Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-76fb5796d-zzh7m Total loading time: 0 Render date: 2024-04-26T18:33:19.528Z Has data issue: false hasContentIssue false

4 - The Molecular Genetics of Obsessive-Compulsive and Related Disorders

from Section 1 - Theoretical Foundations of Obsessive-Compulsive and Related Disorders

Published online by Cambridge University Press:  14 December 2018

By
Fabiana Barzotti Kohlrausch
Edited by
Leonardo F. Fontenelle  and
Murat Yücel
Leonardo F. Fontenelle
Affiliation:
Federal University of Rio de Janeiro
Murat Yücel
Affiliation:
Monash University, Victoria
Get access
Type
Chapter
Information
A Transdiagnostic Approach to Obsessions, Compulsions and Related Phenomena , pp. 29 - 38
Publisher: Cambridge University Press
Print publication year: 2019

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

Grunblatt, E, Hauser, TU, Walitza, S. Imaging genetics in obsessive-compulsive disorder: linking genetic variations to alterations in neuroimaging. Prog Neurobiol. 2014;121:114–124.Google Scholar
Pauls, DL, Abramovitch, A, Rauch, SL, et al. Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci. 2014;15:410–424.Google Scholar
Browne, HA, Gair, SL, Scharf, JM, et al. Genetics of obsessive-compulsive disorder and related disorders. Psychiatr Clin North Am. 2014;37:319–335.CrossRefGoogle ScholarPubMed
Ross, J, Badner, J, Garrido, H, et al. Genomewide linkage analysis in Costa Rican families implicates chromosome 15q14 as a candidate region for OCD. Hum Genet. 2011;130:795–805.CrossRefGoogle ScholarPubMed
Mathews, CA, Badner, JA, Andresen, JM, et al. Genome-wide linkage analysis of obsessive-compulsive disorder implicates chromosome 1p36. Biol Psychiatry. 2012;72:629–636.Google Scholar
Shugart, YY, Samuels, J, Willour, VL, et al. Genomewide linkage scan for obsessive-compulsive disorder: evidence for susceptibility loci on chromosomes 3q, 7p, 1q, 15q, and 6q. Mol Psychiatry. 2006;11:763–770.Google Scholar
Nestadt, G, Samuels, J, Riddle, M, et al. A family study of obsessive-compulsive disorder. Arch Gen Psychiatry. 2000;57:358–363.Google Scholar
Hanna, GL, Veenstra-VanderWeele, J, Cox, NJ, et al. Genome-wide linkage analysis of families with obsessive-compulsive disorder ascertained through pediatric probands. Am J Med Genet. 2002;114:541–552.CrossRefGoogle ScholarPubMed
Willour, VL, Yao Shugart, Y, Samuels, J, et al. Replication study supports evidence for linkage to 9p24 in obsessive-compulsive disorder. Am J Hum Genet. 2004;75:508–513.Google Scholar
Wang, Y, Samuels, JF, Chang, YC, et al. Gender differences in genetic linkage and association on 11p15 in obsessive-compulsive disorder families. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:33–40.Google Scholar
den Braber, A, Zilhao, NR, Fedko, IO, et al. Obsessive-compulsive symptoms in a large population-based twin-family sample are predicted by clinically based polygenic scores and by genome-wide SNPs. Transl Psychiatry. 2016;6:e731.Google Scholar
Hanna, GL, Veenstra-Vanderweele, J, Cox, NJ, et al. Evidence for a susceptibility locus on chromosome 10p15 in early-onset obsessive-compulsive disorder. Biol Psychiatry. 2007;62:856–862.Google Scholar
Grisham, JR, Anderson, TM, Sachdev, PS. Genetic and environmental influences on obsessive-compulsive disorder. Eur Arch Psychiatry Clin Neurosci. 2008;258:107–116.Google Scholar
Samuels, J, Shugart, YY, Grados, MA, et al. Significant linkage to compulsive hoarding on chromosome 14 in families with obsessive-compulsive disorder: results from the OCD Collaborative Genetics Study. Am J Psychiatry. 2007;164:493–499.Google Scholar
Murphy, DL, Moya, PR, Fox, MA, et al. Anxiety and affective disorder comorbidity related to serotonin and other neurotransmitter systems: obsessive-compulsive disorder as an example of overlapping clinical and genetic heterogeneity. Philos Trans R Soc Lond B Biol Sci. 2013;368:20120435.Google Scholar
Pittenger, C, Bloch, MH. Pharmacological treatment of obsessive-compulsive disorder. Psychiatr Clin North Am. 2014;37:375–391.Google Scholar
Taylor, S. Disorder-specific genetic factors in obsessive-compulsive disorder: a comprehensive meta-analysis. Am J Med Genet B Neuropsychiatr Genet. 2016;171B:325–332.Google Scholar
Melo-Felippe, FB, de Salles Andrade, JB, Giori, IG, et al. Catechol-O-methyltransferase gene polymorphisms in specific obsessive-compulsive disorder patients’ subgroups. J Mol Neurosci. 2016;58:129–136.Google Scholar
Ting, JT, Feng, G. Glutamatergic synaptic dysfunction and obsessive-compulsive disorder. Curr Chem Genomics. 2008;2:62–75.CrossRefGoogle ScholarPubMed
Wu, K, Hanna, GL, Rosenberg, DR, et al. The role of glutamate signaling in the pathogenesis and treatment of obsessive-compulsive disorder. Pharmacol Biochem Behav. 2012;100:726–735.CrossRefGoogle ScholarPubMed
Zhu, Y, Fan, Q, Han, X, et al. Decreased thalamic glutamate level in unmedicated adult obsessive-compulsive disorder patients detected by proton magnetic resonance spectroscopy. J Affect Disord. 2015;178:193–200.Google Scholar
Pittenger, C, Bloch, MH, Williams, K. Glutamate abnormalities in obsessive compulsive disorder: neurobiology, pathophysiology, and treatment. Pharmacol Ther. 2011;132:314–332.Google Scholar
Arnold, PD, Sicard, T, Burroughs, E, et al. Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Arch Gen Psychiatry. 2006;63:769–776.Google Scholar
Stewart, SE, Mayerfeld, C, Arnold, PD, et al. Meta-analysis of association between obsessive-compulsive disorder and the 3’ region of neuronal glutamate transporter gene SLC1A1. Am J Med Genet B Neuropsychiatr Genet. 2013;162B:367–379.Google Scholar
Su, AI, Cooke, MP,Ching, KA, et al. Large-scale analysis of the human and mouse transcriptomes. Proc Natl Acad Sci USA. 2002;99:4465–4470.CrossRefGoogle ScholarPubMed
Arnold, PD, Macmaster, FP, Richter, MA, et al. Glutamate receptor gene (GRIN2B) associated with reduced anterior cingulate glutamatergic concentration in pediatric obsessive-compulsive disorder. Psychiatry Res. 2009;172:136–139.Google Scholar
Alonso, P, Gratacos, M, Segalas, C, et al. Association between the NMDA glutamate receptor GRIN2B gene and obsessive-compulsive disorder. J Psychiatry Neurosci. 2012;37:273–281.CrossRefGoogle ScholarPubMed
Wu, K, Hanna, GL, Easter, P, et al. Glutamate system genes and brain volume alterations in pediatric obsessive-compulsive disorder: a preliminary study. Psychiatry Res. 2013;211:214–220.Google Scholar
Kohlrausch, FB, Giori, IG, Melo-Felippe, FB, et al. Association of GRIN2B gene polymorphism and obsessive compulsive disorder and symptom dimensions: a pilot study. Psychiatry Res. 2016;243:152–155.Google Scholar
Saxena, S, Rauch, SL. Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder. Psychiatr Clin North Am. 2000;23:563–586.Google Scholar
Stewart, SE, Yu, D, Scharf, JM, et al. Genome-wide association study of obsessive-compulsive disorder. Mol Psychiatry. 2013;18:788–798.Google Scholar
Mattheisen, M, Samuels, JF, Wang, Y, et al. Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS. Mol Psychiatry. 2015;20:337–344.Google Scholar
Pe’er, I, Yelensky, R, Altshuler, D, et al. Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet Epidemiol. 2008;32:381–385.Google Scholar
Dudbridge, F, Gusnanto, A. Estimation of significance thresholds for genomewide association scans. Genet Epidemiol. 2008;32:227–234.Google Scholar
Costas, J, Carrera, N, Alonso, P, et al. Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia. Transl Psychiatry. 2016;6:e768.Google Scholar
Cappi, C, Brentani, H, Lima, L, et al. Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways. Transl Psychiatry. 2016;6:e764.Google Scholar
Ripke, S, O’Dushlaine, C, Chambert, K, et al. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat Genet. 2013;45:1150–1159.Google Scholar
Jones, CA, Watson, DJ, Fone, KC. Animal models of schizophrenia. Br J Pharmacol. 2011;164:1162–1194.Google Scholar
Burguiere, E, Monteiro, P, Mallet, L, et al. Striatal circuits, habits, and implications for obsessive-compulsive disorder. Curr Opin Neurobiol. 2015;30:59–65.Google Scholar
Feusner, JD, Hembacher, E, Phillips, KA. The mouse who couldn’t stop washing: pathologic grooming in animals and humans. CNS Spectr. 2009;14:503–513.Google Scholar
Grados, M, Prazak, M, Saif, A, et al. A review of animal models of obsessive-compulsive disorder: a focus on developmental, immune, endocrine and behavioral models. Expert Opin Drug Discov. 2016;11:27–43.Google Scholar
Greer, JM, Capecchi, MR. Hoxb8 is required for normal grooming behavior in mice. Neuron. 2002;33:23–34.Google Scholar
Capecchi, MR. Hox genes and mammalian development. Cold Spring Harb Symp Quant Biol. 1997;62:273–281.Google Scholar
Zike, I, Xu, T, Hong, N, et al. Rodent models of obsessive compulsive disorder: evaluating validity to interpret emerging neurobiology. Neuroscience. 2017;345:256–273.Google Scholar
Welch, JM, Lu, J, Rodriguiz, RM, et al. Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice. Nature. 2007;448:894–900.Google Scholar
Menzies, L, Chamberlain, SR, Laird, AR, et al. Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited. Neurosci Biobehav Rev. 2008;32:525–549.CrossRefGoogle ScholarPubMed
Wan, Y, Ade, KK, Caffall, Z, et al. Circuit-selective striatal synaptic dysfunction in the Sapap3 knockout mouse model of obsessive-compulsive disorder. Biol Psychiatry. 2014;75:623–630.Google Scholar
Burguiere, E, Monteiro, P, Feng, G, et al. Optogenetic stimulation of lateral orbitofronto-striatal pathway suppresses compulsive behaviors. Science. 2013;340:1243–1246.Google Scholar
Shmelkov, SV, Hormigo, A, Jing, D, et al. Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive-like behaviors in mice. Nat Med. 2010;16:598–602, 1p following 02.CrossRefGoogle ScholarPubMed
Peghini, P, Janzen, J, Stoffel, W. Glutamate transporter EAAC-1-deficient mice develop dicarboxylic aminoaciduria and behavioral abnormalities but no neurodegeneration. EMBO J. 1997;16:3822–3832.Google Scholar
Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511:421–427.Google Scholar
O’Donovan, MC. What have we learned from the Psychiatric Genomics Consortium. World Psychiatry. 2015;14:291–293.CrossRefGoogle ScholarPubMed
Pigott, TA, Seay, SM. A review of the efficacy of selective serotonin reuptake inhibitors in obsessive-compulsive disorder. J Clin Psychiatry. 1999;60:101–106.Google Scholar
Brandl, EJ, Muller, DJ, Richter, MA. Pharmacogenetics of obsessive-compulsive disorders. Pharmacogenomics. 2012;13:71–81.Google Scholar
Zai, G, Brandl, EJ, Muller, DJ, et al. Pharmacogenetics of antidepressant treatment in obsessive-compulsive disorder: an update and implications for clinicians. Pharmacogenomics. 2014;15:1147–1157.Google Scholar
Qin, H, Samuels, JF, Wang, Y, et al. Whole-genome association analysis of treatment response in obsessive-compulsive disorder. Mol Psychiatry. 2016;21:270–276.Google Scholar
Goldstein, DB, Need, AC, Singh, R, et al. Potential genetic causes of heterogeneity of treatment effects. Am J Med. 2007;120:S21–S25.Google Scholar
Billett, EA, Richter, MA, King, N, et al. Obsessive compulsive disorder, response to serotonin reuptake inhibitors and the serotonin transporter gene. Mol Psychiatry. 1997;2:403–406.CrossRefGoogle ScholarPubMed
Denys, D, Van Nieuwerburgh, F, Deforce, D, et al. Association between serotonergic candidate genes and specific phenotypes of obsessive compulsive disorder. J Affect Disord. 2006;91:39–44.Google Scholar
Di Bella, D, Erzegovesi, S, Cavallini, MC, et al. Obsessive-Compulsive Disorder, 5-HTTLPR polymorphism and treatment response. Pharmacogenomics J. 2002;2:176–181.Google Scholar
Grunblatt, E, Tschakarjan, S, Brezinka, V, et al. Extraordinarily fast response to low-dose sertraline in a child with severe obsessive-compulsive disorder and high functioning serotonin transporter genotype. J Child Adolesc Psychopharmacol. 2014;24:102–104.Google Scholar
McDougle, CJ, Epperson, CN, Price, LH, et al. Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder. Mol Psychiatry. 1998;3:270–273.Google Scholar
Miguita, K, Cordeiro, Q, Shavitt, RG, et al. Association study between genetic monoaminergic polymorphisms and OCD response to clomipramine treatment. Arq Neuropsiquiatr. 2011;69:283–287.Google Scholar
Zhang, L, Liu, X, Li, T, et al. Molecular pharmacogenetic studies of drug responses to obsessive-compulsive disorder and six functional genes. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2004;21:479–481.Google Scholar
Corregiari, FM, Bernik, M, Cordeiro, Q, et al. Endophenotypes and serotonergic polymorphisms associated with treatment response in obsessive-compulsive disorder. Clinics (Sao Paulo). 2012;67:335–340.Google Scholar
Denys, D, Van Nieuwerburgh, F, Deforce, D, et al. Prediction of response to paroxetine and venlafaxine by serotonin-related genes in obsessive-compulsive disorder in a randomized, double-blind trial. J Clin Psychiatry. 2007;68:747–753.Google Scholar
Sallee, FR, DeVane, CL, Ferrell, RE. Fluoxetine-related death in a child with cytochrome P-450 2D6 genetic deficiency. J Child Adolesc Psychopharmacol. 2000;10:27–34.Google Scholar
Baumann, P, Barbe, R, Vabre-Bogdalova, A, et al. Epileptiform seizure after sertraline treatment in an adolescent experiencing obsessive-compulsive disorder and presenting a rare pharmacogenetic status. J Clin Psychopharmacol. 2006;26:679–681.Google Scholar
Brandl, EJ, Tiwari, AK, Zhou, X, et al. Influence of CYP2D6 and CYP2C19 gene variants on antidepressant response in obsessive-compulsive disorder. Pharmacogenomics J. 2014;14:176–181.Google Scholar
Van Nieuwerburgh, FC, Denys, DA, Westenberg, HG, et al. Response to serotonin reuptake inhibitors in OCD is not influenced by common CYP2D6 polymorphisms. Int J Psychiatry Clin Pract. 2009;13:345–348.Google Scholar
Muller, DJ, Brandl, EJ, Hwang, R, et al. The AmpliChip(R) CYP450 test and response to treatment in schizophrenia and obsessive compulsive disorder: a pilot study and focus on cases with abnormal CYP2D6 drug metabolism. Genet Test Mol Biomarkers. 2012;16:897–903.Google Scholar
Mostafavi Abdolmaleky, H. Horizons of psychiatric genetics and epigenetics: where are we and where are we heading? Iran J Psychiatry Behav Sci. 2014;8:1–10.Google Scholar
Weinhold, B. Epigenetics: the science of change. Environ Health Perspect. 2006;114:A160–A167.Google Scholar
Mostafavi-Abdolmaleky, H, Glatt, ST. Epigenetics in psychiatry. In Roach, HI, Bronner, F, Oreffo, RO, eds., Epigenetic Aspects of Chronic Diseases. London: Springer; 2011: 163–174.Google Scholar
Abdolmaleky, HM, Nohesara, S, Ghadirivasfi, M, et al. DNA hypermethylation of serotonin transporter gene promoter in drug naive patients with schizophrenia. Schizophr Res. 2014;152:373–380.Google Scholar
Aberg, KA, McClay, JL, Nerella, S, et al. Methylome-wide association study of schizophrenia: identifying blood biomarker signatures of environmental insults. JAMA Psychiatry. 2014;71:255–264.Google Scholar
Liu, J, Chen, J, Ehrlich, S, et al. Methylation patterns in whole blood correlate with symptoms in schizophrenia patients. Schizophr Bull. 2014;40:769–776.Google Scholar
Wockner, LF, Noble, EP, Lawford, BR, et al. Genome-wide DNA methylation analysis of human brain tissue from schizophrenia patients. Transl Psychiatry. 2014;4:e339.Google Scholar
Sanders, AR, Goring, HH, Duan, J, et al. Transcriptome study of differential expression in schizophrenia. Hum Mol Genet. 2013;22:5001–5014.Google Scholar
Glatt, SJ, Stone, WS, Nossova, N, et al. Similarities and differences in peripheral blood gene-expression signatures of individuals with schizophrenia and their first-degree biological relatives. Am J Med Genet B Neuropsychiatr Genet. 2011;156B:869–887.CrossRefGoogle ScholarPubMed
Banigan, MG, Kao, PF, Kozubek, JA, et al. Differential expression of exosomal microRNAs in prefrontal cortices of schizophrenia and bipolar disorder patients. PLoS One. 2013;8:e48814.Google Scholar
Beveridge, NJ, Gardiner, E, Carroll, AP, et al. Schizophrenia is associated with an increase in cortical microRNA biogenesis. Mol Psychiatry. 2010;15:1176–1189.Google Scholar
Perkins, DO, Jeffries, CD, Jarskog, LF, et al. microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol. 2007;8:R27.Google Scholar
Glatt, SJ, Cohen, OS, Faraone, SV, et al. Dysfunctional gene splicing as a potential contributor to neuropsychiatric disorders. Am J Med Genet B Neuropsychiatr Genet. 2011;156B:382–392.Google Scholar
Zhang, Y, Bertolino, A, Fazio, L, et al. Polymorphisms in human dopamine D2 receptor gene affect gene expression, splicing, and neuronal activity during working memory. Proc Natl Acad Sci USA. 2007;104:20552–20557.Google Scholar
Zhao, C, Xu, Z, Wang, F, et al. Alternative-splicing in the exon-10 region of GABA(A) receptor beta(2) subunit gene: relationships between novel isoforms and psychotic disorders. PLoS One. 2009;4:e6977.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×