TY  - JOUR
A1  - Prelog, Martina
A1  - Hilligardt, Deborah
A1  - Schmidt, Christian A.
A1  - Przybylski, Grzegorz K.
A1  - Leierer, Johannes
A1  - Almanzar, Giovanni
A1  - El Hajj, Nady
A1  - Lesch, Klaus-Peter
A1  - Arolt, Volker
A1  - Zwanzger, Peter
A1  - Haaf, Thomas
A1  - Domschke, Katharina
T1  - Hypermethylation of FOXP3 Promoter and Premature Aging of the Immune System in Female Patients with Panic Disorder?
JF  - PLoS ONE
N2  - Immunological abnormalities associated with pathological conditions, such as higher infection rates, inflammatory diseases, cancer or cardiovascular events are common in patients with panic disorder. In the present study, T cell receptor excision circles (TRECs), Forkhead-Box-Protein P3 gene (FOXP3) methylation of regulatory T cells (Tregs) and relative telomere lengths (RTLs) were investigated in a total and subsamples of 131 patients with panic disorder as compared to 131 age- and sex-matched healthy controls in order to test for a potential dysfunction and premature aging of the immune system in anxiety disorders. Significantly lower TRECs (p = 0.004) as well as significant hypermethylation of the FOXP3 promoter region (p = 0.005) were observed in female (but not in male) patients with panic disorder as compared to healthy controls. No difference in relative telomere length was discerned between patients and controls, but significantly shorter telomeres in females, smokers and older persons within the patient group. The presently observed reduced TRECs in panic disorder patients and FOXP3 hypermethylation in female patients with panic disorder potentially reflect impaired thymus and immunosuppressive Treg function, which might partly account for the known increased morbidity and mortality of anxiety disorders conferred by e.g. cancer and cardiovascular disorders.
KW  - DNA methylation
KW  - antidepressants
KW  - regulatory T cells
KW  - panic disorder
KW  - treatment guidelines
KW  - telomere length
KW  - inflammatory diseases
KW  - anxiety disorders
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-179684
VL  - 11
IS  - 6
ER  - 
TY  - JOUR
A1  - Weidner, Magdalena T.
A1  - Lardenoije, Roy
A1  - Eijssen, Lars
A1  - Mogavero, Floriana
A1  - De Groodt, Lilian P. M. T.
A1  - Popp, Sandy
A1  - Palme, Rupert
A1  - Förstner, Konrad U.
A1  - Strekalova, Tatyana
A1  - Steinbusch, Harry W. M.
A1  - Schmitt-Böhrer, Angelika G.
A1  - Glennon, Jeffrey C.
A1  - Waider, Jonas
A1  - van den Hove, Daniel L. A.
A1  - Lesch, Klaus-Peter
T1  - Identification of cholecystokinin by genome-wide profiling as potential mediator of serotonin-dependent behavioral effects of maternal separation in the amygdala
JF  - Frontiers in Neuroscience
N2  - Converging evidence suggests a role of serotonin (5-hydroxytryptamine, 5-HT) and tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme of 5-HT synthesis in the brain, in modulating long-term, neurobiological effects of early-life adversity. Here, we aimed at further elucidating the molecular mechanisms underlying this interaction, and its consequences for socio-emotional behaviors, with a focus on anxiety and social interaction. In this study, adult, male Tph2 null mutant (Tph2\(^{-/-}\)) and heterozygous (Tph2\(^{+/-}\)) mice, and their wildtype littermates (Tph2\(^{+/+}\)) were exposed to neonatal, maternal separation (MS) and screened for behavioral changes, followed by genome-wide RNA expression and DNA methylation profiling. In Tph2\(^{-/-}\) mice, brain 5-HT deficiency profoundly affected socio-emotional behaviors, i.e., decreased avoidance of the aversive open arms in the elevated plus-maze (EPM) as well as decreased prosocial and increased rule breaking behavior in the resident-intruder test when compared to their wildtype littermates. Tph2\(^{+/-}\) mice showed an ambiguous profile with context-dependent, behavioral responses. In the EPM they showed similar avoidance of the open arm but decreased prosocial and increased rule breaking behavior in the resident-intruder test when compared to their wildtype littermates. Notably, MS effects on behavior were subtle and depended on the Tph2 genotype, in particular increasing the observed avoidance of EPM open arms in wildtype and Tph2\(^{+/-}\) mice when compared to their Tph2\(^{-/-}\) littermates. On the genomic level, the interaction of Tph2 genotype with MS differentially affected the expression of numerous genes, of which a subset showed an overlap with DNA methylation profiles at corresponding loci. Remarkably, changes in methylation nearby and expression of the gene encoding cholecystokinin, which were inversely correlated to each other, were associated with variations in anxiety-related phenotypes. In conclusion, next to various behavioral alterations, we identified gene expression and DNA methylation profiles to be associated with TPH2 inactivation and its interaction with MS, suggesting a gene-by-environment interaction-dependent, modulatory function of brain 5-HT availability.
KW  - serotonin
KW  - maternal separation
KW  - mouse
KW  - emotional behavior
KW  - DNA methylation
KW  - RNA expression
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201340
VL  - 13
ER  -