ABSTRACT
The gene known as Disrupted-in-Schizophrenia-1, DISC1, was originally discovered in a large family, in which it also co-segregated with bipolar affective disorder (BD) and with major depressive disorder (MDD). The TSNAX (Translin-associated factor X) gene, located immediately upstream of DISC1, has also been suggested as a candidate gene in relation to psychiatric illness, as one transcript resulting from intergenic splicing encodes a novel TSNAX-DISC1 fusion protein. We explored the TSNAX-DISC1 gene region for an association with BD and MDD in a sample of 1984 patients (1469 MDD, 515 BD) and 1376 ethnically matched controls. Eight single nucleotide polymorphisms (SNPs) within the TSNAX-DISC1 region (rs766288, rs3738401, rs2492367, rs6675281, rs12133766, rs1000731, rs7546310 and rs821597) were investigated using the SNPlex Genotyping System. We found a significant allelic and genotypic association of the TSNAX-DISC1 gene region with BD, whereas a haplotypic association was found for both BD and MDD. Therefore, our results suggest an association between the TSNAX-DISC1 region and both forms of affective disorders, and support the hypothesis that a portion of the genotypic overlap between schizophrenia and affective disorders is attributable to this gene.
Subject(s)
Bipolar Disorder/genetics , DNA-Binding Proteins/genetics , Depression/genetics , Genetic Predisposition to Disease , Nerve Tissue Proteins/genetics , Polymorphism, Single Nucleotide/genetics , Adult , Case-Control Studies , Female , Gene Frequency , Genome-Wide Association Study/methods , Genotype , Humans , Male , Middle AgedABSTRACT
The Neuregulin 1 (NRG1) gene was initially implicated in schizophrenia (SZ) and has recently been associated with bipolar disorder (BPD) in two studies. An association with major depressive disorder (MDD) has not yet been investigated but is warranted in view of the genetic overlap between MDD and BPD. We have performed a large-scale case-control study investigating the association between NRG1 polymorphisms and MDD, genotyping a selection of 14 single nucleotide polymorphisms (SNPs) spanning the NRG1 gene in a sample of 1,398 patients of White European ancestry with a diagnosis of MDD and 1,304 ethnically matched controls from three clinical sites in the UK. We found no single marker or haplotype associations that withstood correction for multiple testing. Our findings do not provide evidence that NRG1 plays a role in MDD or that this gene explains part of the genetic overlap with BPD.
Subject(s)
Depressive Disorder, Major/genetics , Neuregulin-1/genetics , Case-Control Studies , Europe , Genetic Markers , Humans , Polymorphism, Single Nucleotide , Recurrence , United KingdomABSTRACT
We study the decay of high spin mesons using the gauge-string theory correspondence. The rate of the process is calculated by studying the splitting of a macroscopic string intersecting a D-brane. The result is applied to the decay of mesons in N=4 super Yang-Mills theory with a small number of flavors and in a gravity dual of large N QCD. In QCD the decay of high spin mesons is found to be heavily suppressed in the regime of validity of the supergravity description.
ABSTRACT
In several reports, the acute oral administration of the partial serotonergic agonist meta-chlorophenylpiperazine (mCPP) in dose of 0. 5 mg/kg induced a significant worsening of obsessive-compulsive (OC) symptoms in a number of patients. The aim of our study was to test the 0.25 mg/kg mCPP dose, which was hypothesized to be more specific for OC symptoms and was until now tested only on healthy subjects. In a double-blind, controlled crossover study, 12 OC patients participated on three test days, receiving one of the following on each day: oral 0.5 mg/kg mCPP (standard dose), 0.25 mg/kg mCPP (low dose), or placebo. Behavioral ratings were obtained by means of Visual Analogue Scale (VAS) ratings. The low dose mCPP induced a significant worsening of OC symptoms in 50% (6/12) of the patients, whereas 8.3% (1/12) of the patients showed a worsening after the standard dose. On the other hand, only the standard dose mCPP induced a worsening, although not statistically significant, of anxiety ratings. Our data show that the 0.25 mg/kg dose mCPP induces a specific response in OC symptoms, with little anxiogenic effect. To confirm these preliminary data, future studies will be needed on larger samples and with more sensitive rating scales.
Subject(s)
Obsessive-Compulsive Disorder/drug therapy , Piperazines/administration & dosage , Piperazines/adverse effects , Serotonin Receptor Agonists/administration & dosage , Serotonin Receptor Agonists/adverse effects , Adult , Affect/drug effects , Anxiety/drug therapy , Behavior/drug effects , Behavior/physiology , Cross-Over Studies , Disease Progression , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Male , Serotonin/metabolism , Treatment OutcomeABSTRACT
Examples of ethical dilemmas, emerging in the context of a resident case-centered seminar, are used to illustrate a proposed approach to instruction in ethics for child and adolescent psychiatry residents. In addition to a rudimentary formal didactic curriculum, a teaching methodology is outlined that intentionally focuses on ethical problems, approaches to analyses, proposed courses of action, and attempts at resolution. Four representative issues are utilized: confidentiality, treatment refusal, treatment termination, and the interface of individual and family therapies. Educational objectives include the increased recognition by child and adolescent psychiatry trainees of potential ethical conflicts, of the utility of ethical analyses to inform choices of clinical interventions, and of the desirability of forestalling premature action before attempts at thoughtful resolution.
