Search

Your search keyword '"Domschke K."' showing total 880 results
Start Over Author "Domschke K."
880 results on '"Domschke K."'

1. Investigating non-inferiority of internet-delivered versus face-to-face cognitive behavioural therapy for insomnia (CBT-I): a randomised controlled trial (iSleep well)

Author

Benz, F., Grolig, L., Hannibal, S., Buntrock, C., Cuijpers, P., Domschke, K., Ebert, D. D., Ell, J., Janneck, M., Jenkner, C., Johann, A. F., Josef, A., Kaufmann, M., Koß, A., Mallwitz, T., Mergan, H., Morin, C. M., Riemann, D., Riper, H., Schmid, S. R., Smit, F., Spille, L., Steinmetz, L., Van Someren, E. J. W., Spiegelhalder, K., and Lehr, D.

Published
2024
Full Text
View/download PDF

6. Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response from 13 clinical studies using genotype imputation: a meta-analysis.

Author

Li, D, Pain, O, Chiara, F, Wong, WLE, Lo, CWH, Ripke, S, Cattaneo, A, Souery, D, Dernovsek, MZ, Henigsberg, N, Hauser, J, Lewis, G, Mors, O, Perroud, N, Rietschel, M, Uher, R, Maier, W, Baune, BT, Biernacka, JM, Bondolfi, G, Domschke, K, Kato, M, Liu, Y-L, Serretti, A, Tsai, S-J, Weinshilboum, R, GSRD Consortium, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, McIntosh, AM, Lewis, CM, Li, D, Pain, O, Chiara, F, Wong, WLE, Lo, CWH, Ripke, S, Cattaneo, A, Souery, D, Dernovsek, MZ, Henigsberg, N, Hauser, J, Lewis, G, Mors, O, Perroud, N, Rietschel, M, Uher, R, Maier, W, Baune, BT, Biernacka, JM, Bondolfi, G, Domschke, K, Kato, M, Liu, Y-L, Serretti, A, Tsai, S-J, Weinshilboum, R, GSRD Consortium, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, McIntosh, AM, and Lewis, CM

Abstract

Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual clinical and genetic data from 13 studies of European and East Asian ancestry populations were collected. The antidepressant response was clinically assessed as remission and percentage improvement. Imputed genotype was used to translate genetic polymorphisms to metabolic phenotypes (poor, intermediate, normal, and rapid+ultrarapid) of CYP2C19 and CYP2D6. CYP2D6 structural variants cannot be imputed from genotype data, limiting the determination of metabolic phenotypes, and precluding testing for association with response. The association of CYP2C19 metabolic phenotypes with treatment response was examined using normal metabolizers as the reference. Among 5843 depression patients, a higher remission rate was found in CYP2C19 poor metabolizers compared to normal metabolizers at nominal significance but did not survive after multiple testing correction (OR = 1.46, 95% CI [1.03, 2.06], p = 0.033, heterogeneity I2 = 0%, subgroup difference p = 0.72). No metabolic phenotype was associated with percentage improvement from baseline. After stratifying by antidepressants primarily metabolized by CYP2C19, no association was found between metabolic phenotypes and antidepressant response. Metabolic phenotypes showed differences in frequency, but not effect, between European- and East Asian-ancestry studies. In conclusion, metabolic phenotypes imputed from genetic variants using genotype were not associated with antidepressant response. CYP2C19 poor metabolizers could potentially contribute to antidepressant efficacy with more evidence needed. Sequencing and targeted pharmacogenetic testing, alongside information on side effects, antidepressant dosage, depression me

Published
2024

7. Investigating non-inferiority of internet-delivered versus face-to-face cognitive behavioural therapy for insomnia (CBT-I): a randomised controlled trial (iSleep well)

Author

Benz, F, Grolig, L, Hannibal, S, Buntrock, C, Cuijpers, P, Domschke, K, Ebert, D D, Ell, J, Janneck, M, Jenkner, C, Johann, A F, Josef, A, Kaufmann, M, Koß, A, Mallwitz, T, Mergan, H, Morin, C M, Riemann, D, Riper, H, Schmid, S R, Smit, F, Spille, L, Steinmetz, L, Van Someren, E J W, Spiegelhalder, K, Lehr, D, Benz, F, Grolig, L, Hannibal, S, Buntrock, C, Cuijpers, P, Domschke, K, Ebert, D D, Ell, J, Janneck, M, Jenkner, C, Johann, A F, Josef, A, Kaufmann, M, Koß, A, Mallwitz, T, Mergan, H, Morin, C M, Riemann, D, Riper, H, Schmid, S R, Smit, F, Spille, L, Steinmetz, L, Van Someren, E J W, Spiegelhalder, K, and Lehr, D

Abstract

BACKGROUND: Insomnia is a highly prevalent disorder associated with numerous adverse health outcomes. Cognitive behavioural therapy for insomnia (CBT-I) is recommended as first-line treatment by clinical guidelines but is accessible to only a minority of patients suffering from insomnia. Internet-delivered CBT-I (iCBT-I) could contribute to the widespread dissemination of this first-line treatment. As there is insufficient evidence regarding non-inferiority, this study directly aims to compare therapist-guided internet-delivered versus face-to-face CBT-I in terms of insomnia severity post-treatment. Furthermore, a health-economic evaluation will be conducted, and potential benefits and disadvantages of therapist-guided iCBT-I will be examined.METHODS: This study protocol describes a randomised controlled two-arm parallel-group non-inferiority trial comparing therapist-guided iCBT-I with face-to-face CBT-I in routine clinical care. A total of 422 patients with insomnia disorder will be randomised and treated at 16 study centres throughout Germany. Outcomes will be assessed at baseline, 10 weeks after randomisation (post), and 6 months after randomisation (follow-up). The primary outcome is insomnia severity measured using the Insomnia Severity Index. Secondary outcomes include depression-related symptoms, quality of life, fatigue, physical activity, daylight exposure, adverse events related to treatment, and a health-economic evaluation. Finally, potential moderator variables and several descriptive and exploratory outcomes will be assessed (e.g. benefits and disadvantages of internet-delivered treatment).DISCUSSION: The widespread implementation of CBT-I is a significant healthcare challenge. The non-inferiority of therapist-guided iCBT-I versus face-to-face CBT-I will be investigated in an adequately powered sample in routine clinical care, with the same therapeutic content and same level of therapist qualifications provided with both interventions

Published
2024

8. Nöropsikofarmakolojide Terapötik İla ç İzlemi İ çin Ortak Görü ş Kılavuzu: 2017 G üncellemesi

Author

Hiemke, C., Bergemann, N., Clement, H. W., Conca, A., Deckert, J., Domschke, K., Eckermann, G., Egberts, K., Gerlach, M., Greiner, C., Grunder, G., Haen, E., Havemann-Reinecke, U., Hefner, G., Helmer, R., Janssen, G., Jaquenoud, E., Laux, G., Messer, T., Mossner, R., Muller, M. J., Paulzen, M., Pfuhlmann, B., Riederer, P., Saria, A., Schoppek, B., Schoretsanitis, G., Schwarz, M., Gracia, M. S., Stegmann, B., Steimer, W., Stingl, J. C., Uhr, M., Ulrich, S., Unterecker, S., Waschgler, R., Zernig, G., Zurek, G., Baumann, P., Hiemke, C., Bergemann, N., Clement, H. W., Conca, A., Deckert, J., Domschke, K., Eckermann, G., Egberts, K., Gerlach, M., Greiner, C., Grunder, G., Haen, E., Havemann-Reinecke, U., Hefner, G., Helmer, R., Janssen, G., Jaquenoud, E., Laux, G., Messer, T., Mossner, R., Muller, M. J., Paulzen, M., Pfuhlmann, B., Riederer, P., Saria, A., Schoppek, B., Schoretsanitis, G., Schwarz, M., Gracia, M. S., Stegmann, B., Steimer, W., Stingl, J. C., Uhr, M., Ulrich, S., Unterecker, S., Waschgler, R., Zernig, G., Zurek, G., and Baumann, P.

Published
2024

13. Reduced discrimination between signals of danger and safety but not overgeneralization is linked to exposure to childhood adversity

Author

Klingelhöfer-Jens, M., primary, Hutterer, K., additional, Schiele, M., additional, Leehr, E.J., additional, Schümann, D., additional, Rosenkrantz, K., additional, Böhnlein, J., additional, Repple, J., additional, Deckert, J., additional, Domschke, K., additional, Dannlowski, U., additional, Lueken, U., additional, Reif, A., additional, Romanos, M., additional, Zwanzger, P., additional, Pauli, P., additional, Gamer, M., additional, and Lonsdorf, T.B., additional

Published
2023
Full Text
View/download PDF

17. Pharmakogenetik in der Psychiatrie: eine Standortbestimmung

Author

Müller, D. J., Brandl, E. J., Degenhardt, F., Domschke, K., Grabe, H., Gruber, O., Hebebrand, J., Maier, W., Menke, A., Riemenschneider, M., Rietschel, M., Rujescu, D., Schulze, T. G., Tebartz van Elst, L., Tüscher, O., Deckert, J., and das DGPPN Referat Neurobiologie und Genetik

Published
2018
Full Text
View/download PDF

20. Impact of NPSR1 gene variation on the neural correlates of sustained and phasic fear in spider phobia

Author

Leehr, E.J., primary, Brede, L.S., additional, Böhnlein, J., additional, Roesmann, K., additional, Gathmann, B., additional, Herrmann, M.J., additional, Junghöfer, M., additional, Schwarzmeier, H., additional, Seger, F., additional, Siminski, N., additional, Straube, T., additional, Klahn, A.L., additional, Weber, H., additional, Schiele, M.A., additional, Domschke, K., additional, Lueken, U., additional, and Dannlowski, U., additional

Published
2023
Full Text
View/download PDF

22. Association between polygenic risk scores of subcortical brain volumes and antidepressant response: a meta-analysis

Author

Oliva, V., primary, Martone, A., additional, Fanelli, G., additional, Domschke, K., additional, Minelli, A., additional, Gennarelli, M., additional, Martini, P., additional, Bortolomasi, M., additional, Maron, E., additional, Squassina, A., additional, Kasper, S., additional, Zohar, J., additional, Souery, D., additional, Montgomery, S., additional, Albani, D., additional, Forloni, G., additional, Ferentinos, P., additional, Rujescu, D., additional, Mendlewicz, J., additional, De Ronchi, D., additional, Baune, B.T., additional, Serretti, A., additional, and Fabbri, C., additional

Published
2023
Full Text
View/download PDF

23. Identifying organic causes of obsessive-compulsive disorder (OCD): The Freiburg-Diagnostic-Protocol for patients with OCD (FDP-OCD)

Author

Runge, K., primary, Reisert, M., additional, Feige, B., additional, Nickel, K., additional, Urbach, H., additional, Venhoff, N., additional, Tzschach, A., additional, Schiele, M.A., additional, Hannibal, L., additional, Prüss, H., additional, Domschke, K., additional, Tebartz van Elst, L., additional, and Endres, D., additional

Published
2023
Full Text
View/download PDF

24. GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: a potential neurogenetic pathway to panic disorder

Author

Deckert, J, Weber, H, Villmann, C, Lonsdorf, T B, Richter, J, Andreatta, M, Arias-Vasquez, A, Hommers, L, Kent, L, Schartner, C, Cichon, S, Wolf, C, Schaefer, N, von Collenberg, C R, Wachter, B, Blum, R, Schümann, D, Scharfenort, R, Schumacher, J, Forstner, A J, Baumann, C, Schiele, M A, Notzon, S, Zwanzger, P, Janzing, J G E, Galesloot, T, Kiemeney, L A, Gajewska, A, Glotzbach-Schoon, E, Mühlberger, A, Alpers, G, Fydrich, T, Fehm, L, Gerlach, A L, Kircher, T, Lang, T, Ströhle, A, Arolt, V, Wittchen, H-U, Kalisch, R, Büchel, C, Hamm, A, Nöthen, M M, Romanos, M, Domschke, K, Pauli, P, and Reif, A

Published
2017
Full Text
View/download PDF

27. Allelic variation in CRHR1 predisposes to panic disorder: evidence for biased fear processing

Author

Weber, H, Richter, J, Straube, B, Lueken, U, Domschke, K, Schartner, C, Klauke, B, Baumann, C, Pané-Farré, C, Jacob, C P, Scholz, C-J, Zwanzger, P, Lang, T, Fehm, L, Jansen, A, Konrad, C, Fydrich, T, Wittmann, A, Pfleiderer, B, Ströhle, A, Gerlach, A L, Alpers, G W, Arolt, V, Pauli, P, Wittchen, H-U, Kent, L, Hamm, A, Kircher, T, Deckert, J, and Reif, A

Published
2016
Full Text
View/download PDF

30. Associations between sleep health and amygdala reactivity to negative facial expressions in the UK Biobank cohort (N = 25,758)

Author

Schiel, JE, Tamm, S, Holub, F, Petri, R, Dashti, HS, Domschke, K, Feige, B, Lane, JM, Riemann, D, Rutter, MK, Saxena, R, Tahmasian, M, Wang, H, Kyle, SD, and Spiegelhalder, K

Abstract

Background Sleep health (SH) is considered a key determinant of human physiological and psychological well-being. In line with this, previous studies have found that poor sleep is associated with various psychiatric disorders, in particular, with anxiety and depression. Although little is known about the neural mechanisms underlying these associations, recent findings suggest that essential dimensions of SH are associated with altered amygdala reactivity (AR); however, evidence to date is inconsistent and reliant on small sample sizes. Methods To address this problem, the current preregistered study investigated associations between SH and AR to negative facial expressions in the UK Biobank cohort (25,758 participants). Drawing on a large sample size and consistent data acquisition, 5 dimensions of SH (insomnia symptoms, sleep duration, daytime sleepiness, chronotype, and sleep medication) were examined. Results Exploratory analyses revealed that short sleep duration was associated with decreased AR. The remaining SH dimensions and a composite measure of all SH dimensions were not associated with AR. Conclusions To our knowledge, this is the largest study to test associations between SH and AR. Habitual short sleep duration may be associated with decreased AR, possibly indicating compensation for impaired prefrontal processes and hampered emotion regulation.

Published
2022

31. Physical and mental health impact of COVID-19 on children, adolescents, and their families: The Collaborative Outcomes study on Health and Functioning during Infection Times - Children and Adolescents (COH-FIT-C&A)

Author

Solmi, M, Estradé, A, Thompson, T, Agorastos, A, Radua, J, Cortese, S, Dragioti, E, Leisch, F, Vancampfort, D, Thygesen, LC, Aschauer, H, Schloegelhofer, M, Akimova, E, Schneeberger, A, Huber, CG, Hasler, G, Conus, P, Cuénod, KQD, von Känel, R, Arrondo, G, Fusar-Poli, P, Gorwood, P, Llorca, PM, Krebs, MO, Scanferla, E, Kishimoto, T, Rabbani, G, Skonieczna-Żydecka, K, Brambilla, P, Favaro, A, Takamiya, A, Zoccante, L, Colizzi, M, Bourgin, J, Kamiński, K, Moghadasin, M, Seedat, S, Matthews, E, Wells, J, Vassilopoulou, E, Gadelha, A, Su, KP, Kwon, JS, Kim, M, Lee, TY, Papsuev, O, Manková, D, Boscutti, A, Gerunda, C, Saccon, D, Righi, E, Monaco, F, Croatto, G, Cereda, G, Demurtas, J, Brondino, N, Veronese, N, Enrico, P, Politi, P, Ciappolino, V, Pfennig, A, Bechdolf, A, Meyer-Lindenberg, A, Kahl, KG, Domschke, K, Bauer, M, Koutsouleris, N, Winter, S, Borgwardt, S, Bitter, I, Balazs, J, Czobor, P, Unoka, Z, Mavridis, D, Tsamakis, K, Bozikas, VP, Tunvirachaisakul, C, Maes, M, Rungnirundorn, T, Supasitthumrong, T, Haque, A, Brunoni, AR, Costardi, CG, Schuch, FB, Polanczyk, G, Luiz, JM, Fonseca, L, Aparicio, LV, Valvassori, SS, Nordentoft, M, Vendsborg, P, Hoffmann, SH, Sehli, J, Sartorius, N, Heuss, S, Guinart, D, Hamilton, J, Kane, J, Rubio, J, Sand, M, Marx, Wolf, Solmi, M, Estradé, A, Thompson, T, Agorastos, A, Radua, J, Cortese, S, Dragioti, E, Leisch, F, Vancampfort, D, Thygesen, LC, Aschauer, H, Schloegelhofer, M, Akimova, E, Schneeberger, A, Huber, CG, Hasler, G, Conus, P, Cuénod, KQD, von Känel, R, Arrondo, G, Fusar-Poli, P, Gorwood, P, Llorca, PM, Krebs, MO, Scanferla, E, Kishimoto, T, Rabbani, G, Skonieczna-Żydecka, K, Brambilla, P, Favaro, A, Takamiya, A, Zoccante, L, Colizzi, M, Bourgin, J, Kamiński, K, Moghadasin, M, Seedat, S, Matthews, E, Wells, J, Vassilopoulou, E, Gadelha, A, Su, KP, Kwon, JS, Kim, M, Lee, TY, Papsuev, O, Manková, D, Boscutti, A, Gerunda, C, Saccon, D, Righi, E, Monaco, F, Croatto, G, Cereda, G, Demurtas, J, Brondino, N, Veronese, N, Enrico, P, Politi, P, Ciappolino, V, Pfennig, A, Bechdolf, A, Meyer-Lindenberg, A, Kahl, KG, Domschke, K, Bauer, M, Koutsouleris, N, Winter, S, Borgwardt, S, Bitter, I, Balazs, J, Czobor, P, Unoka, Z, Mavridis, D, Tsamakis, K, Bozikas, VP, Tunvirachaisakul, C, Maes, M, Rungnirundorn, T, Supasitthumrong, T, Haque, A, Brunoni, AR, Costardi, CG, Schuch, FB, Polanczyk, G, Luiz, JM, Fonseca, L, Aparicio, LV, Valvassori, SS, Nordentoft, M, Vendsborg, P, Hoffmann, SH, Sehli, J, Sartorius, N, Heuss, S, Guinart, D, Hamilton, J, Kane, J, Rubio, J, Sand, M, and Marx, Wolf

Published
2022

32. The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults): Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic

Author

Solmi, M, Estradé, A, Thompson, T, Agorastos, A, Radua, J, Cortese, S, Dragioti, E, Leisch, F, Vancampfort, D, Thygesen, LC, Aschauer, H, Schloegelhofer, M, Akimova, E, Schneeberger, A, Huber, CG, Hasler, G, Conus, P, Cuénod, KQD, von Känel, R, Arrondo, G, Fusar-Poli, P, Gorwood, P, Llorca, PM, Krebs, MO, Scanferla, E, Kishimoto, T, Rabbani, G, Skonieczna-Żydecka, K, Brambilla, P, Favaro, A, Takamiya, A, Zoccante, L, Colizzi, M, Bourgin, J, Kamiński, K, Moghadasin, M, Seedat, S, Matthews, E, Wells, J, Vassilopoulou, E, Gadelha, A, Su, KP, Kwon, JS, Kim, M, Lee, TY, Papsuev, O, Manková, D, Boscutti, A, Gerunda, C, Saccon, D, Righi, E, Monaco, F, Croatto, G, Cereda, G, Demurtas, J, Brondino, N, Veronese, N, Enrico, P, Politi, P, Ciappolino, V, Pfennig, A, Bechdolf, A, Meyer-Lindenberg, A, Kahl, KG, Domschke, K, Bauer, M, Koutsouleris, N, Winter, S, Borgwardt, S, Bitter, I, Balazs, J, Czobor, P, Unoka, Z, Mavridis, D, Tsamakis, K, Bozikas, VP, Tunvirachaisakul, C, Maes, M, Rungnirundorn, T, Supasitthumrong, T, Haque, A, Brunoni, AR, Costardi, CG, Schuch, FB, Polanczyk, G, Luiz, JM, Fonseca, L, Aparicio, LV, Valvassori, SS, Nordentoft, M, Vendsborg, P, Hoffmann, SH, Sehli, J, Sartorius, N, Heuss, S, Guinart, D, Hamilton, J, Kane, J, Rubio, J, Sand, M, Berk, Michael, Solmi, M, Estradé, A, Thompson, T, Agorastos, A, Radua, J, Cortese, S, Dragioti, E, Leisch, F, Vancampfort, D, Thygesen, LC, Aschauer, H, Schloegelhofer, M, Akimova, E, Schneeberger, A, Huber, CG, Hasler, G, Conus, P, Cuénod, KQD, von Känel, R, Arrondo, G, Fusar-Poli, P, Gorwood, P, Llorca, PM, Krebs, MO, Scanferla, E, Kishimoto, T, Rabbani, G, Skonieczna-Żydecka, K, Brambilla, P, Favaro, A, Takamiya, A, Zoccante, L, Colizzi, M, Bourgin, J, Kamiński, K, Moghadasin, M, Seedat, S, Matthews, E, Wells, J, Vassilopoulou, E, Gadelha, A, Su, KP, Kwon, JS, Kim, M, Lee, TY, Papsuev, O, Manková, D, Boscutti, A, Gerunda, C, Saccon, D, Righi, E, Monaco, F, Croatto, G, Cereda, G, Demurtas, J, Brondino, N, Veronese, N, Enrico, P, Politi, P, Ciappolino, V, Pfennig, A, Bechdolf, A, Meyer-Lindenberg, A, Kahl, KG, Domschke, K, Bauer, M, Koutsouleris, N, Winter, S, Borgwardt, S, Bitter, I, Balazs, J, Czobor, P, Unoka, Z, Mavridis, D, Tsamakis, K, Bozikas, VP, Tunvirachaisakul, C, Maes, M, Rungnirundorn, T, Supasitthumrong, T, Haque, A, Brunoni, AR, Costardi, CG, Schuch, FB, Polanczyk, G, Luiz, JM, Fonseca, L, Aparicio, LV, Valvassori, SS, Nordentoft, M, Vendsborg, P, Hoffmann, SH, Sehli, J, Sartorius, N, Heuss, S, Guinart, D, Hamilton, J, Kane, J, Rubio, J, Sand, M, and Berk, Michael

Published
2022

33. Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Author

Maihofer, AX, Choi, KW, Coleman, JR, Daskalakis, NP, Denckla, CA, Ketema, E, Morey, RA, Polimanti, R, Ratanatharathorn, A, Torres, K, Wingo, AP, Zai, CC, Aiello, AE, Almli, LM, Amstadter, AB, Andersen, SB, Andreassen, OA, Arbisi, PA, Ashley-Koch, AE, Austin, SB, Avdibegovic, E, Borglum, AD, Babic, D, Baekvad-Hansen, M, Baker, DG, Beckham, JC, Bierut, LJ, Bisson, J, Boks, MP, Bolger, EA, Bradley, B, Brashear, M, Breen, G, Bryant, RA, Bustamante, AC, Bybjerg-Grauholm, J, Calabrese, JR, Caldas-de-Almeida, JM, Chen, C-Y, Dale, AM, Dalvie, S, Deckert, J, Delahanty, DL, Dennis, MF, Disner, SG, Domschke, K, Duncan, LE, Kulenovic, AD, Erbes, CR, Evans, A, Farrer, LA, Feeny, NC, Flory, JD, Forbes, D, Franz, CE, Galea, S, Garrett, ME, Gautam, A, Gelaye, B, Gelernter, J, Geuze, E, Gillespie, CF, Goci, A, Gordon, SD, Guffanti, G, Hammamieh, R, Hauser, MA, Heath, AC, Hemmings, SMJ, Hougaard, DM, Jakovljevic, M, Jett, M, Johnson, EO, Jones, I, Jovanovic, T, Qin, X-J, Karstoft, K-I, Kaufman, ML, Kessler, RC, Khan, A, Kimbrel, NA, King, AP, Koen, N, Kranzler, HR, Kremen, WS, Lawford, BR, Lebois, LAM, Lewis, C, Liberzon, I, Linnstaedt, SD, Logue, MW, Lori, A, Lugonja, B, Luykx, JJ, Lyons, MJ, Maples-Keller, JL, Marmar, C, Martin, NG, Maurer, D, Mavissakalian, MR, McFarlane, A, McGlinchey, RE, McLaughlin, KA, McLean, SA, Mehta, D, Mellor, R, Michopoulos, V, Milberg, W, Miller, MW, Morris, CP, Mors, O, Mortensen, PB, Nelson, EC, Nordentoft, M, Norman, SB, O'Donnell, M, Orcutt, HK, Panizzon, MS, Peters, ES, Peterson, AL, Peverill, M, Pietrzak, RH, Polusny, MA, Rice, JP, Risbrough, VB, Roberts, AL, Rothbaum, AO, Rothbaum, BO, Roy-Byrne, P, Ruggiero, KJ, Rung, A, Rutten, BPF, Saccone, NL, Sanchez, SE, Schijven, D, Seedat, S, Seligowski, A, Seng, JS, Sheerin, CM, Silove, D, Smith, AK, Smoller, JW, Sponheim, SR, Stein, DJ, Stevens, JS, Teicher, MH, Thompson, WK, Trapido, E, Uddin, M, Ursano, RJ, van den Heuvel, LL, Van Hooff, M, Vermetten, E, Vinkers, CH, Voisey, J, Wang, Y, Wang, Z, Werge, T, Williams, MA, Williamson, DE, Winternitz, S, Wolf, C, Wolf, EJ, Yehuda, R, Young, KA, Young, RM, Zhao, H, Zoellner, LA, Haas, M, Lasseter, H, Provost, AC, Salem, RM, Sebat, J, Shaffer, RA, Wu, T, Ripke, S, Daly, MJ, Ressler, KJ, Koenen, KC, Stein, MB, Nievergelt, CM, Maihofer, AX, Choi, KW, Coleman, JR, Daskalakis, NP, Denckla, CA, Ketema, E, Morey, RA, Polimanti, R, Ratanatharathorn, A, Torres, K, Wingo, AP, Zai, CC, Aiello, AE, Almli, LM, Amstadter, AB, Andersen, SB, Andreassen, OA, Arbisi, PA, Ashley-Koch, AE, Austin, SB, Avdibegovic, E, Borglum, AD, Babic, D, Baekvad-Hansen, M, Baker, DG, Beckham, JC, Bierut, LJ, Bisson, J, Boks, MP, Bolger, EA, Bradley, B, Brashear, M, Breen, G, Bryant, RA, Bustamante, AC, Bybjerg-Grauholm, J, Calabrese, JR, Caldas-de-Almeida, JM, Chen, C-Y, Dale, AM, Dalvie, S, Deckert, J, Delahanty, DL, Dennis, MF, Disner, SG, Domschke, K, Duncan, LE, Kulenovic, AD, Erbes, CR, Evans, A, Farrer, LA, Feeny, NC, Flory, JD, Forbes, D, Franz, CE, Galea, S, Garrett, ME, Gautam, A, Gelaye, B, Gelernter, J, Geuze, E, Gillespie, CF, Goci, A, Gordon, SD, Guffanti, G, Hammamieh, R, Hauser, MA, Heath, AC, Hemmings, SMJ, Hougaard, DM, Jakovljevic, M, Jett, M, Johnson, EO, Jones, I, Jovanovic, T, Qin, X-J, Karstoft, K-I, Kaufman, ML, Kessler, RC, Khan, A, Kimbrel, NA, King, AP, Koen, N, Kranzler, HR, Kremen, WS, Lawford, BR, Lebois, LAM, Lewis, C, Liberzon, I, Linnstaedt, SD, Logue, MW, Lori, A, Lugonja, B, Luykx, JJ, Lyons, MJ, Maples-Keller, JL, Marmar, C, Martin, NG, Maurer, D, Mavissakalian, MR, McFarlane, A, McGlinchey, RE, McLaughlin, KA, McLean, SA, Mehta, D, Mellor, R, Michopoulos, V, Milberg, W, Miller, MW, Morris, CP, Mors, O, Mortensen, PB, Nelson, EC, Nordentoft, M, Norman, SB, O'Donnell, M, Orcutt, HK, Panizzon, MS, Peters, ES, Peterson, AL, Peverill, M, Pietrzak, RH, Polusny, MA, Rice, JP, Risbrough, VB, Roberts, AL, Rothbaum, AO, Rothbaum, BO, Roy-Byrne, P, Ruggiero, KJ, Rung, A, Rutten, BPF, Saccone, NL, Sanchez, SE, Schijven, D, Seedat, S, Seligowski, A, Seng, JS, Sheerin, CM, Silove, D, Smith, AK, Smoller, JW, Sponheim, SR, Stein, DJ, Stevens, JS, Teicher, MH, Thompson, WK, Trapido, E, Uddin, M, Ursano, RJ, van den Heuvel, LL, Van Hooff, M, Vermetten, E, Vinkers, CH, Voisey, J, Wang, Y, Wang, Z, Werge, T, Williams, MA, Williamson, DE, Winternitz, S, Wolf, C, Wolf, EJ, Yehuda, R, Young, KA, Young, RM, Zhao, H, Zoellner, LA, Haas, M, Lasseter, H, Provost, AC, Salem, RM, Sebat, J, Shaffer, RA, Wu, T, Ripke, S, Daly, MJ, Ressler, KJ, Koenen, KC, Stein, MB, and Nievergelt, CM

Abstract

BACKGROUND: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). METHODS: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. RESULTS: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. CONCLUSIONS: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.

Published
2022

34. Identifying the Common Genetic Basis of Antidepressant Response.

Author

Pain, O, Hodgson, K, Trubetskoy, V, Ripke, S, Marshe, VS, Adams, MJ, Byrne, EM, Campos, AI, Carrillo-Roa, T, Cattaneo, A, Als, TD, Souery, D, Dernovsek, MZ, Fabbri, C, Hayward, C, Henigsberg, N, Hauser, J, Kennedy, JL, Lenze, EJ, Lewis, G, Müller, DJ, Martin, NG, Mulsant, BH, Mors, O, Perroud, N, Porteous, DJ, Rentería, ME, Reynolds, CF, Rietschel, M, Uher, R, Wigmore, EM, Maier, W, Wray, NR, Aitchison, KJ, Arolt, V, Baune, BT, Biernacka, JM, Bondolfi, G, Domschke, K, Kato, M, Li, QS, Liu, Y-L, Serretti, A, Tsai, S-J, Turecki, G, Weinshilboum, R, GSRD Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, McIntosh, AM, Lewis, CM, Pain, O, Hodgson, K, Trubetskoy, V, Ripke, S, Marshe, VS, Adams, MJ, Byrne, EM, Campos, AI, Carrillo-Roa, T, Cattaneo, A, Als, TD, Souery, D, Dernovsek, MZ, Fabbri, C, Hayward, C, Henigsberg, N, Hauser, J, Kennedy, JL, Lenze, EJ, Lewis, G, Müller, DJ, Martin, NG, Mulsant, BH, Mors, O, Perroud, N, Porteous, DJ, Rentería, ME, Reynolds, CF, Rietschel, M, Uher, R, Wigmore, EM, Maier, W, Wray, NR, Aitchison, KJ, Arolt, V, Baune, BT, Biernacka, JM, Bondolfi, G, Domschke, K, Kato, M, Li, QS, Liu, Y-L, Serretti, A, Tsai, S-J, Turecki, G, Weinshilboum, R, GSRD Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, McIntosh, AM, and Lewis, CM

Abstract

BACKGROUND: Antidepressants are a first-line treatment for depression. However, only a third of individuals experience remission after the first treatment. Common genetic variation, in part, likely regulates antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic analysis of prospectively assessed antidepressant response in major depressive disorder to gain insight into the underlying biology and enable out-of-sample prediction. METHODS: Genome-wide analysis of remission (n remit = 1852, n nonremit = 3299) and percentage improvement (n = 5218) was performed. Single nucleotide polymorphism-based heritability was estimated using genome-wide complex trait analysis. Genetic covariance with eight mental health phenotypes was estimated using polygenic scores/AVENGEME. Out-of-sample prediction of antidepressant response polygenic scores was assessed. Gene-level association analysis was performed using MAGMA and transcriptome-wide association study. Tissue, pathway, and drug binding enrichment were estimated using MAGMA. RESULTS: Neither genome-wide association study identified genome-wide significant associations. Single nucleotide polymorphism-based heritability was significantly different from zero for remission (h 2 = 0.132, SE = 0.056) but not for percentage improvement (h 2 = -0.018, SE = 0.032). Better antidepressant response was negatively associated with genetic risk for schizophrenia and positively associated with genetic propensity for educational attainment. Leave-one-out validation of antidepressant response polygenic scores demonstrated significant evidence of out-of-sample prediction, though results varied in external cohorts. Gene-based analyses identified ETV4 and DHX8 as significantly associated with antidepressant response. CONCLUSIONS: This study demonstrates that antidepressant response is influenced by common genetic variation, has a genetic overlap sc

Published
2022

35. Rare copy number variation in posttraumatic stress disorder.

Author

Maihofer, AX, Engchuan, W, Huguet, G, Klein, M, MacDonald, JR, Shanta, O, Thiruvahindrapuram, B, Jean-Louis, M, Saci, Z, Jacquemont, S, Scherer, SW, Ketema, E, Aiello, AE, Amstadter, AB, Avdibegović, E, Babic, D, Baker, DG, Bisson, JI, Boks, MP, Bolger, EA, Bryant, RA, Bustamante, AC, Caldas-de-Almeida, JM, Cardoso, G, Deckert, J, Delahanty, DL, Domschke, K, Dunlop, BW, Dzubur-Kulenovic, A, Evans, A, Feeny, NC, Franz, CE, Gautam, A, Geuze, E, Goci, A, Hammamieh, R, Jakovljevic, M, Jett, M, Jones, I, Kaufman, ML, Kessler, RC, King, AP, Kremen, WS, Lawford, BR, Lebois, LAM, Lewis, C, Liberzon, I, Linnstaedt, SD, Lugonja, B, Luykx, JJ, Lyons, MJ, Mavissakalian, MR, McLaughlin, KA, McLean, SA, Mehta, D, Mellor, R, Morris, CP, Muhie, S, Orcutt, HK, Peverill, M, Ratanatharathorn, A, Risbrough, VB, Rizzo, A, Roberts, AL, Rothbaum, AO, Rothbaum, BO, Roy-Byrne, P, Ruggiero, KJ, Rutten, BPF, Schijven, D, Seng, JS, Sheerin, CM, Sorenson, MA, Teicher, MH, Uddin, M, Ursano, RJ, Vinkers, CH, Voisey, J, Weber, H, Winternitz, S, Xavier, M, Yang, R, McD Young, R, Zoellner, LA, Psychiatric Genomics Consortium PTSD Working Group, Psychiatric Genomics Consortium CNV Working Group, Salem, RM, Shaffer, RA, Wu, T, Ressler, KJ, Stein, MB, Koenen, KC, Sebat, J, Nievergelt, CM, Maihofer, AX, Engchuan, W, Huguet, G, Klein, M, MacDonald, JR, Shanta, O, Thiruvahindrapuram, B, Jean-Louis, M, Saci, Z, Jacquemont, S, Scherer, SW, Ketema, E, Aiello, AE, Amstadter, AB, Avdibegović, E, Babic, D, Baker, DG, Bisson, JI, Boks, MP, Bolger, EA, Bryant, RA, Bustamante, AC, Caldas-de-Almeida, JM, Cardoso, G, Deckert, J, Delahanty, DL, Domschke, K, Dunlop, BW, Dzubur-Kulenovic, A, Evans, A, Feeny, NC, Franz, CE, Gautam, A, Geuze, E, Goci, A, Hammamieh, R, Jakovljevic, M, Jett, M, Jones, I, Kaufman, ML, Kessler, RC, King, AP, Kremen, WS, Lawford, BR, Lebois, LAM, Lewis, C, Liberzon, I, Linnstaedt, SD, Lugonja, B, Luykx, JJ, Lyons, MJ, Mavissakalian, MR, McLaughlin, KA, McLean, SA, Mehta, D, Mellor, R, Morris, CP, Muhie, S, Orcutt, HK, Peverill, M, Ratanatharathorn, A, Risbrough, VB, Rizzo, A, Roberts, AL, Rothbaum, AO, Rothbaum, BO, Roy-Byrne, P, Ruggiero, KJ, Rutten, BPF, Schijven, D, Seng, JS, Sheerin, CM, Sorenson, MA, Teicher, MH, Uddin, M, Ursano, RJ, Vinkers, CH, Voisey, J, Weber, H, Winternitz, S, Xavier, M, Yang, R, McD Young, R, Zoellner, LA, Psychiatric Genomics Consortium PTSD Working Group, Psychiatric Genomics Consortium CNV Working Group, Salem, RM, Shaffer, RA, Wu, T, Ressler, KJ, Stein, MB, Koenen, KC, Sebat, J, and Nievergelt, CM

Abstract

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10-8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q < 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further.

Published
2022

40. P.0882 A meta-analysis of polygenic risk scores for mood disorders, neuroticism, and schizophrenia in antidepressant response

Author

Fanelli, G., primary, Fabbri, C., additional, Domschke, K., additional, Minelli, A., additional, Gennarelli, M., additional, Martini, P., additional, Bortolomasi, M., additional, Maron, E., additional, Squassina, A., additional, Kasper, S., additional, Zohar, J., additional, Souery, D., additional, Montgomery, S., additional, Albani, D., additional, Forloni, G., additional, Ferentinos, P., additional, Rujescu, D., additional, Mendlewicz, J., additional, De Ronchi, D., additional, Pharmacogenomics & Transcriptomics TWG, E.C.N.P., additional, Baune, B.T., additional, and Serretti, A., additional

Published
2021
Full Text
View/download PDF

41. P.0636 A common CDH13 variant is associated with agreeableness and neural responses to working memory tasks in attention-deficit/hyperactivity disorder

Author

Ziegler, G., primary, Ehlis, A.C., additional, Weber, H., additional, Vitale, M.R., additional, Zöller, J.E.M., additional, Ku, H.P., additional, Schiele, M.A., additional, Kürbitz, L.I., additional, Romanos, M., additional, Pauli, P., additional, Kalisch, R., additional, Zwanzger, P., additional, Domschke, K., additional, Fallgatter, A.J., additional, Reif, A., additional, and Lesch, K.P., additional

Published
2021
Full Text
View/download PDF

43. A Common CDH13 Variant Is Associated with Low Agreeableness and Neural Responses to Working Memory Tasks in ADHD

Author

Ziegler, G.C., Ehlis, A.C., Weber, H., Vitale, M.R., Zoller, J.E.M., Ku, H.P., Schiele, M.A., Kurbitz, L.I., Romanos, M., Pauli, P., Kalisch, R., Zwanzger, P., Domschke, K., Fallgatter, A.J., Reif, A., Lesch, K.P., RS: MHeNs - R3 - Neuroscience, and Psychiatrie & Neuropsychologie

Subjects
RISK, neurodevelopment, ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, agreeableness, AUTISM SPECTRUM DISORDER, executive functions, GENE, working memory, POLYMORPHISM, Big Five, ADHD, PERSONALITY-TRAITS, GENOME-WIDE ASSOCIATION, BRAIN, COMORBIDITY, CDH13, METAANALYSIS
Abstract

The cell-cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-dependent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was significantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect limited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited significantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of CDH13 is associated with personality traits and impacts neural processing during working memory tasks. Thus, CDH13 might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD.

Published
2021

49. Assessment of Bidirectional Relationships Between Physical Activity and Depression Among Adults A 2-Sample Mendelian Randomization Study

Author

Choi, K.W., Chen, C.Y., Stein, M.B., Klimentidis, Y.C., Wang, M.J., Koenen, K.C., Smoller, J.W., Wray, N.R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E.M., Abdellaoui, A., Adams, M.J., Agerbo, E., Air, T., 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., Hvarregaard, J., 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., Forstner, A.J., Frank, J., 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., Jorgenson, E., Knowles, J.A., Kohane, I.S., Kraft, J., Kretzschmar, W., Krogh, J., Kutalik, Z., Li, Y.H., Lind, P.A., MacIntyre, D.J., MacKinnon, D.F., Maier, R.M., Marchini, J., 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., Saeed, 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., Streit, F., Strohmaier, J., Tansey, K.E., Teismann, H., Teumer, A., Thompson, W., Thomson, P.A., Thorgeirsson, T.E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A.G., Umbricht, D., Auwera, S. van der, Hemert, A.M. van, Viktorin, A., Visscher, P.M., Wang, Y.P., Webb, B.T., Weinsheimer, S.M., Wellmann, J., Willemsen, G., Witt, S.H., Wu, Y., Xi, H.L.S., Yang, J., Zhang, F.T., Arolt, V., Baune, B.T., 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., Nordentoft, M., Nothen, M.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., Rietschel, M., Schaefer, C., Schulze, T.G., Stefansson, K., Tiemeier, H., Uher, R., Volzke, H., Weissman, M.M., Werge, T., Lewis, C.M., Levinson, D.F., Breen, G., Borglum, A.D., Sullivan, P.F., Major Depressive Disorder Working, Epidemiology, Internal Medicine, Child and Adolescent Psychiatry / Psychology, Psychiatry, Biological Psychology, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, and Adult Psychiatry

Subjects
Adult, DISORDER, medicine.medical_specialty, Genome-wide association study, EXERCISE, CAUSALITY, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, PEOPLE, Internal medicine, Accelerometry, Mendelian randomization, SCHIZOPHRENIA, Humans, Medicine, ANXIETY, Exercise, RISK, Depressive Disorder, Major, business.industry, Case-control study, SEDENTARY BEHAVIOR, Mendelian Randomization Analysis, Odds ratio, ASSOCIATION, Protective Factors, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Sample size determination, Case-Control Studies, Meta-analysis, Major depressive disorder, Self Report, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Importance: Increasing evidence shows that physical activity is associated with reduced risk for depression, pointing to a potential modifiable target for prevention. However, the causality and direction of this association are not clear; physical activity may protect against depression, and/or depression may result in decreased physical activity.Objective: To examine bidirectional relationships between physical activity and depression using a genetically informed method for assessing potential causal inference.Design, Setting, and Participants: This 2-sample mendelian randomization (MR) used independent top genetic variants associated with 2 physical activity phenotypes-self-reported (n = 377 234) and objective accelerometer-based (n = 91 084)-and with major depressive disorder (MDD) (n = 143 265) as genetic instruments from the largest available, nonoverlapping genome-wide association studies (GWAS). GWAS were previously conducted in diverse observational cohorts, including the UK Biobank (for physical activity) and participating studies in the Psychiatric Genomics Consortium (for MDD) among adults of European ancestry. Mendelian randomization estimates from each genetic instrument were combined using inverse variance weighted meta-analysis, with alternate methods (eg, weighted median, MR Egger, MR-Pleiotropy Residual Sum and Outlier [PRESSO]) and multiple sensitivity analyses to assess horizontal pleiotropy and remove outliers. Data were analyzed from May 10 through July 31, 2018.Main Outcomes and Measures: MDD and physical activity.Results: GWAS summary data were available for a combined sample size of 611 583 adult participants. Mendelian randomization evidence suggested a protective relationship between accelerometer-based activity and MDD (odds ratio [OR], 0.74 for MDD per 1-SD increase in mean acceleration; 95% CI, 0.59-0.92; P = .006). In contrast, there was no statistically significant relationship between MDD and accelerometer-based activity (β = -0.08 in mean acceleration per MDD vs control status; 95% CI, -0.47 to 0.32; P = .70). Furthermore, there was no significant relationship between self-reported activity and MDD (OR, 1.28 for MDD per 1-SD increase in metabolic-equivalent minutes of reported moderate-to-vigorous activity; 95% CI, 0.57-3.37; P = .48), or between MDD and self-reported activity (β = 0.02 per MDD in standardized metabolic-equivalent minutes of reported moderate-to-vigorous activity per MDD vs control status; 95% CI, -0.008 to 0.05; P = .15).Conclusions and Relevance: Using genetic instruments identified from large-scale GWAS, robust evidence supports a protective relationship between objectively assessed-but not self-reported-physical activity and the risk for MDD. Findings point to the importance of objective measurement of physical activity in epidemiologic studies of mental health and support the hypothesis that enhancing physical activity may be an effective prevention strategy for depression.

Published
2019

Catalog

Books, media, physical & digital resources
See catalog results