Vadaskert Hospital

Budapest, Hungary

Vadaskert Hospital

Budapest, Hungary
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Dempster E.L.,Western Research Institute | Kiss E.,University of Szeged | Kapornai K.,University of Szeged | Daroczi G.,University of Szeged | And 15 more authors.
American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics | Year: 2010

Recent evidence supports a pathological link between heart disease and depressive symptoms, suggesting that depression is both etiologic and prognostic to heart disease. Thus, biological molecules which are at the interface between heart and mind are plausible candidate genes for depressive disorders. To investigate this line of enquiry we have investigated two genes, Endothelin 1 (EDN1) and Angiotensin-converting enzyme (ACE) in a family-based sample with childhood-onset mood disorders (COMDs). EDN1 is highly expressed in endothelium where it acts as a potent vasoconstrictor, and is also expressed in the brain where it exhibits neurotransmitter characteristics. ACE acts as a potent vasopressor, and interacts with the hypothalamic-pituitary-adrenocortical (HPA) system, which is often dysregulated in mood disorders. Furthermore, ACE has recently been found to be associated with major depression. Polymorphisms were selected to best capture the genetic variation at the two loci, and to replicate previous associations. The markers were genotyped across EDN1 and ACE in a sample comprised of 382 Hungarian nuclear families ascertained through affected probands diagnosed with a mood disorders before the age of 15. We found no evidence of association between either of these genes and COMD. Consequently, we were unable to support our hypothesis that these two genes, which are involved in both vascular and brain functions are contributing to the susceptibility to mood disorders of children/adolescents. © 2009 Wiley-Liss, Inc.

Feng Y.,University of Western Ontario | Kapornai K.,University of Szeged | Kiss E.,University of Szeged | Tamas Z.,Vadaskert Hospital | And 15 more authors.
Genes, Brain and Behavior | Year: 2010

The chromosome 1p36 region was previously indicated as a locus for susceptibility to recurrent major depressive disorder based on a linkage study in a sample of 497 sib pairs. We investigated the gamma-aminobutyric acid A (GABAA) δ receptor subunit gene, GABRD, as a susceptibility gene to childhood-onset mood disorders (COMD) because of substantial evidence implicating GABAergic dysfunction in mood disorders and the position of this gene near the 1p36 linkage region. Using a sample consisting of 645 Hungarian families with a child/adolescent proband diagnosed with a mood disorder with the onset of the first episode before age 15, we found some evidence for the association of two polymorphisms located within the gene, rs2376805 and rs2376803, as well as significant evidence for biased transmission of the haplotypes of these two markers (global χ2 test for haplotypes = 12.746, 3 df, P = 0.0052). Furthermore, significant evidence of association was only observed in male subjects (n = 438) when the results were analyzed by sex (χ2 = 9.000 1 df, P = 0.003 for rs2376805). This was in contrast with the previous linkage findings, as LOD scores exceeding 3 were only in female-female pairs in that study. These findings point to the GABRD gene as a susceptibility gene for COMD; however, this gene may not explain the previous linkage finding. © 2010 Blackwell Publishing Ltd/International Behavioural and Neural Genetics Society.

Strauss J.S.,University of Toronto | Freeman N.L.,University of Toronto | Shaikh S.A.,University of Toronto | Vetro A.,University of Szeged | And 17 more authors.
Psychoneuroendocrinology | Year: 2010

Background: Oxytocin (OXT) and prolactin (PRL) are neuropeptide hormones that interact with the serotonin system and are involved in the stress response and social affiliation. In human studies, serum OXT and PRL levels have been associated with depression and related phenotypes. Our purpose was to determine if single nucleotide polymorphisms (SNPs) at the loci for OXT, PRL and their receptors, OXTR and PRLR, were associated with childhood-onset mood disorders (COMD). Methods: Using 678 families in a family-based association design, we genotyped 16 SNPs at OXT, PRL, OXTR and PRLR to test for association with COMD. Results: No significant associations were found for SNPs in the OXTR, PRL, or PRLR genes. Two of three SNPs 3' of the OXT gene were associated with COMD (p≤ 0.02), significant after spectral decomposition, but were not significant after additionally correcting for the number of genes tested. Supplementary analyses of parent-of-origin and proband sex effects for OXT SNPs by Fisher's Exact test were not significant after Bonferroni correction. Conclusions: We have examined 16 OXT and PRL system gene variants, with no evidence of statistically significant association after correction for multiple tests. © 2010 Elsevier Ltd.

Rottenberg J.,University of South Florida | Yaroslavsky I.,University of Pittsburgh | Carney R.M.,University of Washington | Freedland K.E.,University of Washington | And 11 more authors.
Psychosomatic Medicine | Year: 2014

Objective: Depression in adults is associated with risk factors for cardiovascular disease (CVD). It is unclear, however, when the association between clinical depression and cardiac risk factors develops or how early in life this association can be detected. METHODS: In an ongoing study of pediatric depression, we compared CVD risk factors including smoking, obesity, physical activity level, sedentary behavior, and parental history of CVD across three samples of adolescents: probands with established histories of childhood-onset major depressive disorder (n = 210), never-depressed siblings of probands (n = 195), and controls with no history of any major psychiatric disorder (n = 161). RESULTS: When assessed during adolescence, 85% of the probands were not in a major depressive episode. Nevertheless, at that assessment, probands had a higher prevalence of regular smoking (odds ratio [OR] = 12.54, 95% confidence interval [CI] = 4.36-36.12) and were less physically active than controls (OR = 0.59, CI = 0.43-0.81) and siblings (OR = 0.70, CI = 0.52-0.94) and had a higher rate of obesity than did controls (OR = 3.67, CI = 1.42-9.52). Parents of probands reported high rates of CVD (significantly higher than did parents of controls), including myocardial infarction and CVD-related hospitalization (ORs = 1.62-4.36, CIs = 1.03-15.40). Differences in CVD risk factors between probands and controls were independent of parental CVD. CONCLUSIONS: Major depression in childhood is associated with an unfavorable CVD risk profile in adolescence, and risks for pediatric depression and CVD may coincide in families. Effective prevention and treatment of childhood depression may be a means to reduce the incidence of adult CVD. © 2014 by the American Psychosomatic Society.

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