitoring zeigte, dass sich die alkoholabhängigen Patienten wie testängstliche Probanden verhalten und nach negativer Rückmeldung leistungsminderndes Bedrohungs- und Verlusterleben vorherrscht, während gesunde Probanden auch nach negativer Rückmeldung an der Einschätzung als Herausforderung festhalten und sich steigern.

Die hier berichtete Studie vergleicht das serotonerge Antidepressivum Nefazodon (SSRI) mit Plazebomedikation (PL) und spezifische kognitive Verhaltenstherapie (CBT) mit psychoedukativer, nichtdirektiver Gruppenunterstützung (GC) hinsichtlich der Effekte auf Rückfallverhinderung bei Alkoholabhängigkeit mittels einer umfangreichen, prospektiven, randomisierten und plazebokontrollierten, doppelblinden Untersuchung an drei psychiatrischen Universitätskliniken. Erwartet wurde, dass die spezifischen und aktiven Interventionen (SSRI, CBT) den unspezifischen, unterstützenden Plazebointerventionen (PL, GC) über den Nachkontrollzeitraum von 12 Monaten überlegen sind.

AimsA linkage of certain alleles of the tryptophan hydroxylase (TPH) intron 7 A218C polymorphism to suicidality and antisocial behaviour has been described. The aim of our study was to find any association between dimensions of the Temperament and Character Inventory (TCI) indicating impulsivity and the TPH polymorphism alleles in unselected alcohol-dependent patients and age-matched controls.MethodsWe examined 159 alcohol-dependent patients and 161 controls with the TCI and genotyped them for the TPH intron 7 A218C polymorphism alleles.ResultsAlthough homozygous TPH genotypes were found more often in alcohol-dependent patients than in controls, an association between TCI dimensions and TPH alleles was not observed in the complete sample. Alcohol-dependent patients, however, scored significantly higher for harm avoidance (HA) and lower for self-directedness (SD) than controls regardless of TPH genotype. Among controls, for those with the A/A genotype, harm avoidance was as high as in the group of alcohol-dependent patients, persistence (P) in that genotype was significantly lower than for all other genotypes in the patient and control group.ConclusionEven if there is no association between TCI dimensions and TPH genotype in our sample, hints to nonspecific psychopathology in connection with the A/A genotype are found.

The present study examined the association of the Tyrosine hydroxylase Val-81-Met polymorphism with alcohol dependence. One hundred and fifty-nine patients in a psychiatric unit with alcohol dependence were genotyped as well as 92 healthy volunteers. The Val allele was more frequent in patients with alcohol dependence (69.5%) than in controls (62.5%). This effect was largely due to the association with early-onset alcoholism (77.8%), whereas no difference was noted between late-onset patients and controls. Our results suggest a role for tyrosine hydroxylase in early-onset alcoholism.

Objective Ethanol-inhibited glutamatergic neurotransmission has been shown to mediate pathophysiological mechanisms in the development of alcoholism, including withdrawal symptoms. NMDA-receptor 2B (NR2B) is a subunit that confers a high sensitivity to ethanol-induced inhibition. Previously we had reported a lack of association between the single nucleotide polymorphism (SNP) rs1806201 in the NR2B gene (GRIN2B) and alcoholism. Shortly thereafter, an association between the polymorphism and early-onset alcoholism has been reported. One aim of the present study was to test whether the association between the GRIN2B polymorphism rs1806201 and early-onset alcoholism can be replicated in a larger sample. Moreover, we hypothesized that another genetic variation within GRIN2B (rs1806191) may have an effect in the etiology of alcoholism or withdrawal-related traits. Methods We extended our original study sample to a size of 377 patients and 464 healthy volunteers and performed a replication study, including the second GRIN2B SNP. Associations between allele, genotype and haplotype frequencies of the two polymorphisms and alcoholism as well as with patients' phenotypes were investigated. Results No associations were found between any of the two polymorphisms, tested individually or as haplotypes, and alcoholism, respectively withdrawal-related traits. Conclusion Neither the analyzed SNPs nor any of their haplotypes likely modify susceptibility to alcohol dependence or withdrawal-related phenotypes.

A major goal of antidepressant development is to improve on preceding drug classes with agents with greater specificity (and therefore fewer unwanted side-effects) and with more rapid onset of antidepressant action. To this end, four antidepressants with significantly distinct pharmacological characteristics have been recently introduced: venlafaxine, nefazodone, mirtazapine, and reboxetine. Venlafaxine is the first antidepressant in a new drug class referred to as the serotonin noradrenergic reuptake inhibitors (SNaRIs). Nefazodone is a weaker serotonin and norepinephrine reuptake inhibitor, but a potent serotonin 5-HT2 receptor antagonist. Mirtazapine is a potent antagonist of central 2α-adrenergic autoreceptors, and heteroreceptors and is an antagonist of serotonin 5-HT2 and 5-HT3 receptors. The result of these actions is to increase both noradrenergic and specific (5-HT1) serotonergic transmission, and mirtazapine has therefore been termed a noradrenergic and specific serotonergic antidepressant (NaSSA). Reboxetine is the first selective noradrenaline reuptake inhibitor (NaRI) to be introduced since the tricyclics, and lacks immediate serotonergic effects.

This study was conducted to detect a possible association of a T941G single nucleotide polymorphism (SNP) in the monoamine oxidase A (MAOA) gene with generalized anxiety disorder (GAD), panic disorder (PD), or major depression (MD). Fifty GAD patients (34 females and 16 males), 38 PD patients (21 females and 17 males), and 108 MD patients (80 females and 28 males) were included. The comparison group consisted of 276 (132 females and 144 males) unrelated healthy individuals. The 941T allele was over-represented in patients suffering from GAD (chi(2) = 6.757; df = 1; P < 0.01, not corrected for multiple testing) when compared to healthy volunteers. No association was observed in MD or PD. This is the first study specifically analyzing the MAOA G941T polymorphism in GAD and thus needs to be replicated in an independent sample. However, the results are in line with previous data suggesting an association between the MAOA locus and regulation of complex human behavior.

BACKGROUND:The presence of the A1 allele of the dopamine D2 receptor TaqI restriction fragment length polymorphism has been reported to be associated with an earlier age of onset of alcohol dependence as a marker for severity.METHODS:We tested this hypothesis with special regard to the definition of the age of onset of alcoholism in 243 patients with alcohol dependence, according to DSM-IV criteria assessed by the standardized interview Münchner Composite International Diagnostic Interview (M-CIDI), consecutively admitted for detoxification. Additionally, the Addiction Severity Index (ASI) was performed. The TaqIA polymorphism was amplified by polymerase chain reaction (PCR), and the PCR product was digested by the restriction enzyme TaqI. Patients were subsequently divided into an A1 (presence of at least one A1 allele, n = 88) and an A2 group (absence of an A1 allele, n = 155). The following criteria for different definitions of age of onset were used: (1) age of onset of the first occurring symptom necessary for the diagnosis of alcohol dependence according to M-CIDI; (2) age of onset of the last symptom of alcohol dependence according to M-CIDI; (3) age of onset of more than 3 drinking days per week on a regular basis according to ASI; (4) age of onset of more than 3 drinking days-of more than five drinks per drinking day-or at least one binge drinking episode per week on a regular basis according to ASI.RESULTS:The frequency of the A1 allele in our patient sample was 0.208. No statistically significant association between the A1 allele and the age of onset of alcoholism was found. The mean age of onset according to criterion 1 was 30.4 +/- 10.8 years for the A1 group and 30.2 +/- 10.2 years for the A2 group (p = 0.89); for criterion 2, it was 33.3 +/- 10.0 years for the A1 group and 33.9 +/- 10.2 years for the A2 group (p = 0.77); for criterion 3, it was 18.0 +/- 7.5 years for the A1 group and 18.1 +/- 6.1 years for the A2 group (p = 0.92); and for criterion 4, it was 22.3 +/- 9.7 years for the A1 group and 21.8 +/- 8.5 years for the A2 group (p = 0.76).CONCLUSIONS:No association was found between the A1 polymorphism and age at onset of alcohol dependence according to different specified criteria.

The HTR1B receptor gene has been linked to antisocial alcoholism in a Finnish population and an American Indian tribe [Lappalainen et al., Arch. Gen. Psychiatry, 55 (1998) 989]. Using a candidate gene approach, we genotyped 209 patients with alcoholism, 108 patients with major depression, 32 patients with panic disorder, 50 patients with generalized anxiety disorder, 58 patients with narcolepsy and 74 healthy volunteers for the HTR1B 861G>C polymorphism. There was a higher frequency of the HTR1B 861G alleles among the alcohol-dependent patients as compared to the control subjects (χ2=4.02, d.f.=2, P=0.04). However, the association resulted from higher frequencies of the opposite alleles (HTR1B 861G), as originally reported by Lappalainen et al. (1998). Although the association in our study might be due to a type I error, the higher degree of HTR1B allele sharing within both populations could also argue for another alcoholism-relevant gene within the proximity of the HTR1B gene on human chromosome 6.