TY  - JOUR
A1  - Rutten, BPF
A1  - Vermetten, E
A1  - Vinkers, CH
A1  - Ursini, G
A1  - Daskalakis, NP
A1  - Pishva, E
A1  - de Nijs, L
A1  - Houtepen, LC
A1  - Eijssen, L
A1  - Jaffe, AE
A1  - Kenis, G
A1  - Viechtbauer, W
A1  - van den Hove, D
A1  - Schraut, KG
A1  - Lesch, K-P
A1  - Kleinman, JE
A1  - Hyde, TM
A1  - Weinberger, DR
A1  - Schalkwyk, L
A1  - Lunnon, K
A1  - Mill, J
A1  - Cohen, H
A1  - Yehuda, R
A1  - Baker, DG
A1  - Maihofer, AX
A1  - Nievergelt, CM
A1  - Geuze, E
A1  - Boks, MPM
T1  - Longitudinal analyses of the DNA methylome in deployed military servicemen identify susceptibility loci for post-traumatic stress disorder
JF  - Molecular Psychiatry
N2  - In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n = 93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions. Evidence for mediation of the relation between combat trauma and PTSD symptoms by longitudinal changes in DNA methylation was observed at several positions and regions. Bioinformatic analyses of the reported associations identified significant enrichment in several pathways relevant for symptoms of PTSD. Targeted analyses of the significant findings from the discovery sample in an independent prospective cohort of male US marines (n = 98) replicated the observed relation between decreases in DNA methylation levels and PTSD symptoms at genomic regions in ZFP57, RNF39 and HIST1H2APS2. Together, our study pinpoints three novel genomic regions where longitudinal decreases in DNA methylation across the period of exposure to combat trauma marks susceptibility for PTSD.
KW  - Molecular biology
KW  - Psychiatric disorders
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227171
VL  - 23
IS  - 5
ER  - 
TY  - JOUR
A1  - Leibold, NK
A1  - van den Hove, DLA
A1  - Viechtbauer, W
A1  - Buchanan, GF
A1  - Goossens, L
A1  - Lange, I
A1  - Knuts, I
A1  - Lesch, KP
A1  - Steinbusch, HWM
A1  - Schruers, KRJ
T1  - CO\(_{2}\) exposure as translational cross-species experimental model for panic
JF  - Translational Psychiatry
N2  - The current diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders are being challenged by the heterogeneity and the symptom overlap of psychiatric disorders. Therefore, a framework toward a more etiology-based classification has been initiated by the US National Institute of Mental Health, the research domain criteria project. The basic neurobiology of human psychiatric disorders is often studied in rodent models. However, the differences in outcome measurements hamper the translation of knowledge. Here, we aimed to present a translational panic model by using the same stimulus and by quantitatively comparing the same outcome measurements in rodents, healthy human subjects and panic disorder patients within one large project. We measured the behavioral–emotional and bodily response to CO\(_{2}\) exposure in all three samples, allowing for a reliable cross-species comparison. We show that CO\(_{2}\) exposure causes a robust fear response in terms of behavior in mice and panic symptom ratings in healthy volunteers and panic disorder patients. To improve comparability, we next assessed the respiratory and cardiovascular response to CO\(_{2}\), demonstrating corresponding respiratory and cardiovascular effects across both species. This project bridges the gap between basic and human research to improve the translation of knowledge between these disciplines. This will allow significant progress in unraveling the etiological basis of panic disorder and will be highly beneficial for refining the diagnostic categories as well as treatment strategies.
KW  - translational panic model
KW  - CO\(_{2}\) exposure
KW  - humans
KW  - mice
KW  - panic disorder
KW  - cross-species comparison
KW  - fear response
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168308
VL  - 6
IS  - e885
ER  -