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27 results on '"Domschke K."'

1. ENIGMA-anxiety working group: Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Author

Bas-Hoogendam, J. M., Groenewold, N. A., Aghajani, M., Freitag, G. F., Harrewijn, A., Hilbert, K., Jahanshad, N., Thomopoulos, S. I., Thompson, P. M., Veltman, D. J., Winkler, A. M., Lueken, U., Pine, D. S., van der Wee, N. J. A., Stein, D. J., Agosta, F., Ahs, F., An, I., Alberton, B. A. V., Andreescu, C., Asami, T., Assaf, M., Avery, S. N., Nicholas, L., Balderston, Barber, J. P., Battaglia, M., Bayram, A., Beesdo-Baum, K., Benedetti, F., Berta, R., Bjorkstrand, J., Blackford, J. U., Blair, J. R., Karina, S., Blair, Boehme, S., Brambilla, P., Burkhouse, K., Cano, M., Canu, E., Cardinale, E. M., Cardoner, N., Clauss, J. A., Cividini, C., Critchley, H. D., Udo, Dannlowski, Deckert, J., Demiralp, T., Diefenbach, G. J., Domschke, K., Doruyter, A., Dresler, T., Erhardt, A., Fallgatter, A. J., Fananas, L., Brandee, Feola, Filippi, C. A., Filippi, M., Fonzo, G. A., Forbes, E. E., Fox, N. A., Fredrikson, M., Furmark, T., Ge, T., Gerber, A. J., Gosnell, S. N., Grabe, H. J., Grotegerd, D., Gur, R. E., Gur, R. C., Harmer, C. J., Harper, J., Heeren, A., Hettema, J., Hofmann, D., Hofmann, S. G., Jackowski, A. P., Andreas, Jansen, Kaczkurkin, A. N., Kingsley, E., Kircher, T., Kosti c, M., Kreifelts, B., Krug, A., Larsen, B., Lee, S. -H., Leehr, E. J., Leibenluft, E., Lochner, C., Maggioni, E., Makovac, E., Mancini, M., Manfro, G. G., Mansson, K. N. T., Meeten, F., Michalowski, J., Milrod, B. L., Muhlberger, A., Lilianne, R., Mujica-Parodi, Munjiza, A., Mwangi, B., Myers, M., Igor Nenadi, C., Neufang, S., Nielsen, J. A., Oh, H., Ottaviani, C., Pan, P. M., Pantazatos, S. P., Martin, P., Paulus, Perez-Edgar, K., Penate, W., Perino, M. T., Peterburs, J., Pfleiderer, B., Phan, K. L., Poletti, S., Porta-Casteras, D., Price, R. B., Pujol, J., Andrea, Reinecke, Rivero, F., Roelofs, K., Rosso, I., Saemann, P., Salas, R., Salum, G. A., Satterthwaite, T. D., Schneier, F., Schruers, K. R. J., Schulz, S. M., Schwarzmeier, H., Seeger, F. R., Smoller, J. W., Soares, J. C., Stark, R., Stein, M. B., Straube, B., Straube, T., Strawn, J. R., Suarez-Jimenez, B., Boris, Suchan, Sylvester, C. M., Talati, A., Tamburo, E., Tukel, R., van den Heuvel, O. A., Van der Auwera, S., van Nieuwenhuizen, H., van Tol, M. -J., van Velzen, L. S., Bort, C. V., Vermeiren, R. R. J. M., Visser, R. M., Volman, I., Wannemuller, A., Wendt, J., Werwath, K. E., Westenberg, P. M., Wiemer, J., Katharina, Wittfeld, M. -J., Wu, Yang, Y., Zilverstand, A., Zugman, A., Zwiebel, H. L., Bas-Hoogendam, J. M., Groenewold, N. A., Aghajani, M., Freitag, G. F., Harrewijn, A., Hilbert, K., Jahanshad, N., Thomopoulos, S. I., Thompson, P. M., Veltman, D. J., Winkler, A. M., Lueken, U., Pine, D. S., van der Wee, N. J. A., Stein, D. J., ENIGMA-anxiety working, Group, Filippi, M, and UCL - SSH/IPSY - Psychological Sciences Research Institute

Subjects
Córtex pré-frontal, Review Article, Anxiety, Prefrontal cortex, Specific phobia, 0302 clinical medicine, limbic system, magnetic resonance imaging, Multicenter Studies as Topic, genetics, Review Articles, prefrontal cortex, neuroimaging, Radiological and Ultrasound Technology, 05 social sciences, Social anxiety, amygdala, Amygdala, Anxiety Disorders, Transtornos de ansiedade, Neurology, multicentric network, Anatomy, medicine.symptom, Psychology, Neurovetenskaper, Clinical psychology, endocrine system, Generalized anxiety disorder, brain, Neuroimaging, Sistema límbico, 050105 experimental psychology, 03 medical and health sciences, Global mental health, Limbic system, Magnetic resonance imaging, Imatges per ressonància magnètica, medicine, Genetics, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Neuroimagem, Psykologi (exklusive tillämpad psykologi), Panic disorder, neurosciences, Imageamento por ressonância magnética, Tonsila do cerebelo, medicine.disease, anxiety disorders, Genética, Psychology (excluding Applied Psychology), Ansietat, Neurology (clinical), Working group, 030217 neurology & neurosurgery, Anxiety disorders
Abstract

Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA‐Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders., Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.

Published
2020

2. Genetic comorbidity between major depression and cardio-metabolic traits, stratified by age at onset of major depression

Author

Hagenaars, SP, Coleman, JR, Choi, SW, Gaspar, H, Adams, MJ, Howard, DM, Hodgson, K, Traylor, M, Air, TM, Andlauer, TFM, Arolt, V, Baune, BT, Binder, EB, Blackwood, DHR, Boomsma, D, Campbell, A, Cearns, M, Czamara, D, Dannlowski, U, Domschke, K, de Geus, EJC, Hamilton, SP, Hayward, C, Hickie, IB, Hottenga, JJ, Ising, M, Jones, I, Jones, L, Kutalik, Z, Lucae, S, Martin, NG, Milaneschi, Y, Mueller-Myhsok, B, Owen, MJ, Padmanabhan, S, Penninx, BWJH, Pistis, G, Porteous, DJ, Preisig, M, Ripke, S, Shyn, S, Sullivan, PF, Whitfield, JB, Wray, NR, McIntosh, AM, Deary, IJ, Breen, G, Lewis, CM, Hagenaars, SP, Coleman, JR, Choi, SW, Gaspar, H, Adams, MJ, Howard, DM, Hodgson, K, Traylor, M, Air, TM, Andlauer, TFM, Arolt, V, Baune, BT, Binder, EB, Blackwood, DHR, Boomsma, D, Campbell, A, Cearns, M, Czamara, D, Dannlowski, U, Domschke, K, de Geus, EJC, Hamilton, SP, Hayward, C, Hickie, IB, Hottenga, JJ, Ising, M, Jones, I, Jones, L, Kutalik, Z, Lucae, S, Martin, NG, Milaneschi, Y, Mueller-Myhsok, B, Owen, MJ, Padmanabhan, S, Penninx, BWJH, Pistis, G, Porteous, DJ, Preisig, M, Ripke, S, Shyn, S, Sullivan, PF, Whitfield, JB, Wray, NR, McIntosh, AM, Deary, IJ, Breen, G, and Lewis, CM

Abstract

It is imperative to understand the specific and shared etiologies of major depression and cardio-metabolic disease, as both traits are frequently comorbid and each represents a major burden to society. This study examined whether there is a genetic association between major depression and cardio-metabolic traits and if this association is stratified by age at onset for major depression. Polygenic risk scores analysis and linkage disequilibrium score regression was performed to examine whether differences in shared genetic etiology exist between depression case control status (N cases = 40,940, N controls = 67,532), earlier (N = 15,844), and later onset depression (N = 15,800) with body mass index, coronary artery disease, stroke, and type 2 diabetes in 11 data sets from the Psychiatric Genomics Consortium, Generation Scotland, and UK Biobank. All cardio-metabolic polygenic risk scores were associated with depression status. Significant genetic correlations were found between depression and body mass index, coronary artery disease, and type 2 diabetes. Higher polygenic risk for body mass index, coronary artery disease, and type 2 diabetes was associated with both early and later onset depression, while higher polygenic risk for stroke was associated with later onset depression only. Significant genetic correlations were found between body mass index and later onset depression, and between coronary artery disease and both early and late onset depression. The phenotypic associations between major depression and cardio-metabolic traits may partly reflect their overlapping genetic etiology irrespective of the age depression first presents.

Published
2020

3. The role of BDNF methylation and Val66Met in amygdala reactivity during emotion processing

Author

Redlich, R, Schneider, I, Kerkenberg, N, Opel, N, Bauhaus, J, Enneking, V, Repple, J, Leehr, EJ, Grotegerd, D, Kaehler, C, Foerster, K, Dohm, K, Meinert, S, Hahn, T, Kugel, H, Schwarte, K, Schettler, C, Domschke, K, Arolt, V, Heindel, W, Baune, BT, Zhang, W, Hohoff, C, Dannlowski, U, Redlich, R, Schneider, I, Kerkenberg, N, Opel, N, Bauhaus, J, Enneking, V, Repple, J, Leehr, EJ, Grotegerd, D, Kaehler, C, Foerster, K, Dohm, K, Meinert, S, Hahn, T, Kugel, H, Schwarte, K, Schettler, C, Domschke, K, Arolt, V, Heindel, W, Baune, BT, Zhang, W, Hohoff, C, and Dannlowski, U

Abstract

Epigenetic alterations of the brain-derived neurotrophic factor (BDNF) gene have been associated with psychiatric disorders in humans and with differences in amygdala BDNF mRNA levels in rodents. This human study aimed to investigate the relationship between the functional BDNF-Val66 Met polymorphism, its surrounding DNA methylation in BDNF exon IX, amygdala reactivity to emotional faces, and personality traits. Healthy controls (HC, n = 189) underwent functional MRI during an emotional face-matching task. Harm avoidance, novelty seeking and reward dependence were measured using the Tridimensional Personality Questionnaire (TPQ). Individual BDNF methylation profiles were ascertained and associated with several BDNF single nucleotide polymorphisms surrounding the BDNF-Val66 Met, amygdala reactivity, novelty seeking and harm avoidance. Higher BDNF methylation was associated with higher amygdala reactivity (x = 34, y = 0, z = -26, t(166) = 3.00, TFCE = 42.39, p(FWE) = .045), whereby the BDNF-Val66 Met genotype per se did not show any significant association with brain function. Furthermore, novelty seeking was negatively associated with BDNF methylation (r = -.19, p = .015) and amygdala reactivity (r = -.17, p = .028), while harm avoidance showed a trend for a positive association with BDNF methylation (r = .14, p = .066). The study provides first insights into the relationship among BDNF methylation, BDNF genotype, amygdala reactivity and personality traits in humans, highlighting the multidimensional relations among genetics, epigenetics, and neuronal functions. The present study suggests a possible involvement of epigenetic BDNF modifications in psychiatric disorders and related brain functions, whereby high BDNF methylation might reduce BDNF mRNA expression and upregulate amygdala reactivity.

Published
2020

4. Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy

Author

Foo, J.C., Streit, F., Frank, J., Witt, S.H., Treutlein, J., Baune, B.T., Moebus, S., Jockel, K.H., Forstner, A.J., Nothen, M.M., Rietschel, M., Sartorius, A., Kranaster, L., Wray, N.R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E.M., Abdellaoui, A., Adams, M.J., Agerbo, E., Air, T.M., Andlauer, T.F.M., Bacanu, S.A., Baekvad-Hansen, M., Beekman, A.T.F., Bigdeli, T.B., Binder, E.B., Blackwood, D.H.R., Bryois, J., Buttenschon, H.N., Bybjerg-Grauholm, J., Cai, N., Castelao, E., Christensen, J.H., Clarke, T.K., Coleman, J.R.I., Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Crawford, G.E., Davies, G., Deary, I.J., Degenhardt, F., Derks, E.M., Direk, N., Dolan, C.V., Dunn, E.C., Eley, T.C., Escott-Price, V., Kiadeh, F.F.H., Finucane, H.K., Gaspar, H.A., Gill, M., Goes, F.S., Gordon, S.D., Grove, J., Hall, L.S., Hansen, C.S., Hansen, T.F., Herms, S., Hickie, I.B., Hoffmann, P., Homuth, G., Horn, C., Hottenga, J.J., Hougaard, D.M., Ising, M., Jansen, R., Jones, I., Jones, L.A., Jorgenson, E., Knowles, J.A., Kohane, I.S., Kraft, J., Kretzschmar, W.W., Krogh, J., Kutalik, Z., Li, Y.H., Lind, P.A., MacIntyre, D.J., MacKinnon, D.F., Maier, R.M., Maier, W., Marchini, J., Mbarek, H., McGrath, P., McGuffin, P., Medland, S.E., Mehta, D., Middeldorp, C.M., Mihailov, E., Milaneschi, Y., Milani, L., Mondimore, F.M., Montgomery, G.W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M.G., Nyholt, D.R., O'Reilly, P.F., Oskarsson, H., Owen, M.J., Painter, J.N., Pedersen, C.B., Pedersen, M.G., Peterson, R.E., Pettersson, E., Peyrot, W.J., Pistis, G., Posthuma, D., Quiroz, J.A., Qvist, P., Rice, J.P., Riley, B.P., Rivera, M., Mirza, S.S., Schoevers, R., Schulte, E.C., Shen, L., Shi, J.X., Shyn, S.I., Sigurdsson, E., Sinnamon, G.C.B., Smit, J.H., Smith, D.J., Stefansson, H., Steinberg, S., Strohmaier, J., Tansey, K.E., Teismann, H., Teumer, A., Thompson, W., Thomson, P.A., Thorgeirsson, T.E., Traylor, M., Trubetskoy, V., Uitterlinden, A.G., Umbricht, D., Auwera, S. van der, Hemert, A.M. van, Viktorin, A., Visscher, P.M., Wang, Y., Webb, B.T., Weinsheimer, S.M., Wellmann, J., Willemsen, G., Wu, Y., Xi, H.L.S., Yang, J., Zhang, F.T., Arolt, V., Berger, K., Boomsma, D.I., Cichon, S., Dannlowski, U., Geus, E.J.C. de, DePaulo, J.R., Domenici, E., Domschke, K., Esko, T., Grabe, H.J., Hamilton, S.P., Hayward, C., Heath, A.C., Kendler, K.S., Kloiber, S., Lewis, G., Li, Q.Q.S., Lucae, S., Madden, P.A.F., Magnusson, P.K., Martin, N.G., McIntosh, A.M., Metspalu, A., Mors, O., Mortensen, P.B., Muller-Myhsok, B., Nordentoft, M., O'Donovan, M.C., Paciga, S.A., Pedersen, N.L., Penninx, B.W.J.H., Perlis, R.H., Porteous, D.J., Potash, J.B., Preisig, M., Schaefer, C., Schulze, T.G., Smoller, J.W., Stefansson, K., Tiemeier, H., Uher, R., Voelzke, H., Weissman, M.M., Werge, T., Lewis, C.M., Levinson, D.F., Breen, G., Borglum, A.D., Sullivan, P.F., and Major Depressive Disorder Worki

Subjects
treatment-resistance, polygenic risk scores, depression, major depression, electroconvulsive therapy
Abstract

Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistantdepression; disorder severity and unfavorable treatment outcomes are shown to be influencedby an increased genetic burden for major depression (MD). Here, we tested whether ECT assign-ment and response/nonresponse are associated with an increased genetic burden for majordepression (MD) using polygenic risk score (PRS), which summarize the contribution of disease-related common risk variants. Fifty-one psychiatric inpatients suffering from a major depressiveepisode underwent ECT. MD-PRS were calculated for these inpatients and a separatepopulation-based sample (n = 3,547 healthy; n = 426 self-reported depression) based on sum-mary statistics from the Psychiatric Genomics Consortium MDD-working group (Cases:n = 59,851; Controls: n = 113,154). MD-PRS explained a significant proportion of disease statusbetween ECT patients and healthy controls (p = .022, R2 = 1.173%); patients showed higherMD-PRS. MD-PRS in population-based depression self-reporters were intermediate betweenECT patients and controls (n.s.). Significant associations between MD-PRS and ECT response(50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indi-cate that ECT cohorts show an increased genetic burden for MD and are consistent with thehypothesis that treatment-resistant MD patients represent a subgroup with an increased geneticrisk for MD. Larger samples are needed to better substantiate these findings.

Published
2019

5. Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy

Author

Foo, JC, Streit, F, Frank, J, Witt, SH, Treutlein, J, Baune, BT, Moebus, S, Joeckel, K-H, Forstner, AJ, Noethen, MM, Rietschel, M, Sartorius, A, Kranaster, L, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Coleman, JRI, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, CV, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, SI, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Berger, K, Boomsma, DI, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Breen, G, Borglum, AD, Sullivan, PF, Foo, JC, Streit, F, Frank, J, Witt, SH, Treutlein, J, Baune, BT, Moebus, S, Joeckel, K-H, Forstner, AJ, Noethen, MM, Rietschel, M, Sartorius, A, Kranaster, L, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Coleman, JRI, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, CV, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, SI, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Berger, K, Boomsma, DI, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Breen, G, Borglum, AD, and Sullivan, PF

Abstract

Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistant depression; disorder severity and unfavorable treatment outcomes are shown to be influenced by an increased genetic burden for major depression (MD). Here, we tested whether ECT assignment and response/nonresponse are associated with an increased genetic burden for major depression (MD) using polygenic risk score (PRS), which summarize the contribution of disease-related common risk variants. Fifty-one psychiatric inpatients suffering from a major depressive episode underwent ECT. MD-PRS were calculated for these inpatients and a separate population-based sample (n = 3,547 healthy; n = 426 self-reported depression) based on summary statistics from the Psychiatric Genomics Consortium MDD-working group (Cases: n = 59,851; Controls: n = 113,154). MD-PRS explained a significant proportion of disease status between ECT patients and healthy controls (p = .022, R2 = 1.173%); patients showed higher MD-PRS. MD-PRS in population-based depression self-reporters were intermediate between ECT patients and controls (n.s.). Significant associations between MD-PRS and ECT response (50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indicate that ECT cohorts show an increased genetic burden for MD and are consistent with the hypothesis that treatment-resistant MD patients represent a subgroup with an increased genetic risk for MD. Larger samples are needed to better substantiate these findings.

Published
2019

7. The catechol-O-methyltransferase (COMT ) Val158Met genotype modulates working memory-related dorsolateral prefrontal response and performance in bipolar disorder

Author

Miskowiak, KW, primary, Kjaerstad, HL, additional, Støttrup, MM, additional, Svendsen, AM, additional, Demant, KM, additional, Hoeffding, LK, additional, Werge, TM, additional, Burdick, KE, additional, Domschke, K, additional, Carvalho, AF, additional, Vieta, E, additional, Vinberg, M, additional, Kessing, LV, additional, Siebner, HR, additional, and Macoveanu, J, additional

Published
2017
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12. Human nuclear transcription factor gene CREM: Genomic organization, mutation screening, and association analysis in panic disorder

Author

Domschke, K., primary, Kuhlenbäumer, G., additional, Schirmacher, A., additional, Lorenzi, C., additional, Armengol, L., additional, DiBella, D., additional, Gratacos, M., additional, Garritsen, H.S., additional, Nöthen, M.M., additional, Franke, P., additional, Sand, P., additional, Fritze, J., additional, Perez, G., additional, Maier, W., additional, Sibrowski, W., additional, Estivill, X., additional, Bellodi, L., additional, Ringelstein, E.B., additional, Arolt, V., additional, Martin‐Santos, R., additional, Catalano, M., additional, Stögbauer, F., additional, and Deckert, J., additional

Published
2002
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13. Reduced structural connectivity in the corpus callosum in patients with anorexia nervosa.

Author

Maier S, Joos A, Tebartz van Elst L, Ebert D, Endres D, Domschke K, Lahmann C, Zeeck A, Runge K, Denzel D, Reisert M, and Nickel K

Subjects
Anisotropy, Corpus Callosum diagnostic imaging, Diffusion Tensor Imaging, Female, Humans, Anorexia Nervosa diagnostic imaging, White Matter
Abstract

Objective: Previous diffusion tensor imaging studies reported a reduced fractional anisotropy in the body of the corpus callosum in patients with anorexia nervosa, which may indicate impaired white matter integrity in interhemispheric connections. The aim of the current study was to investigate whether structural connectivity is affected in patients with anorexia nervosa., Method: To this end, we compared the number of streamlines (a model of the white matter fibre tracts) and the total volume filled by these streamlines in different subsections of the corpus callosum in 33 women with and 33 without anorexia nervosa as well as in 20 recovered individuals., Results: The volume of streamlines in the anterior and mid-anterior subsection of the corpus callosum was reduced in women with, but not in those who had recovered from anorexia nervosa. No differences in number of streamlines was detected in the corpus callosum between patients with anorexia nervosa, healthy controls and recovered patients., Conclusions: Alterations of the corpus callosum have been repeatedly reported in anorexia nervosa. Since the recovered group did not differ from the healthy control group, the reported alterations in acute patients appear to represent a state and not a trait marker., (© 2022 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Published
2022
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14. Efficacy of temporally intensified exposure for anxiety disorders: A multicenter randomized clinical trial.

Author

Pittig A, Heinig I, Goerigk S, Thiel F, Hummel K, Scholl L, Deckert J, Pauli P, Domschke K, Lueken U, Fydrich T, Fehm L, Plag J, Ströhle A, Kircher T, Straube B, Rief W, Koelkebeck K, Arolt V, Dannlowski U, Margraf J, Totzeck C, Schneider S, Neudeck P, Craske MG, Hollandt M, Richter J, Hamm A, and Wittchen HU

Subjects
Anxiety therapy, Anxiety Disorders epidemiology, Anxiety Disorders therapy, Comorbidity, Humans, Treatment Outcome, Implosive Therapy, Quality of Life
Abstract

Background: The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions., Methods: This multicenter randomized controlled trial compared two variants of prediction error-based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx-I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx-S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6-months follow-up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression., Results: Both treatments resulted in substantial improvements at post (PeEx-I: d within  = 1.50, PeEx-S: d within  = 1.78) and follow-up (PeEx-I: d within  = 2.34; PeEx-S: d within  = 2.03). Both groups showed formally equivalent symptom reduction at post and follow-up. However, time until response during treatment was 32% shorter in PeEx-I (median = 68 days) than PeEx-S (108 days; TR PeEx-I  = 0.68). Interestingly, drop-out rates were lower during intensified exposure. PeEx-I was also superior in reducing disability days and improving quality of life at follow-up without increasing relapse., Conclusions: Both treatment variants focusing on the transdiagnostic exposure-based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop-out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner., (© 2021 The Authors. Depression and Anxiety Published by Wiley Periodicals LLC.)

Published
2021
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15. Polypharmacy and the risk of drug-drug interactions and potentially inappropriate medications in hospital psychiatry.

Author

Wolff J, Hefner G, Normann C, Kaier K, Binder H, Hiemke C, Toto S, Domschke K, Marschollek M, and Klimke A

Subjects
Aged, Drug Interactions, Female, Hospitals, Humans, Inappropriate Prescribing, Male, Polypharmacy, Potentially Inappropriate Medication List, Pharmaceutical Preparations, Psychiatry
Abstract

Purpose: The aim of this study was to analyze the epidemiology of polypharmacy in hospital psychiatry. Another aim was to investigate predictors of the number of drugs taken and the associated risks of drug-drug interactions and potentially inappropriate medications in the elderly., Methods: Daily prescription data were obtained from a pharmacovigilance project sponsored by the Innovations Funds of the German Federal Joint Committee., Results: The study included 47 071 inpatient hospital cases from eight different study centers. The mean number of different drugs during the entire stay was 6.1 (psychotropic drugs = 2.7; others = 3.4). The mean number of drugs per day was 3.8 (psychotropic drugs = 1.6; others = 2.2). One third of cases received at least five different drugs per day on average during their hospital stay (polypharmacy). Fifty-one percent of patients received more than one psychotropic drug simultaneously. Hospital cases with polypharmacy were 18 years older (p < 0.001), more likely to be female (52% vs. 40%, p < 0.001) and had more comorbidities (5 vs. 2, p < 0.001) than hospital cases without polypharmacy. The risks of drug-drug interactions (OR = 3.7; 95% CI = 3.5-3.9) and potentially inappropriate medication use in the elderly (OR = 2.2; CI = 1.9-2.5) substantially increased in patients that received polypharmacy., Conclusion: Polypharmacy is frequent in clinical care. The number of used drugs is a proven risk factor of adverse drug reactions due to drug-drug interactions and potentially inappropriate medication use in the elderly. The potential interactions and the specific pharmacokinetics and -dynamics of older patients should always be considered when multiple drugs are used., (© 2021 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Published
2021
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16. The interaction of 5-HTT variation, recent stress, and resilience on current anxiety levels in adolescents and young adults from the general population.

Author

Ollmann TM, Voss C, Venz J, Seidl E, Hoyer J, Kische H, Pieper L, Schiele MA, Domschke K, and Beesdo-Baum K

Subjects
Adolescent, Adult, Anxiety genetics, Child, Genotype, Germany, Humans, Stress, Psychological, Surveys and Questionnaires, Young Adult, Anxiety Disorders epidemiology, Anxiety Disorders genetics, Resilience, Psychological, Serotonin Plasma Membrane Transport Proteins genetics
Abstract

Background: Previous work on gene-environment (GxE) interplay concerning anxiety has focused on the interaction of 5-HTTLPR with childhood adversities or traumatic events whereas the impact of recent stressors is understudied, as is the integration of resilience. The current study aimed to investigate the interactive effect of 5-HTTLPR and recent stress on anxiety in adolescents considering resilience as buffer of a GxE risk constellation., Method: In a random population-based sample of 14-21 years old from Dresden, Germany, (N = 1180; genotyped = 942) recent stress (Daily Hassles [DH] Scale, Perceived Stress Scale, Screening Scale of the Trier Inventory for the Assessment of Chronic Stress), resilience (Connor-Davidson resilience scale) and anxiety (Patient Reported Outcome Measurement Information System Anxiety Short Form) were assessed via questionnaire in 2015 or 2016., Results: Fractional regression models revealed that resilience interacted with recent stress in form of DH as well as recent chronic stress and 5-HTTLPR regarding anxiety. Participants carrying the more active L A L A genotype reported consistently higher levels of anxiety when experiencing more DH or more recent chronic stress and having low levels of resilience. When the resilience scores were high, L A L A carriers reported the lowest anxiety scores despite DH or recent chronic stress., Conclusion: Findings revealed an interactive relationship between 5-HTTLPR genotype and recent stress suggesting resilience to function as an additional dimension buffering the impact of a GxE risk constellation. Early interventions to build resilience may be useful to prevent an escalation of distress and associated unfavorable health outcomes., (© 2020 The Authors. Depression and Anxiety Published by Wiley Periodicals LLC.)

Published
2021
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17. The role of BDNF methylation and Val 66 Met in amygdala reactivity during emotion processing.

Author

Redlich R, Schneider I, Kerkenberg N, Opel N, Bauhaus J, Enneking V, Repple J, Leehr EJ, Grotegerd D, Kähler C, Förster K, Dohm K, Meinert S, Hahn T, Kugel H, Schwarte K, Schettler C, Domschke K, Arolt V, Heindel W, Baune BT, Zhang W, Hohoff C, and Dannlowski U

Subjects
Adult, Amygdala diagnostic imaging, Brain-Derived Neurotrophic Factor genetics, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Polymorphism, Genetic, Psychomotor Performance physiology, Young Adult, Amygdala physiology, Brain-Derived Neurotrophic Factor metabolism, DNA Methylation physiology, Emotions physiology, Epigenesis, Genetic genetics, Facial Recognition physiology, Personality physiology
Abstract

Epigenetic alterations of the brain-derived neurotrophic factor (BDNF) gene have been associated with psychiatric disorders in humans and with differences in amygdala BDNF mRNA levels in rodents. This human study aimed to investigate the relationship between the functional BDNF-Val 66 Met polymorphism, its surrounding DNA methylation in BDNF exon IX, amygdala reactivity to emotional faces, and personality traits. Healthy controls (HC, n = 189) underwent functional MRI during an emotional face-matching task. Harm avoidance, novelty seeking and reward dependence were measured using the Tridimensional Personality Questionnaire (TPQ). Individual BDNF methylation profiles were ascertained and associated with several BDNF single nucleotide polymorphisms surrounding the BDNF-Val 66 Met, amygdala reactivity, novelty seeking and harm avoidance. Higher BDNF methylation was associated with higher amygdala reactivity (x = 34, y = 0, z = -26, t (166) = 3.00, TFCE = 42.39, p (FWE) = .045), whereby the BDNF-Val 66 Met genotype per se did not show any significant association with brain function. Furthermore, novelty seeking was negatively associated with BDNF methylation (r = -.19, p = .015) and amygdala reactivity (r = -.17, p = .028), while harm avoidance showed a trend for a positive association with BDNF methylation (r = .14, p = .066). The study provides first insights into the relationship among BDNF methylation, BDNF genotype, amygdala reactivity and personality traits in humans, highlighting the multidimensional relations among genetics, epigenetics, and neuronal functions. The present study suggests a possible involvement of epigenetic BDNF modifications in psychiatric disorders and related brain functions, whereby high BDNF methylation might reduce BDNF mRNA expression and upregulate amygdala reactivity., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Published
2020
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18. Neurobiological signature of intimacy in anorexia nervosa.

Author

Maier S, Spiegelberg J, van Zutphen L, Zeeck A, Tebartz van Elst L, Hartmann A, Holovics L, Reinert E, Sandholz A, Lahmann C, Domschke K, Glauche V, Tüscher O, and Joos AAB

Subjects
Adult, Female, Humans, Magnetic Resonance Imaging, Young Adult, Anorexia Nervosa physiopathology, Sexual Behavior
Abstract

Background: Intimacy and psychosexual development represent core problems of anorexia nervosa (AN). Experiential and neurobiological evidence however is scarce., Material and Methods: Thirty-one female AN patients were compared with 35 non-patients (NP) and 22 recovered participants (REC) by using functional magnetic resonance imaging. Participants viewed pictures of couples in intimate relationships and control stimuli., Results: AN patients experienced intimate stimuli with lower valence and dominance. AN showed decreased activation of parietal cortices. NP decreased the prefrontal cortex response, which AN patients did not. REC participants did not differ from NP on a behavioural level, though with regard to the neural signature., Discussion: Parietal cortices are related to processing of erotic themes, which seems to be deficient in AN. Dysfunction of prefrontal cortices likely mirrors dysfunctional control in AN. The neural signature does not seem to be state-related considering results of REC., (© 2019 John Wiley & Sons, Ltd and Eating Disorders Association.)

Published
2019
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19. A functional variant of the neuropeptide S receptor-1 gene modulates clinical outcomes and healthcare utilization in patients with systolic heart failure: results from the Interdisciplinary Network Heart Failure (INH) Study.

Author

Angermann CE, Kaspar M, Marx A, Kittel-Schneider S, Menhofer D, Störk S, Ertl G, Domschke K, Deckert J, and Reif A

Subjects
Aged, Aged, 80 and over, Cause of Death, Disease Management, Female, Genotype, Health Services statistics & numerical data, Heart Failure, Systolic mortality, Humans, Male, Middle Aged, Practice Patterns, Nurses', Prognosis, Proportional Hazards Models, Randomized Controlled Trials as Topic, Risk Factors, Heart Failure, Systolic genetics, Hospitalization statistics & numerical data, Mortality, Receptors, G-Protein-Coupled genetics
Abstract

Aims: Psychopathologies may occur in heart failure (HF) and can be associated with adverse outcomes. Amongst neuropeptide S receptor gene functional sequence variants, the T-allele [asparagine(107)isoleucine, NPSR1 rs324981] has been identified as a risk factor for increased anxiety/overinterpretation of bodily symptoms. We investigated all-cause death and re-hospitalization (composite primary endpoint, CPEP) and healthcare utilization in patients hospitalized for decompensated systolic HF with the TT vs. the AT/AA genotype., Methods and Results: Participants in the Interdisciplinary Network Heart Failure programme were eligible if consenting to genetic testing (n = 924) and randomization to usual care (UC, n = 464) or nurse-co-ordinated disease management (DM, n = 460). Follow-up was 180 days (100% complete). Compared with AT/AA carriers (n = 726), TT genotype carriers (n = 198) had more CPEP events [47% vs. 39%, hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.01-1.61, P = 0.044] and were more frequently re-hospitalized (43% vs. 35%, HR 1.31, 95% CI 1.02-1.67, P = 0.033); mortality rate was similar in both groups (HR 1.11, 95% CI 0.68-1.81, P = 0.664). In subjects undergoing DM, CPEP and re-hospitalization occurred more often in TT (51% and 47%) than in AT/AA carriers (36% and 33%; HR 2.14, 95% CI 1.44-3.19, and HR 2.29, 95% CI 1.52-3.44, genotype/treatment interaction both P = 0.007). Furthermore, TT genotype carriers undergoing DM visited cardiologists and other specialists more often than AT/AA carriers (P = 0.009 and P = 0.005). With UC, event rates did not differ between genotype subgroups., Conclusion: We identified a psychogenetic determinant of clinical outcomes and healthcare utilization after acute HF, which was modulated by the type of care. Future investigations need to clarify whether NPSR1 genotyping might further enhance the concept of 'personalized' medicine in HF., Trial Registration: ISRCTN23325295., (© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.)

Published
2017
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20. Serotonin transporter gene methylation is associated with hippocampal gray matter volume.

Author

Dannlowski U, Kugel H, Redlich R, Halik A, Schneider I, Opel N, Grotegerd D, Schwarte K, Schettler C, Ambrée O, Rust S, Domschke K, Arolt V, Heindel W, Baune BT, Suslow T, Zhang W, and Hohoff C

Subjects
Adult, Brain Mapping, Female, Genotype, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Psychiatric Status Rating Scales, Young Adult, DNA Methylation physiology, Gray Matter anatomy & histology, Hippocampus anatomy & histology, Polymorphism, Genetic genetics, Serotonin Plasma Membrane Transport Proteins genetics
Abstract

Background: The serotonin transporter (5-HTT) and the 5-HTTLPR/rs25531 polymorphisms in its gene (SLC6A4) have been associated with depression, increased stress-response, and brain structural alterations such as reduced hippocampal volumes. Recently, epigenetic processes including SLC6A4 promoter methylation were shown to be affected by stress, trauma, or maltreatment and are regarded to be involved in the etiology of affective disorders. However, neurobiological correlates of SLC6A4 promoter methylation have never been studied or compared to genotype effects by means of human neuroimaging hitherto, Methods: Healthy subjects were recruited in two independent samples (N = 94, N = 95) to obtain structural gray matter images processed by voxel-based morphometry (VBM8), focusing on hippocampal, amygdala, and anterior cingulate gyrus gray matter structure. SLC6A4 promoter methylation within an AluJb element and 5-HTTLPR/rs25531 genotypes were analyzed in view of a possible impact on local gray matter volume, Results: Strong associations of AluJb methylation and hippocampal gray matter volumes emerged within each sample separately, which in the combined sample withstood most conservative alpha-corrections for the entire brain. The amygdala, insula, and caudate nucleus showed similar associations. The 5-HTTLPR/rs25531 showed no main effect on gray matter, and the effect of methylation rates on hippocampal structure was comparable among the genotype groups, Conclusions: Methylation within the AluJb appears to have strong effects on hippocampal gray matter volumes, indicating that epigenetic processes can alter brain structures crucially involved in stress-related disorders. Different ways of regulating SLC6A4 expression might involve exonization or transcription factor binding as potentially underlying mechanisms, which, however, is speculative and warrants further investigation., (Copyright © 2014 Wiley Periodicals, Inc.)

Published
2014
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21. Gender-specific association of variants in the AKR1C1 gene with dimensional anxiety in patients with panic disorder: additional evidence for the importance of neurosteroids in anxiety?

Author

Quast C, Reif A, Brückl T, Pfister H, Weber H, Mattheisen M, Cichon S, Lang T, Hamm A, Fehm L, Ströhle A, Arolt V, Domschke K, Kircher T, Wittchen HU, Pauli P, Gerlach AL, Alpers GW, Deckert J, Rupprecht R, Binder EB, and Erhardt A

Subjects
3-Hydroxysteroid Dehydrogenases genetics, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase genetics, Adult, Aldo-Keto Reductase Family 1 Member C3, Anxiety metabolism, Anxiety psychology, Case-Control Studies, Female, Genetic Predisposition to Disease, Humans, Hydroxyprostaglandin Dehydrogenases genetics, Hydroxysteroid Dehydrogenases genetics, Male, Membrane Proteins genetics, Middle Aged, Panic Disorder metabolism, Panic Disorder psychology, Polymorphism, Single Nucleotide, Receptors, GABA genetics, Sex Factors, 20-Hydroxysteroid Dehydrogenases genetics, Anxiety genetics, Panic Disorder genetics, Pregnanolone metabolism, Progesterone metabolism
Abstract

Background: Neurosteroids are synthesized both in brain and peripheral steroidogenic tissue from cholesterol or steroidal precursors. Neurosteroids have been shown to be implicated in neural proliferation, differentiation, and activity. Preclinical and clinical studies also suggest a modulatory role of neurosteroids in anxiety-related phenotypes. However, little is known about the contribution of genetic variants in genes relevant for the neurosteroidogenesis to anxiety disorders., Methods: We performed an association analysis of single nucleotide polymorphisms (SNPs) in five genes related to the neurosteroidal pathway with emphasis on progesterone and allopregnanolone biosynthesis (steroid-5-alpha-reductase 1A (SRD5A1), aldo-keto reductase family 1 C1-C3 (AKR1C1-AKR1C3) and translocator protein 18 kDA (TSPO) with panic disorder (PD) and dimensional anxiety in two German PD samples (cases N = 522, controls N = 1,115)., Results: Case-control analysis for PD and SNPs in the five selected genes was negative in the combined sample. However, we detected a significant association of anticipatory anxiety with two intronic SNPs (rs3930965, rs41314625) located in the gene AKR1C1 surviving correction for multiple testing in PD patients. Stratification analysis for gender revealed a female-specific effect of the associations of both SNPs., Conclusions: These results suggest a modulatory effect of AKR1C1 activity on anxiety levels, most likely through changes in progesterone and allopregnanolone levels within and outside the brain. In summary, this is the first evidence for the gender-specific implication of the AKR1C1 gene in the expression of anticipatory anxiety in PD. Further analyses to unravel the functional role of the SNPs detected here and replication analyses are needed to validate our results., (© 2014 Wiley Periodicals, Inc.)

Published
2014
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22. Neuronal network of panic disorder: the role of the neuropeptide cholecystokinin.

Author

Zwanzger P, Domschke K, and Bradwejn J

Subjects
Animals, Brain metabolism, Cholecystokinin genetics, Humans, Mice, Panic Disorder metabolism, Rats, Receptors, Cholecystokinin genetics, Synaptic Transmission genetics, Cholecystokinin metabolism, Nerve Net metabolism, Panic Disorder etiology, Receptors, Cholecystokinin metabolism, Synaptic Transmission physiology
Abstract

Panic disorder (PD) is characterized by panic attacks, anticipatory anxiety and avoidance behavior. Its pathogenesis is complex and includes both neurobiological and psychological factors. With regard to neurobiological underpinnings, anxiety in humans seems to be mediated through a neuronal network, which involves several distinct brain regions, neuronal circuits and projections as well as neurotransmitters. A large body of evidence suggests that the neuropeptide cholecystokinin (CCK) might be an important modulator of this neuronal network. Key regions of the fear network, such as amygdala, hypothalamus, peraqueductal grey, or cortical regions seem to be connected by CCKergic pathways. CCK interacts with several anxiety-relevant neurotransmitters such as the serotonergic, GABA-ergic and noradrenergic system as well as with endocannabinoids, NPY and NPS. In humans, administration of CCK-4 reliably provokes panic attacks, which can be blocked by antipanic medication. Also, there is some support for a role of the CCK system in the genetic pathomechanism of PD with particularly strong evidence for the CCK gene itself and the CCK-2R (CCKBR) gene. Thus, it is hypothesized that genetic variants in the CCK system might contribute to the biological basis for the postulated CCK dysfunction in the fear network underlying PD. Taken together, a large body of evidence suggests a possible role for the neuropeptide CCK in PD with regard to neuroanatomical circuits, neurotransmitters and genetic factors. This review article proposes an extended hypothetical model for human PD, which integrates preclinical and clinical findings on CCK in addition to existing theories of the pathogenesis of PD., (© 2012 Wiley Periodicals, Inc.)

Published
2012
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23. Serotonin transporter gene and childhood trauma--a G × E effect on anxiety sensitivity.

Author

Klauke B, Deckert J, Reif A, Pauli P, Zwanzger P, Baumann C, Arolt V, Glöckner-Rist A, and Domschke K

Subjects
Adult, Child, Female, Genotype, Humans, Male, Models, Statistical, Phenotype, Polymorphism, Genetic, Surveys and Questionnaires, Young Adult, Anxiety genetics, Anxiety psychology, Anxiety Disorders etiology, Anxiety Disorders genetics, Child Abuse psychology, Gene-Environment Interaction, Serotonin Plasma Membrane Transport Proteins genetics
Abstract

Background: Genetic factors and environmental factors are assumed to interactively influence the pathogenesis of anxiety disorders. Thus, a gene-environment interaction (G × E) study was conducted with respect to anxiety sensitivity (AS) as a promising intermediate phenotype of anxiety disorders., Method: Healthy subjects (N = 363) were assessed for AS, childhood maltreatment (Childhood Trauma Questionnaire), and genotyped for functional serotonin transporter gene variants (5-HTTLPR/5-HTT rs25531). The influence of genetic and environmental variables on AS and its subdimensions was determined by a step-wise hierarchical regression and a multiple indicator multiple cause (MIMIC) model., Results: A significant G × E effect of the more active 5-HTT genotypes and childhood maltreatment on AS was observed. Furthermore, genotype (LL)-childhood trauma interaction particularly influenced somatic AS subdimensions, whereas cognitive subdimensions were affected by childhood maltreatment only., Conclusions: Results indicate a G × E effect of the more active 5-HTT genotypes and childhood maltreatment on AS, with particular impact on its somatic subcomponent., (© 2011 Wiley Periodicals, Inc.)

Published
2011
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24. Effect of gender on processing threat-related stimuli in patients with panic disorder: sex does matter.

Author

Ohrmann P, Pedersen A, Braun M, Bauer J, Kugel H, Kersting A, Domschke K, Deckert J, and Suslow T

Subjects
Adult, Amygdala physiopathology, Brain Mapping, Dominance, Cerebral physiology, Female, Frontal Lobe physiopathology, Gyrus Cinguli physiopathology, Humans, Male, Middle Aged, Nerve Net physiopathology, Panic Disorder diagnosis, Panic Disorder psychology, Personality Inventory statistics & numerical data, Prefrontal Cortex physiopathology, Psychometrics, Thalamus physiopathology, Brain physiopathology, Emotions physiology, Facial Expression, Fear physiology, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Panic Disorder physiopathology, Pattern Recognition, Visual physiology, Sex Characteristics, Social Perception
Abstract

Background: Several studies have shown that female and male subjects process emotions differently. As women appear to be especially sensitive and responsive to negative and threatening stimuli, gender-specific emotional processing might be an important factor contributing to the increased likelihood of women compared to men to develop anxiety disorders, e.g. panic disorder (PD)., Methods: In this study, gender-specific neural activation during facial emotion processing was investigated in 20 PD patients (12 women, 8 men) by functional magnetic resonance imaging., Results: Overall, significantly stronger activation, encompassing the amygdala, prefrontal, temporal, and occipital cortical areas, basal ganglia, and thalamus, was observed in women than in men during the processing of angry, fearful, or neutral but not happy facial expressions. Additionally, functional connectivity between the amygdala and prefrontal cortical areas and thalamus during the processing of angry facial expressions was significantly stronger in women than in men., Conclusions: These results emphasize gender as an important variable in neural activation patterns of emotional processing and may help to further elucidate the biological substrate of gender-specific susceptibility for PD., (© 2010 Wiley-Liss, Inc.)

Published
2010
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25. Life events in panic disorder-an update on "candidate stressors".

Author

Klauke B, Deckert J, Reif A, Pauli P, and Domschke K

Subjects
Adolescent, Adult, Age of Onset, Agoraphobia diagnosis, Agoraphobia genetics, Agoraphobia psychology, Anxiety Disorders diagnosis, Anxiety Disorders genetics, Anxiety Disorders psychology, Child, Child, Preschool, Comorbidity, Depressive Disorder, Major diagnosis, Depressive Disorder, Major genetics, Depressive Disorder, Major psychology, Epigenesis, Genetic genetics, Female, Genetic Association Studies, Genetic Predisposition to Disease genetics, Genetic Predisposition to Disease psychology, Humans, Infant, Male, Panic Disorder diagnosis, Phenotype, Risk Factors, Young Adult, Life Change Events, Panic Disorder genetics, Panic Disorder psychology, Social Environment
Abstract

Studies on gene-environment interactions in mental disorders are characterized by powerful genetic techniques and well defined "candidate genes," whereas a definition of "candidate stressors," in most cases assessed in the form of life events (LEs), is inconsistent or not even provided. This review addresses this problem, with particular attention to the clinical phenotype of panic disorder (PD), by providing an overview and critical discussion for which life events are known to contribute to the etiology of the disease and how they may be conceptualized. There is converging evidence for a significant impact of cumulative as well as specific life events, such as threat, interpersonal and health-related events in adulthood, and abuse or loss/separation experiences in childhood, respectively, on the pathogenesis of panic disorder with some overlapping effect across the anxiety disorder spectrum as well as on comorbid major depression. Besides genetic vulnerability factors, personality and behavioral characteristics, such as anxiety sensitivity, neuroticism, and cognitive appraisal might moderate the influence of LEs on the development of panic disorder. The present state of knowledge regarding the specification and conceptualization of LEs in PD within a more complex multifactorial model, involving mediating and moderating factors in between genes and the clinical phenotype, is hoped to aid in informing future gene-environment interaction studies in panic disorder.

Published
2010
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26. Functional 5-HT1a receptor polymorphism selectively modulates error-specific subprocesses of performance monitoring.

Author

Beste C, Domschke K, Kolev V, Yordanova J, Baffa A, Falkenstein M, and Konrad C

Subjects
Adaptation, Psychological physiology, Adult, Electroencephalography, Evoked Potentials, Executive Function physiology, Female, Genotype, Humans, Male, Neuropsychological Tests, Reaction Time, Sequence Analysis, DNA, White People genetics, Brain physiology, Feedback, Psychological physiology, Polymorphism, Genetic, Psychomotor Performance physiology, Receptor, Serotonin, 5-HT1A genetics, Receptor, Serotonin, 5-HT1A metabolism
Abstract

Our study investigates the dependence of response monitoring and error detection on genetic influences modulating the serotonergic system. This was done using the event-related potentials (ERPs) after error (Ne/ERN) and correct trials (Nc/CRN). To induce a sufficient amount of errors, a standard flanker task was used. The subjects (N = 94) were genotyped for the functional 5-HT1A C(-1019)G polymorphism. The results show that the 5-HT1A C(-1019)G polymorphism specifically modulates error detection. Neurophysiological modulations on error detection were paralleled by a similar modulation of response slowing after an error, reflecting the behavioral adaptation. The 5-HT1A -1019 CC genotype group showed a larger Ne and stronger posterror slowing than the CG and GG genotype groups. More general processes of performance monitoring, as reflected in the Nc/CRN, were not affected. The finding that error-specific processes, but not general response monitoring processes, are modulated by the 5-HT1A C(-1019)G polymorphism is underlined by a wavelet analysis. In summary, the results suggest a specific effect of the 5-HT1A C(-1019)G polymorphism on error monitoring, as reflected in the Ne, and suggest a neurobiological dissociation between processes of error monitoring and general response monitoring at the level of the serotonin 1A receptor system., (Copyright 2009 Wiley-Liss, Inc.)

Published
2010
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27. Serotonin transporter polymorphism (5-HTTLPR) association with melancholic depression: a female specific effect?

Author

Baune BT, Hohoff C, Mortensen LS, Deckert J, Arolt V, and Domschke K

Subjects
DNA Primers genetics, Depressive Disorder diagnosis, Depressive Disorder, Major diagnosis, Diagnostic and Statistical Manual of Mental Disorders, Female, Genetic Variation genetics, Genotype, Humans, Male, Middle Aged, Polymerase Chain Reaction, Sex Factors, Depressive Disorder genetics, Depressive Disorder, Major genetics, Polymorphism, Genetic genetics, Serotonin Plasma Membrane Transport Proteins genetics
Abstract

Earlier studies yielded inconsistent results on the association between variation in the serotonin transporter (5-HTT) gene and depression, with evidence for a differential effect of the 5-HTTLPR on melancholic versus atypical depression. To further delineate the impact of 5-HTT gene variation on psychopathology in depression, in this analysis the influence of the 5-HTTLPR and the functionally closely related 5-HTT rs25531 was investigated in 340 Caucasian patients with a major depressive episode (DSM-IV) with particular attention to the subtype of depression (melancholic depression versus atypical depression) applying logistic regression models adjusted for age and gender. The homozygous, more active 5-HTTLPR LL genotype was significantly associated with melancholic depression (odds ratio, OR, 1.7; 95% confidence interval, CI, 1.1-2.6; P=0.04), with the effect originating in the female subgroup of patients (OR 1.9; 95%CI 1.0-3.4; P=0.05). Also, the more active 5-HTTLPR/5-HTT rs25531 haplotype L(A)L(A) conveyed a significant risk for melancholic depression (OR 2.0; 95%CI 1.3-3.1; P=0.001), again only in the female subsample of patients (OR 2.1; 95%CI 1.1-4.1; P=0.02). The present results provide further support for an association of genetic variation increasing serotonin transporter activity with the melancholic subtype of depression as well as evidence for a potential female-specific mechanism underlying this effect., (2007 Wiley-Liss, Inc.)

Published
2008
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