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2. Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression

Author

Culverhouse, R C, Saccone, N L, Horton, A C, Ma, Y, Anstey, K J, Banaschewski, T, Burmeister, M, Cohen-Woods, S, Etain, B, Fisher, H L, Goldman, N, Guillaume, S, Horwood, J, Juhasz, G, Lester, K J, Mandelli, L, Middeldorp, C M, Olié, E, Villafuerte, S, Air, T M, Araya, R, Bowes, L, Burns, R, Byrne, E M, Coffey, C, Coventry, W L, Gawronski, K AB, Glei, D, Hatzimanolis, A, Hottenga, J-J, Jaussent, I, Jawahar, C, Jennen-Steinmetz, C, Kramer, J R, Lajnef, M, Little, K, zu Schwabedissen, H M, Nauck, M, Nederhof, E, Petschner, P, Peyrot, W J, Schwahn, C, Sinnamon, G, Stacey, D, Tian, Y, Toben, C, Van der Auwera, S, Wainwright, N, Wang, J-C, Willemsen, G, Anderson, I M, Arolt, V, Åslund, C, Bagdy, G, Baune, B T, Bellivier, F, Boomsma, D I, Courtet, P, Dannlowski, U, de Geus, E JC, Deakin, J FW, Easteal, S, Eley, T, Fergusson, D M, Goate, A M, Gonda, X, Grabe, H J, Holzman, C, Johnson, E O, Kennedy, M, Laucht, M, Martin, N G, Munafò, M R, Nilsson, K W, Oldehinkel, A J, Olsson, C A, Ormel, J, Otte, C, Patton, G C, Penninx, B WJH, Ritchie, K, Sarchiapone, M, Scheid, J M, Serretti, A, Smit, J H, Stefanis, N C, Surtees, P G, Völzke, H, Weinstein, M, Whooley, M, Nurnberger, J I, Jr, Breslau, N, and Bierut, L J

Published
2018
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3. GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium

Author

Trampush, J W, Yang, M LZ, Yu, J, Knowles, E, Davies, G, Liewald, D C, Starr, J M, Djurovic, S, Melle, I, Sundet, K, Christoforou, A, Reinvang, I, DeRosse, P, Lundervold, A J, Steen, V M, Espeseth, T, Räikkönen, K, Widen, E, Palotie, A, Eriksson, J G, Giegling, I, Konte, B, Roussos, P, Giakoumaki, S, Burdick, K E, Payton, A, Ollier, W, Horan, M, Chiba-Falek, O, Attix, D K, Need, A C, Cirulli, E T, Voineskos, A N, Stefanis, N C, Avramopoulos, D, Hatzimanolis, A, Arking, D E, Smyrnis, N, Bilder, R M, Freimer, N A, Cannon, T D, London, E, Poldrack, R A, Sabb, F W, Congdon, E, Conley, E D, Scult, M A, Dickinson, D, Straub, R E, Donohoe, G, Morris, D, Corvin, A, Gill, M, Hariri, A R, Weinberger, D R, Pendleton, N, Bitsios, P, Rujescu, D, Lahti, J, Le Hellard, S, Keller, M C, Andreassen, O A, Deary, I J, Glahn, D C, Malhotra, A K, and Lencz, T

Published
2017
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4. Erratum: GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium

Author

Trampush, J W, Yang, M L Z, Yu, J, Knowles, E, Davies, G, Liewald, D C, Starr, J M, Djurovic, S, Melle, I, Sundet, K, Christoforou, A, Reinvang, I, DeRosse, P, Lundervold, A J, Steen, V M, Espeseth, T, Räikkönen, K, Widen, E, Palotie, A, Eriksson, J G, Giegling, I, Konte, B, Roussos, P, Giakoumaki, S, Burdick, K E, Payton, A, Ollier, W, Horan, M, Chiba-Falek, O, Attix, D K, Need, A C, Cirulli, E T, Voineskos, A N, Stefanis, N C, Avramopoulos, D, Hatzimanolis, A, Arking, D E, Smyrnis, N, Bilder, R M, Freimer, N A, Cannon, T D, London, E, Poldrack, R A, Sabb, F W, Congdon, E, Conley, E D, Scult, M A, Dickinson, D, Straub, R E, Donohoe, G, Morris, D, Corvin, A, Gill, M, Hariri, A R, Weinberger, D R, Pendleton, N, Bitsios, P, Rujescu, D, Lahti, J, Le Hellard, S, Keller, M C, Andreassen, O A, Deary, I J, Glahn, D C, Malhotra, A K, and Lencz, T

Published
2017
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11. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G., Lam, M., Harris, S. E., TRAMPUSH, J. W., LUCIANO, M., HILL, W. D., HAGENAARS, S. P., RITCHIE, S. J., MARIONI, R. E., FAWNS-RITCHIE, C., LIEWALD, D. C. M., OKELY, J. A., AHOLA-OLLI, A. V., BARNES, C. L. K., Bertram, L., BIS, J. C., BURDICK, K. E., CHRISTOFOROU, A., DEROSSE, P., Djurovic, S., ESPESETH, T., GIAKOUMAKI, S., GIDDALURU, S., GUSTAVSON, D. E., Hayward, C., Hofer, E., KARLSSON, R., KNOWLES, E., Lahti, J., Leber, M., MATHER, K. A., Melle, I., Morris, D., OLDMEADOW, C., PALVIAINEN, T., PAYTON, A., PAZOKI, R., PETROVIC, K., Reynolds, C. A., SARGURUPREMRAJ, M., Scholz, M., Smith, J. A., SMITH, A. V., TERZIKHAN, N., THALAMUTHU, A., TROMPET, S., VAN DER LEE, S. J., WARE, E. B., WINDHAM, B. G., WRIGHT, M. J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., ANDREASSEN, O. A., ARMSTRONG, N. J., ASSAREH, A. A., ATTIA, J. R., ATTIX, D., AVRAMOPOULOS, D., BENNETT, D. A., BOHMER, A. C., BOYLE, P. A., BRODATY, H., Campbell, H., CANNON, T. D., CIRULLI, E. T., CONGDON, E., CONLEY, E. D., CORLEY, J., COX, S. R., DALE, A. M., DEHGHAN, A., Dick, D., Dickinson, D., ERIKSSON, J. G., EVANGELOU, E., FAUL, J. D., Ford, I., FREIMER, N. A., Gao, H., Giegling, I., GILLESPIE, N. A., GORDON, S. D., GOTTESMAN, R. F., GRISWOLD, M. E., GUDNASON, V., HARRIS, T. B., HARTMANN, A. M., Hatzimanolis, A., Heiss, G., HOLLIDAY, E. G., Joshi, P. K., KAHONEN, M., KARDIA, S. L. R., KARLSSON, I., KLEINEIDAM, L., KNOPMAN, D. S., KOCHAN, N. A., Konte, B., KWOK, J. B., LE HELLARD, S., Lee, T., LEHTIMAKI, T., Li, S. C., Lill, C. M., Liu, T., KOINI, M., London, E., LONGSTRETH, W. T., Jr., LOPEZ, O. L., LOUKOLA, A., LUCK, T., LUNDERVOLD, A. J., LUNDQUIST, A., LYYTIKAINEN, L. P., Martin, N. G., MONTGOMERY, G. W., MURRAY, A. D., NEED, A. C., NOORDAM, R., Nyberg, L., OLLIER, W., PAPENBERG, G., PATTIE, A., POLASEK, O., POLDRACK, R. A., PSATY, B. M., REPPERMUND, S., RIEDEL-HELLER, S. G., ROSE, R. J., ROTTER, J. I., ROUSSOS, P., ROVIO, S. P., SABA, Y., SABB, F. W., SACHDEV, P. S., SATIZABAL, C. L., Schmid, M., Scott, R. J., SCULT, M. A., SIMINO, J., SLAGBOOM, P. E., SMYRNIS, N., Soumare, A., Stefanis, N. C., STOTT, D. J., STRAUB, R. E., SUNDET, K., Taylor, A. M., TAYLOR, K. D., TZOULAKI, I., Tzourio, C., Uitterlinden, A., Vitart, V., VOINESKOS, A. N., Kaprio, J., Wagner, M., Wagner, H., WEINHOLD, L., WEN, K. H., WIDEN, E., Yang, Q., Zhao, W., ADAMS, H. H. H., ARKING, D. E., Bilder, R. M., BITSIOS, P., BOERWINKLE, E., CHIBA-FALEK, O., Corvin, A., DE JAGER, P. L., Debette, S., Donohoe, G., Elliott, P., FITZPATRICK, A. L., Gill, M., GLAHN, D. C., HAGG, S., HANSELL, N. K., HARIRI, A. R., Ikram, M. A., JUKEMA, J. W., VUOKSIMAA, E., KELLER, M. C., KREMEN, W. S., LAUNER, L., LINDENBERGER, U., Palotie, A., PEDERSEN, N. L., PENDLETON, N., PORTEOUS, D. J., RAIKKONEN, K., RAITAKARI, O. T., Ramirez, A., REINVANG, I., RUDAN, I., DAN, Rujescu, Schmidt, R., Schmidt, H., SCHOFIELD, P. W., STARR, J. M., STEEN, V. M., TROLLOR, J. N., TURNER, S. T., VAN DUIJN, C. M., VILLRINGER, A., WEINBERGER, D. R., WEIR, D. R., WILSON, J. F., Malhotra, A., MCINTOSH, A. M., GALE, C. R., SESHADRI, S., MOSLEY, T. H., Jr., BRESSLER, J., Lencz, T., DEARY, I. J., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
VINTAGE, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, HEALTHY, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Abstract

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

Published
2019
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15. Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression

Author

Culverhouse, R. C., Saccone, N. L., Horton, A. C., Ma, Y., Anstey, K. J., Banaschewski, T., Burmeister, M., Cohen-Woods, S., Etain, B., Fisher, H. L., Goldman, N., Guillaume, S., Horwood, J., Juhasz, G., Lester, K. J., Mandelli, L., Middeldorp, C. M., Olie, E., Villafuerte, S., Air, T. M., Araya, R., Bowes, L., Burns, R., Byrne, E. M., Coffey, C., Coventry, W. L., Gawronski, K. A. B., Glei, D., Hatzimanolis, A., Hottenga, J-J, Jaussent, I., Jawahar, C., Jennen-Steinmetz, C., Kramer, J. R., Lajnef, M., Little, K., zu Schwabedissen, H. M., Nauck, M., Nederhof, E., Petschner, P., Peyrot, W. J., Schwahn, C., Sinnamon, G., Stacey, D., Tian, Y., Toben, C., Van der Auwera, S., Wainwright, N., Wang, J-C, Willemsen, G., Anderson, I. M., Arolt, V., Åslund, Cecilia, Bagdy, G., Baune, B. T., Bellivier, F., Boomsma, D. I., Courtet, P., Dannlowski, U., de Geus, E. J. C., Deakin, J. F. W., Easteal, S., Eley, T., Fergusson, D. M., Goate, A. M., Gonda, X., Grabe, H. J., Holzman, C., Johnson, E. O., Kennedy, M., Laucht, M., Martin, N. G., Munafo, M. R., Nillson, Kent W., Oldehinkel, A. J., Olsson, C. A., Ormel, J., Otte, C., Patton, G. C., Penninx, B. W. J. H., Ritchie, K., Sarchiapone, M., Scheid, J. M., Serretti, A., Smit, J. H., Stefanis, N. C., Surtees, P. G., Voelzke, H., Weinstein, M., Whooley, M., Nurnberger, J. I., Jr., Breslau, N., Bierut, L. J., Culverhouse, R. C., Saccone, N. L., Horton, A. C., Ma, Y., Anstey, K. J., Banaschewski, T., Burmeister, M., Cohen-Woods, S., Etain, B., Fisher, H. L., Goldman, N., Guillaume, S., Horwood, J., Juhasz, G., Lester, K. J., Mandelli, L., Middeldorp, C. M., Olie, E., Villafuerte, S., Air, T. M., Araya, R., Bowes, L., Burns, R., Byrne, E. M., Coffey, C., Coventry, W. L., Gawronski, K. A. B., Glei, D., Hatzimanolis, A., Hottenga, J-J, Jaussent, I., Jawahar, C., Jennen-Steinmetz, C., Kramer, J. R., Lajnef, M., Little, K., zu Schwabedissen, H. M., Nauck, M., Nederhof, E., Petschner, P., Peyrot, W. J., Schwahn, C., Sinnamon, G., Stacey, D., Tian, Y., Toben, C., Van der Auwera, S., Wainwright, N., Wang, J-C, Willemsen, G., Anderson, I. M., Arolt, V., Åslund, Cecilia, Bagdy, G., Baune, B. T., Bellivier, F., Boomsma, D. I., Courtet, P., Dannlowski, U., de Geus, E. J. C., Deakin, J. F. W., Easteal, S., Eley, T., Fergusson, D. M., Goate, A. M., Gonda, X., Grabe, H. J., Holzman, C., Johnson, E. O., Kennedy, M., Laucht, M., Martin, N. G., Munafo, M. R., Nillson, Kent W., Oldehinkel, A. J., Olsson, C. A., Ormel, J., Otte, C., Patton, G. C., Penninx, B. W. J. H., Ritchie, K., Sarchiapone, M., Scheid, J. M., Serretti, A., Smit, J. H., Stefanis, N. C., Surtees, P. G., Voelzke, H., Weinstein, M., Whooley, M., Nurnberger, J. I., Jr., Breslau, N., and Bierut, L. J.

Abstract

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.

Published
2018
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16. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G., Lam, M., Harris, S. E., Trampush, J. W., Luciano, M., Hill, W. D., Hagenaars, S. P., Ritchie, S. J., Marioni, R. E., Fawns-Ritchie, C., Liewald, D. C. M., Okely, J. A., Ahola-Olli, A. V., Barnes, C. L. K., Bertram, L., Bis, J. C., Burdick, K. E., Christoforou, A., Derosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D. E., Hayward, C., Hofer, E., Ikram, M. A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K. A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C. A., Sargurupremraj, M., Scholz, M., Smith, J. A., Smith, A. V., Terzikhan, N., Thalamuthu, A., Trompet, S., Van Der Lee, S. J., Ware, E. B., Windham, B. G., Wright, M. J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O. A., Armstrong, N. J., Assareh, A. A., Attia, J. R., Attix, D., Avramopoulos, D., Bennett, D. A., Böhmer, A. C., Boyle, P. A., Brodaty, H., Campbell, H., Cannon, T. D., Cirulli, E. T., Congdon, E., Conley, E. D., Corley, J., Cox, S. R., Dale, A. M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J. G., Evangelou, E., Faul, J. D., Ford, I., Freimer, N. A., Gao, H., Giegling, I., Gillespie, N. A., Gordon, S. D., Gottesman, R. F., Griswold, M. E., Gudnason, V., Harris, T. B., Hartmann, A. M., Hatzimanolis, A., Heiss, G., Holliday, E. G., Joshi, P. K., Kähönen, M., Kardia, S. L. R., Karlsson, Ida K., Kleineidam, L., Knopman, D. S., Kochan, N. A., Konte, B., Kwok, J. B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S. -C, Liu, T., Koini, M., London, E., Longstreth, W.T., Jr., Lopez, O. L., Loukola, A., Luck, T., Lundervold, A. J., Lundquist, A., Lyytikäinen, L. -P, Martin, N. G., Montgomery, G. W., Murray, A. D., Need, A. C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R. A., Psaty, B. M., Reppermund, S., Riedel-Heller, S. G., Rose, R. J., Rotter, J. I., Roussos, P., Rovio, S. P., Saba, Y., Sabb, F. W., Sachdev, P. S., Satizabal, C. L., Schmid, M., Scott, R. J., Scult, M. A., Simino, J., Slagboom, P. E., Smyrnis, N., Soumaré, A., Stefanis, N. C., Stott, D. J., Straub, R. E., Sundet, K., Taylor, A. M., Taylor, K. D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A. N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K. H., Widen, E., Yang, Q., Zhao, W., Adams, H. H. H., Arking, D. E., Bilder, R. M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P. L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A. L., Gill, M., Glahn, D. C., Hägg, S., Hansell, N. K., Hariri, A. R., Ikram, M. K., Jukema, J. W., Vuoksimaa, E., Keller, M. C., Kremen, W. S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N. L., Pendleton, N., Porteous, D. J., Räikkönen, K., Raitakari, O. T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P. W., Schofield, P. R., Starr, J. M., Steen, V. M., Trollor, J. N., Turner, S. T., Van Duijn, C. M., Villringer, A., Weinberger, D. R., Weir, D. R., Wilson, J. F., Malhotra, A., McIntosh, A. M., Gale, C. R., Seshadri, S., Mosley, T.H., Jr., Bressler, J., Lencz, T., Deary, I. J., Davies, G., Lam, M., Harris, S. E., Trampush, J. W., Luciano, M., Hill, W. D., Hagenaars, S. P., Ritchie, S. J., Marioni, R. E., Fawns-Ritchie, C., Liewald, D. C. M., Okely, J. A., Ahola-Olli, A. V., Barnes, C. L. K., Bertram, L., Bis, J. C., Burdick, K. E., Christoforou, A., Derosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D. E., Hayward, C., Hofer, E., Ikram, M. A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K. A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C. A., Sargurupremraj, M., Scholz, M., Smith, J. A., Smith, A. V., Terzikhan, N., Thalamuthu, A., Trompet, S., Van Der Lee, S. J., Ware, E. B., Windham, B. G., Wright, M. J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O. A., Armstrong, N. J., Assareh, A. A., Attia, J. R., Attix, D., Avramopoulos, D., Bennett, D. A., Böhmer, A. C., Boyle, P. A., Brodaty, H., Campbell, H., Cannon, T. D., Cirulli, E. T., Congdon, E., Conley, E. D., Corley, J., Cox, S. R., Dale, A. M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J. G., Evangelou, E., Faul, J. D., Ford, I., Freimer, N. A., Gao, H., Giegling, I., Gillespie, N. A., Gordon, S. D., Gottesman, R. F., Griswold, M. E., Gudnason, V., Harris, T. B., Hartmann, A. M., Hatzimanolis, A., Heiss, G., Holliday, E. G., Joshi, P. K., Kähönen, M., Kardia, S. L. R., Karlsson, Ida K., Kleineidam, L., Knopman, D. S., Kochan, N. A., Konte, B., Kwok, J. B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S. -C, Liu, T., Koini, M., London, E., Longstreth, W.T., Jr., Lopez, O. L., Loukola, A., Luck, T., Lundervold, A. J., Lundquist, A., Lyytikäinen, L. -P, Martin, N. G., Montgomery, G. W., Murray, A. D., Need, A. C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R. A., Psaty, B. M., Reppermund, S., Riedel-Heller, S. G., Rose, R. J., Rotter, J. I., Roussos, P., Rovio, S. P., Saba, Y., Sabb, F. W., Sachdev, P. S., Satizabal, C. L., Schmid, M., Scott, R. J., Scult, M. A., Simino, J., Slagboom, P. E., Smyrnis, N., Soumaré, A., Stefanis, N. C., Stott, D. J., Straub, R. E., Sundet, K., Taylor, A. M., Taylor, K. D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A. N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K. H., Widen, E., Yang, Q., Zhao, W., Adams, H. H. H., Arking, D. E., Bilder, R. M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P. L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A. L., Gill, M., Glahn, D. C., Hägg, S., Hansell, N. K., Hariri, A. R., Ikram, M. K., Jukema, J. W., Vuoksimaa, E., Keller, M. C., Kremen, W. S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N. L., Pendleton, N., Porteous, D. J., Räikkönen, K., Raitakari, O. T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P. W., Schofield, P. R., Starr, J. M., Steen, V. M., Trollor, J. N., Turner, S. T., Van Duijn, C. M., Villringer, A., Weinberger, D. R., Weir, D. R., Wilson, J. F., Malhotra, A., McIntosh, A. M., Gale, C. R., Seshadri, S., Mosley, T.H., Jr., Bressler, J., Lencz, T., and Deary, I. J.

Abstract

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

Published
2018
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17. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Author

Savage, J. E., Jansen, P. R., Stringer, S., Watanabe, K., Bryois, J., De Leeuw, C. A., Nagel, M., Awasthi, S., Barr, P. B., Coleman, J. R. I., Grasby, K. L., Hammerschlag, A. R., Kaminski, J. A., Karlsson, R., Krapohl, E., Lam, M., Nygaard, M., Reynolds, C. A., Trampush, J. W., Young, H., Zabaneh, D., Hägg, S., Hansell, N. K., Karlsson, Ida K., Linnarsson, S., Montgomery, G. W., Muñoz-Manchado, A. B., Quinlan, E. B., Schumann, G., Skene, N. G., Webb, B. T., White, T., Arking, D. E., Avramopoulos, D., Bilder, R. M., Bitsios, P., Burdick, K. E., Cannon, T. D., Chiba-Falek, O., Christoforou, A., Cirulli, E. T., Congdon, E., Corvin, A., Davies, G., Deary, I. J., Derosse, P., Dickinson, D., Djurovic, S., Donohoe, G., Conley, E. D., Eriksson, J. G., Espeseth, T., Freimer, N. A., Giakoumaki, S., Giegling, I., Gill, M., Glahn, D. C., Hariri, A. R., Hatzimanolis, A., Keller, M. C., Knowles, E., Koltai, D., Konte, B., Lahti, J., Le Hellard, S., Lencz, T., Liewald, D. C., London, E., Lundervold, A. J., Malhotra, A. K., Melle, I., Morris, D., Need, A. C., Ollier, W., Palotie, A., Payton, A., Pendleton, N., Poldrack, R. A., Räikkönen, K., Reinvang, I., Roussos, P., Rujescu, D., Sabb, F. W., Scult, M. A., Smeland, O. B., Smyrnis, N., Starr, J. M., Steen, V. M., Stefanis, N. C., Straub, R. E., Sundet, K., Tiemeier, H., Voineskos, A. N., Weinberger, D. R., Widen, E., Yu, J., Abecasis, G., Andreassen, O. A., Breen, G., Christiansen, L., Debrabant, B., Dick, D. M., Heinz, A., Hjerling-Leffler, J., Ikram, M. A., Kendler, K. S., Martin, N. G., Medland, S. E., Pedersen, N. L., Plomin, R., Polderman, T. J. C., Ripke, S., Van Der Sluis, S., Sullivan, P. F., Vrieze, S. I., Wright, M. J., Posthuma, D., Savage, J. E., Jansen, P. R., Stringer, S., Watanabe, K., Bryois, J., De Leeuw, C. A., Nagel, M., Awasthi, S., Barr, P. B., Coleman, J. R. I., Grasby, K. L., Hammerschlag, A. R., Kaminski, J. A., Karlsson, R., Krapohl, E., Lam, M., Nygaard, M., Reynolds, C. A., Trampush, J. W., Young, H., Zabaneh, D., Hägg, S., Hansell, N. K., Karlsson, Ida K., Linnarsson, S., Montgomery, G. W., Muñoz-Manchado, A. B., Quinlan, E. B., Schumann, G., Skene, N. G., Webb, B. T., White, T., Arking, D. E., Avramopoulos, D., Bilder, R. M., Bitsios, P., Burdick, K. E., Cannon, T. D., Chiba-Falek, O., Christoforou, A., Cirulli, E. T., Congdon, E., Corvin, A., Davies, G., Deary, I. J., Derosse, P., Dickinson, D., Djurovic, S., Donohoe, G., Conley, E. D., Eriksson, J. G., Espeseth, T., Freimer, N. A., Giakoumaki, S., Giegling, I., Gill, M., Glahn, D. C., Hariri, A. R., Hatzimanolis, A., Keller, M. C., Knowles, E., Koltai, D., Konte, B., Lahti, J., Le Hellard, S., Lencz, T., Liewald, D. C., London, E., Lundervold, A. J., Malhotra, A. K., Melle, I., Morris, D., Need, A. C., Ollier, W., Palotie, A., Payton, A., Pendleton, N., Poldrack, R. A., Räikkönen, K., Reinvang, I., Roussos, P., Rujescu, D., Sabb, F. W., Scult, M. A., Smeland, O. B., Smyrnis, N., Starr, J. M., Steen, V. M., Stefanis, N. C., Straub, R. E., Sundet, K., Tiemeier, H., Voineskos, A. N., Weinberger, D. R., Widen, E., Yu, J., Abecasis, G., Andreassen, O. A., Breen, G., Christiansen, L., Debrabant, B., Dick, D. M., Heinz, A., Hjerling-Leffler, J., Ikram, M. A., Kendler, K. S., Martin, N. G., Medland, S. E., Pedersen, N. L., Plomin, R., Polderman, T. J. C., Ripke, S., Van Der Sluis, S., Sullivan, P. F., Vrieze, S. I., Wright, M. J., and Posthuma, D.

Abstract

Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.

Published
2018
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18. GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium

Author

Trampush, J. W. Yang, M. L. Z. Yu, J. Knowles, E. and Davies, G. Liewald, D. C. Starr, J. M. Djurovic, S. and Melle, I. Sundet, K. Christoforou, A. Reinvang, I. and DeRosse, P. Lundervold, A. J. Steen, V. M. Espeseth, T. and Raikkonen, K. Widen, E. Palotie, A. Eriksson, J. G. and Giegling, I. Konte, B. Roussos, P. Giakoumaki, S. and Burdick, K. E. Payton, A. Ollier, W. Horan, M. and Chiba-Falek, O. Attix, D. K. Need, A. C. Cirulli, E. T. and Voineskos, A. N. Stefanis, N. C. Avramopoulos, D. and Hatzimanolis, A. Arking, D. E. Smyrnis, N. Bilder, R. M. and Freimer, N. A. Cannon, T. D. London, E. Poldrack, R. A. and Sabb, F. W. Congdon, E. Conley, E. D. Scult, M. A. and Dickinson, D. Straub, R. E. Donohoe, G. Morris, D. and Corvin, A. Gill, M. Hariri, A. R. Weinberger, D. R. and Pendleton, N. Bitsios, P. Rujescu, D. Lahti, J. Le Hellard, S. Keller, M. C. Andreassen, O. A. Deary, I. J. and Glahn, D. C. Malhotra, A. K. Lencz, T.

Abstract

The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (similar to 8M single-nucleotide polymorphisms (SNP) with minor allele frequency >= 1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (P

Published
2017

20. Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression

Author

Culverhouse, R C, primary, Saccone, N L, additional, Horton, A C, additional, Ma, Y, additional, Anstey, K J, additional, Banaschewski, T, additional, Burmeister, M, additional, Cohen-Woods, S, additional, Etain, B, additional, Fisher, H L, additional, Goldman, N, additional, Guillaume, S, additional, Horwood, J, additional, Juhasz, G, additional, Lester, K J, additional, Mandelli, L, additional, Middeldorp, C M, additional, Olié, E, additional, Villafuerte, S, additional, Air, T M, additional, Araya, R, additional, Bowes, L, additional, Burns, R, additional, Byrne, E M, additional, Coffey, C, additional, Coventry, W L, additional, Gawronski, K A B, additional, Glei, D, additional, Hatzimanolis, A, additional, Hottenga, J-J, additional, Jaussent, I, additional, Jawahar, C, additional, Jennen-Steinmetz, C, additional, Kramer, J R, additional, Lajnef, M, additional, Little, K, additional, zu Schwabedissen, H M, additional, Nauck, M, additional, Nederhof, E, additional, Petschner, P, additional, Peyrot, W J, additional, Schwahn, C, additional, Sinnamon, G, additional, Stacey, D, additional, Tian, Y, additional, Toben, C, additional, Van der Auwera, S, additional, Wainwright, N, additional, Wang, J-C, additional, Willemsen, G, additional, Anderson, I M, additional, Arolt, V, additional, Åslund, C, additional, Bagdy, G, additional, Baune, B T, additional, Bellivier, F, additional, Boomsma, D I, additional, Courtet, P, additional, Dannlowski, U, additional, de Geus, E J C, additional, Deakin, J F W, additional, Easteal, S, additional, Eley, T, additional, Fergusson, D M, additional, Goate, A M, additional, Gonda, X, additional, Grabe, H J, additional, Holzman, C, additional, Johnson, E O, additional, Kennedy, M, additional, Laucht, M, additional, Martin, N G, additional, Munafò, M R, additional, Nilsson, K W, additional, Oldehinkel, A J, additional, Olsson, C A, additional, Ormel, J, additional, Otte, C, additional, Patton, G C, additional, Penninx, B W J H, additional, Ritchie, K, additional, Sarchiapone, M, additional, Scheid, J M, additional, Serretti, A, additional, Smit, J H, additional, Stefanis, N C, additional, Surtees, P G, additional, Völzke, H, additional, Weinstein, M, additional, Whooley, M, additional, Nurnberger Jr, J I, additional, Breslau, N, additional, and Bierut, L J, additional

Published
2017
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21. GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function

Author

University of Helsinki, Medicum, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Clinicum, University of Helsinki, Helsinki Collegium for Advanced Studies, Trampush, J. W., Yang, M. L. Z., Yu, J., Knowles, E., Davies, G., Liewald, D. C., Starr, J. M., Djurovic, S., Melle, I., Sundet, K., Christoforou, A., Reinvang, I., DeRosse, P., Lundervold, A. J., Steen, V. M., Espeseth, T., Räikkönen, Katri, Widen, E., Palotie, A., Eriksson, J. G., Giegling, I., Konte, B., Roussos, P., Giakoumaki, S., Burdick, K. E., Payton, A., Ollier, W., Horan, M., Chiba-Falek, O., Attix, D. K., Need, A. C., Cirulli, E. T., Voineskos, A. N., Stefanis, N. C., Avramopoulos, D., Hatzimanolis, A., Arking, D. E., Smyrnis, N., Bilder, R. M., Freimer, N. A., Cannon, T. D., London, E., Poldrack, R. A., Sabb, F. W., Congdon, E., Conley, E. D., Scult, M. A., Dickinson, D., Straub, R. E., Donohoe, G., Morris, D., Corvin, A., Gill, M., Hariri, A. R., Weinberger, D. R., Pendleton, N., Bitsios, P., Rujescu, D., Lahti, J., Le Hellard, S., Keller, M. C., Andreassen, O. A., Deary, I. J., Glahn, D. C., Malhotra, A. K., Lencz, T., University of Helsinki, Medicum, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Clinicum, University of Helsinki, Helsinki Collegium for Advanced Studies, Trampush, J. W., Yang, M. L. Z., Yu, J., Knowles, E., Davies, G., Liewald, D. C., Starr, J. M., Djurovic, S., Melle, I., Sundet, K., Christoforou, A., Reinvang, I., DeRosse, P., Lundervold, A. J., Steen, V. M., Espeseth, T., Räikkönen, Katri, Widen, E., Palotie, A., Eriksson, J. G., Giegling, I., Konte, B., Roussos, P., Giakoumaki, S., Burdick, K. E., Payton, A., Ollier, W., Horan, M., Chiba-Falek, O., Attix, D. K., Need, A. C., Cirulli, E. T., Voineskos, A. N., Stefanis, N. C., Avramopoulos, D., Hatzimanolis, A., Arking, D. E., Smyrnis, N., Bilder, R. M., Freimer, N. A., Cannon, T. D., London, E., Poldrack, R. A., Sabb, F. W., Congdon, E., Conley, E. D., Scult, M. A., Dickinson, D., Straub, R. E., Donohoe, G., Morris, D., Corvin, A., Gill, M., Hariri, A. R., Weinberger, D. R., Pendleton, N., Bitsios, P., Rujescu, D., Lahti, J., Le Hellard, S., Keller, M. C., Andreassen, O. A., Deary, I. J., Glahn, D. C., Malhotra, A. K., and Lencz, T.

Abstract

The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (similar to 8M single-nucleotide polymorphisms (SNP) with minor allele frequency >= 1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (P

Published
2017

22. Steinberg and Durell (1968) revisited: increased rates of First Episode Psychosis following military induction in Greek Army Recruits.

Author

Dimitrakopoulos, S., Vitoratou, S., Mougiakos, T., Bogeas, N., Giotakos, O., van Os, J., and Stefanis, N. C.

Subjects
PSYCHOSES, AGE factors in disease, BIRTH rate, MILITARY hospitals, RURAL conditions, PSYCHOLOGICAL stress, TIME, MILITARY service, DIAGNOSIS
Abstract

Since the seminal study of Steinbeck and Durell (1968), few epidemiological studies have attempted to replicate whether psychosocial stress precipitates the onset of a first psychotic episode. Our aim was to support or refute the finding of elevated psychosis incidence in the first month of army induction and to examine factors impacting the timing of onset. Data were collected from medical files of 186 army conscripts, hospitalized with a diagnosis of First Episode Psychosis (FEP) between 2005 and 2014 in the Psychiatric Military Hospital in Athens, Greece. FEP rates were at least 4.5 times higher in the first month of military service, compared with any other month. Earlier FEP onset was associated with rural environment at the time of birth, multiple drug use and service away from home. Psychosocial stress precipitates FEP, particularly in those exposed to other risk factors. [ABSTRACT FROM AUTHOR]

Published
2018
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23. Association of RGS4 variants with schizotypy and cognitive endophenotypes at the population level

Author

Stefanis, N. C., Trikalinos, T. A., Avramopoulos, D., Smyrnis, N., Evdokimidis, I., Ntzani, E. E., Hatzimanolis, A., Ioannidis, J. P., and Stefanis, C. N.

Abstract

BACKGROUND: While association studies on schizophrenia show conflicting results regarding the importance of the regulator of the G-protein signaling 4 (RGS4) gene, recent work suggests that RGS4 may impact on the structural and functional integrity of the prefrontal cortex. We aimed to study associations of common RGS4 variants with prefrontal dependent cognitive performance and schizotypy endophenotypes at the population level. METHODS: Four RGS4 single nucleotide polymorphisms (SNP1 [rs10917670], SNP4 [rs951436], SNP7 [rs951439], and SNP18 [rs2661319]) and their haplotypes were selected. Their associations with self-rated schizotypy (SPQ), vigilance, verbal, spatial working memory and antisaccade eye performance were tested with regressions in a representative population of 2,243 young male military conscripts. RESULTS: SNP4 was associated with negative schizotypy (higher SPQ negative factor for common T allele, p = 0.009; p = 0.031 for differences across genotypes) and a similar trend was seen also for common A allele of SNP18 (p = 0.039 for allele-load model; but p = 0.12 for genotype differences). Haplotype analyses showed a similar pattern with a dose-response for the most common haplotype (GGGG) on the negative schizotypy score with or without adjustment for age, IQ and their interaction (p = 0.011 and p = 0.024, respectively). There was no clear evidence for any association of the RGS4 variants with cognitive endophenotypes, except for an isolated effect of SNP18 on antisaccade error rate (p = 0.028 for allele-load model). CONCLUSION: Common RGS4 variants were associated with negative schizotypal personality traits amongst a large cohort of young healthy individuals. In accordance with recent findings, this may suggest that RGS4 variants impact on the functional integrity of the prefrontal cortex, thus increasing susceptibility for psychotic spectrum disorders. Behav Brain Funct

Published
2008

24. Impact of schizophrenia candidate genes on schizotypy and cognitive endophenotypes at the population level

Author

Stefanis, N. C., Trikalinos, T. A., Avramopoulos, D., Smyrnis, N., Evdokimidis, I., Ntzani, E. E., Ioannidis, J. P., and Stefanis, C. N.

Subjects
Adult, Intelligence Tests, Male, Personality Tests, Risk, Schizotypal Personality Disorder/*genetics/*psychology, Schizophrenia/*genetics, Adolescent, Genotype, Population, DNA/genetics, Neuropsychological Tests, Polymorphism, Single Nucleotide, Cognition/*physiology, Neuregulin-1/genetics/physiology, Phenotype, Haplotypes, Carrier Proteins/*genetics/physiology, Humans, Linkage Disequilibrium/genetics, Alleles, Schizophrenic Psychology
Abstract

BACKGROUND: Aspects of cognitive function and schizotypy have been proposed as potential endophenotypes for schizophrenia. It is unknown whether the expression of these endophenotypes at the population level is modulated by the genetic variability of candidate susceptibility genes for schizophrenia. METHODS: We examined the potential impact of 18 single nucleotide polymorphisms (SNPs) within the DTNBP1, NRG1, DAOA/G32, and DAAO genes, on cognition and self-rated schizotypy, in a representative population of 2243 young male military conscripts. Single SNP and haplotype associations were evaluated. RESULTS: The DTNBP1 SNPs rs2619522 and rs760761 exhibited several single marker associations, the minor alleles being associated with lower attention capacity but also a decrease in positive and paranoid schizotypy scores. The DTNBP1 haplotype load had borderline associations with nonverbal IQ, paranoid schizotypy, and sustained attention. For individual NRG1 polymorphisms, isolated but weak signals of association were noted with sustained attention and working memory but not schizotypy. The risk allele of functional SNP8NRG243177 was associated with reduced spatial working memory capacity. An isolated effect of DAAO haplotype variability was noted on negative and disorganization schizotypy. No convincing association of DAOA/G32 variability was detected. CONCLUSIONS: The DTNBP1 and, less so, NRG1 and DAAO variants might exert gene-specific modulating effects on schizophrenia endophenotypes at the population level. Biol Psychiatry

Published
2007

33. Community Assessment of Psychic Experiences

Author

Stefanis, N. C., primary, Hanssen, M., additional, Smirnis, N. K., additional, Avramopoulos, D. A., additional, Evdokimidis, I. K., additional, Stefanis, C. N., additional, Verdoux, H, additional, and Van Os, J., additional

Published
2002
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37. Stigma and schizophrenia.

Author

Karidi, M. V., Theleritis, C., and Stefanis, N. C.

Subjects
*LETTERS to the editor, *SCHIZOPHRENIA
Abstract

A letter to the editor is presented in response to the article "Global Pattern of Experienced and Anticipated Discrimination Against People With Schizophrenia: A Cross-Sectional Survey" by G. Thorncroft, E. Brohan, D. Rose, N. Satorius and M. Leese in the January 31, 2009 issue.

Published
2009
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38. [A proposal for the implementation of Early Intervention in Psychosis (EIP) services in Greece: If not now, when?]

Author

Stefanis NC, Mavreas V, Νimatoudis Ι, Gourzis F, Samakouri Μ, Vgontzas A, and Douzenis A

Subjects
Early Medical Intervention economics, Greece, Humans, Mental Health Services, Psychotic Disorders economics, Quality of Life, Schizophrenia economics, Schizophrenia therapy, Early Medical Intervention methods, Psychotic Disorders therapy
Abstract

The disorders of the psychosis spectrum, with the most severe being schizophrenia, are prevalent and have a great impact on the patients' quality of life. The purpose of this article is to highlight the need for a novel national strategic approach to the management of psychotic disorders in accordance with the international principles of early intervention. Even though outpatient treatment is considered adequate, there is an urgent need to adopt an early and more comprehensive and effective intervention strategy for young patients with psychosis and their families whose clinical and personal needs are clearly not met by the existing infrastructure of our mental health services. This can be accomplished by the legislation and implementation within the national health system of EIP services which on the one hand actively engage community organizations with the purpose of early identification of cases, reduction of the duration of untreated psychosis and on the other, offer assertive community-based support and treatment, based on a multi-disciplinary community team model. The effectiveness of early intervention in psychosis is supported by evidence provided by 9 international RCTs. The results of these programs indicate a superior effect in indexes of quality of life, retention in treatment, psychopathology, judicious use of medication and return to work/school as well as the patient's effective recovery. International experience (Denmark, Norway, Australia, UK, USA, Canada and Italy) and the corresponding prevention programs emphasize the effectiveness of EIP services and thus the patients' reintegration. However, in contrast to Northern European countries, Southern European countries have not yet incorporated EIP services in their national health system. From a financial perspective, EIP services seem to be cost-effective for the national health system, since the economic burden is compensated in the long term through their qualitative benefits. In Greece, specialized services for those young afflicted for the first time by the most serious of mental disorders are non-existent and no local information exists for the patient's outcome and social integration after a first psychotic-episode nor for the financial burden, placed on mental health services. Overall, the implementation of EIP services is expected to have long-term benefits for our country's National Health System as well as for the patients and their families.

Published
2018
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39. Temperament and character dimensions assessed in general population, in individuals with psychoactive substance dependence and in young male conscripts.

Author

Vitoratou S, Ntzoufras I, Theleritis C, Smyrnis N, and Stefanis NC

Subjects
Adult, Aggression, Factor Analysis, Statistical, Humans, Male, Military Personnel statistics & numerical data, Personality Disorders epidemiology, Personality Inventory statistics & numerical data, Psychometrics statistics & numerical data, Reproducibility of Results, Substance-Related Disorders epidemiology, Young Adult, Military Personnel psychology, Personality, Personality Disorders psychology, Substance-Related Disorders psychology, Temperament
Abstract

Background: In this work we consider Cloninger's psychobiological model, which measures two dimensions of personality: character and temperament. Temperament refers to the biological basis of personality and its characteristics, while character refers to an individual's attitudes towards own self, towards humanity and as part of the universe., Methods: The Temperament and Character Inventory-Revised-140 (TCI-R-140) was administered to 3 divergent samples: a general population sample, a sample of male conscripts and a sample of individuals attending a substance abuse rehabilitation programme. Score differences among the three samples were assessed controlling for age and gender and reliability coefficients are reported. The latent structure was studied in all samples, using exploratory and confirmatory factor analysis methods (EFA and CFA respectively)., Results: The proposed structure was partially replicated via EFA. CFA however indicated less than satisfactory fit, as in previously reported results. To improve the fit, the path diagram was augmented to account for multiple factor complexity, as suggested by the EFA results in all samples. While retaining the original seven-factor structure, the augmented model provided adequate fit. The consistency of the inventory was satisfactory in all samples. Evidence for the construct validity was found in relation to aggression., Conclusions: This is the first study to conclude in adequate fit, after allowing for the indicators to load on more than one factor within each dimension. While cross-national differences apply, our results were similar (when comparable) with previously reported ones in the literature., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Published
2015
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40. The antisaccade task in a sample of 2,006 young males. II. Effects of task parameters.

Author

Smyrnis N, Evdokimidis I, Stefanis NC, Constantinidis TS, Avramopoulos D, Theleritis C, Paximadis C, Efstratiadis C, Kastrinakis G, and Stefanis CN

Subjects
Adolescent, Adult, Asthenopia physiopathology, Fixation, Ocular, Humans, Learning physiology, Linear Models, Male, Neurophysiology, Photic Stimulation, Reaction Time physiology, Reference Values, Regression Analysis, Psychomotor Performance physiology, Saccades physiology
Abstract

Antisaccade performance was investigated in a sample of 2,006 young males as part of a large epidemiological study investigating psychosis proneness. This report summarizes the effects of task parameters on performance using a sample of 55,678 antisaccade trials collected from a subpopulation of 947 individuals. Neither the amplitude nor the latency of an error prosaccade in the antisaccade task was correlated with the latency of the ensuing corrective antisaccade that almost always followed an error. However, the latency of the corrective antisaccade decreased with increasing stimulus distance. Concerning the effects of specific task parameters, trials with stimuli closer to the central fixation point and trials preceded by shorter fixation intervals resulted in more errors and longer latencies for the antisaccades. Finally, there were learning and fatigue effects reflected mainly in the error rate, which was greater at the beginning and at the end of the 5-min task. We used a model to predict whether an error or a correct antisaccade would follow a particular trial. All task parameters were significant predictors of the trial outcome but their power was negligible. However, when modeled alone, response latency of the first movement predicted 40% of errors. In particular, the smaller this latency was, the higher the probability of an error. These findings are discussed in light of current hypotheses on antisaccade production mechanisms involving mainly the superior colliculus.

Published
2002
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41. The antisaccade task in a sample of 2,006 young men. I. Normal population characteristics.

Author

Evdokimidis I, Smyrnis N, Constantinidis TS, Stefanis NC, Avramopoulos D, Paximadis C, Theleritis C, Efstratiadis C, Kastrinakis G, and Stefanis CN

Subjects
Adolescent, Adult, Computer Graphics, Epidemiologic Methods, Humans, Male, Reaction Time physiology, Reference Values, Psychomotor Performance physiology, Saccades physiology
Abstract

A population of 2,075 young men aged 18-25 years selected from the conscripts of the Greek Air Force performed an antisaccade task as part of a prospective study for the identification of risk factors in the development of psychoses. The aim of this study, which is ongoing, is to follow this population and investigate the possible predictive value of oculomotor, cognitive, and psychometric factors for the development of psychosis and other psychiatric conditions. In this report we present data concerning the antisaccade task in this population. We measured performance indices, including the percentage of errors (PE), the latencies of different eye movement responses (latency for correct antisaccades, errors, corrections), and performance in perseveration-prone trials. These indices were also evaluated with respect to IQ (measured by the Raven progressive matrices test) and educational level. Mean PE was 23%, with 17% variance. This large variance is of particular importance whenever the detection of a putative deviant behavior is explored. As mean latency of the first eye movement decreased, the PE increased, as did the latency variance. While the negative correlation between percentage of error and mean latency is well established, the relationship of the latency variability of the first response to error production has not been studied before. Thus, optimal performance appears to require both an intermediate mean latency and a small variability. Furthermore, performance seems to be affected by IQ (the higher the IQ score, the lower the percentage of errors). This report offers an analysis of the interindividual variation in the performance of the antisaccade task and discusses some of the sources of this variation.

Published
2002
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42. Elevation of D4 dopamine receptor mRNA in postmortem schizophrenic brain.

Author

Stefanis NC, Bresnick JN, Kerwin RW, Schofield WN, and McAllister G

Subjects
Aged, Analysis of Variance, Caudate Nucleus metabolism, Female, Frontal Lobe metabolism, Humans, Male, Middle Aged, Oligonucleotide Probes, Postmortem Changes, Receptors, Dopamine D4, Reference Values, Brain metabolism, RNA, Messenger biosynthesis, Receptors, Dopamine D2 biosynthesis, Schizophrenia metabolism, Transcription, Genetic
Abstract

The D4 dopamine (DA) receptor has been proposed to be a target for the development of a novel antipsychotic drug based on its pharmacological and distribution profile. There is much interest in whether D4 DA receptor levels are altered in schizophrenia, but the lack of an available receptor subtype-specific radioligand made this difficult to quantitate. In this study, we examined whether D4 mRNA levels are altered in different brain regions of schizophrenics compared to controls. Ribonuclease protection assays were carried out on total RNA samples isolated postmortem from frontal cortex and caudate brain regions of schizophrenics and matched controls. 32P-labelled RNA probes to the D4 DA receptor and to the housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (G3PDH), were hybridised with the RNA samples, digested with ribonucleases to remove unhybridised probe, and separated on 6% sequencing gels. Densitometer analysis on the subsequent autoradiogams was used to calculate the relative optical density of D4 mRNA compared to G3PDH mRNA. Statistical analysis of the data revealed a 3-fold higher level (P<0.011) of D4 mRNA in the frontal cortex of schizophrenics compared to controls. No increase was seen in caudate. D4 receptors could play a role in mediating dopaminergic activity in frontal cortex, an activity which may be malfunctioning in schizophrenia.

Published
1998
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