Hostname: page-component-848d4c4894-v5vhk Total loading time: 0 Render date: 2024-06-19T00:26:22.720Z Has data issue: false hasContentIssue false

Effect of DISC1 Polymorphisms on the Long-term Course of Neurocognitive Deficits in Non-affective Psychosis

Published online by Cambridge University Press:  16 April 2020

J. Vázquez-Bourgon*
Affiliation:
University Hospital Marqués de Valdecilla, Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Spain IDIVAL, Instituto de Investigación Marqués de Valdecilla, Santander, Spain
R. Ayesa-Arriola
Affiliation:
University Hospital Marqués de Valdecilla, Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Spain IDIVAL, Instituto de Investigación Marqués de Valdecilla, Santander, Spain
M. Fatjó-Vilas
Affiliation:
CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Spain Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain
R. Roiz-Santiañez
Affiliation:
University Hospital Marqués de Valdecilla, Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Spain IDIVAL, Instituto de Investigación Marqués de Valdecilla, Santander, Spain
L. Fañanás
Affiliation:
CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Spain Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain
B. Crespo-Facorro
Affiliation:
University Hospital Marqués de Valdecilla, Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Spain IDIVAL, Instituto de Investigación Marqués de Valdecilla, Santander, Spain
*
*Corresponding author. E-mail address: javazquez@humv.es (J. Vázquez-Bourgon).
Get access

Abstract

Neurocognitive deficits are core symptoms of schizophrenia that determine a poorer outcome. High variability in the progression of neuropsychological deficits in schizophrenia has been described. It is still unknown whether genetic variations can affect the course of cognitive deficits. Variations in the Disrupted in Schizophrenia 1 (DISC1) gene have previously been associated with neurocognitive deficits. This study investigated the association between 3 DISC1 polymorphisms (rs6675281 (Leu607Phe), rs1000731, and rs821616 (Ser704Cys)) and long-term (3 years) cognitive performance. One-hundred-thirty-three Caucasian drug-naive patients experiencing a first episode of non-affective psychosis were genotyped. Cognitive function was assessed at baseline and after 3 years of initiating treatment. Other clinical and socio-demographic variables were recorded to eliminate potential confounding effects. Patients carrying the A allele of rs1000731 exhibited a significant improvement in Working Memory and Attention domains, and the homozygosity of the A allele of rs821616 showed a significant improvement in Motor Dexterity performance over 3 years of follow-up. In conclusion, DISC1 gene variations may affect the course of cognitive deficits found in patients suffering from the first episode of non-affective psychosis.

Type
Original article
Copyright
European Psychiatric Association 2015

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Addington, J, Saeedi, H, Addington, D. The course of cognitive functioning in first episode psychosis: changes over time and impact on outcome. Schizophr Res 2005;78:3543.CrossRefGoogle Scholar
Albus, M, Hubmann, W, Mohr, F, Hecht, S, Hinterberger-Weber, P, Seitz, NN, et al.Neurocognitive functioning in patients with first-episode schizophrenia: results of a prospective 5-year follow-up study. Eur Arch Psychiatry Clin Neurosci 2006;256(7):442451.CrossRefGoogle ScholarPubMed
Allott, K, Liu, P, Proffitt, TM, Killackey, E. Cognition at illness onset as a predictor of later functional outcome in early psychosis: systematic review and methodological critique. Schizophr Res 2011;125(2–3):221235.CrossRefGoogle ScholarPubMed
Austin, CP, Ma, L, Ky, B, Morris, JA, Shughrue, PJ. DISC1 (Disrupted in Schizophrenia-1) is expressed in limbic regions of the primate brain. Neuroreport 2003;14:951954.CrossRefGoogle ScholarPubMed
Austin, CP, Ma, L, Ky, B, Morris, JA, Shughrue, PJ. Expression of Disrupted-in-Schizophrenia-1, a schizophrenia-associated gene, is prominent in the mouse hippocampus throughout brain development. Neuroscience 2004;124:310.CrossRefGoogle ScholarPubMed
Ayesa-Arriola, R, Pérez-Iglesias, R, Rodríguez-Sánchez, JM, Pardo-García, G, Tabares-Seisdedos, R, Ayuso-Mateos, JL, et al.Predictors of neurocognitive impairment at 3 years after a first episode non-affective psychosis. Prog Neuropsychopharmacol Biol Psychiatry 2013;43:2328.CrossRefGoogle ScholarPubMed
Becker, HE, Nieman, DH, Wiltink, S, Dingemans, PM, van de Fliert, JR, Velthorst, E, et al.Neurocognitive functioning before and after the first psychotic episode: does psychosis result in cognitive deterioration? Psychol Med 2010;40(10):15991606.CrossRefGoogle ScholarPubMed
Bilder, RM, Howe, A, Novak, N, Sabb, F, Parker, DS. The genetics of cognitive impairment in schizophrenia: a phenomic perspective. Trends Cogn Sci 2011;15(9):428435.CrossRefGoogle ScholarPubMed
Bonner-Jackson, A, Grossman, LS, Harrow, M, Rosen, C. Neurocognition in schizophrenia: a 20-year multi-follow-up of the course of processing speed and stored knowledge. Compr Psychiatry 2010;51(5):471479.CrossRefGoogle ScholarPubMed
Bora, E, Yucel, M, Pantelis, C. Cognitive functioning in schizophrenia, schizoaffective disorder and affective psychoses: meta-analytic study. Br J Psychiatry 2009;195(6):475482.CrossRefGoogle ScholarPubMed
Brandon, NJ, Millar, JK, Korth, C, Sive, H, Singh, KK, Sawa, A. Understanding the role of DISC1 in psychiatric disease and during normal development. J Neurosci 2009;29(41):1276812775.CrossRefGoogle ScholarPubMed
Brauns, S, Gollub, RL, Roffman, JL, Yendiki, A, Ho, BC, Wassink, TH, et al.DISC1 is associated with cortical thickness and neural efficiency. Neuroimage 2011;57(4):15911600.CrossRefGoogle ScholarPubMed
Burdick, KE, Hodgkinson, CA, Szeszko, PR, Lencz, T, Ekholm, JM, Kane, JM, et al.DISC1 and neurocognitive function in schizophrenia. Neuroreport 2005;16:13991402.CrossRefGoogle Scholar
Callicott, JH, Straub, RE, Pezawas, L, Egan, MF, Mattay, VS, Hariri, AR, et al.Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proc Natl Acad Sci USA 2005;102:86278632.CrossRefGoogle ScholarPubMed
Callicott, JH, Feighery, EL, Mattay, VS, White, MG, Chen, Q, Baranger, DA, et al.DISC1 and SLC12A2 interaction affects human hippocampal function and connectivity. J Clin Invest 2013;123(7):29612964.CrossRefGoogle ScholarPubMed
Camargo, LM, Collura, V, Rain, JC, Mizuguchi, K, Hermjakob, H, Kerrien, S, et al.Disrupted in Schizophrenia 1 interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia. Mol Psychiatry 2007;12:7486.CrossRefGoogle Scholar
Cannon, TD, Hennah, W, van Erp, TG, Thompson, PM, Lonnqvist, J, Huttunen, M, et al.Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory. Arch Gen Psychiatry 2005;62:12051213.CrossRefGoogle ScholarPubMed
Cegalis, J, Bowlin, JVigil: software for the assessment of attention. Nashua, NH: Forthought; 1991.Google Scholar
Chubb, JE, Bradshaw, NJ, Soares, DC, Porteous, DJ, Millar, JK, The, DISC. locus in psychiatric illness. Mol Psychiatry 2008;13:3664.CrossRefGoogle ScholarPubMed
Crespo-Facorro, B, Barbadillo, L, Pelayo-Teran, JM, Rodriguez-Sanchez, JM. Neuropsychological functioning and brain structure in schizophrenia. Int Rev Psychiatr 2007;19:325336.CrossRefGoogle Scholar
Deary, IJ, Yang, J, Davies, G, Harris, SE, Tenesa, A, Liewald, D, et al.Genetic contributions to stability and change in intelligence from childhood to old age. Nature 2012;482(7384):212215.CrossRefGoogle ScholarPubMed
Di Giorgio, A, Blasi, G, Sambataro, F, Rampino, A, Papazacharias, A, Gambi, F, et al.Association of the Ser704Cys DISC1 polymorphism with human hippocampal formation gray matter and function during memory encoding. Eur J Neurosci 2008;28:21292136.CrossRefGoogle Scholar
Duff, BJ, Macritchie, KA, Moorhead, TW, Lawrie, SM, Blackwood, DH. Human brain imaging studies of DISC1 in schizophrenia, bipolar disorder and depression: a systematic review. Schizophr Res 2013;147(1):113.CrossRefGoogle ScholarPubMed
Greenwood, TA, Braff, DL, Light, GA, Cadenhead, KS, Calkins, ME, Dobie, DJ, et al.Initial heritability analyses of endophenotypic measures for schizophrenia: the consortium on the genetics of schizophrenia. Arch Gen Psychiatry 2007;64(11):12421250.CrossRefGoogle Scholar
Haijma, SV, Van Haren, N, Cahn, W, Koolschijn, PC, Hulshoff Pol, HE, et al.Brain volumes in schizophrenia: a meta-analysis in over 18 000 subjects. Schizophr Bull 2013;39:11291138.CrossRefGoogle ScholarPubMed
Heaton, RK, Gladsjo, JA, Palmer, BW, Kuck, J, Marcotte, TD, Jeste, DV. Stability and course of neuropsychological deficits in schizophrenia. Arch Gen Psychiatry 2001;58(1):2432.CrossRefGoogle Scholar
Heinrichs, RW, Zakzanis, KK. Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 1998;12(3):426445.CrossRefGoogle Scholar
Hennah, W, Porteus, D. The DISC1 pathway modulates expression of neurodevelopmental, synaptogenic and sensory perception genes. PLoS ONE 2009;4:e4906.CrossRefGoogle ScholarPubMed
Hennah, W, Varilo, T, Kestila, M, Paunio, T, Arajarvi, R, Haukka, J, et al.Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects. Hum Mol Genet 2003;12:31513159.CrossRefGoogle ScholarPubMed
Hennah, W, Tuulio-Henriksson, A, Paunio, T, Ekelund, J, Varilo, T, Partonen, T, et al.A haplotype within the DISC1 gene is associated with visual memory functions in families with a high density of schizophrenia. Mol Psychiatry 2005;10:10971103.CrossRefGoogle ScholarPubMed
Hoff, AL, Svetina, C, Shields, G, Stewart, J, DeLisi, LE. Ten year longitudinal study of neuropsychological functioning subsequent to a first episode of schizophrenia. Schizophr Res 2005;78(1):2734.CrossRefGoogle ScholarPubMed
Jung, RE, Haier, RJ. The parieto-frontal integration theory (P-FIT) of intelligence: converging neuroimaging evidence. Behav Brain Sci 2007;30(2):135154. discussion 154–87.CrossRefGoogle ScholarPubMed
Knickmeyer, RC, Wang, J, Zhu, H, Geng, X, Woolson, S, Hamer, RM, et al.Common variants in psychiatric risk genes predict brain structure at birth. Cereb Cortex 2014;24(5):12301246.CrossRefGoogle ScholarPubMed
Lezak, MDNeuropsychological assessment. O.U. Press; 1995.Google Scholar
Lipska, BK, Peters, T, Hyde, TH, Halim, N, Horowitz, C, Mitkus, S, et al.Expression of DISC1 binding partners is reduced in schizophrenia and associated with DISC1 SNPs. Hum Mol Genet 2006;15:12451258.CrossRefGoogle ScholarPubMed
Liu, YL, Fann, CS, Liu, CM, Chen, WJ, Wu, JY, Hung, SI, et al.A single nucleotide polymorphism fine mapping study of chromosome 1q42.1 reveals the vulnerability genes for schizophrenia, GNPAT and DISC1: association with impairment of sustained attention. Biol Psychiatry 2006;60:554562.CrossRefGoogle ScholarPubMed
Liu, B, Fan, L, Cui, Y, Zhang, X, Hou, B, Li, Y, et al.DISC1 Ser704Cys impacts thalamic-prefrontal connectivity. Brain Struct Funct 2015;220(1):91100.CrossRefGoogle ScholarPubMed
Mackie, S, Millar, JK, Porteous, DJRole of DISC1 in neural development and schizophrenia. Curr Opin Neurobiol 2007;17:95102.CrossRefGoogle Scholar
Manoach, DSPrefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophr Res 2003;60(2–3):285298.CrossRefGoogle ScholarPubMed
McIntosh, AM, Gow, A, Luciano, M, Davies, G, Liewald, DC, Harris, SE, et al.Polygenic risk for schizophrenia is associated with cognitive change between childhood and old age. Biol Psychiatry 2013;73(10):938943.CrossRefGoogle ScholarPubMed
Mesholam-Gately, RI, Giuliano, AJ, Goff, KP, Faraone, SV, Seidman, LJNeurocognition in first-episode schizophrenia: a meta-analytic review. Neuropsychology 2009;23(3):315336.CrossRefGoogle ScholarPubMed
Millar, JK, Christie, S, Porteous, DJYeast two-hybrid screens implicate DISC1 in brain development and function. Biochem Biophys Res Commun 2003;311:10191025.CrossRefGoogle ScholarPubMed
Millar, JK, Pickard, BS, Mackie, S, James, R, Christie, S, Buchanan, SR, et al.DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signalling. Science 2005;310:11871191.CrossRefGoogle Scholar
Nicodemus, KK, Elvevåg, B, Foltz, PW, Rosenstein, M, Diaz-Asper, C, Weinberger, DRCategory fluency, latent semantic analysis and schizophrenia: a candidate gene approach. Cortex 2014;55:182191.CrossRefGoogle ScholarPubMed
Osterrieth, PAContribution a l’étude de la perception et de la memoire The test of copying a complex figure: a contribution to the study of perception and memory Arch Psychol 1944;30:286350.Google Scholar
Palo, OM, Antila, M, Silander, K, Hennah, W, Kilpinen, H, Soronen, P, et al.Association of distinct allelic haplotypes of DISC1 with psychotic and bipolar spectrum disorders and with underlying cognitive impairments. Hum Mol Genet 2007;16:25172528.CrossRefGoogle ScholarPubMed
Pelayo-Terán, JM, Pérez-Iglesias, R, Ramírez-Bonilla, M, González-Blanch, C, Martínez-García, O, Pardo-García, G, et al.Epidemiological factors associated with treated incidence of first-episode non-affective psychosis in Cantabria: insights from the Clinical Programme on Early Phases of Psychosis. Early Interv Psychiatry 2008;2(3):178187.CrossRefGoogle ScholarPubMed
Plomin, R, Deary, IJ. Genetics and intelligence differences: five special findings. Mol Psychiatry 2015;20(1):98108.CrossRefGoogle ScholarPubMed
Prata, DP, Mechelli, A, Fu, CH, Picchioni, M, Kane, F, Kalidindi, S, et al.Effect of disrupted-in-schizophrenia-1 on pre-frontal cortical function. Mol Psychiatry 2008;13:915917.CrossRefGoogle ScholarPubMed
Rampino, A, Walker, RM, Torrance, HS, Anderson, SM, Fazio, L, Di Giorgio, A, et al.Expression of DISC1-interactome members correlates with cognitive phenotypes related to schizophrenia. PLoS One 2014;9(6):e99892.CrossRefGoogle Scholar
Reitan, RM, Wolfson, DThe Halstead–Reitan neuropsychological test battery: therapy and clinical interpretation. Neuropsychological Press; 1985.Google Scholar
Rey, AL’examenclinique en psychologie. Presses Universitaires de France; 1964.Google Scholar
Rodríguez-Sánchez, JM, Ayesa-Arriola, R, Rérez-Iglesias, R, Periañez, JA, Martinez-Garcia, O, Gomez-Ruiz, E, et al.Course of cognitive deficits in first episode of non-affective psychosis: a 3-year follow-up study. Schizophr Res 2013;150:121128.CrossRefGoogle ScholarPubMed
Roiser, JP, Wigton, R, Kilner, JM, Mendez, MA, Hon, N, Friston, KJ, et al.Dysconnectivity in the frontoparietal attention network in schizophrenia. Front Psychiatry 2013;4:176.CrossRefGoogle Scholar
Sánchez-Cubillo, I, Periáñez, JA, Adrover-Roig, D, Rodríguez-Sánchez, JM, Ríos-Lago, M, Tirapu, J, et al.Construct validity of the Trail Making Test: role of task-switching, working memory, inhibition/interference control, and visuomotor abilities. J Int Neuropsychol Soc 2009;15(3):438450.CrossRefGoogle ScholarPubMed
Sawa, A, Snyder, SH. Schizophrenia: neural mechanisms for novel therapies. Mol Med 2003;9:39.CrossRefGoogle ScholarPubMed
Sprooten, E, Sussmann, JE, Moorhead, TW, Whalley, HC, French-Constant, C, Blumberg, HP, et al.Association of white matter integrity with genetic variation in an exonic DISC1 SNP. Mol Psychiatry 2011;6(7):685689.CrossRefGoogle Scholar
Stacey, D, Redlich, R, Opel, N, Grotegerd, D, Arolt, V, Kugel, H, et al.No evidence of DISC1-associated morphological changes in the hippocampus, anterior cingulate cortex, or striatum in major depressive disorder cases and healthy controls. J Affect Disord 2014;166:103107.CrossRefGoogle ScholarPubMed
Sullivan, PF, Kendler, KS, Neale, MC. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry 2003;60(12):11871192.CrossRefGoogle ScholarPubMed
Szöke, A, Trandafir, A, Dupont, ME, Méary, A, Schürhoff, F, Leboyer, M. Longitudinal studies of cognition in schizophrenia: meta-analysis. Br J Psychiatry 2008;192(4):248257.CrossRefGoogle ScholarPubMed
Thomson, PA, Harris, SE, Starr, JM, Whalley, LJ, Porteous, DJ, Deary, IJ. Association between genotype at an exonic SNP in DISC1 and normal cognitive aging. Neurosci Lett 2005;389:4145.CrossRefGoogle ScholarPubMed
Wang, Q, Jaaro-Peled, H, Sawa, A, Brandon, NJ. How has DISC1 enabled drug discovery?. Mol Cell Neurosci 2008;37:187195.CrossRefGoogle ScholarPubMed
Weschsler, DWeschsler Adult Intelligence Scale-III. The Psychological Corporation; 1997.Google Scholar
Whalley, HC, Dimitrova, R, Sprooten, E, Dauvermann, MR, Romaniuk, L, Duff, B, et al.Effects of a balanced translocation between chromosomes 1 and 11 disrupting the DISC1 locus on white matter integrity. PLoS One 2015;10(6):e0130900.CrossRefGoogle ScholarPubMed
Woods, SWChlorpromazine equivalent doses for the newer atypical antipsychotics. J Clin Psychiatry 2003;64(6):663667.CrossRefGoogle ScholarPubMed
Zipursky, RB, Reilly, TJ, Murray, RMThe myth of schizophrenia as a progressive brain disease. Schizophr Bull 2013;39(6):13631372.CrossRefGoogle ScholarPubMed
Submit a response

Comments

No Comments have been published for this article.