Publications (6)30.1 Total impact
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Article: TMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies.
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ABSTRACT: The lifetime prevalence of panic disorder (PD) is up to 4% worldwide and there is substantial evidence that genetic factors contribute to the development of PD. Single-nucleotide polymorphisms (SNPs) in TMEM132D, identified in a whole-genome association study (GWAS), were found to be associated with PD in three independent samples, with a two-SNP haplotype associated in each of three samples in the same direction, and with a P-value of 1.2e-7 in the combined sample (909 cases and 915 controls). Independent SNPs in this gene were also associated with the severity of anxiety symptoms in patients affected by PD or panic attacks as well as in patients suffering from unipolar depression. Risk genotypes for PD were associated with higher TMEM132D mRNA expression levels in the frontal cortex. In parallel, using a mouse model of extremes in trait anxiety, we could further show that anxiety-related behavior was positively correlated with Tmem132d mRNA expression in the anterior cingulate cortex, central to the processing of anxiety/fear-related stimuli, and that in this animal model a Tmem132d SNP is associated with anxiety-related behavior in an F2 panel. TMEM132D may thus be an important new candidate gene for PD as well as more generally for anxiety-related behavior.Molecular psychiatry 04/2010; 16(6):647-63. · 15.05 Impact Factor -
Article: Proteomic-based genotyping in a mouse model of trait anxiety exposes disease-relevant pathways.
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ABSTRACT: In our biomarker identification efforts, we have reported earlier on a protein that differs in its electrophoretic mobility between mouse lines bred either for high or low trait anxiety. The altered electrophoretic behavior of enolase phosphatase (EP) is now identified to be caused by two single-nucleotide polymorphisms. In both cases, the genetic polymorphism introduces an amino acid change in the protein's sequence resulting in differential mobility on SDS gels. This was shown by recombinantly expressing the two EP isoforms. Functional studies indicate that the EP isoform from the high anxiety mouse line has a lower enzymatic activity than does its low anxiety mouse counterpart. EP is a member of the methionine salvage pathway that is responsible for the synthesis of S-adenosyl-L-methionine, a natural compound with potential antidepressant activities. In addition, it is linked to the polyamine pathway whose members have functions in anxiety/depression-related behaviors. In a freely-segregating F2 panel, both single-nucleotide polymorphisms were significantly associated with locomotion-independent trait anxiety, further supporting a functional role of EP for this phenotype. The study shows that proteomic analysis can reveal genotypic differences relevant for the phenotype. The identified protein alterations, in turn, can expose metabolic pathways pertinent to the behavioral phenotype.Molecular psychiatry 02/2009; 15(7):702-11. · 15.05 Impact Factor -
Article: Proteomic genotyping in a mouse model of trait anxiety exposes disease relevant pathways
Pharmacopsychiatry, v.42, 215-216 (2009). -
Article: Proteomic-based genotyping in a mouse model of trait anxiety exposes disease-relevant pathways
Molecular Psychiatry, v.15, 702-711 (2010). -
Article: A Hypomorphic Vasopressin Allele Prevents Anxiety-Related Behavior
PLoS ONE, v.4 (2009). -
Article: Genome-Wide Gene-Expression Profiles Following Glucocorticoid Stimulation Associated with Major Depression
Biological Psychiatry, v.67, 129S-129S (2010).
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Institutions
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2009
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Max-Planck-Institut für Psychiatrie
München, Bavaria, Germany
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