Obsessive-compulsive disorder (OCD) clinical presentation is remarkably diverse, and can vary both within and across patients over time. This variability in the phenotypic expression has led to the hypothesis that OCD is a heterogeneous disorder and that this heterogeneity obscures the findings of clinical, natural history and treatment response studies and complicates the search for vulnerability genes. A complete understanding of what comprises OCD and the underlying etiological mechanisms will require a dramatic change in how the disorder is conceptualized. In this review, several different approaches that may represent the first steps in this reconceptualization are discussed. These approaches include (1) narrowing the phenotype to identify categorically defined more homogeneous and mutually exclusive subtypes of OCD, (2) considering OC symptom dimensions as quantitative components of the more complex OCD phenotype and (3) broadening the phenotype to include other etiologically related conditions. A combined dimensional approach within distinctive subgroups is proposed as probably the most effective in helping to identify the heritable components of OCD. By identifying heritable components of OCD, it should be possible to find genes for these separate components. The review continues with the illustration of the possible role of some epigenetic risk and protective factors in the OCD presentation and the relevance of examining associated traits and/or endophenotypes to enhance our ability to understand the genetic basis of OCD. To conclude, we discuss the variability in treatment outcome and the significance of the development of specific pharmacological and/or behavioral based therapies tailored to each of these phenotypes.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
A dimensional perspective on the genetics of obsessive-compulsive disorder
Translational Psychiatry Open Access 21 July 2021
Evolution of gamma knife capsulotomy for intractable obsessive-compulsive disorder
Molecular Psychiatry Open Access 09 May 2018
OCD-like behavior is caused by dysfunction of thalamo-amygdala circuits and upregulated TrkB/ERK-MAPK signaling as a result of SPRED2 deficiency
Molecular Psychiatry Open Access 10 January 2017
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Karno M, Golding JM, Sorenson SB, Burnam MA . The epidemiology of obsessive-compulsive disorder in five US communities. Arch Gen Psychiatry 1988; 45: 1094–1099.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association: Washington, DC, 1994, p 886.
World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. World Health Organization: Geneva, 1992.
Leckman JF, Grice DE, Boardman J, Zhang H, Vitale A, Bondi C et al. Symptoms of obsessive-compulsive disorder. Am J Psychiatry 1997; 154: 911–917.
Gottesman II, Gould TD . The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003; 160: 636–645.
Pauls DL, Alsobrook JP, Goodman W, Rassmussen S, Leckman JF . A family study of obsessive-compulsive disorder. Am J Psychiatry 1995; 152: 76–84.
Nestadt G, Samuels J, Riddle M, Bienvenu JO, Liang KY, LaBuda M et al. A family study of obsessive-compulsive disorder. Arch Gen Psychiatry 2000; 57: 358–363.
Rasmussen SA, Tsuang MT . The epidemiology of obsessive compulsive disorder. Clin Psychiatry 1984; 45: 450–457, (review).
Grados M, Riddle MA, Samuels JF, Liang KY, Hoehn-Saric R, Bienvenu OJ et al. The familial phenotype of obsessive-compulsive disorder in relation to tic disorders. Biol Psychiatry 2001; 50: 559–565.
Bienvenu OJ, Samuels J, Riddle MA, Hoehn-Saric R, Liang KY, Cullen BAM et al. The relationship of obsessive-compulsive disorder to possible spectrum disorders: results from a family study. Biol Psychiatry 2000; 48: 287–293.
Samuels J, Nestadt G, Bienvenu OJ, Costa Jr PT, Riddle MA, Liang KY et al. Personality disorders and normal personality dimensions in obsessive-compulsive disorder. Br J Psychiatry 2000; 177: 457–462.
Nicolini H, Hanna G, Baxter L, Schwartz J, Weissbacker K, Spence MA . Segregation analysis of obsessive-compulsive and associated disorders. Preliminary results. Ursus Medicus 1991; 1: 25–28.
Cavallini MC, Perna G, Caldirola D, Bellodi L . A segregation study of panic disorder in families of panic patients responsive to the 35% CO2 challenge. Biol Psychiatry 1999; 46: 815–820.
Alsobrook JP, Leckman JF, Goodman WK, Rasmussen SA, Pauls DL . Segregation analysis of obsessive-compulsive disorder using symptom-based factor scores. Am J Med Genet 1999; 88: 669–675.
Pato MT, Pato CN, Pauls DL . Recent findings in the genetics of OCD. J Clin Psychiatry 2002; 63(Suppl 6): 30–33.
McDougle CJ, Goodman WK, Leckman JF, Lee NC, Heninger GR, Price LH . Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder. A double-blind, placebo-controlled study in patients with and without tics. Arch Gen Psychiatry 1994; 51: 302–308.
Nordstron EJ, Burton FH . A transgenic model of comorbid Tourette's syndrome and obsessive-compulsive disorder circuitry. Mol Psychiatry 2002; 7: 617–625, 524.
Rosenberg D, Hanna G . Genetic and imaging strategies in obsessive-compulsive disorder: potential implications for treatment development. Biol Psychiatry 2000; 48: 1210–1222.
Geller D, Biederman J, Jones J, Park K, Schwartz S, Shapiro S et al. Is juvenile obsessive-compulsive disorder a developmental subtype of the disorder? A review of the pediatric literature. J Am Acad Child Adolesc Psychiatry 1998; 37: 420–427.
Eichstedt JA, Arnold SL . Childhood-onset obsessive-compulsive disorder: a tic-related subtype of OCD? Clin Psychol Rev 2001; 21: 137–158.
Rosario-Campos MC, Leckman F, Mercadante MT, Shavitt G, Prado HS, Sada P et al. Adults with early-onset obsessive-compulsive disorder. Am J Psychiatry 2001; 158: 1899–1903.
Diniz J, Rosario-Campos MC, Shavitt RG, Curi M, Hounie AG, Brotto SA et al. Impact of age of onset and duration of illness in the expression of comorbidities in obsessive-compulsive disorder. J Clin Psychiatry 2004; 65: 22–27.
Swedo SE, Rapoport JL . Phenomenology and differential diagnosis of obsessive-compulsive disorder in children and adolescents. In: Rapoport JL (ed) Obsessive-compulsive Disorder in Children and Adolescents. American Psychiatric Press: Washington, DC, 1989, pp 13–32.
Zohar AH, Pauls DL, Ratzone G, Apter A, Dycian A, Binder M et al. Obsessive-compulsive disorder with and without tics in an epidemiological sample of adolescents. Am J Psychiatry 1997; 154: 274–276.
Geller DA, Biederman J, Faraone SV, Cradock K, Hagermoser L, Zaman N et al. Attention-deficit/hyperactivity disorder in children and adolescents with obsessive-compulsive disorder: fact or artifact? J Am Acad Child Adolesc Psychiatry 2002; 41: 52–58.
Geller DA, Biederman J, Griffin S, Jones J, Lefkowitz TR . Comorbidity of juvenile obsessive-compulsive disorder with disruptive behavior disorders. J Am Acad Child Adolesc Psychiatry 1996; 35: 1637–1646.
Piacentini J . Cognitive behavioral therapy of childhood OCD. Child Adolesc Psychiatric Clin N Am 1999; 8: 599–616.
Leonard HL, Lenane MC, Swedo SE, Rettew DC, Gershon ES, Rapopport JL . Tics and Tourette's disorder: a 2- to 7- year follow-up of 54 obsessive-compulsive children. Am J Psychiatry 1992; 149: 1244–1251.
Reddy PS, Reddy YC, Srinath S, Khanna S, Sheshadri SP, Girimaji SR . A family study of juvenile obsessive-compulsive disorder. Can J Psychiatry 2001; 46: 346–351.
Lenane MC, Swedo SE, Leonard H, Pauls DL, Sceery W, Rapoport J . Psychiatric disorders in first degree relatives of children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry 1990; 29: 407–412.
Riddle MA, Scahill L, King R, Hardin MT, Towbin KE, Ort SI et al. Obsessive-compulsive disorder in children and adolescents: phenomenology and family history. J Am Acad Child Adolesc Psychiatry 1990; 29: 766–772.
Rosario-Campos MC, Leckman JF, Curi M, Quatrano S, Katsovitch L, Miguel EC et al A family study of early-onset obsessive-compulsive disorder. Am J Med Genet, in press.
March JS, Leonard HL . Obsessive-compulsive disorder in children and adolescents: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 1996; 35: 1265–1273.
Busatto GF, Zamignani DR, Buchpiguel CA, Garrido GEJ, Glabus MF, Rocha ET et al. A voxel based investigation of regional cerebral blood flow abnormalities in obsessive-compulsive disorder using single photon emission computed tomography (SPECT). Psychiatry Res 2000; 99: 15–27.
Ackerman DL, Greenland S, Bystritsky A, Morgenstern H, Katz RJ . Predictors of treatment response in obsessive-compulsive disorder: multivariate analyses from a multicenter trial of clomipramine. J Clin Psychopharmacol 1994; 14: 247–254.
Ravizza L, Barzega G, Bellino S, Bogetto F, Maina G . Predictors of drug treatment response in obsessive-compulsive disorder. J Clin Psychiatry 1995; 56: 368–373.
Shavitt RG, Belotto C, Curi M, Hounie AG, Rosário-Campos MC, Diniz JB et al. Sensory phenomena and treatment response in obsessive-compulsive disorder, submitted.
Miguel EC, Shavitt RG, Ferrão YA, Brotto SA, Diniz JB . How to treat OCD in patients with Tourette's syndrome. J Psychosom Res 2003; 55: 49–57.
Walitza S, Wewetzer C, Warnke A, Gerlach M, Geller F, Gerber G et al. 5-HT2A promoter polymorphism −1438G/A in children and adolescents with obsessive-compulsive disorders. Mol Psychiatry 2002; 7: 1054–1057.
Hanna GL, Piacentini J, Cantwell DP, Fischer DJ, Himle JA, Van Etten M . Obsessive-compulsive disorder with and without tics in a clinical sample of children and adolescents. Depress Anxiety 2002; 16: 59–63.
Veenstra-VanderWeele J, Kim SJ, Gonen D, Hanna GL, Leventhal BL, Cook EH . Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder. Mol Psychiatry 2001; 6: 160–167.
Fontanelle L, Marques C, Versiani M . The effect of gender on the clinical features and therapeutic response in obsessive-compulsive disorder. Rev Bras Psiquiatria 2002; 24: 7–11.
Miguel EC, Coffey BJ, Baer L, Savage CR, Rauch SL, Jenike MA . Phenomenology of intentional repetitive behaviors in obsessive-compulsive disorder and Tourette's syndrome. J Clin Psychiatry 1995; 56: 246–255.
Miguel EC, Rauch SL, Jenike MA . Obsessive-compulsive disorder. Psychiatric Clin N Am 1997; 20: 863–883.
Pauls DL, Towbin KE, Leckman JF, Zahner GE, Cohen DJ . Gilles de la Tourette's syndrome and obsessive-compulsive disorder: evidence supporting a genetic relationship. Arch Gen Psychiatry 1986; 43: 1180–1182.
Pauls DL, Raymond CL, Stevenson JM, Leckman JF . A family study of Gilles de la Tourette syndrome. Am J Hum Genet 1991; 48: 154–163.
Comings DE, Comings BG . A controlled study of Tourette syndrome. IV. Obsessions, compulsions, and schizoid behaviors. Am J Hum Genet 1987; 41: 782–803.
Robertson MM, Trimble MR, Lees AJ . The psychopathology of the Gilles de la Tourette syndrome. A phenomenological analysis. Br J Psychiatry 1988; 152: 383–390.
Pauls DL, Leckman JF . The inheritance of Gilles de la Tourette's syndrome and associated behaviors: evidence for autosomal dominant transmission. N Engl J Med 1986; 315: 993–997.
Eapen V, Pauls DL, Robertson MM . Evidence for autosomal dominant transmission in Tourette's syndrome—United Kingdom Cohort Study. Br J Psychiatry 1993; 162: 593–596.
Van de Wetering BJM . The Gilles de la Tourette syndrome. A psychiatric–genetic study. PhD theses, Erasmus University, Rotterdam.
Miguel EC, do Rosario-Campos MC, Shavitt RG, Hounie AG, Mercadante MT . The tic-related obsessive-compulsive disorder phenotype and treatment implications. Adv Neurol 2001; 85: 43–55, (review).
Miguel EC, Rosario-Campos MC, Shavitt RG, Hounie AG, Mercadante MT . The tic-related obsessive-compulsive disorder phenotype. Adv Neurol 2000; 85: 43–55.
Swerdlow NR, Zinner S, Farber RH, Seacrist C, Hartston H . Symptoms in obsessive-compulsive disorder and Tourette syndrome: a spectrum? CNS Spectrums 1999; 4: 21–33.
Petter T, Richter MA, Sandor P . Clinical features distinguishing patients with Tourette's syndrome and obsessive-compulsive disorder from patients with obsessive-compulsive disorder without tics. J Clin Psychiatry 1998; 59: 456–459.
Eapen V, Robertson MM, Alsobrook II JP, Pauls DL . Obsessive-compulsive symptoms in Gilles de la Tourette's syndrome and obsessive-compulsive disorder: differences by diagnosis and family history. Am J Med Genet 1997; 74: 432–438.
Holzer JC, Goodman WK, McDougle CJ, Baer L, Boyarsky BK, Leckman JF et al. Obsessive-compulsive disorder with and without a chronic tic disorder: a comparison of symptoms in 70 patients. Br J Psychiatry 1994; 164: 469–473.
George MS, Trimble MR, Ring HA, Sallee FR, Robertson MM . Obsessions in obsessive-compulsive disorder with and without Gilles de la Tourette's syndrome. Am J Psychiatry 1993; 105: 93–97.
Pitman RK . Pierre Janet on obsessive-compulsive disorder (1903). Arch Gen Psychiatry 1987; 44: 226–232.
Rasmussen AS, Tsuang MT . Clinical characteristics and family history in DSM-III obsessive compulsive disorder. Am J Psychiatry 1986; 143: 317–322.
Leckman JF, Walker DE, Goodman WK, Pauls DL, Cohen DJ . ‘Just-right’ perceptions associated with compulsive behavior in Tourette's syndrome. Am J Psychiatry 1994; 151: 675–680.
Leckman JF, Goodman WK, Anderson GM, Riddle MA, Chappell PB, McSwiggan-Hardin Mt et al. Cerebrospinal fluid biogenic amines in obsessive compulsive disorder, Tourette's syndrome, and healthy controls. Neuropsychopharmacology 1995; 12: 73–86.
Mataix-Cols D, Rauch SL, Manzo PA, Jenike MA, Baer L . Use of factor-analyzed symptom dimensions to predict outcome with serotonin reuptake inhibitors and placebo in the treatment of obsessive-compulsive disorder. Am J Psychiatry 1999; 156: 1409–1416.
Baer L . Factor analysis of symptom subtypes of obsessive compulsive disorder and their relation to personality and tic disorders. J Clin Psychiatry 1994; 55: 18–23.
Coffey BJ, Miguel EC, Biederman J, Baer L, Rauch SL, O'Sullivan RL et al. Tourette's disorder with and without obsessive-compulsive disorder in adults: are they different? J Nerv Ment Dis 1998; 186: 201–206.
Bliss J . Sensory experiences of Gilles de la Tourette syndrome. Arch Gen Psychiatry 1980; 37: 1343–1347.
Shapiro AK, Shapiro ES, Young JG, Feinberg TE . Gilles de la Tourette Syndrome. Raven Press: New York, 1988.
Kurlan R, Lichter D, Hewitt D . Sensory tics in Tourette's syndrome. Neurology 1989; 39: 731–734.
Cohen AJ, Leckman JF . Sensory phenomena associated with Gilles de la Tourette's syndrome. J Clin Psychiatry 1992; 53: 319–323.
Leckman JF, Walker DE, Cohen DJ . Premonitory urges in Tourette's syndrome. Am J Psychiatry 1993; 150: 98–102.
Chee KY, Sachdev P . A controlled study of sensory tics in Gilles de la Tourette syndrome and obsessive-compulsive disorder using a structured interview. J Neurol Neurosurg Psychiatry 1997; 62: 188–192.
Rosário-Campos MC . Transtorno obsessivo-compulsivo de início precoce e de início tardio: características clínicas, psicopatológicas e de comorbidade. Dissertação de mestrado, Faculdade de Medicina da Universidade de São Paulo, São Paulo 1998, p 99.
Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischman RL, Hill CL et al. The Yale–Brown obsessive-compulsive scale: I. development use and reliability. Arch Gen Psychiatry 1989; 46: 1006–1011.
Hantouche EG, Lancrenon S . Modern typology of symptoms and obsessive-compulsive syndromes: results of a large French study of 615 patients. Encephale 1996; 22: 9–21.
Summerfeldt LJ, Richter MA, Anthony MM, Huta VM, Swinson RP . Symptom structure in obsessive-compulsive disorder: factor analytic evidence for subgroups. Poster presented at the 150th Annual Meeting of the American Psychiatric Association, San Diego, CA, May 1997.
Summerfeldt LJ, Richter MA, Antony MM, Swinson RP . Symptom structure in obsessive-compulsive disorder: a confirmatory factor-analytic study. Behav Res Ther 1999; 37: 297–311.
Mataix-Cols D, Rauch SL, Baer L, Eisen JL, Shera DM, Goodman WK et al. Symptom stability in adult obsessive compulsive disorder: data from a naturalistic two-year follow-up study. Am J Psychiatry 2002; 159: 263–268.
Tek C, Ulug B . Religiosity and religious obsessions in obsessive-compulsive disorder. Psychiatry Res 2001; 104: 99–108.
Cavallini MC, Di Bella D, Siliprandi F, Malchiodi F, Bellodi L . Exploratory factor analysis of obsessive-compulsive patients and association with 5-HTTLPR polymorphism. Am J Med Genet 2002; 114: 347–353.
Foa EB, Huppert JD, Leiberg S, Langner R, Kichic R, Hajcak G et al. The obsessive-compulsive inventory: development and validation of a short version. Psychol Assess 2002; 14: 485–496.
Feinstein SB, Fallon BA, Petkova E, Liebowitz MR . Item-by-item factor analysis of the Yale–Brown Obsessive Compulsive Scale Symptom Checklist. J Neuropsychiatry Clin Neurosci 2003; 15: 187–193.
Leckman JF, Pauls DL, Zhang H, Rosario-Campos MC, Katsovich L, Kidd KK et al. Tourette Syndrome Association International Consortium for Genetics. Obsessive-compulsive symptom dimensions in affected sibling pairs diagnosed with Gilles de la Tourette syndrome. Am J Med Genet 2003; 116B: 60–68.
Mataix-Cols D, Rosario-Campos MC, Leckman JF . A multidimensional model of obsessive-compulsive disorder. Am J Psychiatry, in press.
Mataix-Cols D, Cullen S, Lange K, Zelaya F, Andrew C, Amaro E et al. Neural correlates of anxiety associated with obsessive-compulsive symptom dimensions in normal volunteers. Biol Psychiatry 2003; 53: 482–493.
Mataix-Cols D, Fullana MA, Alonso P, Menchon JM, Vallejo J . Convergent and discriminate validity of the Yale–Brown Obsessive-Compulsive Scale Symptom Checklist. Psychother Psychosom, in press.
Zhang H, Leckman JF, Tsai C-P, Kidd KK, Rosario Campos MC . The Tourette Syndrome Association International Consortium for Genetics: genome wide scan of hoarding in sibling pairs both diagnosed with Gilles de la Tourette syndrome. Am J Hum Genet 2002; 70: 896–904.
Black DW, Monahan P, Gable J, Blum N, Clancy G, Baker P . Hoarding and treatment response in 38 nondepressed subjects with obsessive-compulsive disorder. J Clin Psychiatry 1998; 59: 420–425.
Alonso P, Menchon JM, Pifarre J, Mataix-Cols D, Torres L, Salgado P et al. Long-term follow-up and predictors of clinical outcome in obsessive-compulsive patients treated with serotonin reuptake inhibitors and behavioral therapy. J Clin Psychiatry 2001; 62: 535–540.
Saxena S, Maidment KM, Vapnik T, Golden G, Rishwain T, Rosen RM et al. Obsessive-compulsive hoarding: symptom severity and response to multimodal treatment. J Clin Psychiatry 2002; 63: 21–27.
Rauch SL, Dougherty DD, Shin LM, Alpert NM, Manzo P, Leahy L et al. Neural correlates of factor-analyzed OCD symptom dimensions: a PET study. CNS Spectrums 1998; 3: 37–43.
The Tourette Syndrome International Consortium for Genetics. A complete genome screen in sib pairs affected by Gilles de la Tourette syndrome. Am J Hum Genet 1999; 65: 1428–1436.
McHugh PR, Slavney PR (eds). The Perspectives of Psychiatry. Johns Hopkins: Baltimore, 1988.
Costa Jr PT, McCrae RR . Revised NEO Personality Inventory (NEO PI-R) Professional Manual. Psychological Assessment Resources: Odessa, FL, 1992.
Lesch K-P, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996; 274: 1527–1531.
Greenberg BD, Li Q, Lucas FR, Hu S, Sirota LA, Benjamin J et al. Association between the serotonin transporter promoter polymorphism and personality traits in a primarily female population sample. Am J Med Genet 2000; 96: 202–216.
Jacob CP, Strobel A, Hohenberger K, Ringel T, Gutknecht L, Reif A et al. Association between allelic variation of serotonin transporter function and neuroticism in anxious cluster C personality disorders. Am J Psychiatry 2004; 161: 569–572.
Nestadt G, Samuels J, Riddle MA, Liang K-Y, Bienvenu OJ, Hoehn-Saric R et al. The relationship between obsessive-compulsive disorder and anxiety and affective disorders: results from the Johns Hopkins OCD family study. Psychol Med 2001; 31: 481–487.
Bienvenu OJ, Samuels JF, Riddle MA, Hoehn-Saric R, Liang KY, Cullen BAM et al. The relationship of obsessive-compulsive disorder to possible spectrum disorders: results from a family study. Biol Psychiatry 2000; 48: 287–293.
Gonzales CH . Estudo de famílias no transtorno obsessivo-compulsivo. Tese de doutorado—Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2003, p 227.
Cavallaro R, Galardi G, Cavallini MC, Henin M, Amodio S, Bellodi L et al. Obsessive compulsive disorder among idiopathic focal dystonia patients: an epidemiological and family study. Biol Psychiatry 2002; 52: 356–361.
Nestadt G, Addington A, Samuels J, Liang K, Bienvenu OJ, Riddle M et al. The identification of OCD-related subgroups based on comorbidity. Biol Psychiatry 2003; 53: 914–920.
Chacon P, Rosario-Campos MC, Hounie AG, Lopes AC, Curi M, Miguel EC . Comment on ‘the identification of OCD-related subgroups based on comorbidity’. Biol Psychiatry 2004; 55: 960–961.
Faraone SV, Tsuang MT, Tsuang DW (eds). Genetics of Mental Disorders: A Guide for Students, Clinicians, and Researchers. The Guilford Press: New York, 1999, p 272.
Torres AR, Dedomenico AM, Crepaldi AL, Miguel EC . Obsessive-compulsive symptoms in patients with panic disorder. Compr Psychiatry 2004; 45: 219–224.
Bellodi L, Cavallini MC, Bertelli S, Chiapparino D, Riboldi C, Smeraldi E . Morbidity risk for obsessive-compulsive spectrum disorders in first-degree relatives of patients with eating disorders. Am J Psychiatry 2001; 158: 563–569.
Dykens E, Shah B . Psychiatric disorders in Prader–Willi syndrome: epidemiology and management. CNS Drugs 2003; 17: 167–178.
Clarke DJ, Boer H, Whittington A, Holland JB . Prader–Willi syndrome, compulsive and ritualistic behaviors: the first population-based survey. Br J Psychiatry 2002; 180: 358–362.
Wigren M, Hansen S . Rituals and compulsivity in Prader–Willi syndrome: profile and stability. J Intellect Disabil Res 2003; 47: 428–438.
Dykens EM, Leckman JF, Cassidy SB . Obsessions and compulsions in Prader–Willi syndrome. J Child Psychol Psychiatry 1996; 37: 995–1002.
State MW, Dykens EM, Rosner B, Martin A, King BH . Obsessive-compulsive symptoms in Prader–Willi and ‘Prader–Willi-like’ patients. J Am Acad Child Adolesc Psychiatry 1999; 38: 329–334.
Wassink TH, Piven J, Patil SR . Chromosomal abnormalities in a clinic sample of individuals with autistic disorder. Psychiatr Genet 2001; 11: 57–63.
Hollander E, King A, Delaney K, Smith CJ, Silverman JM . Obessive-compulsive behaviors in parents of multiplex autism families. Psychiatry Res 2003; 117: 11–16.
Millet B, Chabane N, Delorme R, Leboyer M, Leroy S, Poirier MF et al. Association between the dopamine receptor D4 (DRD4) gene and obsessive-compulsive disorder. Am J Med Genet 2003; 116B: 55–59.
Cruz C, Camarena B, King N, Páez F, Sidenberg D, Fuente JR et al. Increased prevalence of the seven- variant of the dopamine D4 receptor gene in patients with obsessive-compulsive disorders with tics. Neurosci Lett 1997; 231: 1–4.
Nicolini H, Cruz C, Camarena B, Orozco B, Kennedy JL, King N et al. DRD2, DRD3, and 5HTDA receptor genes polymorphisms in obsessive-compulsive disorder. Mol Psychiatry 1996; 1: 461–465.
Nicolini H, Cruz C, Páez F, Camarena B . Los genes de los receptores a dopamina D2 y D4 distinguen la presencia clínica de tics en el trastorno obsesivo-compulsivo. Gac Med Mex 1998; 8: 163–169.
Urraca N, Camarena B, Gomez-Caudillo L, Esmer MC, Nicolini H . Micro opioid receptor gene as a candidate for the study of obsessive compulsive disorder with and without tics. Am J Med Genet 2004; 127B: 94–96.
Kelsoe JR . Arguments for the genetic basis of the bipolar spectrum. J Affect Disord 2003; 73: 183–197.
Reif A, Lesch KP . Toward a molecular architecture of personality. Behav Brain Res 2003; 139: 1–20.
Jonnal AH, Gardner CO, Prescott CA, Kendler KS . Obsessive and compulsive symptoms in a general population sample of female twins. Am J Med Genet 2000; 96: 791–796.
Eley TC, Bolton D, O'Connor TG, Perrin S, Smith P, Plomin R . A twin study of anxiety-related behaviours in pre-school children. J Child Psychol Psychiatry 2003; 44: 945–960.
Capstick N, Seldrup J . Obsessional states. A study in the relationship between abnormalities occurring at the time of birth and the subsequent development of obsessional symptoms. Acta Psychiatr Scand 1977; 56: 427–431.
Lensi P, Cassano GB, Correddu G, Ravagli S, Kunovac JL, Akiskal HS . Obsessive-compulsive disorder—familial–developmental history, symptomatology, comorbidity and course with special reference to gender-related differences. Br J Psychiat 1996; 169: 101–107.
Santangelo SL, Pauls DL, Goldstein J, Faraone SV, Tsuang MT, Leckman JF . Tourette's syndrome: what are the influences of gender and comorbid obsessive-compulsive disorder? J Am Acad Child Adolesc Psychiatry 1994; 33: 795–804.
Peterson BS, Leckman JF, Scahill L, Naftolin F, Keefe D, Charest NJ et al. Hypothesis: steroid hormones and sexual dimorphisms modulate symptom expression in Tourette's syndrome. Psychoneuroendocrinology 1992; 17: 553–563.
Altemus M, Greenberg BD, Keuler D, Jacobson KR, Murphy DL . Open trial of flutamide for treatment of obsessive-compulsive disorder. J Clin Psychiatry 1999; 60: 442–445.
Pollitt J . Natural history of obsessional states. BMJ 1957; 9: 133–140.
Ingram IM . Obsessional illness in mental hospital patients. J Mental Sci 1961; 107: 382–402.
Lo WH . A follow-up study of obsessional neurotics in Hong Kong Chinese. Br J Psychiatry 1967; 113: 823–832.
Neziroglu F, Anemone R, Yaryura-Tobias J . Onset of obsessive-compulsive disorder in pregnancy. Am J Psychiatry 1992; 149: 947–950.
Maina G, Albert U, Bogetto F, Vaschetto P, Ravizza L . Recent life events and obsessive-compulsive disorder (OCD): the role of pregnancy/delivery. Psychiatry Res 1999; 89: 49–58.
Abramowitz JS, Schwartz SA, Moore KM, Luenzmann KR . Obsessive-compulsive symptoms in pregnancy and the puerperium: a review of the literature. J Anxiety Disord 2003; 17: 461–478.
Abramowitz J, Moore K, Carmin C, Wiegartz PS, Purdon C . Acute onset of obsessive-compulsive disorder in males following childbirth. Psychossomatics 2001; 42: 429–431.
Leckman JF, Goodman WK, North WG, Chappell PB, Price LH, Pauls DL et al. Elevated levels of CSF oxytocin in obsessive compulsive disorder: comparison with Tourette's syndrome and healthy controls. Arch Gen Psychiatry 1994; 51: 782–792.
Leckman JF, Mayes LC, Feldman R, Evans D, King RA, Cohen DJ . Early parental preoccupations and behaviors and their possible relationship to the symptoms of obsessive-compulsive disorder. Acta Psychiat Scand 1999; 100(Suppl 396): 1–26.
McKeon J, Roa B, Mann A . Life events and personality traits in obsessive-compulsive neurosis. Br J Psychiatry 1984; 144: 185–189.
Khanna S, Rajendra PN, Channabasavanna SM . Live events and onset of obsessive-compulsive disorder. Int J Soc Psychiatry 1988; 34: 305–309.
Gershuny BS, Baer L, Radomsky AS, Wilson KA, Jenike MA . Connections among symptoms of obsessive-compulsive disorder and posttraumatic stress disorder: a case series. Behav Res Ther 2003; 41: 1029–1041.
Gershuny BS, Baer L, Radomsky AS, Wilson KA, Jenike MA . Comorbid posttraumatic stress disorder: impact on treatment outcome for obsessive-compulsive disorder. Am J Psychiatry 2002; 159: 852–854.
Swedo SE . Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Mol Psychiatry 2002; 7(Suppl 2): S24–S25.
Asbahr FR, Negrao AB, Gentil V, Zanetta DM, da Paz JA, Marques-Dias MJ et al. Obsessive-compulsive and related symptoms in children and adolescents with rheumatic fever with and without chorea: a prospective 6-month study. Am J Psychiatry 1998; 155: 1122–1124.
Mercadante MT, Busatto GF, Lombroso PJ, Prado L, Rosario-Campos MC, do Valle R et al. The psychiatric symptoms of rheumatic fever. Am J Psychiatry 2000; 157: 2036–2038.
Hounie AG, Pauls DL, Mercadante MT, Rosario-Campos MC, Shavitt RG, De Mathis MA et al. Obsessive-compulsive spectrum disorders in rheumatic fever with and without Sydenham's chorea. J Clin Psychiatry 2004; 65: 994–999.
Mercadante MT, Hounie AG, Muniz JB, Miguel EC, Lombroso PJ . The basal ganglia and immune-based neuropsychiatric disorders. Psychiatric Annals 2001; 31: 534–540.
Guilherme L, Kalil J . Rheumatic fever: the T cell response leading to autoimmune aggression in the heart. Autoimmun Rev 2002; 1: 261–266.
Kirvan CA, Swedo SE, Heuser JS, Cunningham MW . Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nat Med 2003; 9: 914–920.
Donadi EA, Smith AG, Louzada-Junior P, Voltarelli JC, Nepom GT . HLA class I and class II profiles of patients presenting with Sydenham's chorea. J Neurol 2000; 247: 122–128.
Stanevicha V, Eglite J, Sochnevs A, Gardovska D, Zavadska D, Shantere R . HLA class II associations with rheumatic heart disease among clinically homogeneous patients in children in Latvia. Arthritis Res Ther 2003; 5: R340–R346.
Cunningham MW . Pathogenesis of groups A streptococcal infections. Microbiol Rev 2000; 13: 470–511.
Murphy T, Goodman W . Genetics of childhood disorders: XXXIV. Autoimmune disorders, part 7: D8/17 reactivity as an immunological marker of susceptibility to neuropsychiatric disorders. J Am Acad Child Adolesc Psychiatry 2002; 41: 98–100.
Inoff-Germain G, Rodriguez RS, Torres-Alcantara S, Diaz-Jimenez MJ, Swedo SE, Rapoport JL . An immunological marker (D8/17) associated with rheumatic fever as a predictor of childhood psychiatric disorders in a community sample. J Child Psychol Psychiatry 2003; 44: 782–790.
Zai G, Bezchlibnyk YB, Richter MA, Arnold P, Burroughs E, Barr CL et al. Myelin oligodendrocyte glycoprotein (MOG) gene is associated with obsessive-compulsive disorder. Am J Med Genet 2004; 129: 64–68.
Lougee L, Perlmutter SJ, Nicolson R, Garvey MA, Swedo SE . Psychiatric disorders in first-degree relatives of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). J Am Acad Child Adolesc Psychiatry 2000; 39: 1120–1126.
Rauch SL . Preparing for psychiatry in the 21st century. In: Stern TA, Herman JB (eds) Psychiatry Update and Board Preparation. McGraw-Hill: New York, 2000, pp 579–583.
Rauch SL, Shin LM, Dougherty DD, Alpert NM, Fischman AJ, Jenike MA . Predictors of fluvoxamine response in contamination-related obsessive-compulsive disorder: a PET symptom provocation study. Neuropsychopharmacology 2002; 27: 782–791.
Saxena S, Rauch SL . Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder. Psychiatr Clin N Am 2000; 23: 563–586.
Kosslyn SM, Plomin R . Toward a neurocognitive genetics: goals and issues. In: Dougherty DD, Rauch SL (eds) Psychiatric Neuroimagaign Research: Contemporary Strategies. American Psychiatric Publishing Inc.: Washington, DC, 2001, pp 383–402.
Saxena S, Brody AL, Ho ML, Alborzian S, Ho MK, Maidment KM et al. Cerebral metabolism in major depression and obsessive-compulsive disorder occurring separately and concurrently. Biol Psychiatry 2001; 50: 159–170.
Busatto GF, Buchpiguel CA, Zamignani DR, Garrido GEJ, Glabus MF, Rosario-Campos MC et al. Regional cerebral blood flow differences in obsessive-compulsive disorder subtyped according to the age of illness onset. J Am Acad Child Adolesc Psychiatry 2001; 40: 347–354.
Phillips ML, Marks IM, Senior C, Lythgoe D, O'Dwyer A-M, Meehan O et al. A differential neural response in obsessive-compulsive disorder patients with washing compared with checking symptoms to disgust. Psychol Med 2000; 30: 1037–1050.
Saxena S, Brody AL, Maidment KM, Smith EC, Zohrabi N, Katz E et al. Cerebral glucose metabolism in obsessive-compulsive hoarding. Am J Psychiatry 2004; 161: 1038–1048.
Mataix-Cols D, Woonderson S, Lawrence N, Brammer MJ, Speckens A, Phillips ML . Distinct neural correlates of washing, checking, and hoarding symptom dimensions in obsessive-compulsive disorder. Arch Gen Psychiatry 2004; 61: 564–576.
Pujol J, Soriano-Mas C, Alonso P, Cardoner N, Menchon JM, Deus J et al. Mapping structural brain alterations in obsessive-compulsive disorder. Arch Gen Psychiatry 2004; 61: 720–730.
Hariri AR, Weinberger DR . Imaging genomics. Br Med Bull 2003; 65: 259–270.
Hariri AR, Mattay VS, Tessitore A, Kolachana B, Fera F, Goldman D et al. Serotonin transporter genetic variation and the response of the human amygdala. Science 2002; 297: 400–403.
McDougle CJ, Goodman WK, Leckman JF, Lee NC, Heninger GR, Price LH . Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder: a double-blind placebo-controlled study in patients with and without tics. Arch Gen Psychiatry 1994; 51: 302–308.
McDougle CJ, Goodman WK, Leckman JF, Barr LC, Heninger GR, Price LH . The efficacy of fluvoxamine in obsessive-compulsive disorder: effects of comorbid chronic tic disorder. J Clin Psychopharmacol 1993; 13: 354–358.
Erzegovesi S, Cavallini MC, Cavedini P, Diaferia G, Locatelli M, Bellodi L . Clinical predictors of drug response in obsessive-compulsive disorder. J Clin Psychopharmacol 2001; 21: 488–492.
Alarcon LD, Llibb JW, Spitler D . A predictive study of obsessive-compulsive disorder response to clomipramine. J Clin Psychopharmacol 1993; 13: 210–213.
Neziroglu FA, Stevens PK, Yaryura-Tobias JA . Overvalued ideas and their impact on treatment outcome. Rev Bras Psiquiatr 1999; 21: 209–216.
Mundo E, Erzegovesi S, Bellodi L . Follow-up of obsessive-compulsive patients treated with proserotonergi agents. J Clin Psychopharmacol 1995; 15: 288–289.
Baer L, Jenike MA, Black DW, Treece C, Rosenfeld R, Greist J . Effects of Axis II diagnoses on treatment outcome with clomipramine in 55 patients with obsessive-compulsive disorder. Arch Gen Psychiatry 1992; 49: 862–866.
McDougle CJ, Goodman WK, Price LH, Delgado PL, Krystal JH, Charney DS et al. Neuroleptic addition in fluvoxamine-refractory obsessive-compulsive disorder. Am J Psychiatry 1990; 147: 652–654.
Minichiello WE, Baer L, Jenike MA . Schizotypal personality disorder: a poor prognostic indicator for behavior therapy in the treatment of obsessive-compulsive disorder. J Anxiety Disord 1987; 1: 273–276.
Hollander E, Bienstock CA, Koran LM, Pallanti S, Marazziti D, Rasmussen SA et al. Refractory obsessive-compulsive disorder state-of-art treatment. J Clin Psychiatry 2002; 63(Suppl 6): 20–29, (review).
Neziroglu F, Pinto A, Yaryura-Tobias JA, McKay D . Overvalued ideation as a predictor of fluvoxamine response in patients with obsessive-compulsive disorder. Psychiatry Res 2004; 125: 53–60.
McDougle CJ, Epperson CN, Price LH, Gelernter J . Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive-compulsive disorder. Mol Psychiatry 1998; 3: 270–273.
Di Bella D, Erzegovesi S, Cavallini MC, Bellodi L . Obsessive-compulsive disorder, 5-HTTLPR polymorphism and treatment response. Pharmacogenomics J 2002; 2: 176–181.
Wong ML, Licinio J . From monoamines to genomic targets: a paradigm shift for drug discovery in depression. Nat Rev Drug Discov 2004; 3: 136–151.
Rosario-Campos MC, Miguel EC, Quatrano S, Chacon P, Ferrao Y, Findley D et al. The Dimensional Yale–Brown Obsessive Compulsive Scales (DY-BOCS): a new instrument for assessing obsessive-compulsive symptom dimensions, submitted.
This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP): #99/08560-6 to Dr Miguel, #99/08560-6 to Dr Mercadante, #98/15013-9 to Dr Hounie, #03/07451-6 to Dr Rosario-Campos and #06697-6 to Dr Chacon. This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ), Brazil (grant #521369/96-7) to Dr Miguel and MackPesquisa to Dr Mercadante.
Rights and permissions
About this article
Cite this article
Miguel, E., Leckman, J., Rauch, S. et al. Obsessive-compulsive disorder phenotypes: implications for genetic studies. Mol Psychiatry 10, 258–275 (2005). https://doi.org/10.1038/sj.mp.4001617
- obsessive-compulsive disorder
- obsessive behaviors
- compulsive behaviors
- molecular genetics
This article is cited by
A dimensional perspective on the genetics of obsessive-compulsive disorder
Translational Psychiatry (2021)
Toward a neurocircuit-based taxonomy to guide treatment of obsessive–compulsive disorder
Molecular Psychiatry (2021)
Perceived Stress in Relation to Obsessions and Compulsions in South Asian Adults: Moderating Role of Socio-demographic Characteristics
Community Mental Health Journal (2020)
Inhibition-related differences between tic-free and tic-related obsessive–compulsive disorder: evidence from the N2 and P3
Experimental Brain Research (2019)
Evolution of gamma knife capsulotomy for intractable obsessive-compulsive disorder
Molecular Psychiatry (2019)