Hostname: page-component-848d4c4894-75dct Total loading time: 0 Render date: 2024-05-13T05:54:38.926Z Has data issue: false hasContentIssue false
  • English
  • Français

Dysbindin (DTNBP1) variants are associated with hallucinations in schizophrenia

Published online by Cambridge University Press:  15 April 2020

S.-Y. Cheah ,
B.R. Lawford ,
R.M. Young ,
C.P. Morris  and
J. Voisey
S.-Y. Cheah
Affiliation:
Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, Queensland4059, Australia
B.R. Lawford
Affiliation:
Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, Queensland4059, Australia Discipline of Psychiatry, Royal Brisbane and Women's Hospital, Herston, Queensland4006, Australia
R.M. Young
Affiliation:
Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, Queensland4059, Australia
C.P. Morris
Affiliation:
Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, Queensland4059, Australia
J. Voisey*
Affiliation:
Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, Queensland4059, Australia
*
*Corresponding author. Tel.: +61 7 3138 6261. E-mail address:j.voisey@qut.edu.au (J. Voisey).
Get access

Abstract

Background:

Dystrobrevin binding protein 1 (DTNBP1) is a schizophrenia susceptibility gene involved with neurotransmission regulation (especially dopamine and glutamate) and neurodevelopment. The gene is known to be associated with cognitive deficit phenotypes within schizophrenia. In our previous studies, DTNBP1 was found associated not only with schizophrenia but with other psychiatric disorders including psychotic depression, post-traumatic stress disorder, nicotine dependence and opiate dependence. These findings suggest that DNTBP1 may be involved in pathways that lead to multiple psychiatric phenotypes. In this study, we explored the association between DTNBP1 SNPs (single nucleotide polymorphisms) and multiple psychiatric phenotypes included in the Diagnostic Interview of Psychosis (DIP).

Methods:

Five DTNBP1 SNPs, rs17470454, rs1997679, rs4236167, rs9370822 and rs9370823, were genotyped in 235 schizophrenia subjects screened for various phenotypes in the domains of depression, mania, hallucinations, delusions, subjective thought disorder, behaviour and affect, and speech disorder. SNP-phenotype association was determined with ANOVA under general, dominant/recessive and over-dominance models.

Results:

Post hoc tests determined that SNP rs1997679 was associated with visual hallucination; SNP rs4236167 was associated with general auditory hallucination as well as specific features including non-verbal, abusive and third-person form auditory hallucinations; and SNP rs9370822 was associated with visual and olfactory hallucinations. SNPs that survived correction for multiple testing were rs4236167 for third-person and abusive form auditory hallucinations; and rs9370822 for olfactory hallucinations.

Conclusion:

These data suggest that DTNBP1 is likely to play a role in development of auditory related, visual and olfactory hallucinations which is consistent with evidence of DTNBP1 activity in the auditory processing regions, in visual processing and in the regulation of glutamate and dopamine activity.

Keywords

SchizophreniaDTNBP1PolymorphismSNPPsychiatric phenotypesHallucinations
Type
Original article
Information
European Psychiatry , Volume 30 , Issue 4 , June 2015 , pp. 486 - 491
Copyright
Copyright © Elsevier Masson SAS 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

Aguilar, EJ, Sanjuan, J, Garcia-Marti, G, Lull, JJ, Robles, MMR and genetics in schizophrenia: focus on auditory hallucinations. Eur J Radiol 2008;67(3):434–439.CrossRefGoogle ScholarPubMed
Alfimova, MV, Monakhov, MV, Abramova, LI, Golubev, SA, Golimbet, VEPolymorphism of serotonin receptor genes (5-HTR2A) and dysbindin (DTNBP1) and individual components of short-term verbal memory processes in schizophrenia. Neurosci Behav Physiol 2010;40(8):934–940.CrossRefGoogle Scholar
Benjamini, Y, Hochberg, YControlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 1995;57(1):289–300.Google Scholar
Benson, MA, Newey, SE, Martin-Rendon, E, Hawkes, R, Blake, DJDysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain. J Biol Chem 2001;276(26):24232–24241.CrossRefGoogle ScholarPubMed
Bray, NJ, Preece, A, Williams, NM, Moskvina, V, Buckland, PR, Owen, MJet al.Haplotypes at the dystrobrevin binding protein 1 (DTNBP1) gene locus mediate risk for schizophrenia through reduced DTNBP1 expression. Hum Mol Genet 2005;14(14):1947–1954.CrossRefGoogle ScholarPubMed
Brugge, JF, Volkov, IO, Oya, H, Kawasaki, H, Reale, RA, Fenoy, Aet al.Functional localization of auditory cortical fields of human: click-train stimulation. Hear Res 2008;238(1–2):12–24.CrossRefGoogle ScholarPubMed
Burdick, KE, Lencz, T, Funke, B, Finn, CT, Szeszko, PR, Kane, JMet al.Genetic variation in DTNBP1 influences general cognitive ability. Hum Mol Genet 2006;15(10):1563–1568.CrossRefGoogle ScholarPubMed
Burdick, KE, Goldberg, TE, Funke, B, Bates, JA, Lencz, T, Kucherlapati, Ret al.DTNBP1 genotype influences cognitive decline in schizophrenia. Schizophr Res 2007;89(1–3):169–172.CrossRefGoogle Scholar
Cascella, NG, Takaki, M, Lin, S, Sawa, ANeurodevelopmental involvement in schizophrenia: the olfactory epithelium as an alternative model for research. J Neurochem 2007;102(3):587–594.CrossRefGoogle ScholarPubMed
Castle, DJ, Jablensky, A, McGrath, JJ, Carr, V, Morgan, V, Waterreus, Aet al.The diagnostic interview for psychoses (DIP): development, reliability and applications. Psychol Med 2006;36(1):69–80.CrossRefGoogle ScholarPubMed
DeRosse, P, Funke, B, Burdick, KE, Lencz, T, Ekholm, JM, Kane, JMet al.Dysbindin genotype and negative symptoms in schizophrenia. Am J Psychiatry 2006;163(3):532–534.CrossRefGoogle Scholar
Desai, PREstimation of direct and indirect costs of treating schizophrenia for community-dwelling US residents. Austin, TX: University of Texas; 2011.Google Scholar
Domschke, K, Lawford, B, Young, R, Voisey, J, Morris, CP, Roehrs, Tet al.Dysbindin (DTNBP1) – A role in psychotic depression?. J Psychiatr Res 2011;45(5):588–595.CrossRefGoogle ScholarPubMed
Donohoe, G, Morris, DW, Clarke, S, McGhee, KA, Schwaiger, S, Nangle, JMet al.Variance in neurocognitive performance is associated with dysbindin-1 in schizophrenia: a preliminary study. Neuropsychologia 2007;45(2):454–458.CrossRefGoogle ScholarPubMed
Donohoe, G, Morris, DW, De Sanctis, P, Magno, E, Montesi, JL, Garavan, HPet al.Early visual processing deficits in dysbindin-associated schizophrenia. Biol Psychiatry 2008;63(5):484–489.CrossRefGoogle ScholarPubMed
Donohoe, G, Frodl, T, Morris, D, Spoletini, I, Cannon, DM, Cherubini, Aet al.Reduced occipital and prefrontal brain volumes in dysbindin-associated schizophrenia. Neuropsychopharmacology 2010;35(2):368–373.CrossRefGoogle ScholarPubMed
Fallgatter, AJ, Herrmann, MJ, Hohoff, C, Ehlis, AC, Jarczok, TA, Freitag, CMet al.DTNBP1 (dysbindin) gene variants modulate prefrontal brain function in healthy individuals. Neuropsychopharmacology 2006;31(9):2002–2010.CrossRefGoogle ScholarPubMed
Fanous, AH, Van Den Oord, EJ, Riley, BP, Aggen, SH, Neale, MC, O’Neill, FAet al.Relationship between a high-risk haplotype in the DTNBP1 (dysbindin) gene and clinical features of schizophrenia. Am J Psychiatry 2005;162(10):1824–1832.CrossRefGoogle ScholarPubMed
Gaysina, D, Cohen-Woods, S, Chow, PC, Martucci, L, Schosser, A, Ball, HAet al.Association of the dystrobrevin binding protein 1 gene (DTNBP1) in a bipolar case-control study (BACCS). Am J Med Genet B Neuropsychiatr Genet 2009;150B(6):836–844.CrossRefGoogle Scholar
Ghiani, CA, Starcevic, M, Rodriguez-Fernandez, IA, Nazarian, R, Cheli, VT, Chan, LNet al.The dysbindin-containing complex (BLOC-1) in brain: developmental regulation, interaction with SNARE proteins and role in neurite outgrowth. Mol Psychiatry 2010;15(2):115[204–15].CrossRefGoogle ScholarPubMed
Harrison, PJ, Weinberger, DRSchizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 2005;10(1):40–68.CrossRefGoogle ScholarPubMed
Hashimoto, R, Noguchi, H, Hori, H, Ohi, K, Yasuda, Y, Takeda, Met al.Association between the dysbindin gene (DTNBP1) and cognitive functions in Japanese subjects. Psychiatry Clin Neurosci 2009;63(4):550–556.CrossRefGoogle ScholarPubMed
Howard, MA, Volkov, IO, Mirsky, R, Garell, PC, Noh, MD, Granner, Met al.Auditory cortex on the human posterior superior temporal gyrus. J Comp Neurol 2000;416(1):79–92.3.0.CO;2-2>CrossRefGoogle ScholarPubMed
Ito, H, Morishita, R, Shinoda, T, Iwamoto, I, Sudo, K, Okamoto, Ket al.Dysbindin-1, WAVE2 and Abi-1 form a complex that regulates dendritic spine formation. Mol Psychiatry 2010;15(10):976–986.CrossRefGoogle Scholar
Javitt, DC, Zukin, SRRecent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 1991;148(10):1301–1308.Google ScholarPubMed
Jentsch, JD, Trantham-Davidson, H, Jairl, C, Tinsley, M, Cannon, TD, Lavin, ADysbindin modulates prefrontal cortical glutamatergic circuits and working memory function in mice. Neuropsychopharmacology 2009;34(12):2601–2608.CrossRefGoogle ScholarPubMed
Ji, Y, Yang, F, Papaleo, F, Wang, HX, Gao, WJ, Weinberger, DRet al.Role of dysbindin in dopamine receptor trafficking and cortical GABA function. Proc Natl Acad Sci U S A 2009;106(46):19593–19598.CrossRefGoogle ScholarPubMed
Karlsgodt, KH, Robleto, K, Trantham-Davidson, H, Jairl, C, Cannon, TD, Lavin, Aet al.Reduced dysbindin expression mediates N-methyl-D-aspartate receptor hypofunction and impaired working memory performance. Biol Psychiatry 2011;69(1):28–34.CrossRefGoogle ScholarPubMed
Kubota, K, Kumamoto, N, Matsuzaki, S, Hashimoto, R, Hattori, T, Okuda, Het al.Dysbindin engages in c-Jun N-terminal kinase activity and cytoskeletal organization. Biochem Biophys Res Commun 2009;379(2):191–195.CrossRefGoogle ScholarPubMed
Kumar, S, Soren, S, Chaudhury, SHallucinations: etiology and clinical implications. Ind Psychiatry J 2009;18(2):119–126.Google ScholarPubMed
Luciano, M, Miyajima, F, Lind, PA, Bates, TC, Horan, M, Harris, SEet al.Variation in the dysbindin gene and normal cognitive function in three independent population samples. Genes Brain Behav 2009;8(2):218–227.CrossRefGoogle ScholarPubMed
Ma, X, Fei, E, Fu, C, Ren, H, Wang, GDysbindin-1, a schizophrenia-related protein, facilitates neurite outgrowth by promoting the transcriptional activity of p53. Mol Psychiatry 2011;16(11):1105–1116.CrossRefGoogle ScholarPubMed
Markov, V, Krug, A, Krach, S, Jansen, A, Eggermann, T, Zerres, Ket al.Impact of schizophrenia-risk gene dysbindin 1 on brain activation in bilateral middle frontal gyrus during a working memory task in healthy individuals. Hum Brain Mapp 2010;31(2):266–275.Google ScholarPubMed
Marley, A, von Zastrow, MDysbindin promotes the post-endocytic sorting of G protein-coupled receptors to lysosomes. PLoS One 2010;5(2):e9325.CrossRefGoogle ScholarPubMed
Neckelmann, G, Specht, K, Lund, A, Ersland, L, Smievoll, AI, Neckelmann, Det al.MR morphometry analysis of grey matter volume reduction in schizophrenia: association with hallucinations. Int J Neurosci 2006;116(1):9–23.CrossRefGoogle ScholarPubMed
Nenadic, I, Smesny, S, Schlosser, RG, Sauer, H, Gaser, CAuditory hallucinations and brain structure in schizophrenia: voxel-based morphometric study. Br J Psychiatry 2010;196(5):412–413.CrossRefGoogle ScholarPubMed
Nestor, PG, Kubicki, M, Kuroki, N, Gurrera, RJ, Niznikiewicz, M, Shenton, MEet al.Episodic memory and neuroimaging of hippocampus and fornix in chronic schizophrenia. Psychiatry Res 2007;155(1):21–28.CrossRefGoogle ScholarPubMed
Numakawa, T, Yagasaki, Y, Ishimoto, T, Okada, T, Suzuki, T, Iwata, Net al.Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia. Hum Mol Genet 2004;13(21):2699–2708.CrossRefGoogle Scholar
Ott, JUtility programs for analysis of genetic linkage, program, hwe version 1.10. New York: Columbia University; 1988.Google Scholar
Perala, J, Suvisaari, J, Saarni, SI, Kuoppasalmi, K, Isometsa, E, Pirkola, Set al.Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch Gen Psychiatry 2007;64(1):19–28.CrossRefGoogle Scholar
Pitcher, GM, Kalia, LV, Ng, D, Goodfellow, NM, Yee, KT, Lambe, EKet al.Schizophrenia susceptibility pathway neuregulin 1-ErbB4 suppresses Src upregulation of NMDA receptors. Nat Med 2011;17(4):470–478.CrossRefGoogle ScholarPubMed
Saggu, S, Cannon, TD, Jentsch, JD, Lavin, APotential molecular mechanisms for decreased synaptic glutamate release in dysbindin-1 mutant mice. Schizophr Res 2013;146(1–3):254–263.CrossRefGoogle ScholarPubMed
Stefanis, NC, Trikalinos, TA, Avramopoulos, D, Smyrnis, N, Evdokimidis, I, Ntzani, EEet al.Impact of schizophrenia candidate genes on schizotypy and cognitive endophenotypes at the population level. Biol Psychiatry 2007;62(7):784–792.CrossRefGoogle ScholarPubMed
Sumich, A, Chitnis, XA, Fannon, DG, O’Ceallaigh, S, Doku, VC, Faldrowicz, Aet al.Unreality symptoms and volumetric measures of Heschl's gyrus and planum temporal in first-episode psychosis. Biol Psychiatry 2005;57(8):947–950.CrossRefGoogle ScholarPubMed
Sweet, RA, Dorph-Petersen, KA, Lewis, DAMapping auditory core, lateral belt, and parabelt cortices in the human superior temporal gyrus. J Comp Neurol 2005;491(3):270–289.CrossRefGoogle ScholarPubMed
Szeszko, PR, Strous, RD, Goldman, RS, Ashtari, M, Knuth, KH, Lieberman, JAet al.Neuropsychological correlates of hippocampal volumes in patients experiencing a first episode of schizophrenia. Am J Psychiatry 2002;159(2):217–226.CrossRefGoogle ScholarPubMed
Talbot, K, Eidem, WL, Tinsley, CL, Benson, MA, Thompson, EW, Smith, RJet al.Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia. J Clin Invest 2004;113(9):1353–1363.CrossRefGoogle Scholar
Talbot, K, Louneva, N, Cohen, JW, Kazi, H, Blake, DJ, Arnold, SESynaptic dysbindin-1 reductions in schizophrenia occur in an isoform-specific manner indicating their subsynaptic location. PLoS One 2011;6(3):e16886.CrossRefGoogle Scholar
Tamminga, CA, Stan, AD, Wagner, ADThe hippocampal formation in schizophrenia. Am J Psychiatry 2010;167(10):1178–1193.CrossRefGoogle Scholar
Tang, J, LeGros, RP, Louneva, N, Yeh, L, Cohen, JW, Hahn, CGet al.Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases is reduced in an isoform-specific manner unrelated to dysbindin-1 mRNA expression. Hum Mol Genet 2009;18(20):3851–3863.CrossRefGoogle Scholar
Tang, TTT, Yang, F, Chen, BS, Lu, Y, Ji, Y, Roche, KWet al.Dysbindin regulates hippocampal LTP by controlling NMDA receptor surface expression. Proc Natl Acad Sci U S A 2009;106(50):21395–21400.CrossRefGoogle ScholarPubMed
Thoma, RJ, Monnig, M, Hanlon, FM, Miller, GA, Petropoulos, H, Mayer, ARet al.Hippocampus volume and episodic memory in schizophrenia. J Int Neuropsychol Soc 2009;15(2):182–195.CrossRefGoogle Scholar
Tognin, S, Viding, E, McCrory, EJ, Taylor, L, O’Donovan, MC, McGuire, Pet al.Effects of DTNBP1 genotype on brain development in children. J Child Psychol Psychiatry 2011;52(12):1287–1294.CrossRefGoogle ScholarPubMed
Toulopoulou, T, Grech, A, Morris, RG, Schulze, K, McDonald, C, Chapple, Bet al.The relationship between volumetric brain changes and cognitive function: a family study on schizophrenia. Biol Psychiatry 2004;56(6):447–453.CrossRefGoogle Scholar
Voisey, J, Swagell, CD, Hughes, IP, Lawford, BR, Young, RM, Morris, CPAnalysis of HapMap tag-SNPs in dysbindin (DTNBP1) reveals evidence of consistent association with schizophrenia. Eur Psychiatry 2010;25(6):314–319.CrossRefGoogle ScholarPubMed
Voisey, J, Swagell, CD, Hughes, IP, Connor, JP, Lawford, BR, Young, RMet al.A polymorphism in the dysbindin gene (DTNBP1) associated with multiple psychiatric disorders including schizophrenia. Behav Brain Funct 2010;6:41.CrossRefGoogle ScholarPubMed
Weickert, CS, Straub, RE, McClintock, BW, Matsumoto, M, Hashimoto, R, Hyde, TMet al.Human dysbindin (DTNBP1) gene expression in normal brain and in schizophrenic prefrontal cortex and midbrain. Arch Gen Psychiatry 2004;61(6):544–555.CrossRefGoogle ScholarPubMed
Weickert, CS, Rothmond, DA, Hyde, TM, Kleinman, JE, Straub, REReduced DTNBP1 (dysbindin-1) mRNA in the hippocampal formation of schizophrenia patients. Schizophr Res 2008;98:(1–3):105–110.CrossRefGoogle ScholarPubMed
Wilson, RS, Gilley, DW, Bennett, DA, Beckett, LA, Evans, DAHallucinations, delusions, and cognitive decline in Alzheimer's disease. J Neurol Neurosurg Psychiatry 2000;69(2):172–177.CrossRefGoogle ScholarPubMed
Zinkstok, JR, de Wilde, O, van Amelsvoort, TA, Tanck, MW, Baas, F, Linszen, DHAssociation between the DTNBP1 gene and intelligence: a case-control study in young patients with schizophrenia and related disorders and unaffected siblings. Behav Brain Funct 2007;3:19.CrossRefGoogle ScholarPubMed
Supplementary material: File

Cheah et al. supplementary material

Table S1

Download Cheah et al. supplementary material(File)
File 20.2 KB
Submit a response

Comments

No Comments have been published for this article.