Skip to main content
Search
Search
    Quick Search anywhere
    Quick search in Citations
Advanced Search
Skip main navigationClose Drawer MenuOpen Drawer Menu
Previous article
Next article
Original Article

Additive Genetic Effects for Schizotypy Support a Fully-Dimensional Model of Psychosis-Proneness

Published Online:January 01, 2015https://doi.org/10.1027/1614-0001/a000155

Abstract

Schizotypy is an organization of traits mirroring psychosis-like symptoms and conveying individual psychosis-proneness. Schizotypy and schizophrenia share a genetic basis, wherefore initial schizotypy definitions considered a schizophrenic genotype as a condicio sine qua non. Since the search for a monogenetic schizotypy marker has proven in vain, it is believed that schizotypy is (genetically) based on multiple alleles, each of small effect-size. Schizophrenia may be viewed as a qualitative entity at the extreme of the schizotypy dimension. To date, however, it has not been shown that effects of individual schizotypy-related alleles or genotypes are additive, which would be necessary for the proposition of latent genetic schizotypy factors. Based on previous findings of significant associations of candidate polymorphisms with schizotypy, we chose to examine if these genetic effects were, indeed, additive regarding positive schizotypy. Using a sample of 288 healthy participants we calculated allele-wise and genotype-wise risk indices and examined, whether levels of positive schizotypy would significantly increase with genetic risk. Our findings show significant additive genetic effects of select polymorphisms on positive schizotypy and, thus, support the notion of a fully-dimensional and partially genetically based model of schizotypy.

References

  • Ahmed, A. H. (1979). Consanguinity and schizophrenia in Sudan. British Journal of Psychiatry, 134, 635–636. First citation in articleCrossref, Google Scholar

  • Alexander, N., Kuepper, Y., Schmitz, A., Osinsky, R., Kozyra, E., & Hennig, J. (2009). Gene-environment interactions predict cortisol responses after acute stress: Implications for the etiology of depression. Psychoneuroendocrinology, 34, 1294–1303. First citation in articleCrossref, Google Scholar

  • Alexander, N., Osinsky, R., Schmitz, A., Mueller, E., Kuepper, Y., & Hennig, J. (2010). The BDNF Val66Met polymorphism affects HPA-axis reactivity to acute stress. Psychoneuroendocrinology, 35, 949–953. First citation in articleCrossref, Google Scholar

  • Arcos-Burgos, M., & Muenke, M. (2002). Genetics of population isolates. Clinical Genetics, 61, 233–247. First citation in articleCrossref, Google Scholar

  • Baron, M., Gruen, R., Asnis, L., & Kane, J. (1983). Familial relatedness of schizophrenia and schizotypal states. The American Journal of Psychiatry, 140, 1437–1442. First citation in articleCrossref, Google Scholar

  • Barrantes-Vidal, N., Gross, G. M., Sheinbaum, T., Mitjavila, M., Ballespi, S., & Kwapil, T. R. (2013). Positive and negative schizotypy are associated with prodromal and schizophrenia-spectrum symptoms. Schizophrenia Research, 145, 50–55. First citation in articleCrossref, Google Scholar

  • Battaglia, M., Bernardeschi, L., Franchini, L., Bellodi, L., & Smeraldi, E. (1995). A family study of schizotypal disorder. Schizophrenia Bulletin, 21, 33–45. First citation in articleCrossref, Google Scholar

  • Battaglia, M., Gasperini, M., Sciuto, G., Scherillo, P., Diaferia, G., & Bellodi, L. (1991). Psychiatric disorders in the families of schizotypal subjects. Schizophrenia Bulletin, 17, 659–668. First citation in articleCrossref, Google Scholar

  • Bland, J. M., & Altman, D. G. (1994). One and two sided tests of significance. BMJ, 309, 248. First citation in articleCrossref, Google Scholar

  • Brod, J. H. (1997). Creativity and schizotypy. In G. ClaridgeEd., Schizotypy – Implications for Illness and Health (pp. 274–298). Oxford, UK: Oxford University Press. First citation in articleCrossref, Google Scholar

  • Claridge, G. (1997). Theoretical background and issues. In G. ClaridgeEd., Schizotypy – Implications for Illness and Health (pp. 3–18). Oxford: Oxford University Press. First citation in articleCrossref, Google Scholar

  • Connolly, P. M., Maxwell, C., Liang, Y., Kahn, J. B., Kanes, S. J., Abel, T., … Siegel, S. J. (2004). The effects of ketamine vary among inbred mouse strains and mimic schizophrenia for the P80, but not P20 or N40 auditory ERP components. Neurochemical Research, 29, 1179–1188. First citation in articleCrossref, Google Scholar

  • Dobrusin, M., Weitzman, D., Levine, J., Kremer, I., Rietschel, M., Maier, W., & Belmaker, R. H. (2009). The rate of consanguineous marriages among parents of schizophrenic patients in the Arab Bedouin population in Southern Israel. The World Journal of Biological Psychiatry, 10, 334–336. First citation in articleCrossref, Google Scholar

  • Ettinger, U., Corr, P. J., Mofidi, A., Williams, S. C., & Kumari, V. (2013). Dopaminergic basis of the psychosis-prone personality investigated with functional magnetic resonance imaging of procedural learning. Frontiers in Human Neuroscience, 7, 130. First citation in articleCrossref, Google Scholar

  • Friston, K. (2012). Ten ironic rules for non-statistical reviewers. Neuroimage, 61, 1300–1310. First citation in articleCrossref, Google Scholar

  • Grant, P. (2013). Schizotypie. In M. A. WirtzEd., Dorsch – Lexikon der Psychologie. Bern, Switzerland: Hans Huber. First citation in articleGoogle Scholar

  • Grant, P. (2015, in press). Genetic associations: The basis of Schizotypy. In O. MasonG. ClaridgeEds., Schizotypy – new dimensions. ISBN: 978-0-415-72203-2. Oxford, UK: Routledge, Taylor & Francis Group. First citation in articleCrossref, Google Scholar

  • Grant, P., Gabriel, F., Kuepper, Y., Wielpuetz, C., & Hennig, J. (2014). Psychosis-proneness correlates with expression levels of dopaminergic genes. European Psychiatry, 29, 304–306. First citation in articleCrossref, Google Scholar

  • Grant, P., Kuepper, Y., Mueller, E., Wielpuetz, C., Mason, O., & Hennig, J. (2013). Dopaminergic foundations of schizotypy as measured by the German version of the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE) – a suitable endophenotype of schizophrenia. Frontiers in Human Neuroscience, 7, Retrieved from http://journal.frontiersin.org/article/10.3389/fn.hum.2013.00001 First citation in articleCrossref, Google Scholar

  • Hariri, A. R., Drabant, E. M., & Weinberger, D. R. (2006). Imaging genetics: Perspectives from studies of genetically driven variation in serotonin function and corticolimbic affective processing. Biological Psychiatry, 59, 888–897. First citation in articleCrossref, Google Scholar

  • Horger, B. A., Iyasere, C. A., Berhow, M. T., Messer, C. J., Nestler, E. J., & Taylor, J. R. (1999). Enhancement of locomotor activity and conditioned reward to cocaine by brain-derived neurotrophic factor. The Journal of Neuroscience, 19, 4110–4122. First citation in articleCrossref, Google Scholar

  • Howes, O. D., & Kapur, S. (2009). The dopamine hypothesis of schizophrenia: Version III – the final common pathway. Schizophrenia Bulletin, 35, 549–562. First citation in articleGoogle Scholar

  • Keller, M. C., Simonson, M. A., Ripke, S., Neale, B. M., Gejman, P. V., Howrigan, D. P., … Sullivan, P. F. (2012). Runs of homozygosity implicate autozygosity as a schizophrenia risk factor. PLoS Genetics, 8, e1002656. First citation in articleGoogle Scholar

  • Kendler, K. S., & Walsh, D. (1995). Schizotypal personality disorder in parents and the risk for schizophrenia in siblings. Schizophrenia Bulletin, 21, 47–52. First citation in articleCrossref, Google Scholar

  • Knabb, J. J., Vogt, R. G., & Newgren, K. P. (2011). MMPI-2 characteristics of the Old Order Amish: A comparison of clinical, nonclinical, and United States normative samples. Psychological Assessment, 23, 865–875. First citation in articleCrossref, Google Scholar

  • Kwapil, T. R., Barrantes-Vidal, N., & Silvia, P. J. (2008). The dimensional structure of the Wisconsin Schizotypy Scales: Factor identification and construct validity. Schizophrenia Bulletin, 34, 444–457. First citation in articleCrossref, Google Scholar

  • Kwapil, T. R., Brown, L. H., Silvia, P. J., Myin-Germeys, I., & Barrantes-Vidal, N. (2012). The expression of positive and negative schizotypy in daily life: An experience sampling study. Psychological Medicine, 42, 2555–2566. First citation in articleCrossref, Google Scholar

  • Lenzenweger, M. F. (2006). Schizotypy – an organizing framework for schizophrenia research. Current Directions in Psychological Science, 15, 162–166. First citation in articleCrossref, Google Scholar

  • Linney, Y. M., Murray, R. M., Peters, E. R., MacDonald, A. M., Rijsdijk, F., & Sham, P. C. (2003). A quantitative genetic analysis of schizotypal personality traits. Psychological Medicine, 33, 803–816. First citation in articleCrossref, Google Scholar

  • Mason, O., & Claridge, G. (2006). The Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE): Further description and extended norms. Schizophrenia Research, 82, 203–211. First citation in articleCrossref, Google Scholar

  • Mansour, H., Fathi, W., Klei, L., Wood, J., Chowdari, K., Watson, A., … Nimgaonkar, V. L. (2010). Consanguinity and increased risk for schizophrenia in Egypt. Schizophrenia Research, 120, 108–112. First citation in articleCrossref, Google Scholar

  • Meehl, P. E. (1962). Schizotaxia, Schizotypy, Schizophrenia. The American Psychologist, 17, 827–838. First citation in articleCrossref, Google Scholar

  • Pettersson-Yeo, W., Benetti, S., Marquand, A. F., Dell’acqua, F., Williams, S. C., Allen, P., … Mechelli, A. (2013). Using genetic, cognitive and multi-modal neuroimaging data to identify ultra-high-risk and first-episode psychosis at the individual level. Psychological Medicine, 43, 2547–2562. First citation in articleCrossref, Google Scholar

  • Plomin, R., Haworth, C. M., & Davis, O. S. (2009). Common disorders are quantitative traits. Nature Reviews. Genetics, 10, 872–878. First citation in articleCrossref, Google Scholar

  • Rado, S. (1953). Dynamics and classification of disordered behavior. The American Journal of Psychiatry, 110, 406–416. First citation in articleCrossref, Google Scholar

  • Ripke, S., O’Dushlaine, C., Chambert, K., Moran, J. L., Kahler, A. K., Akterin, S., Bergen, S. E., … Sullivan, P. F. (2013). Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nature Genetics, 45, 1150–1159. First citation in articleCrossref, Google Scholar

  • Sanua, V. D. (1981). Psychopathology and social deviance among Jews. Journal of Jewish Communal Service, 58, 12–23. First citation in articleGoogle Scholar

  • Skoblo, G. V. (1975). Inbreeding in the population and the spread of schizophrenia in one of the rural regions of Azerbaijan. Genetika, 11, 149–152. First citation in articleGoogle Scholar

  • Stefanis, N. C., Hatzimanolis, A., Avramopoulos, D., Smyrnis, N., Evdokimidis, I., … Straub, R. E. (2013). Variation in psychosis gene ZNF804A is associated with a refined schizotypy phenotype but not neurocognitive performance in a large young male population. Schizophrenia Bulletin, 39, 1252–1260. First citation in articleCrossref, Google Scholar

  • Sullivan, P. F., Kendler, K. S., & Neale, M. C. (2003). Schizophrenia as a complex trait: Evidence from a meta-analysis of twin studies. Archives of General Psychiatry, 60, 1187–1192. First citation in articleCrossref, Google Scholar

  • Thaker, G., Adami, H., Moran, M., Lahti, A., & Cassady, S. (1993). Psychiatric illnesses in families of subjects with schizophrenia-spectrum personality disorders: High morbidity risks for unspecified functional psychoses and schizophrenia. The American Journal of Psychiatry, 150, 66–71. First citation in articleCrossref, Google Scholar

  • Thakur, G. A., Grizenko, N., Sengupta, S. M., Schmitz, N., & Joober, R. (2010). The 5-HTTLPR polymorphism of the serotonin transporter gene and short term behavioral response to methylphenidate in children with ADHD. BMC Psychiatry, 10, 50. First citation in articleCrossref, Google Scholar

  • van Wingen, G., Rijpkema, M., Franke, B., van Eijndhoven, P., Tendolkar, I., Verkes, R. J., … Fernández, G. (2010). The brain-derived neurotrophic factor Val66Met polymorphism affects memory formation and retrieval of biologically salient stimuli. Neuroimage, 50, 1212–1218. First citation in articleCrossref, Google Scholar

  • Vargas-Perez, H., Ting-A Kee, R., Walton, C. H., Hansen, D. M., Razavi, R., Clarke, L., … van der Kooy, D. (2009). Ventral tegmental area BDNF induces an opiate-dependent-like reward state in naive rats. Science, 324, 1732–1734. First citation in articleCrossref, Google Scholar

  • Yasuda, Y., Hashimoto, R., Ohi, K., Fukumoto, M., Umeda-Yano, S., Yamamori, H., … Takeda, M. (2011). Impact on schizotypal personality trait of a genome-wide supported psychosis variant of the ZNF804A gene. Neuroscience Letters, 495, 216–220. First citation in articleCrossref, Google Scholar

  • Zammit, S., Hamshere, M., Dwyer, S., Georgiva, L., Timpson, N., Moskvina, V., … O’Donovan, M. C. (2014). A population-based study of genetic variation and psychotic experiences in adolescents. Schizophrenia Bulletin, 40, 1254–1262. First citation in articleCrossref, Google Scholar

  • Zipursky, R. B., Reilly, T. J., & Murray, R. M. (2013). The myth of schizophrenia as a progressive brain disease. Schizophrenia Bulletin, 39, 1363–1372. First citation in articleCrossref, Google Scholar