BDNF Val66Met polymorphism and stressful life events in melancholic childhood-onset depression

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) polymorphisms have been examined for their contribution toward depression with equivocal results. More homogeneous phenotypes might be used to improve our understanding of genetic liability to depression. The aim of our study was to (a) test for an association between the BDNF Val66Met polymorphism and childhood-onset melancholic depression and (b) to examine the interactive effects of stressful life events (SLE) and the Val66Met polymorphism on the risk of childhood-onset melancholic depression. MATERIALS AND METHODS: A total of 583 depressed probands were involved in this study (162 of the melancholic subtype). Diagnoses were derived through the Interview Schedule for Children and Adolescents - Diagnostic Version and life event data were collected using an Intake General Information Sheet. RESULTS: Overall, 27.8% of the participants fulfilled the criteria for melancholy. In the melancholic group, the proportion of females was higher (53.1%), although there were more males in the overall depressed sample. We detected no significant differences in genotype or allele frequency between the melancholic and the nonmelancholic depressed group. The BDNF Val66Met polymorphism and SLE interaction was not significantly associated with the melancholy outcome. CONCLUSION: In our study, females were more prone to developing the early-onset melancholic phenotype. To our knowledge, this is the first study to investigate the differentiating effect of the genotype and the GxE interaction on the melancholic phenotype in a large sample of depressed young patients. We did not find an association between the melancholic subtype of major depression and the BDNF genotype and SLE interaction in this sample, which is representative of the Hungarian clinic-referred population of depressed youths

Salicylaldehyde thiosemicarbazone copper complexes: impact of hybridization with estrone on cytotoxicity, solution stability and redox activity

An estrone–salicylaldehyde thiosemicarbazone hybrid (estrone–TSC) containing integrated domains was designed and synthesized with excellent yield via the condensation reaction of thiosemicarbazide and 2-formyl-estrone under optimized microwave reaction conditions. A structurally related bicyclic derivative (thn-TSC) starting from 5, 6, 7, 8-tetrahydro-1-naphtol (th-1-n) was also prepared in addition to their copper(II) complexes. The ligands have somewhat higher pKa values determined for the deprotonation of the hydroxyl group by UV-visible spectrophotometric and fluorometric titrations than the reference compound salicylaldehyde thiosemicarbazone (STSC), and are neutral at physiological pH. The novel conjugates are more lipophilic and possess higher membrane permeability than STSC based on the n-octanol/water partitioning and the parallel artificial membrane permeability assays, respectively. The isolated [Cu(estrone–TSCH−2)] and [Cu(thn-TSCH−2)] complexes were characterized by ESI-MS, UV-visible and EPR spectroscopy and a detailed solution study was performed to reveal their stoichiometry, stability and reduction by glutathione. The crystal structure of the ligand thn-TSC and its complex [Cu(thn-TSCH−1)Cl] was studied by single crystal X-ray diffraction method. The complexes are fairly stable at pH 7.4, the observed stability order is STSC < thn-TSC < estrone–TSC, and are able to oxidize glutathione readily. The novel ligands thn-TSC and estrone–TSC were found to be only moderately cytotoxic against several human cancer cell lines ; however rather low IC50 values were measured in the hormone-responsive MCF-7 breast cancer cell lines (thn-TSC: 3.7 μM, estrone–TSC: 6.4 μM). The copper(II) complexes exhibited high cytotoxicity (IC50 < 0.3–2 μM) and were considerably more cytotoxic than the respective ligands. Low level of reactive oxygen species was measured and a weak GSH depletion was observed for the complexes of thn-TSC and estrone–TSC in SUM159 breast cancer cells, thus their mechanism of action might be related to the induction of oxidative stress

Organometallic Ru(II), Rh(III) and Re(I) complexes of sterane-based bidentate ligands: Synthesis, solution speciation, interaction with biomolecules and anticancer activity

In this study, we present the synthesis, characterization and in vitro cytotoxicity of six organometallic [Ru(II)(η6-p-cymene)(N,N)Cl]Cl, [Rh(III)(η5-C5Me5)(N,N)Cl]Cl and [Re(I)(CO)3(N,N)Cl] complexes, in which the (N,N) ligands are sterane-based 2,2’-bipyridine derivatives (4-Me-bpy-St-OH,..