Showing papers by "Eduard Maron published in 2013"

Unedited in vivo detection and quantification of γ-aminobutyric acid in the occipital cortex using short-TE MRS at 3 T.

Abstract: Short-TE MRS has been proposed recently as a method for the in vivo detection and quantification of gamma-aminobutyric acid (GABA) in the human brain at 3 T. In this study, we investigated the accuracy and reproducibility of short-TE MRS measurements of GABA at 3 T using both simulations and experiments. LCModel analysis was performed on a large number of simulated spectra with known metabolite input concentrations. Simulated spectra were generated using a range of spectral linewidths and signal-to-noise ratios to investigate the effect of varying experimental conditions, and analyses were performed using two different baseline models to investigate the effect of an inaccurate baseline model on GABA quantification. The results of these analyses indicated that, under experimental conditions corresponding to those typically observed in the occipital cortex, GABA concentration estimates are reproducible (mean reproducibility error, <20%), even when an incorrect baseline model is used. However, simulations indicate that the accuracy of GABA concentration estimates depends strongly on the experimental conditions (linewidth and signal-to-noise ratio). In addition to simulations, in vivo GABA measurements were performed using both spectral editing and short-TE MRS in the occipital cortex of 14 healthy volunteers. Short-TE MRS measurements of GABA exhibited a significant positive correlation with edited GABA measurements (R = 0.58, p < 0.05), suggesting that short-TE measurements of GABA correspond well with measurements made using spectral editing techniques. Finally, within-session reproducibility was assessed in the same 14 subjects using four consecutive short-TE GABA measurements in the occipital cortex. Across all subjects, the average coefficient of variation of these four GABA measurements was 8.7 +/- 4.9%. This study demonstrates that, under some experimental conditions, short-TE MRS can be employed for the reproducible detection of GABA at 3 T, but that the technique should be used with caution, as the results are dependent on the experimental conditions. Copyright (c) 2013 John Wiley & Sons, Ltd.

Whole-exome sequencing identifies a polymorphism in the BMP5 gene associated with SSRI treatment response in major depression

Abstract: Although antidepressants are widely used in the pharmacotherapy of major depressive disorder (MDD), their efficacy is still insufficient as approximately one-third of the patients do not fully recover even after several treatment trials. Inter-individual genetic differences are thought to contribute to the variability in antidepressant response; however, current findings from pharmacogenetic studies are uncertain or not clearly replicated. Here we report the first application of full exome sequencing for the analysis of pharmacogenomics on antidepressant treatment. After 12 weeks of treatment with the selective serotonin re-uptake inhibitor escitalopram, we selected five clear responders and five clear non-responders for exome sequencing. By comparing the allele counts of previously known single nucleotide polymorphisms and novel polymorphisms we selected 38 markers for further genotyping in two independent patient samples treated with escitalopram (n=116 and n=394). The A allele, carried by approximately 30% of the patients with MDD, of rs41271330 in the bone morphogenetic protein (BMP5) gene showed strong association with worse treatment response in both sample sets (p=0.001), indicating that this is an promising pharmacogenetic marker for prediction of antidepressant therapeutic outcome.

Genetic factors in anxiety disorders.

Abstract: Presently available clinical genetic studies point to a considerable heritability of anxiety disorders (30-67%), with multiple vulnerability genes such as 5-HT1A, 5-HTT, MAO-A, COMT, CCK-B, ADORA2A, CRHR1, FKBP5, ACE, RGS2/7 and NPSR1 suggested by molecular genetic association studies. These genes have been shown to partially interact with each other as well as with environmental factors to shape the overall disease risk in a complex genetic model. Additionally, recent studies have pointed out the crucial role of epigenetic signatures such as methylation patterns in modifying environmental influences as well as in driving the functional impact of anxiety disorder risk genes. On a systems level, vulnerability genes of anxiety disorders seem to confer some of the disease risk via intermediate phenotypes like behavioral inhibition, anxiety sensitivity or several neurobiological traits such as increased startle reactivity or dysfunctional corticolimbic activity during emotional processing. Finally, first pharmaco- and psychotherapy-genetic studies provide evidence for certain risk genes to confer interindividual variability in response to a pharmacological or psychotherapeutic intervention in anxiety disorders. Genetic research in anxiety disorders will be discussed regarding its potential to foster innovative and individually tailored therapeutic approaches for patients with anxiety disorders.

Subjective Well-Being Under Neuroleptics Scale short form (SWN-K): reliability and validity in an Estonian speaking sample

Abstract: Background The Subjective Well-Being Under Neuroleptic Treatment Scale short form (SWN-K) is a self-rating scale developed to measure mentally ill patients' well-being under the antipsychotic drug treatment. This paper reports on adaptation and psychometric properties of the instrument in an Estonian psychiatric sample.

Genetics of Panic Disorder

Abstract: The molecular genetic research on panic disorder (PD) has grown tremendously in the past decade. To date, several hundreds of candidate genes have been examined in association studies, but most of the results have been negative, inconsistent or awaiting replication. Perhaps most intriguing have been findings involving the genes of biological systems known to be pertinent to anxiety phenotypes, such as serotonin, cholecystokinin and adenosine. An array of other genes related to hormonal, neurotrophic and intracellular systems has also been implicated in disposition to PD. The recent advances in bioinformatics and genotyping technologies, including genome-wide association and gene expression methods, promise more comprehensive discovery in PD. Preliminary findings point to a number of novel gene targets with still unknown pathogenetic relationship to PD. The progress in clinical and neurobiological concepts of PD may further guide genetic research through the current ambiguity to more definitive findings. Key Concepts: The linkage and candidate gene association studies have so far showed only weak success to identify reliable and replicated evidence for the genetic substrate of PD. The genetic research in PD to date has been mostly restricted to small phenotypically and ethnically diverse datasets with genotyping of limited numbers of SNPs. An improved understanding of neurobiological pathways of PD could contribute to a more effective identification of candidate genes. Novel conceptual and analytic approaches, such as pathways-based analyses, may help to advance GWA studies in PD. Laboratory panic challenge models may provide clues to genetic predisposition to PD. The understanding of genetic underpinnings of PD will not be of full value without a conceptual integration of the clinical phenomena of PD with psychological models and neurobiological or molecular substrates underlying its development and course. The course of PD may depend on the balance between pathogenetic and compensatory or recovery processes, accompanied by activation or inhibition of relevant genes. PD might exist in many distinct genetic forms, each with a different set of genes, but also in one form with certain genes reflecting broader vulnerability to panicogenesis. The heterogeneity in PD phenotypes, age of onset, subtypes and severity of panic attacks, gender and familial aggregation were not sufficiently accounted for in most of published studies and should be more carefully addressed in further analyses. Other comprehensive genetic approaches, including GWA, the analysis of copy number variants and the study of regulatory small noncoding RNAs, may lead to uncovering new genomic mechanisms of PD. Keywords: panic disorder; anxiety; gene; polymorphism; association; genome wide

A method and a kit to predict response to antidepressant treatment

Abstract: The present invention relates to the method for predicting the pharmacoresponse of antidepressants in patients diagnosed with major depression and panic disorder. According to the invention, SNP (rs41271330) in the coding region of the BMP5 gene together with the markers in linkage disequilibrium with this SNP could be used as predictors of SSRI treatment efficacy. The knowledge obtained by using the method disclosed in present invention has potential to increase the efficacy of pharmacological treatment in patients with major depression and panic disorder. The invention also provides a kit for detecting individual who are likely to respond to antidepressant treatment.