B Bondy

..The design and development of this project as well as interconnections with the others subprojects are described. Preliminary results about the stress hormone system and suicidality are presented...

..The inclusion of functional genomics, which investigates the complex gene and/or protein expression in response to a given drug, may lead to the development of novel and safer drugs...

..This paper reviews the status of current knowledge in this area, points to the weakness of the investigations and presents new approaches beyond the serotonergic system...

..This article reviews recent advances in this field with respect to their importance for the clinician...

..The inclusion of functional genomics, which investigates the complex gene and/or protein expression in response to a given drug, could help lead to the development of novel and safer drugs...

..Our data might further suggest that patients with a haplotype combining the CC and DD/ID genotypes respond better to treatment than those with either single allele. These results should however be replicated in future research...

..This finding indicates that the serotonin transporter does not appear to be a major susceptibility factor in the pathophysiology of Alzheimer's disease and other psychogeriatric disorders...

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..However, if we combine our results with three previous published positive reports there seems to be an association between the -491A/T polymorphism and AD, though its size is less than found in the original publication...

..These findings support the hypothesis that the GRIN1 locus may modify the susceptibility to seizures during alcohol withdrawal. This novel finding warrants replication...

..Patients with depression show reduced GM volumes, particularly when they are homozygous for the L(A)-allele, suggesting that these patients are more vulnerable for morphological changes during depressive episodes...

..These results may open up new research strategies for the analysis of the observed disturbances in the serotonergic system in patients suffering from several other psychiatric disorders...

..We could show that SNP rs4291 influences ACE activity and HPA-axis hyperactivity and might therefore represent a common pathophysiologic link for unipolar depression and cardiovascular disease...

..However, subtypes might be identified at least on a basis of differential treatment response...

..Furthermore, we found no association with suicidal behavior. These findings do not support the hypothesis that ABCG1 is a susceptibility gene for affective disorders or suicidal behavior...

..We hypothesized that due to the multiple interactions between the sympathetic and the HPA systems via adrenoceptors, polymorphisms in these genes could have an impact on HPA axis activity in major depression...

..Nevertheless our study reports for the first time that the same allelic combination of two genes that have been shown to increase the risk for myocardial infarction (Naber et al, 2000) increase the vulnerability for depressive disorder...

..The aim of this study is to test the potential influence of a bi-allelic cannabinoid receptor gene (CNR1) polymorphism (G1359A) on severe alcohol withdrawal syndromes...

..The possible implications of these findings are discussed...

..Adult antisocial personality occurred more often in males than females. Possible implications of these findings are discussed...

..A significant association between suicide attempts and the 5-HTT promoter polymorphisms (5-HTTLPR) S-allele has been reported in a sample of French alcohol-dependent subjects, and this paper evaluates this phenomenon in a German sample...

..Pharmacogenetic influences on therapeutic response to neuroleptic treatment are poorly understood. This study investigates the association of response to short-term haloperidol treatment with a Taq I polymorphism in the DRD2 gene...

..We analysed the MAOAuVNTR functional polymorphism in the promoter region of the X-chromosomal monoamine oxidase A (MAOA) gene. Genotypes with three-repeat alleles were reported to be associated with antisocial as well as impulsive traits...

..These findings are in line with a number of more recent studies questioning the association between novelty-seeking and DRD4 dopamine receptor gene polymorphism. Possible implications of these findings are discussed...

..These observations may open up new research strategies not only for several psychiatric disorders, but also for the relationship between psychiatric and somatic diseases...

..05), and especially for the sustained influx at the end of the observation period (P = 0.001). The detailed mechanisms of this disturbed calcium homeostasis need further investigation...

..These findings support the hypothesis that the A218C and the A779C SNP in the TPH gene may be associated with anger-related traits in German samples...

..Although further studies have to confirm our results, this might be a possible pathway that may increase our understanding of drug addiction...

..Future research is recommended to clarify possible interactions between this functional polymorphism and symptoms, course and treatment responses in this disorder...

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..Thus, our results suggest that this polymorphism may not commonly be involved in the susceptibility to suicidality. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:831-835, 2000...

..Direct sequencing of the RT-PCR product assured that it corresponds to the human DRD4 sequence. However, because of the unusual high G/C content of the DRD4, several precautions have to be applied for reliable results...

..Although some controversy exists among the results, many studies are supportive of the hypothesis that psychopharmacogenetics will be helpful in predicting an individual patient's drug response while minimising the rate of side effects...

..However, there might be some difference in [Ca2+]i values between early- and late-onset AD, which could have pathophysiological importance...

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..Alcohol dependents were investigated because these personality disorders and impulsive behavior are very frequent in alcohol dependence anf of clinical relevance...

..Our data do not support the hypothesis of A-6526G, G-5806T or A-779C polymorphisms to be associated with suicide attempts in alcohol-dependent individuals...

..These findings support and extend the three previous studies implicating a GABA-A receptor subunit as contributing to the genetic risk for alcohol dependence. Possible implications of these findings are discussed...

..Our findings question the hypothesis of reduced platelet MAO activity to be a possible vulnerability marker for alcoholism...

..K(D) might be influenced by duration of alcohol dependence, but not sufficiently to yield differences between alcohol-dependent and control subjects...

..In conclusion, structurally different types of antidepressants modulate the function of this ligand-gated ion channel. This may represent a yet unrecognized pharmacological principle of antidepressants...

..A detailed methodological description of the binding assay and subsequent calculations has therefore been given in this paper...

..Moreover, 5-HIAA was strongly related to good quality of sleep (P = .000), while SP was related to sleep disturbance (P = .005). These data are valid to support the hypothesis of a systemic involvement of 5-HT and SP in fibromyalgia...

..The elevated rate of affective disorders in relatives of patients with SAD and PMDD suggests higher genetic vulnerability in this subgroup when compared to patients with SAD alone...

..This result supports the involvement of the SERTPR gene in response to antidepressant treatments...

..We studied the behavioral responses to tryptophan depletion (TD) in healthy women with and without a first-degree family history of depression and examined the relationship to 5HTTLPR alleles...

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..The HPA axis stimulating properties of higher ACE and consecutively higher AT-II and/or lower substance P concentrations may be crucial factors for the HPA system hyperactivity during major depressive episodes...

..Thus genes coding for proteins of the serotonergic pathways are leading candidates for investigating possible associations...

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..Our results suggest that the investigated polymorphisms are not major susceptibility factors in the etiology of major depression...

..Further analysis are needed to confirm these results...

..The results of this study agree with the reported parent-of-origin effects on chromosome 18, but do not support the hypothesis that the Golf gene is a major susceptibility factor for major depression...

..Higher serotonin levels among carriers of the S allele might exhibit increased liability of serotonin-mediated, psychopathology-like anxiety and depression and may impair social skills reflected by harm avoidance...

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..The aim of the present study was to analyze these variants in a large sample of the Munich Gene Bank of Alcoholism...

..In conclusion our study can at least partly replicate the previous findings concerning the impact of SNAP-25 gene polymorphisms on weight gain during antipsychotic treatment...

..5-HTTLPR was not associated with any of the 5-HTT parameters. In sum, we conclude that the 5-HTT is in a hyperfunctional state during depression in SAD and normalizes after light therapy and in natural summer remission...

..Results provide evidence that the investigated 5HT-1B receptor gene variants are not implicated in the susceptibility to suicide...

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..Brain-derived neurotrophic factor (BDNF) modulates hippocampal plasticity, which is believed to be altered in patients with major depression...

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..Our investigation gives the first hint that the speed of onset of antidepressant therapies may be dependent on both variants of the ACE genes and the gender of the patients...

..In conclusion, the mutation ClC-Kb(T481S) of the renal epithelial Cl- channel ClC-Kb strongly activates ClC-Kb chloride channel function in vitro and may predispose to the development of essential hypertension in vivo...

..Previous studies are not conclusive in regard to the specificity of this marker. Therefore, oculomotor pursuit was evaluated in unaffected family members of index probands diagnosed as having either schizophrenia or affective disorders...

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..The alpha-subunit of the G(olf) gene maps to a region on chromosome 18p that has been implicated in several linkage studies as a potential site of a bipolar disorder susceptibility loci...

..05). However, after correction for multiple testing (Bonferroni) these results did not remain significant. Nevertheless, these findings suggest that the presence of the C allele might be an indicator for antidepressant treatment response...

..Several studies have found reciprocal interactions between the serotonergic system and both brain-derived neurotrophic factor and glutamate, which are known to modulate or affect hippocampal morphologic characteristics...

..Thus, the previously reported influence of the serotonin transporter gene on PSD outcome in bipolar depression could not be confirmed in unipolar depressed patients...

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..The s allele was associated with lower Self-Directedness scores in SAD patients, whereas there were no significant differences in TCI dimensions between patients and controls in carriers of the long allele...

..Our finding may open up new research strategies for the analysis of the repeatedly observed disturbances in the serotonergic system in patients suffering from several psychiatric disorders...

..Future studies are needed to clarify whether the observed SP decrease in treatment responders can be attributed to a specific class of drugs...

..Moreover, we hypothesized that another genetic variation within GRIN2B (rs1806191) may have an effect in the etiology of alcoholism or withdrawal-related traits...

..These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs...

..In a previous postmortem study of our own group, we could demonstrate that TPH2 is also expressed in the human brain but not in peripheral tissues...

..49, 95% CI: 0.3-0.82; genotype-wise: 15,5% vs. 29,0%, P = 0.005, OR = 0.45, 95% CI: 0.26-0.77). We suggest that this deletion may influence translational efficiency, thereby possibly affecting the development of bipolar affective disease...

..Results did not provide supporting evidence for the potential involvement of the investigated variants of 5HT-2C receptor in the susceptibility to suicide...

..Sequence variants of the serotonin receptor subunit genes HTR3A and HTR3B indicate no obvious significance in the aetiology of fibromyalgia, yet they represent the basis for future studies on their pharmacogenetic relevance...

..This should result in earlier and more intense additional therapeutic interventions in this group of patients...

..Further analysis are needed to confirm these results...

..Nevertheless patients with bipolar depression irrespective of previous treatments and duration of illness, and unipolar patients not previously treated demonstrated a significant benefit from pindolol augmentation...

..Better understanding of the mechanisms involved in docosahexaenoic acid (DHA) transfer to the neonate may contribute to improve dietary support for infants born prematurely to mothers with placental lipid transport disorders...

..A number of personality traits were assessed in order to provide a basis for a psychobiological model of suicidal behavior...

..Increased affinity of the transporter may also be related to conduct disturbance...

..Proteomics is a powerful method to investigate modifications in protein expression...